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  • Review Article
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New approaches for managing antiphospholipid syndrome

Nature Reviews Rheumatology volume 5, pages 160–170 (2009)Cite this article

Abstract

Antiphospholipid antibodies (aPL) are a family of autoantibodies directed against phospholipid-binding plasma proteins, most commonly β2-glycoprotein-I. Primary thrombosis prevention in persistently aPL-positive individuals requires a risk-stratified approach; elimination of reversible thrombosis risk factors and aggressive prophylaxis during high-risk periods are crucial. The effectiveness of aspirin in persistently aPL-positive patients without vascular involvement is not supported by data from prospective, controlled studies. For the secondary prevention of thrombosis in persistently aPL-positive individuals, the current recommendation is life-long warfarin; however, determining the intensity and duration of warfarin treatment, as well as the role of alternative anticoagulants, requires further research. The effectiveness of high-intensity anticoagulation in patients with antiphospholipid syndrome (APS) and vascular involvement is not supported by data from prospective, controlled studies. Patients with catastrophic APS usually receive a combination of anticoagulants, corticosteroids, intravenous immunoglobulin and plasma exchange; however, despite this aggressive approach, the mortality rate remains high. Potential new approaches for the management of persistently aPL-positive patients include hydroxychloroquine, statins, rituximab, complement inhibition, and other targeted therapies that have been effective in experimental APS models.

Key Points

  • Elimination of reversible thrombosis risk factors and prophylaxis during high-risk periods are crucial for primary and secondary thrombosis prevention in persistently antiphospholipid antibody (aPL)-positive individuals

  • Our recommendation is an international normalized ratio (INR) target of 2.5 for patients with a single previous venous event and an INR target of 3.0 for those with a single previous arterial event for the prevention of recurrent thrombosis in persistently aPL-positive patients; oral factor Xa and thrombin inhibitors might replace warfarin as a treatment of choice in these patients

  • The current recommendation is low-dose aspirin and heparin for the prevention of fetal loss in persistently aPL-positive women with a history of pregnancy morbidities

  • Patients with catastrophic antiphospholipid syndrome usually receive a combination of anticoagulation therapy, corticosteroids, intravenous immunoglobulin and plasma exchange

  • The role of immunomodulation (blocking or eliminating aPL) in the management of aPL-positive patients has been increasingly investigated

  • Hydroxychloroquine, statins, and biologic agents with selected aPL-related targets will potentially be part of antiphospholipid syndrome research and management in the future

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Figure 1: Proposed mechanism of aPL-mediated thrombosis.

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Authors and Affiliations

  1. D Erkan is an Associate Physician-Scientist at The Barbara Volcker Center for Women and Rheumatic Disease, an Assistant Attending Physician and Clinical Researcher at the Hospital for Special Surgery, and an Assistant Professor of Medicine at Weill Medical College of Cornell University. MD Lockshin is Director of The Barbara Volcker Center for Women and Rheumatic Disease, an Attending Physician at the Hospital for Special Surgery, and is Professor of Medicine and Obstetrics at Weill Medical College of Cornell University, New York, NY, USA.,

    Doruk Erkan & Michael D Lockshin

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Correspondence to Doruk Erkan.

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D Erkan has declared that he has acted as consultant for Genentech and Wyeth, and he has received grant/research support (including clinical trials) from Genentech, Human Genome Sciences, Lupus Clinical Trials Consortium and Merck Serono.

MD Lockshin has declared that he has received grant/research support (including clinical trials) from Genentech, Human Genome Sciences, Lupus Clinical Trials Consortium and Merck Serono.

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Erkan, D., Lockshin, M. New approaches for managing antiphospholipid syndrome. Nat Rev Rheumatol 5, 160–170 (2009). https://doi.org/10.1038/ncprheum1017

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