array:22 [ "pii" => "S0025775324002537" "issn" => "00257753" "doi" => "10.1016/j.medcli.2024.04.004" "estado" => "S300" "fechaPublicacion" => "2024-08-01" "aid" => "6655" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2024" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2024;163 Supl 1:S1-S3" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S0025775324004330" "issn" => "00257753" "doi" => "10.1016/j.medcli.2024.06.002" "estado" => "S300" "fechaPublicacion" => "2024-08-01" "aid" => "6739" "copyright" => "The Author(s)" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2024;163 Supl 1:S4-S9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Antiphospholipid antibody testing" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S4" "paginaFinal" => "S9" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diagnóstico de laboratorio de anticuerpos antifosfolípidos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Savino Sciascia, Barbara Montaruli, Maria Infantino" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Savino" "apellidos" => "Sciascia" ] 1 => array:2 [ "nombre" => "Barbara" "apellidos" => "Montaruli" ] 2 => array:2 [ "nombre" => "Maria" "apellidos" => "Infantino" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775324004330?idApp=UINPBA00004N" "url" => "/00257753/00000163000000S1/v2_202409180553/S0025775324004330/v2_202409180553/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Hughes syndrome: The discovery of the antiphospholipid syndrome" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S1" "paginaFinal" => "S3" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Munther Khamashta, Graham R.V. Hughes" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Munther" "apellidos" => "Khamashta" "email" => array:1 [ 0 => "munther.a.khamashta@gsk.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Graham R.V." "apellidos" => "Hughes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Emeritus Professor of Medicine, King's College London, GSK Global Medical Expert-Lupus, Dubai, United Arab Emirates" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Emeritus Professor of Rheumatology, King's College London, The London Lupus & Rheumatology Centre, London, United Kingdom" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de Hughes: El descubrimiento del síndrome antifosfolipídico" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hughes syndrome/antiphospholipid syndrome is now 40 years old. Our first publications were in the British Medical Journal,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a> The Lancet<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> and in Clinical and Experimental Dermatology.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The discovery was a very clinical one. Our lupus centre, then at Hammersmith Hospital was busy, with an enormous turnover of lupus and other Connective Tissue Diseases. We were also blessed with an exceptional group of trainees. The emphasis was on clinical observation, with stimulating coffee breaks in the middle of long ward rounds. One of our areas of focus was on neurological<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a> aspects of lupus, in particular the possible role of anti-neuronal antibodies. Soon, however, we realised that we were quite frequently seeing a group of patients with a similar constellation of features – thrombosis, migraine, a history of recurrent miscarriages, and crucially, differences from classical lupus – such as ANA-negativity, and a low incidence of nephritis.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The thromboses were not confined to deep venous thrombosis (DVT) but could affect the brain (in particular), the kidney, the eye. Intriguingly, the thrombotic tendency could affect arteries as well as veins. One of our visiting fellows, Dr. Helen Englert, from Australia, christened it “GRVH Syndrome” (GRVH being the initials of Professor Hughes's full name).</p><p id="par0020" class="elsevierStylePara elsevierViewall">In our laboratory, Dr. Nigel Harris and Aziz Gharavi worked on the serological profiles of these patients and succeeded in producing a reproducible test for antibodies to cardiolipin – a major help in our efforts to characterise the new syndrome.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> We called the syndrome the anti-cardiolipin syndrome, but soon it became clear that other phospholipids could equally be involved and led to the more correct title – the antiphospholipid syndrome.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Although 1983 was the ‘keynote’ year for the birth of the syndrome, our first public presentation was a year earlier in 1982, at the annual ‘Heberden Society’ meeting of the British Rheumatology Society, held on this occasion on our home territory, the Hammersmith Hospital. The tradition was for our Rheumatologist to present (with patients) his or her observations. Graham Hughes presented 9 patients with lupus, three of whom had the antiphospholipid syndrome (and in fact, no evidence for lupus).</p><p id="par0030" class="elsevierStylePara elsevierViewall">The second ‘presentation’ was in 1983, at the annual meeting of the British Dermatology Society, “the Prosser-White Oration”. The text of this talk was published a year later in 1984.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">3</span></a> Some excerpts from this paper are included here:<span class="elsevierStyleDisplayedQuote" id="dsq0005"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">------although many of these patients fall under the general heading of lupus, or lupus-like disease, I believe that the group is sufficiently homogeneous, and in some ways (such as the frequently negative ANA serology) sufficiently different from typical SLE to warrant separate consideration. The manifestations of this syndrome are thrombosis (often multiple), spontaneous abortion, neurological disease, thrombocytopenia, and livedo reticularis. These patients’ blood pressure often fluctuates, apparently suggesting a possible renovascular aetiology. The cerebral features are prominent, headaches, often migrainous, epilepsy, chorea, cerebro-vascular accidents, visual defects, and progressive cerebral ischaemia. Other features of the syndrome are multiple spontaneous abortions, Budd-Chiari syndrome, renal vein thrombosis and Sjogren's syndrome.