Guidelines of the Spanish ITP Group for the diagnosis, treatment and follow-up of patients with immune thrombocytopenia

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Lozano, Miguel A. Sanz, Vicente Vicente" "autores" => array:4 [ 0 => array:4 [ "nombre" => "María L." "apellidos" => "Lozano" "email" => array:1 [ 0 => "mllozano@um.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Miguel A." "apellidos" => "Sanz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Vicente" "apellidos" => "Vicente" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:2 [ "colaborador" => "Spanish ITP Group - GEPTI" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "◊" "identificador" => "fn0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Grupo de Investigación CB15/00055, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Hospital General Universitario Morales Meseguer, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Hospital Universitari i Politècnic La Fe, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recomendaciones del Grupo Español de PTI para el diagnóstico, tratamiento y seguimiento de pacientes con trombocitopenia inmune" ] ] "textoCompleto" => "Primary immune thrombocytopenia (ITP, immune thrombocytopenic purpura, also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia) is a complex acquired autoimmune disease in which there is humoral and cellular dysregulation leading to defects in platelet production and increased platelet destruction. The fact that the presentation, characteristics, and clinical course are highly variable and heterogeneous makes decision-making regarding diagnosis, treatment, and follow-up of these patients particularly difficult.In 2011, a consensus document was prepared for the first time in our country, which became the reference for the diagnosis and treatment of ITP in Spain<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. The introduction of new therapeutic options in the last decade has led to the reissuing of a series of international guidelines for the treatment of these patients in the last 2 years<a class="elsevierStyleCrossRefs" href="#bib0010">2–5</a>. In our country, promoted by the Spanish ITP Group and the Spanish Society of Haematology and Hemotherapy, we have also updated the guidelines for the diagnosis, treatment, and follow-up of patients with ITP<a class="elsevierStyleCrossRef" href="#bib0030">6</a>. The main recommendations of the manual have been included in this document, which aims to serve as a practical tool to facilitate the comprehensive management of the different aspects related to this disease.We are aware that this is a rapidly evolving field and that the therapeutic approach to the disease is expected to change in the near future. We recognise that guidelines are intended to provide guidance only and that many of the guidelines and recommendations in the Spanish consensus document, as in other available guidelines, are derived from expert opinion and non-comparative studies with a low level of evidence.General concepts, diagnosis and quality of life, and complementary and alternative treatmentsITP is defined as a platelet count below 100 × 109/l with no identified cause (primary ITP) or related to other conditions leading to immune-mediated destruction of platelets (secondary ITP). Its incidence in both adults and children is 2–4 cases per 100,000 inhabitants-year. Prevalence is higher in adults (10 per 100,000) compared to children (5 per 100,000), as the disease resolves in most children. Not only does ITP present with haemorrhagic manifestations, when platelet counts are below 20−30 × 109/l, but fatigue is also a common symptom. A predisposition to thrombotic events, infections and the development of other autoimmune diseases has been observed in some cases. Most children and more than a third of adults will experience a self-limiting disease course. According to the standardised terminology adopted in 2009<a class="elsevierStyleCrossRef" href="#bib0035">7</a>, the following disease stages are defined: (i) newly diagnosed (less than 3 months); (ii) persistent (3–12 months since diagnosis); and (iii) chronic (lasting more than 12 months).In contrast to the therapeutic advances of the last decade, the diagnosis of the disease has not evolved, with a lack of a reliable biomarker and unequivocal confirmatory tests. The diagnosis remains primarily a clinical one and one of exclusion of other causes of thrombocytopenia. For the typical patient with suspected ITP, the rule of thumb is to restrict testing that is usually going to be non-informative, after confirming that there are no findings on history, physical examination, peripheral blood smear, immunoglobulin levels and viral serologies that may be indicative of another process. Routine bone marrow study is not recommended, except if the response to treatment is inadequate or if there are other abnormalities in the blood smear or in the clinical presentation that raise suspicions for other diagnoses (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Because of these limitations, it has been estimated that one in every 7 patients may be misdiagnosed with ITP<a class="elsevierStyleCrossRef" href="#bib0040">8</a>, so efforts need to be made in this area.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The quality of life of patients with ITP is reduced to levels comparable to those experienced by patients with other chronic diseases such as cancer, arthritis and diabetes<a class="elsevierStyleCrossRef" href="#bib0045">9</a>. Appropriate treatment of ITP includes not only increasing the platelet count, but also considering that in adults it often behaves as a chronic disease, with a relatively good prognosis in terms of survival, therefore attempts should be made to minimise the impact of the disease on the patient's quality of life. Patients with ITP often use alternative and complementary treatments<a class="elsevierStyleCrossRef" href="#bib0050">10</a>; the lack of information about the safety and interactions of many of these products means that they may need to be monitored more closely.The key points of the guidelines regarding general concepts, diagnosis and quality of life, and alternative and complementary therapies are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.First-line, second-line and multidrug-resistant patient treatmentThe goal of treatment is to stop any active bleeding and prevent future haemorrhage. Treatment should be initiated in newly diagnosed adult patients with bleeding or platelet counts below 20 × 109/l (less than 30 × 109/l if they are older than 65 years or have predisposing factors for bleeding). During the course of the disease, these criteria do not necessarily apply to second treatments, when the patient's decisions become especially important.First-line treatment has not changed much, as glucocorticoids remain the primary agent, but the recommended duration of treatment to minimise side-effects has been modified. The initial dose of prednisone (0.5−1 mg/kg/day; maximum 80 mg/day) should not be maintained for more than 3 weeks (2 weeks if no response) and should be discontinued within 8 weeks of initiation after tapering. An alternative is dexamethasone 40 mg/day for 4 days every 2 weeks, for a maximum of 3 cycles. Although the increases in platelet counts after dexamethasone are faster than with prednisone, in the long term there is no difference in response rates between the two agents<a class="elsevierStyleCrossRef" href="#bib0055">11</a>. In patients with bleeding or contraindication to steroid treatment, the use of intravenous immunoglobulins (IV Ig) is recommended at a dose of 1 g/kg 1–2 days, or 0.4 g/kg for 3–5 days in people over 65 years of age. If severe bleeding is present, in addition to IV Ig, high-dose methylprednisolone, platelet transfusion and consideration of thrombopoietin receptor agonists (TPO-RA, "thrombopoietin receptor agonists") are recommended. There is more experience with romiplostim at doses of 5−10 μg/kg<a class="elsevierStyleCrossRef" href="#bib0060">12</a>, although there is no reason to think that 75 mg/day of eltrombopag would not also be effective. Combination treatments of first-line steroids with rituximab, TPO-RA or immunosuppressants are not recommended, as although they are more effective in the long term, they are also associated with more adverse reactions<a class="elsevierStyleCrossRefs" href="#bib0065">13–15</a>.Although initial response rates to glucocorticoids may be high, most adult patients will relapse, with re-exposure to these treatments in non-emergency situations being inappropriate. Second-line treatment presents solid evidence based on randomized studies with TPO-RA (romiplostim and eltrombopag are currently approved in our country, and it is foreseeable that avatrombopag will be approved in the future), fostamatinib and rituximab. So far, no randomised trials comparing them have been conducted. The mechanism of action of these agents is different in that while rituximab and fostamatinib would reduce platelet destruction by different pathways (decreased autoantibody synthesis and phagocytosis, respectively), TPO-RAs would promote platelet production. Due to the excellent efficacy and safety profile, and the existing experience of more than a decade, the Spanish guidelines state that the second-line treatment of choice in most patients should be a TPO-RA. With these agents, a response is achieved in more than 80% of patients<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a>, without showing cross resistance<a class="elsevierStyleCrossRef" href="#bib0090">18</a>. As will be shown in a later section, a significant percentage of patients will be able to discontinue other treatments and even the TPO-RA themselves, while maintaining platelet counts. If there is resistance to a TPO-RA, switching to another TPO-RA, adding an immunosuppressant, or switching to rituximab, fostamatinib or even performing a splenectomy should be considered. Fostamatinib also produces rapid and long-lasting platelet increases in 40–45% of patients with previous treatment failure<a class="elsevierStyleCrossRef" href="#bib0095">19</a>. Fostamatinib also produces rapid and long-lasting platelet increases in 40–45% of patients with failed previous treatments19. Lower responses are seen in heavily pre-treated patients, but efficacy reaches 75% when initiated as the first second-line treatment option<a class="elsevierStyleCrossRef" href="#bib0100">20</a>. Since this is a relatively new agent, there is no robust data on long-term remissions yet. Rituximab has no approved indication in ITP, but there is extensive experience with its use<a class="elsevierStyleCrossRef" href="#bib0105">21</a>. Global responses have been reported in 40–60% of patients, but less than 20% of adults maintain a long-lasting response. The efficacy is remarkably similar between the standard dose of anti-CD20 (375 mg/m2), and the reduced dose (100 mg) administered in 4 consecutive weeks, although in the second case the cost and adverse reactions are lower<a class="elsevierStyleCrossRef" href="#bib0110">22</a>. The main advantages of splenectomy are efficacy and cost, with initial responses in approximately 80% of patients and long-term responses in 50–60%<a class="elsevierStyleCrossRef" href="#bib0115">23</a>. The limitations that must be weighed in recommending this treatment are the lifetime risks of thrombosis and serious infections. Splenectomy (ideally laparoscopic) should only be considered in chronic phases of the disease, when at least one second-line drug therapy has failed.Multidrug-resistant ITP is a serious and life-threatening situation that affects 5−15% of patients. In these cases, the diagnosis of ITP should be reconsidered, and a bone marrow study is indicated, and a combination of therapeutic agents with different mechanisms of action that promote platelet production and inhibit platelet destruction should be used. These combinations usually include TPO-RA and immunosuppressants<a class="elsevierStyleCrossRef" href="#bib0120">24</a> (mycophenolate, azathioprine, or rituximab). If there is significant bleeding and the patient does not respond to IV Ig, a combined treatment with TPO-RA and vinca derivatives (vincristine or vinblastine) may be indicated.The key points of the guidelines regarding first and second line treatment, as well as the multidrug-resistant patient, are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Patient follow-up, vaccination, preparation for surgery and treatment discontinuationPatients should be admitted if they present with: (i) bleeding WHO grade ii (moderate) and platelet < 30 × 109/l, or ii) haemorrhage ≥ iii (requiring red blood cell transfusion) regardless of platelet count. Even in the absence of bleeding episodes, newly diagnosed patients with platelets < 20 × 109/l (but not those with established ITP) should be hospitalised. This is due to the uncertainty that may initially exist about the diagnosis, the need to assess platelet progression and haemorrhagic complications, as well as to ensure the correct administration of treatment. Patients with established disease and severe thrombocytopenia who are not hospitalised should be informed about the symptoms that warrant medical attention.Without appropriate vaccination, splenectomised patients have severe bacterial infections up to 50 times more often than those who have not undergone surgery, caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis in 50–90%, 5−15% and 5−15% of cases, respectively<a class="elsevierStyleCrossRef" href="#bib0125">25</a>. Vaccines reduce, but do not eliminate, this risk; they should be administered at least 2 weeks before splenectomy and in case of an emergency intervention, they will be vaccinated as soon as possible and up to 2 weeks after surgery. In the follow-up of ITP patients, certain diseases that are over-represented should be monitored: diabetes, renal failure, hypertension, and vascular disease (2 times higher), thyroid disease (2.5 times), other