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"documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2016;146:49-54" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Study of prognostic factors and prevalence of post-thrombotic syndrome in patients with deep vein thrombosis in Spain" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "49" "paginaFinal" => "54" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudio de factores pronósticos y de la prevalencia del síndrome postrombótico en España en pacientes con trombosis venosa profunda" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1489 "Ancho" => 2475 "Tamanyo" => 201279 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">DVT risk factors.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Josep Ordi, Luis Salmerón, Fernando Acosta, Isabel Camacho, Núria Marín" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Josep" "apellidos" => "Ordi" ] 1 => array:2 [ "nombre" => "Luis" "apellidos" => "Salmerón" ] 2 => array:2 [ "nombre" => "Fernando" "apellidos" => "Acosta" ] 3 => array:2 [ "nombre" => "Isabel" "apellidos" => "Camacho" ] 4 => array:2 [ "nombre" => "Núria" "apellidos" => "Marín" ] 5 => array:1 [ "colaborador" => "on behalf of the study investigators ESPOT-TVP" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775315003231" "doi" => "10.1016/j.medcli.2015.04.030" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315003231?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301292?idApp=UINPBA00004N" "url" => "/23870206/0000014600000002/v1_201605240650/S2387020616301292/v1_201605240650/en/main.assets" ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial article</span>" "titulo" => "Post-thrombotic syndrome: A pending issue" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "65" "paginaFinal" => "66" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Francisco Gabriel Botella" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Francisco" "apellidos" => "Gabriel Botella" "email" => array:1 [ 0 => "fgabrielbotella@hotmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Interna, Hospital Casa de Salud, Valencia, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome postrombótico: una asignatura pendiente" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The post-thrombotic syndrome (PTS), the most common chronic complication of deep vein thrombosis (DVT) affects approximately 50% of these patients within the 2 years following its emergence.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1,2</span></a> These data are consistent with the results of Ordi et al. study.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> Its cumulative incidence is increased 10–20 years after the thrombotic event, and 5–10% of these patients develop a serious PTS.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Its socio-economic consequences are considerable due both to increased medical visits, with the subsequent working days lost, and medical and surgical treatments used. In the USA it is estimated that the annual cost per patient per year is $7000.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Although the pathophysiology of PTS is complex and only partially known, venous hypertension appears to play a central role in it: after the thrombotic episode, recanalization of thrombosed vessels results in a residual venous obstruction that may interfere with the function of the calf muscle pumps and cause valvular incompetence with the subsequent venous reflux.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">4,5</span></a> Likewise, thrombosis causes an inflammatory response characterized by the involvement of the 3 major anticoagulant pathways (antithrombin, protein C and systemic tissue factor inhibitor).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> In the intense inflammatory response, antithrombin levels are decreased due to their intake, synthesis deficiency and neutrophil elastase-mediated degradation. Protein C levels are low not only because of the decreasing synthesis and neutrophil elastase-mediated degradation, but also due to the proinflammatory cytokines (mainly tumor necrosis factorα). Endogenous levels of tissue factor pathway inhibitor, the major inhibitor of tissue factor-factor VIIa complex during inflammation is insufficient to activate the coagulation cascade. These findings show that inflammation might move the hemostatic balance toward a prothrombotic state. All this would cause damage to the venous wall and valves. The end result would also be the occurrence of venous hypertension to be transmitted to the capillary bed with fluid transudation and large molecules and the emergence of tissue edema, subcutaneous fibrosis and cellular hypoxia and ulcerations.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The most important risk factor for the development of PTS is recurrent ipsilateral DVT.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2,4</span></a> The iliofemoral veins are at a higher risk than the popliteal veins, and popliteal veins at a higher risk than the distal veins, because the obstruction is located generally above the entrance of the deep femoral vein, worsening collateral flow.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The presence of residual signs and symptoms one month after thrombosis is a predisposing factor of PTS. The subtherapeutic anticoagulation (INR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>2) increases the risk of suffering PTS, especially in the months immediately after the post-thrombotic episode. Obesity, advanced age, hormone therapy, cancer and postoperative state are other risk factors of PTS,<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2,4,5</span></a> and they are reflected in the results reported by the authors.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> By contrast, the duration of anticoagulation (<6, 6–12, or >12 months) does not appear to have an influence, nor hereditary or acquired thrombophilia.