</span></p></span></p><p id="par0035" class="elsevierStylePara elsevierViewall">Between 1983 and 1987, we published detailed description of the association with recurrent miscarriage,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> livedo,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> renal thrombosis,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> strokes,<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">7</span></a> liver thrombosis,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a> pulmonary hypertension,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a> myelopathy,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a> chorea,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a> large bowel infarction,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> thrombocytopenia<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a> and dementia.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a> We published similar features seen in patients without systemic lupus, including Behcet's disease, Degos disease, transverse myelopathy, and idiopathic thrombocytopenia.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">15</span></a> Subsequent reports included migraine, epilepsy,<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">16</span></a> heart valve disease<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">17</span></a> and Addison's disease.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a> We also introduced standards for anti-phospholipid antibodies, work led largely by Aziz Gharavi and Nigel Harris.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">19</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In 1984 we held the first international workshop on antiphospholipid antibodies at Hammersmith Hospital, followed by second (now in St Thomas hospital in 1986), and every 2 years since. At the fourth of these meetings, organised by Dr. Angela Tincani in Sirmione, Italy in 1990, a major new observation was reported. Three groups, led by Takao Koike (Japan), Steve Krilis (Australia) and Monica Galli (Netherlands), reported that a specific protein was required for the thrombotic process in antiphospholipid syndrome (APS). This discovery led to a clearer understanding of the process, though it did potentially complicate the name – was anti-phospholipid-cofactor antibody too cumbersome. So, at the 6th international conference in Louvain, several attendees proposed the name Hughes Syndrome.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The biannual conference and international collaborative studies have grown, and some of the outcomes of these studies will be discussed in this issue of the journal.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Advances have come in treatment, in classification, and, critically within specific specialties such as obstetrics, cardiology, neurology and haematology. Publications on APS have included the journal LUPUS, and the keynote 46-chapter volume “Hughes syndrome: antiphospholipid syndrome” (Springer) edited by Munther Khamashta.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> Dr. Khamashta, as head of research in the Lupus Centre in London has had the major benefit of the brilliant link with Spain (where he was trained in Medicine), and in particular, the number of visiting fellows to our unit, many of whom have gone on to medical success in Spain and elsewhere.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">The 21st century</span><p id="par0055" class="elsevierStylePara elsevierViewall">The growth of APS continues, with published studies, lectures, international congresses, and collaborative workshops. One of the striking observations has been the size of the impact on the number of major conditions, a rough estimate of 20% of aPL positivity being reported in stroke, DVT, myocardial infarction, “idiopathic” epilepsy and migraine.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In pregnancy APS/Hughes syndrome has come to be recognised as the commonest, treatable cause of recurrent miscarriage. In lupus sera, percentage positive aPL cases range between 20% and 50% – yet, despite this, in some recently published (large) lupus clinical series, aPL was scarcely mentioned – indeed, in a few such studies, not mentioned at all.</p><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> lists a number of features seen in a lupus patient in whom APS is possibly a contributor to the clinical picture, potentially having a pivotal influence on treatment decisions.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">A large number of related conditions have been linked to APS – some soon after the initial reports of the syndrome, and some more recently (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">From this (incomplete) list, it is easy to conclude that APS impacts on all specialties in medicine, if tested for.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Tests and testing</span><p id="par0080" class="elsevierStylePara elsevierViewall">It is now well-recognised that some patients with classical features of APS remain doggedly ‘sero-negative’.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">21</span></a> As expected, a number of these patients turn out positive when ‘newer’ tests, such as anti-phosphatidyl-serine/prothrombin antibodies are applied.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a> More recently, the old, much unloved lupus anticoagulant test has been reassessed by Sciascia and colleagues… “we observed up to 45% of overall discrepant results for lupus anticoagulant. The introduction of aPS/PT testing might represent a future diagnostic tool”.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Aspects of treatment</span><p id="par0085" class="elsevierStylePara elsevierViewall">Good news and bad news. The discovery of APS has led to improvement-sometimes dramatic, in large numbers of APS patients started on anticoagulation (low molecular weight heparin, or coumadin/warfarin). One lesson learnt early-on that in some patients, a conventional INR of, say, 2.0–2.5 was insufficient, clinical improvement only seen with a higher INR range of, say, 3.5–4.0.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">24</span></a> Low molecular weight heparin is also very successful in APS, particularly in APS pregnancy or during the initiation of treatment. Newer oral anticoagulants (NOACs) were introduced with fanfare, but to date, have proved less than totally effective in severe (especially strokes) APS.