autoimmune diseases (5 times) and haematological malignancies (between 6 and 20 times).If the patient is to undergo a surgical procedure during follow-up, the optimal platelet target required remains controversial. However, counts above 50 × 109/l are recommended for minor surgery with standard risk of bleeding, but above 80−100 × 109/l for major surgery and central nervous system interventions. In emergency situations, platelet transfusion along with IV Ig should be considered. The onset of action of Ig iv is approximately 24–48 h, while glucocorticoids may take 3–10 days. If a 3-week interval is available before elective surgery, TPO-RA may be a reasonable alternative. The administration of romiplostim (weekly dose of 3 μg/kg) or eltrombopag (conventional doses of 50 mg/day) for 14–21 days before surgery is effective and safe. For most cases, the limited duration of administration of these drugs does not raise concerns about potential adverse reactions, such as prothrombotic effects.Except for surgical preparation, TPO-RAs are generally administered as an ongoing treatment. It is currently known that between 20−30% of patients can maintain a sustained platelet response after tapering and discontinuation of TPO-RA. It is recommended to assess in patients with stable platelet counts (between 50 and 100 × 109/l more than 6 months or > 100 × 109/l maintained for 3 months) the gradual reduction of these agents and eventual discontinuation of treatment. More caution should be exercised in patients with a significant bleeding history, age over 75, common platelet fluctuations, or with concomitant treatments that predispose to bleeding. TPO-RA treatment should not be discontinued abruptly. It is preferred to taper, and if possible, discontinue, the drug progressively over a period of 3–12 months. The decisive factor in determining the rate at which tapering occurs is the patient's response to the dose reduction. This discontinuation should be stopped if the platelet count falls between 30 and 50 × 109/l; in this case, patients should resume TPO-RA at the lowest dose capable of inducing a response.The key points of the guidelines regarding patient follow-up and vaccination, preparation for surgery, and treatment discontinuation are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Immune thrombocytopenia in children, the elderly and pregnant womenITP in children is generally self-limiting. The diagnostic approach is similar to that of adults. Most children with newly diagnosed ITP lack significant bleeding symptoms and do not require treatment. However, it is essential that parents and children with ITP understand the risks of serious or life-threatening bleeding. At the time of diagnosis, hospital admission should be considered in patients with active grade iii-iv bleeding or bleeding risk factors in addition to the platelet count. Treatment is aimed at preventing, but above all at treating bleeding, with IV Ig and/or glucocorticoids being the most widely used first-line treatments. Steroids are given in higher doses and in much shorter regimens than in adults. In second-line treatment, in case of a haemorrhagic emergency, IV Ig and/or glucocorticoids will be administered, but if the patient requires maintenance treatment, TPO-RA is the treatment of choice. In multidrug-resistant patients, in addition to performing a bone marrow study, hereditary thrombocytopenia must be ruled out. If the diagnosis of ITP is confirmed, additional treatments in this situation would include rituximab, splenectomy or immunosuppressants such as mycophenolate mofetil.The incidence of ITP in adults increases with age, reaching 9/100,000 person-years in men > 75 years of age<a class="elsevierStyleCrossRefs" href="#bib0130">26,27</a>. Isolated thrombocytopenia may be the consequence of a myelodysplastic syndrome in this population; if there are reasonable diagnostic doubts, it is recommended to consider performing a bone marrow study that includes cytogenetics and flow cytometry. Elderly patients with ITP are at increased risk of bleeding, thrombosis, and infections, have more adverse reactions related to ITP treatments, and require more concomitant therapies such as antiplatelet or anticoagulant agents. A more active therapeutic strategy may be considered in clinical practice for a platelet count between 30−50 × 109/l in ≥ 65 years with comorbidities or a history of bleeding. The possibility of modulating the dose of first-line treatments should be considered in older patients. Dexamethasone will be avoided, and prednisone will be increased to 0.5 mg/kg/day or Ig IV at 0.4 g/kg/day for 5 days with abundant hydration before and after infusion, and renal function monitoring. Second line splenectomy is not recommended except in exceptional situations due to the greater thrombotic and infectious risk. Infectious complications are also somewhat more common than in young patients after B-cell depletion with rituximab, although it is not contraindicated. TPO-RAs have a good safety and efficacy profile in the elderly and have become the main second-line therapeutic option in this group of patients, even if their use is associated with a possible increased risk of thrombosis. This increased risk of vascular phenomena is partly justified by the significantly more unfavourable prothrombotic conditions prior to its administration. Other drugs, such as dapsone and danazol, have a well-known efficacy and safety profile and could be a valid option among elderly patients with moderate disease.In pregnant women with suspected ITP, other causes of thrombocytopenia due to specific pregnancy conditions should also be ruled out. About 80% of cases of thrombocytopenia during pregnancy are attributed to gestational thrombocytopenia, characterised by a gradual decrease in platelet count that usually begins in the mid-second trimester and lasts into the third trimester. If platelet counts decrease before this time or if thrombocytopenia is severe and abrupt (platelets < 30−50 × 109/l), in 9% of cases it is due to hypertensive disorders and in a similar percentage to immune conditions. Glucocorticoids and IV Ig are the basis of ITP treatment in pregnancy. Rituximab is not recommended in this period, and mycophenolate mofetil or vinca alkaloids are contraindicated. Azathioprine (although it has a slow onset of action) or cyclosporine (with blood pressure monitoring) could be used instead. Data on the safety and efficacy of splenectomy during pregnancy are limited. In exceptional situations, the use of TPO-RA may be considered. There are preliminary data that support that the temporary and off-label use of these agents in severe or refractory disease is safe for the mother and the new-born, especially if they are administered in the third trimester<a class="elsevierStyleCrossRef" href="#bib0140">28</a>. In women who cannot maintain a stable platelet count above 30 × 109/l with standard treatment or if there is a history of previous pregnancies with severe thrombocytopenia in the new-born, future pregnancies are contraindicated.The type of delivery recommended in pregnancies of women with ITP should be based only on obstetric considerations. Spinal or epidural anaesthesia is considered acceptable with stable platelet counts greater than or equal to 70 × 109/l. Neonatal involvement is rare, and the course is generally very good. After delivery, a platelet count should be performed as soon as possible in every new-born of a woman with ITP. The frequency of determinations depends on the progression of the figures. The neonate counts are less than 50 × 109/l, imaging techniques should be performed to rule out intracranial haemorrhage, and if they are less than 30 × 109/l, even in the absence of haemorrhage, IV Ig should be administered.The key points of the guidelines regarding ITP in children, the elderly and pregnant women are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Special Situations: thrombosis, other immune thrombocytopenia and ITP, and COVID-19Patients with ITP have a 2-fold increased risk of venous thrombosis, with a lower predisposition to arterial episodes<a class="elsevierStyleCrossRef" href="#bib0145">29</a>; thrombocytopenia does not protect against vascular complications. The first-line treatment for subjects with thrombotic events prior to the diagnosis of ITP would continue to be glucocorticoids. The use of agents that are not prothrombotic, such as rituximab, dapsone, hydroxychloroquine, or fostamatinib, should be considered as second-line. However, due to its thrombogenicity, splenectomy should be avoided. If the patient is unable to receive these treatments, is unresponsive, or is already receiving antithrombotic treatment, TPO-RA may be administered. Caution should be exercised with the use of TPO-RA after venous episodes in patients with lupus anticoagulants or active cancer, especially if they are not receiving anticoagulation. Antithrombotic treatment should be individualized based on previous bleeding history and thrombotic risk. Aspirin may in some cases be recommended in a patient experiencing an acute arterial event with platelet counts above 10−20 × 109/l. There are no specific studies that have evaluated the safety and efficacy of anticoagulant therapy in patients with ITP, although it is generally accepted that therapeutic doses of anticoagulants can be administered with platelet counts above 50 × 109/l, and 50% of the dose of low molecular weight heparin with counts between 20-50 × 109/l.Secondary forms of immune thrombocytopenia account for approximately 20% of all ITP cases in adulthood, and this rate increases with age<a class="elsevierStyleCrossRef" href="#bib0150">30</a>. Some causes can influence both the prognosis and the treatment of the disease. Chronic lymphocytic leukaemia, B-lymphomas, systemic autoimmune diseases such as systemic lupus erythematosus (SLE), or primary immunodeficiencies mainly represented by common variable immunodeficiency (CVID) are the most frequent causes of secondary ITP in adults, in addition to vaccinations or infections, the latter being the most common causes in children. Others include autoimmune lymphoproliferative syndrome (ALPS), immune thrombocytopenia following allogeneic haematopoietic stem cell transplantation, and also those associated with drugs, including the particular case of heparin-induced thrombocytopenia. It is essential that in drug-induced thrombocytopenia the triggering agent is withdrawn, but in heparin-induced thrombocytopenia the triggering agent must be replaced by another anticoagulant. While the first-line treatment used in most cases of secondary and primary ITP is usually similar and based mainly on glucocorticoids with or without immunoglobulins, the second-line treatment must consider the underlying disease. The benefit-risk ratio of TPO-RA, as well as that of splenectomy, should be well assessed in cases of ITP secondary to SLE or antiphospholipid syndrome, and also the use of rituximab in the context of CVID. The treatment of choice for ALPS-related thrombocytopenia will be mycophenolate mofetil or sirolimus; in the case of ITP secondary to lymphoproliferative syndromes or SLE, control of the underlying disease generally improves platelet counts.The COVID-19 pandemic has raised concern about the use of possible immunosuppressive treatments in ITP, although clinical evidence has not identified that this disease confers an increased risk. During the health alert for this infection, the first-line treatment in adults newly diagnosed with ITP without COVID-19 would continue to be glucocorticoids (consider initial dose of 0.5 mg/kg/day), keeping them to the minimum necessary and remembering that they should be withdrawn within a maximum of 8 weeks. In this context, non-immunosuppressive treatments such as IV Ig and/or TPO-RA can also be considered. In a pandemic situation, the second lines do not vary, except for the recommendation to avoid the use of rituximab due to the possible reduction in antibody generation. In stable patients, no therapeutic changes should be made, and splenectomised patients should be informed that the risk of COVID-19 severity is not higher. In case of COVID-19 disease and thrombocytopenia < 20 × 109/l, the treatment of choice is IV Ig, and dexamethasone should be considered.The key points of the guidelines on thrombosis, other immune thrombocytopenia and ITP, and COVID-19 are shown in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Conflict of interestsMLL has received grant funding or consultancy fees from Amgen, Novartis, Terumo S. A., Macopharma, Sobi, UCB Pharma and Grifols S. A., which are independent of this work.MAS has received consultancy fees from Teva Pharmaceutical Industries, Daiichi Sankyo, Orsenix, AbbVie, Novartis, and Pfizer, which are independent of this work.VV has received consultancy fees from Amgen, Novartis, Boehringer-Ingelheim, Pfizer, Bayer, and Daiichi Sankyo, which are independent of this work." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0041" "titulo" => "General concepts, diagnosis and quality of life, and complementary and alternative treatments" ] 1 => array:2 [ "identificador" => "sec0005" "titulo" => "First-line, second-line and multidrug-resistant patient treatment" ] 2 => array:2 [ "identificador" => "sec0042" "titulo" => "Patient follow-up, vaccination, preparation for surgery and treatment discontinuation" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Immune thrombocytopenia in children, the elderly and pregnant women" ] 4 => array:2 [ "identificador" => "sec0043" "titulo" => "Special Situations: thrombosis, other immune thrombocytopenia and ITP, and COVID-19" ] 5 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interests" ] 6 => array:2 [ "identificador" => "xack578854" "titulo" => "Acknowledgements" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-01-08" "fechaAceptado" => "2021-03-05" "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Lozano ML, Sanz MA, Vicente V, Grupo Español de PTI (GEPTI), Recomendaciones del Grupo Español de PTI para el diagnóstico, tratamiento y seguimiento de pacientes con trombocitopenia immune. Med Clin (Barc). 