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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EAntiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis or pregnancy complications combined with the persistent presence of antiphospholipid antibodies. This article provides an overview of the latest research in APS.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatological Autoimmune Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPregnancy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EThromboembolic Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatological Autoimmune Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPregnancy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EThromboembolic Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EAntiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis or pregnancy complications combined with the persistent presence of antiphospholipid antibodies (aPL). Ronald HWM Derksen, MD, PhD, University Medical Center, Utrecht, The Netherlands, gave an overview of the latest research in APS.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ESerologic studies are required for the diagnosis of APS. Lupus anticoagulation (LAC), anti-cardiolipin (aCL), and anti-\u03b2\u003Csub\u003E2\u003C\/sub\u003E-glycoprotein I (anti-\u03b2\u003Csub\u003E2-\u003C\/sub\u003EGPI) assays are typically used to determine whether a patient has APS. Several studies have found that a positive LAC test correlates better with thrombosis and pregnancy loss than the aCL assay, but performing these tests can be challenging. Although there are numerous LAC assays, no single test has 100% sensitivity and specificity. The LAC tests cannot be performed in patients receiving anticoagulation therapy, and there is no standardized definition of a positive test. In addition, a high degree of inter-laboratory variability has been observed in aCL tests, standards have a lot-to-lot variability, and no universally accepted, clinically relevant level currently exists. The anti-\u03b2\u003Csub\u003E2-\u003C\/sub\u003EGPI assay is also problematic, as there are no uniformly accepted calibrators and units, and a clinically relevant cut-off has not been defined.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn an attempt to better define patients with APS, a group of international experts developed a formal list of APS classification criteria in 1999, which was updated in 2006 [Myakis S et al. \u003Cem\u003EJ Thromb Haemost\u003C\/em\u003E 2006]. The APS classification requires one clinical and one laboratory criterion, as summarized in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/14612\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/14612\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14612\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EClassification Criteria for Antiphospholipid Syndrome\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EWhereas the original intent was to use these criteria in research studies to determine the serological profile and clinical characteristics of patients at the highest risk for complications and, thus, ascertain the optimal treatment plan, these criteria are often used for diagnosing APS. The presenters stated that the presence of non-aPL risk factors for thrombosis does not preclude the diagnosis of APS. In a study of 183 patients with aPL-associated thrombosis, more than 50% of patients had coexisting or inherited non-aPL risk factors for thrombosis [Kaul M et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2007]. Examples of non-APL thrombosis risk factors include hypertension, diabetes mellitus, high cholesterol levels, family history of cardiovascular disease, obesity, cigarette smoking, oral contraceptive use, and coexisting autoimmune disease, such as systemic lupus erythematosus (SLE). The frequency of these risk factors requires they be considered to judge the thrombotic risk in aPL patients, noted Prof. Derksen.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003ESome believe that the 99\u003Csup\u003Eth\u003C\/sup\u003E percentile cut-off for APS may be set too high. A recent study of 145 APS patients found that \u223c50% of those patients with obstetric APS had low levels of aCL or anti-\u03b2\u003Csub\u003E2-\u003C\/sub\u003EGPI (between the 95\u003Csup\u003Eth\u003C\/sup\u003E and 99\u003Csup\u003Eth\u003C\/sup\u003E percentile) [Gardiner C et al. \u003Cem\u003ELupus\u003C\/em\u003E 2013]. These data show that patients with non-obstetric, thrombotic APS have much higher levels of these antibodies, indicating a difference between the obstetric and thrombotic subsets, stated Prof. Derksen. Gardiner and colleagues recommended a cut-off at the 95\u003Csup\u003Eth\u003C\/sup\u003E percentile to diagnose obstetric APS.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EThe importance of the serological profile in APS patients has been demonstrated in several studies. In a prospective study of 200 women, 53 were classified with obstetric APS and followed for 7 years [Ruffatti A et al. \u003Cem\u003EThromb Haemost\u003C\/em\u003E 2006]. The authors reported that LAC, aCL, and anti-\u03b2\u003Csub\u003E2\u003C\/sub\u003EPI positivity (triple positivity) had a significant association with late pregnancy loss (OR, 16.2; 95% CI, 0.9 to 292; p=0.01) and thrombosis (OR, 122.5; 95% CI, 16 to 957; p\u0026lt;0.001). In addition, the immunoglobulin (Ig) G-aCL and IgG anti-\u03b2\u003Csub\u003E2-\u003C\/sub\u003EPI levels were significantly higher in triple-positive patients when compared with double-positive patients. Sixteen triple-positive patients and 37 double-positive patients (no positivity for LAC) were followed for a mean 6.3 years (range, 0.5 to 15 years). A total of 47 patients became pregnant and were treated with aspirin and low molecular weight heparin. Seven pregnancies were unsuccessful (15%), and triple positivity or previous thromboembolism were independent markers for pregnancy failure (OR, 34.4; 95% CI, 3.5 to 335.1; p=0.003). There was a new thrombotic episode in 8 patients, and a significant association was seen between thrombotic events and triple positivity or thromboembolism (OR, 57.5; 95% CI, 2.7 to 1160; p=0.0004).\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EIn another multicenter study of obstetric APS, the following independent risk factors for pregnancy failure were identified: history of thrombosis and pregnancy morbidity (OR, 12.1; 95% CI, 1.3 to 115.3; p=0.03), presence of SLE or other autoimmune diseases (OR, 6.0; 95% CI, 1.7 to 20.8; p=0.01), and triple positivity (OR, 4.1; 95% CI, 1.0 to 16.7; p=0.05) [Ruffatti A et al. \u003Cem\u003ERheumatology (Oxford)\u003C\/em\u003E 2011]. In addition, babies born to women who were triple positive were more likely to have a low birth weight and Apgar score, be small for their gestational age, require resuscitation, require neonatal intensive care unit admission, and have infections [Ruffatti A et al. \u003Cem\u003EArthritis Care Res\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EIn the Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus and Antiphospholipid Syndrome study [PROMISSE; Lockshin MD et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2012], 144 pregnant patients with aPL were treated with aspirin and heparin and followed prospectively. Out of 144 pregnancies, 28 (19%) were not successful. The authors reported that adverse pregnancy outcomes (APO) were not associated with IgM-aCL at any level, IgG- or IgM anti-\u03b2\u003Csub\u003E2-\u003C\/sub\u003EPI, or a combination of aCL or anti-\u03b2\u003Csub\u003E2-\u003C\/sub\u003EGPI. Instead, LAC positivity was the primary predictor of APO and was the only component of triple positivity that had predictive value. The differences in the findings between this study and that by Ruffatti and colleagues may be due to the cut-off values used for the assays, stated Prof. Derksen.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EIn his concluding remarks, Prof. Derksen emphasized that well-designed studies are needed to define which aPL profiles are the most important in regard to treatment decisions and which require long-term or short-term thromboprophylaxis, among other issues.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/17\/29.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzp432\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzp432\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}