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Other treatments such as biologics are being tried in APS on the basis that this disease is antibody mediated. Perhaps one of the most important lessons in treatment of APS has come from ‘catastrophic APS’ studies. An international collaborative study led by Professor Cervera has collected data from colleagues worldwide dealing with this extreme, highly fatal form of APS. This unique, detailed (and ongoing) study has already improved the outcome in this dangerous condition.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusion</span><p id="par0095" class="elsevierStylePara elsevierViewall">The discovery of the anti-phospholipid syndrome/APS/Hughes syndrome has had a major impact on all branches of medicine, from obstetrics to neurology to cardiology and beyond.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Postscript</span><p id="par0100" class="elsevierStylePara elsevierViewall">We are indebted to Professor Miquel Vilardell for his vital support and insight into this major, ‘40-year-old’ clinical discovery.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Ethical considerations</span><p id="par0105" class="elsevierStylePara elsevierViewall">Not applicable.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">MK is a full-time employee of GSK since 2020.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres2245401" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1878061" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2245400" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1878062" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "The 21st century" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Tests and testing" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Aspects of treatment" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Postscript" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Ethical considerations" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2024-02-02" "fechaAceptado" => "2024-04-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1878061" "palabras" => array:4 [ 0 => "Thrombosis" 1 => "Miscarriage" 2 => "Anticardiolipin" 3 => "Lupus anticoagulant" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1878062" "palabras" => array:4 [ 0 => "Trombosis" 1 => "Aborto" 2 => "Anticardiolipina" 3 => "Anticoagulante lúpico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In the 40 years since the original detailed description of antiphospholipid syndrome (APS), the condition has come to be regarded as one of the most common autoimmune diseases. The impact of the description has been enormous – for example, the recognition that some individuals with connective tissue diseases require anticoagulation rather than corticosteroids or anti-inflammatory treatment has bought about fundamental change in medical practice. In obstetrics, APS is now regarded as the most important prothrombotic cause of recurrent pregnancy loss – with pregnancy success improving from below 20% to current live birth rate over 80%. In neurology, APS may be associated with up to 20% of strokes in people under 40 – a striking figure not least in terms of medical economics, let alone in potentially preventable suffering. In vascular medicine, APS links immunology with thrombosis and vascular disease and may well provide insights into immunological factors in the pathogenesis of atherosclerosis.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">En los 40 años transcurridos desde la descripción detallada original del síndrome antifosfolípidico (SAF), la condición ha llegado a ser considerada una de las enfermedades autoinmunes más frecuentes. El impacto de la descripción ha sido enorme; por ejemplo, el reconocimiento de que algunas personas con enfermedades autoinmunes requieren anticoagulación en lugar de glucocorticoides o tratamiento antiinflamatorio ha provocado un cambio fundamental en la práctica médica. En obstetricia, el SAF ahora se considera la causa protrombótica más importante de pérdida recurrente de la gestación. Se ha observado una mejoría significativa en la tasa de éxito del embarazo, que ha pasado de menos del 20% a una tasa actual de nacidos vivos superior al 80%. En neurología, el SAF podría estar asociado con hasta el 20% de los accidentes cerebrovasculares en personas menores de 40 años, una cifra sorprendente, en especial en términos de economía médica, por no hablar del sufrimiento potencialmente evitable. En medicina vascular, el SAF vincula la inmunología con la trombosis y la enfermedad vascular, y puede aportar información sobre los factores inmunológicos en la patogénesis de la aterosclerosis.</p></span>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Recurrent pregnancy loss2. Severe migraine headaches3. Severe memory loss4. Stroke and TIA5. Angina (especially in women under 45)6. Myelopathy (Spinal thrombosis)7. Seizures8. Deep venous thrombosis9. Marked livedo reticularis10. Marked visual symptoms11. Low platelet counts12. Avascular necrosis of bones \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3658940.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Features in a lupus patient suggesting associated Hughes syndrome.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Budd-Chiari syndrome2. Late (as well as early) pregnancy loss3. Immune thrombocytopenia4. Leg ulcers5. Sneddon's syndrome6. Evans syndrome7. Pulmonary hypertension8. Accelerated atherosclerosis9. Ischaemic necrosis of bone10. Addison's disease11. Guillain–Barre syndrome12. Peripheral neuropathy13. Autonomic neuropathy and POTS14. Renal artery and vein thrombosis15. Digital gangrene16. Multi-infarct dementia17. Heart valve lesions18. Epilepsy/Seizures/movement disorders19. Retinal artery/vein thrombosis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3658941.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Conditions “overlapping” with antiphospholipid Syndrome/Hughes syndrome.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib0130" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thrombosis, abortion, cerebral disease, and the lupus anticoagulant" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.R.V. 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Journal Information
Review
Hughes syndrome: The discovery of the antiphospholipid syndrome
Síndrome de Hughes: El descubrimiento del síndrome antifosfolipídico