2021. https://doi.org/10.1016/j.medcli.2021.03.017" ] 1 => array:3 [ "etiqueta" => "◊" "nota" => "Working Group of the Spanish Society of Haematology and Hemotherapy (SEHH), Madrid, Spain." "identificador" => "fn0005" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "PTI: primary immune thrombocytopenia, also known as immune thrombocytopenic purpura, idiopathic thrombocytopenic purpura, or immune thrombocytopenia.Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy (SEHH) and the Spanish ITP Group (GEPTI)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">General</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) The terminology adopted in this document is consistent with the PTI international working group consensus statement published in 2009<a class="elsevierStyleCrossRef" href="#bib0035">7</a>. Given that there are several limitations to the definitions in that document, work is currently underway to undertake new terminology in a future consensus document. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) The incidence of ITP in both adults and children is 0.2−0.4 cases per 10,000 person-years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) The main manifestations associated with ITP are hemorrhagic, although an increased risk of thrombosis, asthenia (sometimes independent of platelet counts) and a tendency to infections can also be observed. Patients can have numerous adverse reactions related to the treatments administered \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) Although the introduction of new therapeutic agents in the last decade has led to a change in the prognosis of ITP patients, the impact on the rate and causes of ITP mortality is unknown. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diagnosis</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) The diagnosis of ITP is made by systematic exclusion of other causes of thrombocytopenia and is based, above all, on the clinical history, physical examination, blood count and peripheral blood smear \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) Observation of the peripheral blood smear is essential in the diagnosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) Complementary studies should be requested based on the presentation and clinical course of the disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) The determination of anti-platelet antibodies is not routinely indicated, although they may be helpful in difficult cases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) The bone marrow study should not be performed routinely. In the event that there is resistance to the treatments, or the existence of another disease is suspected, the bone marrow study is recommended, which should include aspirate and biopsy, immunophenotyping by flow cytometry, cytogenetics, and molecular biology \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Quality of life and alternative treatments</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) ITP patients have an impaired quality of life, especially in the early phase of the disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) Assessment of quality-of-life parameters in ITP patients, before and during the treatment of the disease, using the ITP-specific scales is recommended. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) The most widely used tool to assess the quality of life in adult patients with ITP is the Immune Thrombocytopenic Purpura-Patient Assessment Questionnaire \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) Patients' use of alternative treatments has not been shown to be therapeutically useful. Closer follow-up is recommended when patients start taking alternative treatments \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) The patient should be provided with detailed information on the heterogeneity of the course of ITP in its clinical manifestations and the limited value of the platelet count \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2793281.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Key points of the guidelines for the diagnosis, treatment and follow-up of primary immune thrombocytopenia concerning general concepts, diagnosis and quality of life, and complementary and alternative treatments." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "IV Ig: intravenous immunoglobulins; TPO-RA: thrombopoietin receptor agonists.Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy (SEHH) and Spanish ITP Group (GEPTI)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First-line treatment</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) The decision to start treatment is based mainly on the hemorrhagic manifestations and the platelet count (< 20 × 109/l) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) First-line treatment consists of glucocorticoids (prednisone 0.5−1 mg/kg or dexamethasone 40 mg/day for 4 days) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) The duration of prednisone treatment consists of a maximum of 8 weeks and dexamethasone treatment consists of 3 cycles. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) The addition of IV Ig is reserved for patients with severe bleeding or contraindications to steroids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) In a situation of severe bleeding, combined treatment should be considered (IVIG, high-dose methylprednisolone, platelet transfusion and whether it is necessary to add antifibrinolytics and/or TPO-RA). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6) Hospital admission for at least 48−72 h is recommended for a newly diagnosed patient with platelet counts < 20 × 109/l \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Second-line treatment</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) The second-line treatment of choice is TPO-RA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) The choice of TPO-RA should be based on the route of administration, the patient's wishes, and possible complications \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) For rituximab, 375 mg/m2 weekly (4 doses) is the most commonly used dose, although lower doses (100 mg × 4) have similar efficacy and may be safer. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) Laparoscopic splenectomy is recommended over laparotomy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) Splenectomy should be considered in chronic phases of the disease, when at least one second-line pharmacological treatment has failed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other second-line treatments. Refractory patients</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) In patients who are resistant to conventional second-line treatments, the best treatment option is not well established \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) Compared to monotherapy, combination therapies are more effective in patients with refractory disease, preferably choosing agents with different mechanisms of action. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) If one treatment is not effective, rather than discontinuing it and starting another, it may be better to add the new agent while continuing with the current one \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) In multidrug-resistant patients, other diagnoses should be considered, such as drug-induced thrombocytopenia, myelodysplastic syndrome, or hereditary thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2793280.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Key points of the guidelines for the diagnosis, treatment, and follow-up of primary immune thrombocytopenia regarding the treatment of first-line, second-line and multidrug-resistant patients." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "IV Ig: intravenous immunoglobulins; PTI: primary immune thrombocytopenia; TPO-RA: thrombopoietin receptor agonists.Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy (SEHH) and the Spanish ITP Group (GEPTI)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Follow-up. Vaccination</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) Hospital admission is recommended for adults with newly diagnosed ITP and platelet count less than 20 × 109/l, even when asymptomatic or with minimal mucocutaneous bleeding. If these circumstances occur in patients with established ITP, treatment will be on an outpatient basis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) Regardless of the time of diagnosis and platelet counts, patients with: a) grade ii haemorrhage and platelets < 30 × 109/l, or b) haemorrhage ≥ iii regardless of platelet count, should be hospitalized \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) To prevent severe post-splenectomy infection, vaccinations should be administered according to the recommendations of each country. Ideally, these vaccinations should be administered at least 2 weeks prior to surgery (if this is not possible, it will be done after surgery), and the patient will follow the recommended revaccination schedule \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) If the patient is receiving immunosuppressive treatment, it is advisable to avoid live-attenuated vaccines \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) Diabetes, renal failure, hypertension, and vascular disease are reported to have a 2-fold higher incidence among patients diagnosed with ITP. Also, thyroid disease is especially prevalent \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6) Among patients with ITP, the incidence of hematologic malignancies, such as lymphomas and leukemias, is higher \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7) Up to 16% of patients with ITP will be recognised as having ITP secondary to connective tissue diseases during their follow-up (sometimes more than 10 years after diagnosis), with systemic lupus erythematosus being the most common. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Surgery</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) In cases of emergency surgery, consider treatment with IV Ig with/without dexamethasone or methylprednisolone at high doses \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) Platelet transfusion continues to be a complementary option in extremely serious or life-threatening situations. The combination of platelet transfusion with Ig iv and transfusion immediately before and/or during the procedure is recommended, as the destruction of the transfused platelets is much faster than usual and thus ensures the haemostatic levels of these cells during surgery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) In preparation for elective surgery in poor responders to steroids, there is an increasing trend to replace the administration of IV Ig with TPO-RA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Discontinuation of ITP treatment</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) A high proportion of patients maintain platelet response after discontinuation of TPO-RA, regardless of the stage of the disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) Patients with persistent or chronic ITP who achieve stable platelet counts > 50−100 × 109/l over several months may be considered candidates for tapering with the goal of a maintained response in the absence of treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) A tapering strategy from 2 to 6 months and regular monitoring of platelet counts is recommended, with gradual increases in the monitoring intervals once an adequate, stable, and untreated platelet count is achieved \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) If the platelet count drops to 20−50 × 109/l, treatment can be restored with the same TPO-RA and the possible addition of immunosuppression \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2793282.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Key points of the guidelines for the diagnosis, treatment, and follow-up of primary immune thrombocytopenia about patient follow-up and vaccination, surgery preparation and treatment discontinuation." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "IV Ig: intravenous immunoglobulins; PTI: primary immune thrombocytopenia; TPO-RA: thrombopoietin receptor agonists.Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy (SEHH) and the Spanish ITP Group (GEPTI)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ITP in children</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) The highest incidence of ITP in children occurs between the ages of 2 and 8. The disease tends to have a spontaneous remission, even after 2 years of progression \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) With a longer projection of years and life expectancy, it is especially important to assess the adverse reactions and possible sequelae of the various approaches in its management \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) A clinical assessment of severity is proposed based on haemorrhagic manifestations and indicators or risk factors which, together with the platelet count, determine the specific therapeutic recommendation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) Diagnosis is based on clinical history and a complete blood count with morphology that excludes other causes of thrombocytopenia. A bone marrow aspirate is recommended in cases of atypical presentation or with progression to chronicity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) High-dose short-term glucocorticoids and IV Ig are the first-line treatment. It is recommended that second-line treatments and those of refractory patients are indicated and controlled in specialized centres for the indication and control of new. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ITP in the elderly</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) The incidence of ITP increases with age \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) Elderly patients with ITP show greater medical complexity due to comorbidities, age, and other treatments. These patients are at higher risk of bleeding and thrombosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) Diagnosis is often difficult due to the coexistence of other diseases and possible drug interference \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) The therapeutic strategy may differ from what is recommended in the guidelines for younger patients. Age can influence efficacy and treatment-related toxicities \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) It is important that these patients are cared for in a way that allows them to return to their daily lives as soon as possible, with as little iatrogenesis as possible and maintaining safe platelet counts. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="13" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ITP in pregnancy</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) Gestational thrombocytopenia is a benign disorder and the most common cause of thrombocytopenia in pregnancy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) In pregnant women with platelet counts below 70−80 × 109/l, other possible causes of thrombocytopenia should be considered: some additional tests, such as blood pressure control, coagulation study, liver function tests, determination of antiphospholipid antibodies or protein in urine can be especially useful for differential diagnosis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) The incidence of neonatal thrombocytopenia and haemorrhagic complications is low and does not correlate with maternal platelet counts \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) Pregnant women with platelet counts > 20−30 × 109/l do not require systematic treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) The first line of treatment in pregnancy are glucocorticoids and IV Ig. In pregnancy, treatment is initiated with lower than usual doses of glucocorticoids to avoid toxicity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6) As IV Igs induce a rapid response, they are of choice in severe bleeding or before performing invasive procedures. Splenectomy should be performed only in severe cases, as should rituximab or TPO-RA administration. Other immunosuppressive agents other than azathioprine or cyclosporine should be avoided during pregnancy due to their possible teratogenicity and because this indication is not approved in the SmPC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7) The recommended platelet count for vaginal deliveries should be 50 >50 × 109/l and for caesarean section or epidural anaesthesia 70 × 109/l. The indication for caesarean section should be based solely on obstetric criteria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8) Invasive procedures such as scalp blood sampling, cordocentesis, and assisted deliveries should be avoided \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9) After delivery, a platelet count from a postnatal cord sample is recommended and, if low (less than 100 × 109/l), it should be repeated daily \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10) If the platelet count is< < 50 × 109/l, the neonate should undergo a cranial ultrasound and, in the case of bleeding, administer IV Ig and steroids (minimum dose and limited time) with the aim of reaching 100 × 109/l \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11) In neonates with hemorrhagic symptoms or platelet counts < 30 × 109/l administration of a single dose of IV Ig induces rapid response \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12) Although breastfeeding is not contraindicated as a general rule, if thrombocytopenia persists in the new-born, breastfeeding should be discontinued \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13) Women who have previously given birth to a child with thrombocytopenia should be counselled about the high probability of this recurring in future pregnancies \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2793283.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Key points of the guidelines for the diagnosis, treatment, and follow-up of primary immune thrombocytopenia regarding ITP in children, the elderly and pregnant women." ] ] 4 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "IV Ig: intravenous immunoglobulins; PTI: primary immune thrombocytopenia (also known as immune thrombocytopenic purpura, idiopathic thrombocytopenic purpura, or immune thrombocytopenia); TPO-RA: thrombopoietin receptor agonists; HCV: hepatitis C virus; HIV: human immunodeficiency virus.Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy (SEHH) and the Spanish ITP Group (GEPTI)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Special situations. Thrombosis</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) There is a risk of both venous thromboembolism and arterial thrombosis in patients with ITP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) It is important to improve modifiable personal risk factors for thrombosis, especially in patients over 60 years of age \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) Splenectomy increases the risk of venous thromboembolism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) TPO-RA increase the risk of venous thromboembolism and arterial thrombosis in patients with ITP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) For patients requiring chronic antiplatelet and/or anticoagulant therapy, the threshold for a safe platelet count should be > 30−50 × 109/l and these treatments should be restarted promptly when this platelet level is reached \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other immune thrombocytopenia</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) Thrombocytopenia of non-primary immune origin can accompany a wide range of clinical situations: autoimmune diseases, immunodeficiencies, lymphoproliferative syndromes and in cases of post-haematopoietic transplantation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) Considering the association between immune thrombocytopenia and infectious diseases (HCV, HIV, cytomegalovirus, Epstein-Barr, varicella zoster, Zika and Helicobacter pylori), the presence of these conditions should be ruled out if there is clinical suspicion when establishing the diagnosis of ITP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) Immune-mediated cases may also occur during the postvaccination period. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) There is immune-mediated thrombocytopenia associated with heparin administration, both unfractionated and, to a lesser extent, low molecular weight (heparin-induced thrombocytopenia) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) They are also observed with the use of anti-GPIIb/IIIa monoclonal antibodies, which are used in the field of cardiovascular disease (abciximab, eptifibatide, tirofiban, etc.) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6) A wide range of drugs have been described as being responsible for transient thrombocytopenia due to an immune-mediated mechanism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ITP and COVID-19</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1) Like any infection: i) SARS-CoV-2 may precede a diagnosis of ITP, and ii) if a patient with ITP is infected with SARS-CoV-2 it may lead to decreased platelet counts. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2) In an emergency health situation, patients with newly diagnosed ITP should be considered for prednisone initiation at 0.5 mg/kg/day, and steroids should be discontinued within a maximum of 8 weeks. If the patient's risk due to comorbidities is high, non-immunosuppressive agents, such as Ig iv or TPO-RA, may be used. However, the absence of immunosuppression must be weighed against the need for more hospital control with TPO-RA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3) Rituximab should be avoided because it may decrease the formation of de novo antibodies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4) There is no evidence that patients who have undergone a splenectomy are more vulnerable to COVID-19. In case of fever, the treatment of a splenectomised patient should be the same as without COVID-19 infection \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5) If a patient with ITP develops severe COVID-19 disease, prophylactic anticoagulation should be sought, and platelet counts should be maintained above 30 × 109/l \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2793279.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Key Points of the primary immune thrombocytopenia diagnosis, treatment, and follow-up guidelines concerning special situations: thrombosis, other immune thrombocytopenia and ITP, and COVID-19." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnóstico, tratamiento y seguimiento de la trombocitopenia inmune primaria" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. 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We acknowledge and appreciate the help of the Spanish Society of Haematology and Hemotherapy, especially Ana Carolina Madrid, Carmen González and Carlos Fernández, for the technical support provided for the development of the guidelines." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015700000004/v2_202201010719/S2387020621003788/v2_202201010719/en/main.assets" "Apartado" => array:4 [ "identificador" => "44145" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Special article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015700000004/v2_202201010719/S2387020621003788/v2_202201010719/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621003788?idApp=UINPBA00004N"]

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Guidelines of the Spanish ITP Group for the diagnosis, treatment and follow-up of patients with immune thrombocytopenia

Recomendaciones del Grupo Español de PTI para el diagnóstico, tratamiento y seguimiento de pacientes con trombocitopenia inmune

María L. Lozanoa,

Corresponding author

mllozano@um.es

Corresponding author.

, Miguel A. Sanzb, Vicente Vicentea, Spanish ITP Group - GEPTI ◊

a Grupo de Investigación CB15/00055, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Hospital General Universitario Morales Meseguer, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain

b Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Hospital Universitari i Politècnic La Fe, Valencia, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Primary immune thrombocytopenia</span> &#40;ITP&#44; immune thrombocytopenic purpura&#44; also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia&#41; is a complex acquired autoimmune disease in which there is humoral and cellular dysregulation leading to defects in platelet production and increased platelet destruction&#46; The fact that the presentation&#44; characteristics&#44; and clinical course are highly variable and heterogeneous makes decision-making regarding diagnosis&#44; treatment&#44; and follow-up of these patients particularly difficult&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In 2011&#44; a consensus document was prepared for the first time in our country&#44; which became the reference for the diagnosis and treatment of ITP in Spain<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; The introduction of new therapeutic options in the last decade has led to the reissuing of a series of international guidelines for the treatment of these patients in the last 2 years<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;5</span></a>&#46; In our country&#44; promoted by the Spanish ITP Group and the Spanish Society of Haematology and Hemotherapy&#44; we have also updated the guidelines for the diagnosis&#44; treatment&#44; and follow-up of patients with ITP<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; The main recommendations of the manual have been included in this document&#44; which aims to serve as a practical tool to facilitate the comprehensive management of the different aspects related to this disease&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">We are aware that this is a rapidly evolving field and that the therapeutic approach to the disease is expected to change in the near future&#46; We recognise that guidelines are intended to provide guidance only and that many of the guidelines and recommendations in the Spanish consensus document&#44; as in other available guidelines&#44; are derived from expert opinion and non-comparative studies with a low level of evidence&#46;</p><span id="sec0041" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0101">General concepts&#44; diagnosis and quality of life&#44; and complementary and alternative treatments</span><p id="par0025" class="elsevierStylePara elsevierViewall">ITP is defined as a platelet count below 100&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l with no identified cause &#40;primary ITP&#41; or related to other conditions leading to immune-mediated destruction of platelets &#40;secondary ITP&#41;&#46; Its incidence in both adults and children is 2&#8211;4 cases per 100&#44;000 inhabitants-year&#46; Prevalence is higher in adults &#40;10 per 100&#44;000&#41; compared to children &#40;5 per 100&#44;000&#41;&#44; as the disease resolves in most children&#46; Not only does ITP present with haemorrhagic manifestations&#44; when platelet counts are below 20&#8722;30&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; but fatigue is also a common symptom&#46; A predisposition to thrombotic events&#44; infections and the development of other autoimmune diseases has been observed in some cases&#46; Most children and more than a third of adults will experience a self-limiting disease course&#46; According to the standardised terminology adopted in 2009<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#44; the following disease stages are defined&#58; &#40;i&#41; newly diagnosed &#40;less than 3 