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2,4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">To try to overcome these problems 4 prognostic risk factors of PTS have recently been identified<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a>: (a) thrombus spread; (b) thrombus regression below 50%; (c) venous filling rate above 2.5<span class="elsevierStyleHsp" style=""></span>ml/s, and (d) normal rate of blood flow (<60% of the volume depleted after 2<span class="elsevierStyleHsp" style=""></span>s). Each of the 4 items are provided with one point, so that patients with 2 or less points will not suffer PTS in the next 5 years, while those who reach a score over 2 points are at a significant risk, with a 100% sensitivity and a 83% specificity. This study has a number of limitations due to the small sample size and the scores are calculated 6 months after acute thrombotic episode, when most of the PTSs have been developed. A series of inflammatory biomarkers have been proposed, such as the interleukin 6, C-reactive protein and intercellular adhesion molecule-1, as PTS prognostic factors, but so far their clinical usefulness is unknown to identify DVT patients at risk.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">No standard diagnostic test is available for PTS. Its diagnosis is based on a series of signs and symptoms. The latter include swelling, heaviness, fatigue, itching and cramps (often nocturnal) in the affected limb. The symptoms can be intermittent or persistent; usually worsens with prolonged sitting position or ambulation, and improves with rest or elevation of the limb. Venous symptoms associated with initial thrombosis may persist for several months and evolve without a transition period to chronic symptomatology. It may occur as a venous claudication, probably caused by an obstruction of the main venous trunks (iliofemoral and popliteal veins). Clinical signs vary from perimalleolar telangiectasias, pitting edema, ocher dermatitis, venous eczema and secondary varicose veins, to white atrophy lipodermatosclerosis and venous ulcerations.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2,4,5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">PTS is a chronic disorder that often follows a growing-shrinking model. Therefore, we recommend to wait at least 3 months so that the initial pain and edema associated with acute thrombosis disappear.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2,4,5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Three tools are available to diagnose and define the PTS: Ginsberg determination and Brandjes and Villalta scales. The latter, used by the authors,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> has been proven to quantify the PTS and assess its treatment and also to establish a significant correlation with the patient's quality of life.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Although no clinical trials have directly evaluated the effect of anticoagulation on the incidence of PTS, indirectly it prevents symptomatic spread and/or recurrent thromboembolism. Moreover, a subtherapeutic INR has been proven to be a PTS prognostic factor.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2,4,5</span></a> Therefore, in the thrombosis caused or not by surgical risk factors, including thrombophilic defects, anticoagulation recommended is up to 3 months because in both situations the risk of recurrence is low. However, if the patient is still recovering from a venous thromboembolism (VTE) or if the triggers have not been fully resolved it can last longer.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In idiopathic thrombosis, anticoagulation duration recommended is 3 months. Only in the case of a second thrombotic event an indefinite treatment would be indicated, as the risk of recurrence in the first year would be 10%, and 30% after 5 years.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In thrombosis secondary to a persistent or progressive factor, such as cancer, to continue anticoagulation is recommended up to 6 months after cure or complete remission, as the risk of recurrence is 8 times higher if it is withdrawn before. After this time, the withdrawal does not increase recurrence or mortality rates. If cancer is in remission but not cured and there is indirect evidence of low risk of recurrence or absence of metastasis, it is reasonable suppressing medication, at least temporarily, or treat it with oral anticoagulants.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">9,10</span></a> The new oral anticoagulants, whether thrombin inhibitors (dabigatran) or factor Xa (rivaroxaban, apixaban or edoxaban), are as effective and probably as safe as conventional treatments. Furthermore, they show 50% fewer intracranial hemorrhages and a small reduction in extracranial bleeding.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Statins may have a potential role in primary prevention and in reducing the risk of VTE recurrence. Although no definitive conclusions can be drawn, its single administration or associated with antithrombotic drugs in VTE long-term anticoagulation may be a valid option, especially when reducing the lipid level or controlling the development of atherosclerotic lesions is required.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The results of SOX randomized prospective study<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">12</span></a> do not appear to justify the use of elastic compression stockings since it has not been shown to have any impact on the PTS rate and severity. However, a detailed study of the results has shown that the degree of compliance after 2 years was very low, only 55.6% of patients used them 3 or more days per week.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> This is because most of them were unable to put them on since they had not been properly trained or were not provided with proper specific tools, especially with 30–40<span class="elsevierStyleHsp" style=""></span>mmHg compression. The result is the high risk of using them improperly.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In conclusion, we believe that further research is required to determine the impact of new oral anticoagulants, and long-term effectiveness of low molecular weight heparins and elastic growing compression stockings on PTS. The aim of these measures is to improve the quality of life of patients and reduce the economic burden of the disease.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Gabriel Botella F. Síndrome postrombótico: una asignatura pendiente. Med Clin (Barc). 2016;146:65–66.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib0070" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of post-thrombotic syndrome and its association with various risk factors in a cohort of Spanish patients after one year of follow-up following acute deep venous thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Gabriel" 1 => "M. Labiós" 2 => "O. Portolés" 3 => "M. Guillén" 4 => "D. Corella" 5 => "F. 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