Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants

Devreese, Katrien; Peerlinck, Kathelijne; Hoylaerts, Marc

doi:10.1182/blood-2009-09-244426

Cited by 82 publications

(86 citation statements)

References 29 publications

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“…27,28 On the basis of previous work that found a very low prevalence in our patient population, 29 our laboratory does not routinely screen for anti-b2GPI. However, only one third of the LAC-positive patients with a history of TEs in our Less than 15 GPL or 25 MPL is considered negative in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

The lupus anticoagulant: results from 2257 patients attending a high-risk pregnancy clinic

Clark

Davidovits

Spitzer

et al. 2013

Blood

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Key Points• Only 62 (2.7%) of 2257 high-risk patients tested positive for LAC over 6 years; only 5 (0.02%) with early recurrent miscarriage tested positive.• The 2 assays recommended by ISTH guidelines were less effective than our 4-assay panel at capturing and describing LACpositive patients.Routine investigation for recurrent pregnancy loss includes measurement of antiphospholipid antibodies under the perception that the lupus anticoagulant (LAC) is prevalent in this population. Our tertiary clinic sees ∼250 new patients with recurrent pregnancy loss annually, in addition to those with systemic lupus erythematosus and/ or antiphospholipid syndrome. We measure LAC using a 4-assay panel that expands on the 2 assays recommended by the International Society on Thrombosis and Haemostatis (ISTH) guidelines. Of 2257 patients tested for LAC during a 6-year period, 62 (2.7%) repeatedly tested positive. Only 5 patients (0.2%) had both a history of early recurrent miscarriage and LAC positivity. Patients with LAC had a significantly more frequent history of thrombosis (35.5% vs 2.4%). LAC was absent in an overwhelming majority of women with exclusively early recurrent pregnancy loss but was associated with sporadic stillbirth. Among our panel of assays, none was predominant, and an increasing number of positive assays was associated with an increased history of morbidity. Therefore, our results do not support the ISTH contention that 2 assays are sufficient to identify and describe patients with LAC. We found that a confirmed, repeated LAC was very infrequent even in a high-risk setting. (Blood. 2013;122(3):341-347) Continuing Medical Education online This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 466. Disclosures Nancy Berliner, Editor, has received grants for clinical research from GlaxoSmithKline. The authors and CME questions author Laurie Barclay, freelance writer and reviewer, Medscape, LLC, declare no competing financial interests. Learning objectives Upon completion of this activity, participants will be able to:1. Describe the prevalence of lupus anticoagulant (LAC) and its associations with obs...

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Section: Discussionmentioning

confidence: 99%

The lupus anticoagulant: results from 2257 patients attending a high-risk pregnancy clinic

Clark

Davidovits

Spitzer

et al. 2013

Blood

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“…A recent epidemiological study was unable to identify clinical or immunological predictors of thrombotic events, pregnancy morbidity, or mortality (80 ). Even a quantitative LAC assay is only partially informative in the prediction/exclusion of thrombosis in APS patients, and additional hemostasis markers may have to be adopted to accomplish this task (35 ).…”

Section: Discussionmentioning

confidence: 99%

“…We recently demonstrated that TG calibration curves constructed with mixtures of monoclonal antibodies against ␤2GPI and prothrombin allow expression of the strength of LACs in arbitrary units. A broad variation in LAC-positive patients was observed, with titers ranging from 0 to 200 U/mL (35 ). High titers discriminated well between LAC patients with and without TEC, with an odds ratio of 3.5.…”

Section: Lupus Anticoagulantsmentioning

confidence: 92%

“…This analysis, however, even with the determination of anti-␤2GPI antibodies, was clinically insufficient to discriminate between LAC patients at risk for thrombosis or not. This study demonstrated that if 1 of these 2 parameters had a low titer, additional procoagulant markers needed to be analyzed to reach clinically useful information in weak LAC patients (35 ).…”

Section: Lupus Anticoagulantsmentioning

confidence: 96%

“…Plasma levels of platelet receptors may therefore be indicators of a thrombotic risk. Accordingly, soluble P-selectin is higher in patients with venous thromboembolism, but its role as predictor for TEC needs to be further evaluated in prospective studies (34,35 ).…”

Section: Clinical Diagnosismentioning

confidence: 99%

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Challenges in the Diagnosis of the Antiphospholipid Syndrome

Devreese

Hoylaerts

2010

Clinical Chemistry

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BACKGROUND:The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. Its diagnosis is based on clinical and laboratory criteria, defined by strict guidelines. The original clinical and laboratory criteria for the identification of APS patients were published in 1999, in the so-called Sapporo criteria. In 2006 these criteria were revised, and recently more precise guidelines for analysis of the lupus anticoagulant have been provided. However, several questions related to the diagnosis of APS remain unanswered.CONTENT: In addition to providing a historical perspective, this review covers several challenges in the diagnosis of APS with respect to clinical and laboratory features, while highlighting pathogenic pathways of the syndrome. We discuss ongoing dilemmas in the diagnosis of this complex disease. Although antiphospholipid antibodies are found in association with various clinical manifestations, the older established clinical criteria were not substantively altered in the 2006 update. Several laboratory tests recommended in the latest criteria, including phospholipid-dependent coagulation tests for the detection of the lupus anticoagulant and ELISAs for measuring anticardiolipin and ␤2-glycoprotein I antibodies, still show methodological and diagnostic shortcomings. In addition, antiphospholipid antibodies have been described against other antigens, but their clinical role remains uncertain.

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Antiphospholipid syndrome: Laboratory testing and diagnostic strategies

Ortel

2012

American J Hematol

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The antiphospholipid syndrome (APS) is diagnosed in patients with recurrent thromboembolic events and/or pregnancy loss in the presence of persistent laboratory evidence for antiphospholipid antibodies. Diagnostic tests for the detection of antiphospholipid antibodies include laboratory assays that detect anticardiolipin antibodies, lupus anticoagulants, and anti‐β2‐glycoprotein I antibodies. These assays have their origins beginning >60 years ago, with the identification of the biologic false positive test for syphilis, the observation of “circulating anticoagulants” in certain patients with systemic lupus erythematosus, the identification of cardiolipin as a key component in the serologic test for syphilis, and the recognition and characterization of a “cofactor” for antibody binding to phospholipids. Although these assays have been used clinically for many years, there are still problems with the accurate diagnosis of patients with this syndrome. For example, lupus anticoagulant testing can be difficult to interpret in patients receiving anticoagulant therapy, but most patients with a thromboembolic event will already be anticoagulated before the decision to perform the tests has been made. In addition to understanding limitations of the assays, clinicians also need to be aware of which patients should be tested and not obtain testing on patients unlikely to have APS. New tests and diagnostic strategies are in various stages of development and should help improve our ability to accurately diagnose this important clinical disorder. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.

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Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants

Cited by 82 publications

References 29 publications

The lupus anticoagulant: results from 2257 patients attending a high-risk pregnancy clinic

The lupus anticoagulant: results from 2257 patients attending a high-risk pregnancy clinic

Challenges in the Diagnosis of the Antiphospholipid Syndrome

Antiphospholipid syndrome: Laboratory testing and diagnostic strategies

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