months&#41;&#59; &#40;ii&#41; persistent &#40;3&#8211;12 months since diagnosis&#41;&#59; and &#40;iii&#41; chronic &#40;lasting more than 12 months&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In contrast to the therapeutic advances of the last decade&#44; the diagnosis of the disease has not evolved&#44; with a lack of a reliable biomarker and unequivocal confirmatory tests&#46; The diagnosis remains primarily a clinical one and one of exclusion of other causes of thrombocytopenia&#46; For the typical patient with suspected ITP&#44; the rule of thumb is to restrict testing that is usually going to be non-informative&#44; after confirming that there are no findings on history&#44; physical examination&#44; peripheral blood smear&#44; immunoglobulin levels and viral serologies that may be indicative of another process&#46; Routine bone marrow study is not recommended&#44; except if the response to treatment is inadequate or if there are other abnormalities in the blood smear or in the clinical presentation that raise suspicions for other diagnoses &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Because of these limitations&#44; it has been estimated that one in every 7 patients may be misdiagnosed with ITP<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#44; so efforts need to be made in this area&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The quality of life of patients with ITP is reduced to levels comparable to those experienced by patients with other chronic diseases such as cancer&#44; arthritis and diabetes<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; Appropriate treatment of ITP includes not only increasing the platelet count&#44; but also considering that in adults it often behaves as a chronic disease&#44; with a relatively good prognosis in terms of survival&#44; therefore attempts should be made to minimise the impact of the disease on the patient&#39;s quality of life&#46; Patients with ITP often use alternative and complementary treatments<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#59; the lack of information about the safety and interactions of many of these products means that they may need to be monitored more closely&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The key points of the guidelines regarding general concepts&#44; diagnosis and quality of life&#44; and alternative and complementary therapies are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">First-line&#44; second-line and multidrug-resistant patient treatment</span><p id="par0045" class="elsevierStylePara elsevierViewall">The goal of treatment is to stop any active bleeding and prevent future haemorrhage&#46; Treatment should be initiated in newly diagnosed adult patients with bleeding or platelet counts below 20&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l &#40;less than 30&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l if they are older than 65 years or have predisposing factors for bleeding&#41;&#46; During the course of the disease&#44; these criteria do not necessarily apply to second treatments&#44; when the patient&#39;s decisions become especially important&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">First-line treatment has not changed much&#44; as glucocorticoids remain the primary agent&#44; but the recommended duration of treatment to minimise side-effects has been modified&#46; The initial dose of prednisone &#40;0&#46;5&#8722;1&#160;mg&#47;kg&#47;day&#59; maximum 80&#160;mg&#47;day&#41; should not be maintained for more than 3 weeks &#40;2 weeks if no response&#41; and should be discontinued within 8 weeks of initiation after tapering&#46; An alternative is dexamethasone 40&#160;mg&#47;day for 4 days every 2 weeks&#44; for a maximum of 3 cycles&#46; Although the increases in platelet counts after dexamethasone are faster than with prednisone&#44; in the long term there is no difference in response rates between the two agents<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; In patients with bleeding or contraindication to steroid treatment&#44; the use of intravenous immunoglobulins &#40;IV Ig&#41; is recommended at a dose of 1&#160;g&#47;kg 1&#8211;2 days&#44; or 0&#46;4&#160;g&#47;kg for 3&#8211;5 days in people over 65 years of age&#46; If severe bleeding is present&#44; in addition to IV Ig&#44; high-dose methylprednisolone&#44; platelet transfusion and consideration of <span class="elsevierStyleItalic">thrombopoietin receptor agonists</span> &#40;TPO-RA&#44; &#34;thrombopoietin receptor agonists&#34;&#41; are recommended&#46; There is more experience with romiplostim at doses of 5&#8722;10&#160;&#956;g&#47;kg<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#44; although there is no reason to think that 75&#160;mg&#47;day of eltrombopag would not also be effective&#46; Combination treatments of first-line steroids with rituximab&#44; TPO-RA or immunosuppressants are not recommended&#44; as although they are more effective in the long term&#44; they are also associated with more adverse reactions<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;15</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Although initial response rates to glucocorticoids may be high&#44; most adult patients will relapse&#44; with re-exposure to these treatments in non-emergency situations being inappropriate&#46; Second-line treatment presents solid evidence based on randomized studies with TPO-RA &#40;romiplostim and eltrombopag are currently approved in our country&#44; and it is foreseeable that avatrombopag will be approved in the future&#41;&#44; fostamatinib and rituximab&#46; So far&#44; no randomised trials comparing them have been conducted&#46; The mechanism of action of these agents is different in that while rituximab and fostamatinib would reduce platelet destruction by different pathways &#40;decreased autoantibody synthesis and phagocytosis&#44; respectively&#41;&#44; TPO-RAs would promote platelet production&#46; Due to the excellent efficacy and safety profile&#44; and the existing experience of more than a decade&#44; the Spanish guidelines state that the second-line treatment of choice in most patients should be a TPO-RA&#46; With these agents&#44; a response is achieved in more than 80&#37; of patients<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a>&#44; without showing cross resistance<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; As will be shown in a later section&#44; a significant percentage of patients will be able to discontinue other treatments and even the TPO-RA themselves&#44; while maintaining platelet counts&#46; If there is resistance to a TPO-RA&#44; switching to another TPO-RA&#44; adding an immunosuppressant&#44; or switching to rituximab&#44; fostamatinib or even performing a splenectomy should be considered&#46; Fostamatinib also produces rapid and long-lasting platelet increases in 40&#8211;45&#37; of patients with previous treatment failure<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; Fostamatinib also produces rapid and long-lasting platelet increases in 40&#8211;45&#37; of patients with failed previous treatments19&#46; Lower responses are seen in heavily pre-treated patients&#44; but efficacy reaches 75&#37; when initiated as the first second-line treatment option<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46; Since this is a relatively new agent&#44; there is no robust data on long-term remissions yet&#46; Rituximab has no approved indication in ITP&#44; but there is extensive experience with its use<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; Global responses have been reported in 40&#8211;60&#37; of patients&#44; but less than 20&#37; of adults maintain a long-lasting response&#46; The efficacy is remarkably similar between the standard dose of anti-CD20 &#40;375&#160;mg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#44; and the reduced dose &#40;100&#160;mg&#41; administered in 4 consecutive weeks&#44; although in the second case the cost and adverse reactions are lower<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#46; The main advantages of splenectomy are efficacy and cost&#44; with initial responses in approximately 80&#37; of patients and long-term responses in 50&#8211;60&#37;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#46; The limitations that must be weighed in recommending this treatment are the lifetime risks of thrombosis and serious infections&#46; Splenectomy &#40;ideally laparoscopic&#41; should only be considered in chronic phases of the disease&#44; when at least one second-line drug therapy has failed&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Multidrug-resistant ITP is a serious and life-threatening situation that affects 5&#8722;15&#37; of patients&#46; In these cases&#44; the diagnosis of ITP should be reconsidered&#44; and a bone marrow study is indicated&#44; and a combination of therapeutic agents with different mechanisms of action that promote platelet production and inhibit platelet destruction should be used&#46; These combinations usually include TPO-RA and immunosuppressants<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> &#40;mycophenolate&#44; azathioprine&#44; or rituximab&#41;&#46; If there is significant bleeding and the patient does not respond to IV Ig&#44; a combined treatment with TPO-RA and vinca derivatives &#40;vincristine or vinblastine&#41; may be indicated&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The key points of the guidelines regarding first and second line treatment&#44; as well as the multidrug-resistant patient&#44; are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0042" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0102">Patient follow-up&#44; vaccination&#44; preparation for surgery and treatment discontinuation</span><p id="par0075" class="elsevierStylePara elsevierViewall">Patients should be admitted if they present with&#58; &#40;i&#41; bleeding WHO grade <span class="elsevierStyleSmallCaps">ii</span> &#40;moderate&#41; and platelet&#160;&#60;&#160;30&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; or ii&#41; haemorrhage&#160;&#8805;&#160;iii &#40;requiring red blood cell transfusion&#41; regardless of platelet count&#46; Even in the absence of bleeding episodes&#44; newly diagnosed patients with platelets&#160;&#60;&#160;20&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l &#40;but not those with established ITP&#41; should be hospitalised&#46; This is due to the uncertainty that may initially exist about the diagnosis&#44; the need to assess platelet progression and haemorrhagic complications&#44; as well as to ensure the correct administration of treatment&#46; Patients with established disease and severe thrombocytopenia who are not hospitalised should be informed about the symptoms that warrant medical attention&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Without appropriate vaccination&#44; splenectomised patients have severe bacterial infections up to 50 times more often than those who have not undergone surgery&#44; caused by <span class="elsevierStyleItalic">Streptococcus pneumoniae</span>&#44; <span class="elsevierStyleItalic">Haemophilus influenzae</span> and <span class="elsevierStyleItalic">Neisseria meningitidis</span> in 50&#8211;90&#37;&#44; 5&#8722;15&#37; and 5&#8722;15&#37; of cases&#44; respectively<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46; Vaccines reduce&#44; but do not eliminate&#44; this risk&#59; they should be administered at least 2 weeks before splenectomy and in case of an emergency intervention&#44; they will be vaccinated as soon as possible and up to 2 weeks after surgery&#46; In the follow-up of ITP patients&#44; certain diseases that are over-represented should be monitored&#58; diabetes&#44; renal failure&#44; hypertension&#44; and vascular disease &#40;2 times higher&#41;&#44; thyroid disease &#40;2&#46;5 times&#41;&#44; other autoimmune diseases &#40;5 times&#41; and haematological malignancies &#40;between 6 and 20 times&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">If the patient is to undergo a surgical procedure during follow-up&#44; the optimal platelet target required remains controversial&#46; However&#44; counts above 50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l are recommended for minor surgery with standard risk of bleeding&#44; but above 80&#8722;100&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l for major surgery and central nervous system interventions&#46; In emergency situations&#44; platelet transfusion along with IV Ig should be considered&#46; The onset of action of Ig iv is approximately 24&#8211;48&#160;h&#44; while glucocorticoids may take 3&#8211;10 days&#46; If a 3-week interval is available before elective surgery&#44; TPO-RA may be a reasonable alternative&#46; The administration of romiplostim &#40;weekly dose of 3&#160;&#956;g&#47;kg&#41; or eltrombopag &#40;conventional doses of 50&#160;mg&#47;day&#41; for 14&#8211;21 days before surgery is effective and safe&#46; For most cases&#44; the limited duration of administration of these drugs does not raise concerns about potential adverse reactions&#44; such as prothrombotic effects&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Except for surgical preparation&#44; TPO-RAs are generally administered as an ongoing treatment&#46; It is currently known that between 20&#8722;30&#37; of patients can maintain a sustained platelet response after tapering and discontinuation of TPO-RA&#46; It is recommended to assess in patients with stable platelet counts &#40;between 50 and 100&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l more than 6 months or &#62;&#160;100&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l maintained for 3 months&#41; the gradual reduction of these agents and eventual discontinuation of treatment&#46; More caution should be exercised in patients with a significant bleeding history&#44; age over 75&#44; common platelet fluctuations&#44; or with concomitant treatments that predispose to bleeding&#46; TPO-RA treatment should not be discontinued abruptly&#46; It is preferred to taper&#44; and if possible&#44; discontinue&#44; the drug progressively over a period of 3&#8211;12 months&#46; The decisive factor in determining the rate at which tapering occurs is the patient&#39;s response to the dose reduction&#46; This discontinuation should be stopped if the platelet count falls between 30 and 50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#59; in this case&#44; patients should resume TPO-RA at the lowest dose capable of inducing a response&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The key points of the guidelines regarding patient follow-up and vaccination&#44; preparation for surgery&#44; and treatment discontinuation are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Immune thrombocytopenia in children&#44; the elderly and pregnant women</span><p id="par0100" class="elsevierStylePara elsevierViewall">ITP in children is generally self-limiting&#46; The diagnostic approach is similar to that of adults&#46; Most children with newly diagnosed ITP lack significant bleeding symptoms and do not require treatment&#46; However&#44; it is essential that parents and children with ITP understand the risks of serious or life-threatening bleeding&#46; At the time of diagnosis&#44; hospital admission should be considered in patients with active grade <span class="elsevierStyleSmallCaps">iii</span>-<span class="elsevierStyleSmallCaps">iv</span> bleeding or bleeding risk factors in addition to the platelet count&#46; Treatment is aimed at preventing&#44; but above all at treating bleeding&#44; with IV Ig and&#47;or glucocorticoids being the most widely used first-line treatments&#46; Steroids are given in higher doses and in much shorter regimens than in adults&#46; In second-line treatment&#44; in case of a haemorrhagic emergency&#44; IV Ig and&#47;or glucocorticoids will be administered&#44; but if the patient requires maintenance treatment&#44; TPO-RA is the treatment of choice&#46; In multidrug-resistant patients&#44; in addition to performing a bone marrow study&#44; hereditary thrombocytopenia must be ruled out&#46; If the diagnosis of ITP is confirmed&#44; additional treatments in this situation would include rituximab&#44; splenectomy or immunosuppressants such as mycophenolate mofetil&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The incidence of ITP in adults increases with age&#44; reaching 9&#47;100&#44;000 person-years in men&#160;&#62;&#160;75 years of age<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a>&#46; Isolated thrombocytopenia may be the consequence of a myelodysplastic syndrome in this population&#59; if there are reasonable diagnostic doubts&#44; it is recommended to consider performing a bone marrow study that includes cytogenetics and flow cytometry&#46; Elderly patients with ITP are at increased risk of bleeding&#44; thrombosis&#44; and infections&#44; have more adverse reactions related to ITP treatments&#44; and require more concomitant therapies such as antiplatelet or anticoagulant agents&#46; A more active therapeutic strategy may be considered in clinical practice for a platelet count between 30&#8722;50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l in&#160;&#8805;&#160;65 years with comorbidities or a history of bleeding&#46; The possibility of modulating the dose of first-line treatments should be considered in older patients&#46; Dexamethasone will be avoided&#44; and prednisone will be increased to 0&#46;5&#160;mg&#47;kg&#47;day or Ig IV at 0&#46;4&#160;g&#47;kg&#47;day for 5 days with abundant hydration before and after infusion&#44; and renal function monitoring&#46; Second line splenectomy is not recommended except in exceptional situations due to the greater thrombotic and infectious risk&#46; Infectious complications are also somewhat more common than in young patients after B-cell depletion with rituximab&#44; although it is not contraindicated&#46; TPO-RAs have a good safety and efficacy profile in the elderly and have become the main second-line therapeutic option in this group of patients&#44; even if their use is associated with a possible increased risk of thrombosis&#46; This increased risk of vascular phenomena is partly justified by the significantly more unfavourable prothrombotic conditions prior to its administration&#46; Other drugs&#44; such as dapsone and danazol&#44; have a well-known efficacy and safety profile and could be a valid option among elderly patients with moderate disease&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In pregnant women with suspected ITP&#44; other causes of thrombocytopenia due to specific pregnancy conditions should also be ruled out&#46; About 80&#37; of cases of thrombocytopenia during pregnancy are attributed to gestational thrombocytopenia&#44; characterised by a gradual decrease in platelet count that usually begins in the mid-second trimester and lasts into the third trimester&#46; If platelet counts decrease before this time or if thrombocytopenia is severe and abrupt &#40;platelets&#160;&#60;&#160;30&#8722;50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#41;&#44; in 9&#37; of cases it is due to hypertensive disorders and in a similar percentage to immune conditions&#46; Glucocorticoids and IV Ig are the basis of ITP treatment in pregnancy&#46; Rituximab is not recommended in this period&#44; and mycophenolate mofetil or vinca alkaloids are contraindicated&#46; Azathioprine &#40;although it has a slow onset of action&#41; or cyclosporine &#40;with blood pressure monitoring&#41; could be used instead&#46; Data on the safety and efficacy of splenectomy during pregnancy are limited&#46; In exceptional situations&#44; the use of TPO-RA may be considered&#46; There are preliminary data that support that the temporary and off-label use of these agents in severe or refractory disease is safe for the mother and the new-born&#44; especially if they are administered in the third trimester<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46; In women who cannot maintain a stable platelet count above 30&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l with standard treatment or if there is a history of previous pregnancies with severe thrombocytopenia in the new-born&#44; future pregnancies are contraindicated&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The type of delivery recommended in pregnancies of women with ITP should be based only on obstetric considerations&#46; Spinal or epidural anaesthesia is considered acceptable with stable platelet counts greater than or equal to 70&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#46; Neonatal involvement is rare&#44; and the course is generally very good&#46; After delivery&#44; a platelet count should be performed as soon as possible in every new-born of a woman with ITP&#46; The frequency of determinations depends on the progression of the figures&#46; The neonate counts are less than 50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; imaging techniques should be performed to rule out intracranial haemorrhage&#44; and if they are less than 30&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; even in the absence of haemorrhage&#44; IV Ig should be administered&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The key points of the guidelines regarding ITP in children&#44; the elderly and pregnant women are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0043" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0103">Special Situations&#58; thrombosis&#44; other immune thrombocytopenia and ITP&#44; and COVID-19</span><p id="par0130" class="elsevierStylePara elsevierViewall">Patients with ITP have a 2-fold increased risk of venous thrombosis&#44; with a lower predisposition to arterial episodes<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#59; thrombocytopenia does not protect against vascular complications&#46; The first-line treatment for subjects with thrombotic events prior to the diagnosis of ITP would continue to be glucocorticoids&#46; The use of agents that are not prothrombotic&#44; such as rituximab&#44; dapsone&#44; hydroxychloroquine&#44; or fostamatinib&#44; should be considered as second-line&#46; However&#44; due to its thrombogenicity&#44; splenectomy should be avoided&#46; If the patient is unable to receive these treatments&#44; is unresponsive&#44; or is already receiving antithrombotic treatment&#44; TPO-RA may be administered&#46; Caution should be exercised with the use of TPO-RA after venous episodes in patients with lupus anticoagulants or active cancer&#44; especially if they are not receiving anticoagulation&#46; Antithrombotic treatment should be individualized based on previous bleeding history and thrombotic risk&#46; Aspirin may in some cases be recommended in a patient experiencing an acute arterial event with platelet counts above 10&#8722;20&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#46; There are no specific studies that have evaluated the safety and efficacy of anticoagulant therapy in patients with ITP&#44; although it is generally accepted that therapeutic doses of anticoagulants can be administered with platelet counts above 50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; and 50&#37; of the dose of low molecular weight heparin with counts between 20-50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Secondary forms of immune thrombocytopenia account for approximately 20&#37; of all ITP cases in adulthood&#44; and this rate increases with age<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&#46; Some causes can influence both the prognosis and the treatment of the disease&#46; Chronic lymphocytic leukaemia&#44; B-lymphomas&#44; systemic autoimmune diseases such as systemic lupus erythematosus &#40;SLE&#41;&#44; or primary immunodeficiencies mainly represented by <span class="elsevierStyleItalic">common variable immunodeficiency</span> &#40;CVID&#41; are the most frequent causes of secondary ITP in adults&#44; in addition to vaccinations or infections&#44; the latter being the most common causes in children&#46; Others include <span class="elsevierStyleItalic">autoimmune lymphoproliferative syndrome</span> &#40;ALPS&#41;&#44; immune thrombocytopenia following allogeneic haematopoietic stem cell transplantation&#44; and also those associated with drugs&#44; including the particular case of heparin-induced thrombocytopenia&#46; It is essential that in drug-induced thrombocytopenia the triggering agent is withdrawn&#44; but in heparin-induced thrombocytopenia the triggering agent must be replaced by another anticoagulant&#46; While the first-line treatment used in most cases of secondary and primary ITP is usually similar and based mainly on glucocorticoids with or without immunoglobulins&#44; the second-line treatment must consider the underlying disease&#46; The benefit-risk ratio of TPO-RA&#44; as well as that of splenectomy&#44; should be well assessed in cases of ITP secondary to SLE or antiphospholipid syndrome&#44; and also the use of rituximab in the context of CVID&#46; The treatment of choice for ALPS-related thrombocytopenia will be mycophenolate mofetil or sirolimus&#59; in the case of ITP secondary to lymphoproliferative syndromes or SLE&#44; control of the underlying disease generally improves platelet counts&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The COVID-19 pandemic has raised concern about the use of possible immunosuppressive treatments in ITP&#44; although clinical evidence has not identified that this disease confers an increased risk&#46; During the health alert for this infection&#44; the first-line treatment in adults newly diagnosed with ITP without COVID-19 would continue to be glucocorticoids &#40;consider initial dose of 0&#46;5&#160;mg&#47;kg&#47;day&#41;&#44; keeping them to the minimum necessary and remembering that they should be withdrawn within a maximum of 8 weeks&#46; In this context&#44; non-immunosuppressive treatments such as IV Ig and&#47;or TPO-RA can also be considered&#46; In a pandemic situation&#44; the second lines do not vary&#44; except for the recommendation to avoid the use of rituximab due to the possible reduction in antibody generation&#46; In stable patients&#44; no therapeutic changes should be made&#44; and splenectomised patients should be informed that the risk of COVID-19 severity is not higher&#46; In case of COVID-19 disease and thrombocytopenia&#160;&#60;&#160;20&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; the treatment of choice is IV Ig&#44; and dexamethasone should be considered&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The key points of the guidelines on thrombosis&#44; other immune thrombocytopenia and ITP&#44; and COVID-19 are shown in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interests</span><p id="par0150" class="elsevierStylePara elsevierViewall">MLL has received grant funding or consultancy fees from <span class="elsevierStyleGrantSponsor" id="gs0005">Amgen</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs0010">Novartis</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs0015">Terumo S&#46; A&#46;</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs0020">Macopharma</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs0025">Sobi</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs0030">UCB Pharma</span> and <span class="elsevierStyleGrantSponsor" id="gs0035">Grifols S&#46; A&#46;</span>&#44; which are independent of this work&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">MAS has received consultancy fees from <span class="elsevierStyleGrantSponsor" id="gs0040">Teva Pharmaceutical Industries</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs0045">Daiichi Sankyo</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs0050">Orsenix</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs0055">AbbVie</span>&#44; Novartis&#44; and <span class="elsevierStyleGrantSponsor" id="gs0060">Pfizer</span>&#44; which are independent of this work&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">VV has received consultancy fees from Amgen&#44; Novartis&#44; <span class="elsevierStyleGrantSponsor" id="gs0065">Boehringer-Ingelheim</span>&#44; Pfizer&#44; <span class="elsevierStyleGrantSponsor" id="gs0070">Bayer</span>&#44; and Daiichi Sankyo&#44; which are independent of this work&#46;</p></span></span>"
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          "titulo" => "First-line&#44; second-line and multidrug-resistant patient treatment"
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          "titulo" => "Patient follow-up&#44; vaccination&#44; preparation for surgery and treatment discontinuation"
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          "titulo" => "Immune thrombocytopenia in children&#44; the elderly and pregnant women"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Lozano ML&#44; Sanz MA&#44; Vicente V&#44; Grupo Espa&#241;ol de PTI &#40;GEPTI&#41;&#44; Recomendaciones del Grupo Espa&#241;ol de PTI para el diagn&#243;stico&#44; tratamiento y seguimiento de pacientes con trombocitopenia immune&#46; Med Clin &#40;Barc&#41;&#46; 2021&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.medcli.2021.03.017">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;medcli&#46;2021&#46;03&#46;017</span></p>"
      ]
      1 => array:3 [
        "etiqueta" => "&#9674;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Working Group of the Spanish Society of Haematology and Hemotherapy &#40;SEHH&#41;&#44; Madrid&#44; Spain&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">PTI&#58; <span class="elsevierStyleItalic">primary immune thrombocytopenia</span>&#44; also known as immune thrombocytopenic purpura&#44; idiopathic thrombocytopenic purpura&#44; or immune thrombocytopenia&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy &#40;SEHH&#41; and the Spanish ITP Group &#40;GEPTI&#41;&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n
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                  \t\t\t\t">General</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; The terminology adopted in this document is consistent with the PTI international working group consensus statement published in 2009<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; Given that there are several limitations to the definitions in that document&#44; work is currently underway to undertake new terminology in a future consensus document&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; The incidence of ITP in both adults and children is 0&#46;2&#8722;0&#46;4 cases per 10&#44;000 person-years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">3&#41; The main manifestations associated with ITP are hemorrhagic&#44; although an increased risk of thrombosis&#44; asthenia &#40;sometimes independent of platelet counts&#41; and a tendency to infections can also be observed&#46; Patients can have numerous adverse reactions related to the treatments administered&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">4&#41; Although the introduction of new therapeutic agents in the last decade has led to a change in the prognosis of ITP patients&#44; the impact on the rate and causes of ITP mortality is unknown&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n
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                  \t\t\t\t">Diagnosis</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; The diagnosis of ITP is made by systematic exclusion of other causes of thrombocytopenia and is based&#44; above all&#44; on the clinical history&#44; physical examination&#44; blood count and peripheral blood smear&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; Observation of the peripheral blood smear is essential in the diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">3&#41; Complementary studies should be requested based on the presentation and clinical course of the disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; The determination of anti-platelet antibodies is not routinely indicated&#44; although they may be helpful in difficult cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">5&#41; The bone marrow study should not be performed routinely&#46; In the event that there is resistance to the treatments&#44; or the existence of another disease is suspected&#44; the bone marrow study is recommended&#44; which should include aspirate and biopsy&#44; immunophenotyping by flow cytometry&#44; cytogenetics&#44; and molecular biology&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Quality of life and alternative treatments</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; ITP patients have an impaired quality of life&#44; especially in the early phase of the disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; Assessment of quality-of-life parameters in ITP patients&#44; before and during the treatment of the disease&#44; using the ITP-specific scales is recommended&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; The most widely used tool to assess the quality of life in adult patients with ITP is the <span class="elsevierStyleItalic">Immune Thrombocytopenic Purpura-Patient Assessment Questionnaire</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; Patients&#39; use of alternative treatments has not been shown to be therapeutically useful&#46; Closer follow-up is recommended when patients start taking alternative treatments&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; The patient should be provided with detailed information on the heterogeneity of the course of ITP in its clinical manifestations and the limited value of the platelet count&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Key points of the guidelines for the diagnosis&#44; treatment and follow-up of primary immune thrombocytopenia concerning general concepts&#44; diagnosis and quality of life&#44; and complementary and alternative treatments&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
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            "identificador" => "at0010"
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">IV Ig&#58; intravenous immunoglobulins&#59; TPO-RA&#58; <span class="elsevierStyleItalic">thrombopoietin receptor agonists&#46;</span></p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy &#40;SEHH&#41; and Spanish ITP Group &#40;GEPTI&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">First-line treatment</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; The decision to start treatment is based mainly on the hemorrhagic manifestations and the platelet count &#40;&#60;&#160;20&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; First-line treatment consists of glucocorticoids &#40;prednisone 0&#46;5&#8722;1&#160;mg&#47;kg or dexamethasone 40&#160;mg&#47;day for 4 days&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; The duration of prednisone treatment consists of a maximum of 8 weeks and dexamethasone treatment consists of 3 cycles&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; The addition of IV Ig is reserved for patients with severe bleeding or contraindications to steroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; In a situation of severe bleeding&#44; combined treatment should be considered &#40;IVIG&#44; high-dose methylprednisolone&#44; platelet transfusion and whether it is necessary to add antifibrinolytics and&#47;or TPO-RA&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#41; Hospital admission for at least 48&#8722;72&#160;h is recommended for a newly diagnosed patient with platelet counts &#60;&#160;20&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Second-line treatment</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; The second-line treatment of choice is TPO-RA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; The choice of TPO-RA should be based on the route of administration&#44; the patient&#39;s wishes&#44; and possible complications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; For rituximab&#44; 375&#160;mg&#47;m<span class="elsevierStyleSup">2</span> weekly &#40;4 doses&#41; is the most commonly used dose&#44; although lower doses &#40;100&#160;mg&#160;&#215;&#160;4&#41; have similar efficacy and may be safer&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; Laparoscopic splenectomy is recommended over laparotomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; Splenectomy should be considered in chronic phases of the disease&#44; when at least one second-line pharmacological treatment has failed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Other second-line treatments&#46; Refractory patients</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; In patients who are resistant to conventional second-line treatments&#44; the best treatment option is not well established&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; Compared to monotherapy&#44; combination therapies are more effective in patients with refractory disease&#44; preferably choosing agents with different mechanisms of action&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; If one treatment is not effective&#44; rather than discontinuing it and starting another&#44; it may be better to add the new agent while continuing with the current one&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; In multidrug-resistant patients&#44; other diagnoses should be considered&#44; such as drug-induced thrombocytopenia&#44; myelodysplastic syndrome&#44; or hereditary thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Key points of the guidelines for the diagnosis&#44; treatment&#44; and follow-up of primary immune thrombocytopenia regarding the treatment of first-line&#44; second-line and multidrug-resistant patients&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">IV Ig&#58; intravenous immunoglobulins&#59; PTI&#58; primary immune thrombocytopenia&#59; TPO-RA&#58; thrombopoietin receptor agonists&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy &#40;SEHH&#41; and the Spanish ITP Group &#40;GEPTI&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Follow-up&#46; Vaccination</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; Hospital admission is recommended for adults with newly diagnosed ITP and platelet count less than 20&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; even when asymptomatic or with minimal mucocutaneous bleeding&#46; If these circumstances occur in patients with established ITP&#44; treatment will be on an outpatient basis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; Regardless of the time of diagnosis and platelet counts&#44; patients with&#58; a&#41; grade <span class="elsevierStyleSmallCaps">ii</span> haemorrhage and platelets&#160;&#60;&#160;30&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; or b&#41; haemorrhage&#160;&#8805;&#160;<span class="elsevierStyleSmallCaps">iii</span> regardless of platelet count&#44; should be hospitalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; To prevent severe post-splenectomy infection&#44; vaccinations should be administered according to the recommendations of each country&#46; Ideally&#44; these vaccinations should be administered at least 2 weeks prior to surgery &#40;if this is not possible&#44; it will be done after surgery&#41;&#44; and the patient will follow the recommended revaccination schedule&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; If the patient is receiving immunosuppressive treatment&#44; it is advisable to avoid live-attenuated vaccines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; Diabetes&#44; renal failure&#44; hypertension&#44; and vascular disease are reported to have a 2-fold higher incidence among patients diagnosed with ITP&#46; Also&#44; thyroid disease is especially prevalent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#41; Among patients with ITP&#44; the incidence of hematologic malignancies&#44; such as lymphomas and leukemias&#44; is higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#41; Up to 16&#37; of patients with ITP will be recognised as having ITP secondary to connective tissue diseases during their follow-up &#40;sometimes more than 10 years after diagnosis&#41;&#44; with systemic lupus erythematosus being the most common&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Surgery</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; In cases of emergency surgery&#44; consider treatment with IV Ig with&#47;without dexamethasone or methylprednisolone at high doses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; Platelet transfusion continues to be a complementary option in extremely serious or life-threatening situations&#46; The combination of platelet transfusion with Ig iv and transfusion immediately before and&#47;or during the procedure is recommended&#44; as the destruction of the transfused platelets is much faster than usual and thus ensures the haemostatic levels of these cells during surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; In preparation for elective surgery in poor responders to steroids&#44; there is an increasing trend to replace the administration of IV Ig with TPO-RA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Discontinuation of ITP treatment</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; A high proportion of patients maintain platelet response after discontinuation of TPO-RA&#44; regardless of the stage of the disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; Patients with persistent or chronic ITP who achieve stable platelet counts&#160;&#62;&#160;50&#8722;100&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l over several months may be considered candidates for tapering with the goal of a maintained response in the absence of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; A tapering strategy from 2 to 6 months and regular monitoring of platelet counts is recommended&#44; with gradual increases in the monitoring intervals once an adequate&#44; stable&#44; and untreated platelet count is achieved&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; If the platelet count drops to 20&#8722;50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; treatment can be restored with the same TPO-RA and the possible addition of immunosuppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Key points of the guidelines for the diagnosis&#44; treatment&#44; and follow-up of primary immune thrombocytopenia about patient follow-up and vaccination&#44; surgery preparation and treatment discontinuation&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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            "identificador" => "at0020"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">IV Ig&#58; intravenous immunoglobulins&#59; PTI&#58; primary immune thrombocytopenia&#59; TPO-RA&#58; thrombopoietin receptor agonists&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy &#40;SEHH&#41; and the Spanish ITP Group &#40;GEPTI&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITP in children</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; The highest incidence of ITP in children occurs between the ages of 2 and 8&#46; The disease tends to have a spontaneous remission&#44; even after 2 years of progression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; With a longer projection of years and life expectancy&#44; it is especially important to assess the adverse reactions and possible sequelae of the various approaches in its management&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; A clinical assessment of severity is proposed based on haemorrhagic manifestations and indicators or risk factors which&#44; together with the platelet count&#44; determine the specific therapeutic recommendation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; Diagnosis is based on clinical history and a complete blood count with morphology that excludes other causes of thrombocytopenia&#46; A bone marrow aspirate is recommended in cases of atypical presentation or with progression to chronicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; High-dose short-term glucocorticoids and IV Ig are the first-line treatment&#46; It is recommended that second-line treatments and those of refractory patients are indicated and controlled in specialized centres for the indication and control of new&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITP in the elderly</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; The incidence of ITP increases with age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; Elderly patients with ITP show greater medical complexity due to comorbidities&#44; age&#44; and other treatments&#46; These patients are at higher risk of bleeding and thrombosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; Diagnosis is often difficult due to the coexistence of other diseases and possible drug interference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; The therapeutic strategy may differ from what is recommended in the guidelines for younger patients&#46; Age can influence efficacy and treatment-related toxicities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; It is important that these patients are cared for in a way that allows them to return to their daily lives as soon as possible&#44; with as little iatrogenesis as possible and maintaining safe platelet counts&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="13" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITP in pregnancy</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; Gestational thrombocytopenia is a benign disorder and the most common cause of thrombocytopenia in pregnancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; In pregnant women with platelet counts below 70&#8722;80&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; other possible causes of thrombocytopenia should be considered&#58; some additional tests&#44; such as blood pressure control&#44; coagulation study&#44; liver function tests&#44; determination of antiphospholipid antibodies or protein in urine can be especially useful for differential diagnosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; The incidence of neonatal thrombocytopenia and haemorrhagic complications is low and does not correlate with maternal platelet counts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; Pregnant women with platelet counts&#160;&#62;&#160;20&#8722;30&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l do not require systematic treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; The first line of treatment in pregnancy are glucocorticoids and IV Ig&#46; In pregnancy&#44; treatment is initiated with lower than usual doses of glucocorticoids to avoid toxicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#41; As IV Igs induce a rapid response&#44; they are of choice in severe bleeding or before performing invasive procedures&#46; Splenectomy should be performed only in severe cases&#44; as should rituximab or TPO-RA administration&#46; Other immunosuppressive agents other than azathioprine or cyclosporine should be avoided during pregnancy due to their possible teratogenicity and because this indication is not approved in the SmPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#41; The recommended platelet count for vaginal deliveries should be 50&#160;&#62;50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l and for caesarean section or epidural anaesthesia 70&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#46; The indication for caesarean section should be based solely on obstetric criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#41; Invasive procedures such as scalp blood sampling&#44; cordocentesis&#44; and assisted deliveries should be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#41; After delivery&#44; a platelet count from a postnatal cord sample is recommended and&#44; if low &#40;less than 100&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#41;&#44; it should be repeated daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#41; If the platelet count is&#60;&#160;&#60;&#160;50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&#44; the neonate should undergo a cranial ultrasound and&#44; in the case of bleeding&#44; administer IV Ig and steroids &#40;minimum dose and limited time&#41; with the aim of reaching 100&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#41; In neonates with hemorrhagic symptoms or platelet counts&#160;&#60;&#160;30&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l administration of a single dose of IV Ig induces rapid response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#41; Although breastfeeding is not contraindicated as a general rule&#44; if thrombocytopenia persists in the new-born&#44; breastfeeding should be discontinued&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#41; Women who have previously given birth to a child with thrombocytopenia should be counselled about the high probability of this recurring in future pregnancies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Key points of the guidelines for the diagnosis&#44; treatment&#44; and follow-up of primary immune thrombocytopenia regarding ITP in children&#44; the elderly and pregnant women&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
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            "identificador" => "at0025"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">IV Ig&#58; intravenous immunoglobulins&#59; PTI&#58; <span class="elsevierStyleItalic">primary immune thrombocytopenia</span> &#40;also known as immune thrombocytopenic purpura&#44; idiopathic thrombocytopenic purpura&#44; or immune thrombocytopenia&#41;&#59; TPO-RA&#58; <span class="elsevierStyleItalic">thrombopoietin receptor agonists</span>&#59; HCV&#58; hepatitis C virus&#59; HIV&#58; human immunodeficiency virus&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Recommendations of the Working Group of the Spanish Society of Haematology and Hemotherapy &#40;SEHH&#41; and the Spanish ITP Group &#40;GEPTI&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Special situations&#46; Thrombosis</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; There is a risk of both venous thromboembolism and arterial thrombosis in patients with ITP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; It is important to improve modifiable personal risk factors for thrombosis&#44; especially in patients over 60 years of age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; Splenectomy increases the risk of venous thromboembolism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; TPO-RA increase the risk of venous thromboembolism and arterial thrombosis in patients with ITP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; For patients requiring chronic antiplatelet and&#47;or anticoagulant therapy&#44; the threshold for a safe platelet count should be&#160;&#62;&#160;30&#8722;50&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l and these treatments should be restarted promptly when this platelet level is reached&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Other immune thrombocytopenia</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; Thrombocytopenia of non-primary immune origin can accompany a wide range of clinical situations&#58; autoimmune diseases&#44; immunodeficiencies&#44; lymphoproliferative syndromes and in cases of post-haematopoietic transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; Considering the association between immune thrombocytopenia and infectious diseases &#40;HCV&#44; HIV&#44; cytomegalovirus&#44; Epstein-Barr&#44; varicella zoster&#44; Zika and <span class="elsevierStyleItalic">Helicobacter pylori</span>&#41;&#44; the presence of these conditions should be ruled out if there is clinical suspicion when establishing the diagnosis of ITP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; Immune-mediated cases may also occur during the postvaccination period&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; There is immune-mediated thrombocytopenia associated with heparin administration&#44; both unfractionated and&#44; to a lesser extent&#44; low molecular weight &#40;heparin-induced thrombocytopenia&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; They are also observed with the use of anti-GPIIb&#47;IIIa monoclonal antibodies&#44; which are used in the field of cardiovascular disease &#40;abciximab&#44; eptifibatide&#44; tirofiban&#44; etc&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#41; A wide range of drugs have been described as being responsible for transient thrombocytopenia due to an immune-mediated mechanism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITP and COVID-19</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#41; Like any infection&#58; i&#41; SARS-CoV-2 may precede a diagnosis of ITP&#44; and ii&#41; if a patient with ITP is infected with SARS-CoV-2 it may lead to decreased platelet counts&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#41; In an emergency health situation&#44; patients with newly diagnosed ITP should be considered for prednisone initiation at 0&#46;5&#160;mg&#47;kg&#47;day&#44; and steroids should be discontinued within a maximum of 8 weeks&#46; If the patient&#39;s risk due to comorbidities is high&#44; non-immunosuppressive agents&#44; such as Ig iv or TPO-RA&#44; may be used&#46; However&#44; the absence of immunosuppression must be weighed against the need for more hospital control with TPO-RA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#41; Rituximab should be avoided because it may decrease the formation of <span class="elsevierStyleItalic">de novo antibodies</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#41; There is no evidence that patients who have undergone a splenectomy are more vulnerable to COVID-19&#46; In case of fever&#44; the treatment of a splenectomised patient should be the same as without COVID-19 infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#41; If a patient with ITP develops severe COVID-19 disease&#44; prophylactic anticoagulation should be sought&#44; and platelet counts should be maintained above 30&#160;&#215;&#160;10<span class="elsevierStyleSup">9</span>&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Key Points of the primary immune thrombocytopenia diagnosis&#44; treatment&#44; and follow-up guidelines concerning special situations&#58; thrombosis&#44; other immune thrombocytopenia and ITP&#44; and COVID-19&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
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        "texto" => "<p id="par0165" class="elsevierStylePara elsevierViewall">We wish to thank the authors of the <span class="elsevierStyleItalic">Guidelines for the diagnosis&#44; treatment&#44; and follow-up of ITP&#46; The</span> SEHH <span class="elsevierStyleItalic">and GEPTI Working Group recommendations&#44;</span> for their contribution to this article&#58; M&#46;T&#46; &#193;lvarez Rom&#225;n&#44; R&#46; Berrueco Moreno&#44; M&#46; Canaro Hirnyk&#44; L&#46; Entrena Ure&#241;a&#44; F&#46; Fern&#225;ndez Fuertes&#44; T&#46;J&#46; Gonz&#225;lez L&#243;pez&#44; J&#46;R&#46; Gonz&#225;lez Porras&#44; C&#46; Grande Garc&#237;a&#44; J&#46;M&#46; Guinea de Castro&#44; I&#46; Jarque Ramos&#44; R&#46; Jim&#233;nez B&#225;rcenas&#44; M&#46;F&#46; L&#243;pez Fern&#225;ndez&#44; R&#46; Mart&#237;nez&#44; M&#46;E&#46; Mingot Castellano&#44; E&#46; Monteagudo Montesinos&#44; C&#46; Pascual Izquierdo&#44; M&#46;M&#46; Perera &#193;lvarez&#44; J&#46;M&#46; Ribera Santasusana&#44; B&#46; S&#225;nchez Gonz&#225;lez&#44; D&#46; Valc&#225;rcel Ferreira&#46; We acknowledge and appreciate the help of the Spanish Society of Haematology and Hemotherapy&#44; especially Ana Carolina Madrid&#44; Carmen Gonz&#225;lez and Carlos Fern&#225;ndez&#44; for the technical support provided for the development of the guidelines&#46;</p>"
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