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The antiphospholipid syndrome as a disorder initiated by inflammation: implications for the therapy of pregnant patients

Nature Clinical Practice Rheumatology volume 3, pages 140–147 (2007)Cite this article

Abstract

Arterial thrombosis, venous thrombosis and morbidity during pregnancy, or a combination of these events, are clinical outcomes associated with antiphospholipid antibodies produced by patients with antiphospholipid syndrome (APS). Our understanding of the etiology and pathogenesis of the syndrome is limited, but it has generally been considered a thrombophilic disease and treatment has focused on anticoagulation. Agents such as aspirin and heparin, administered alone or in combination, are empirical treatments that are used in the management of obstetric patients with APS. Clinical features, such as heart valve abnormalities, thrombocytopenia and livedo reticularis, suggest multiple pathogenic mechanisms and provide other therapeutic targets. Findings from research in animal models of APS challenge the dogma that this syndrome is a noninflammatory, thrombotic disease and provide evidence that activation of complement is crucial for complications in pregnancy. These studies, in addition to evidence of inflammatory-mediated tissue damage in placentae of patients with APS, suggest that therapy should also be directed towards preventing inflammation. This Review describes the potential mechanisms of tissue injury by antiphospholipid antibodies, the management of pregnant patients with APS and how heparin therapy might inhibit the pathogenic mediators of disease.

Key Points

  • Antiphospholipid syndrome is characterized by thrombosis and morbidity during pregnancy, or a combination of these events, in association with antiphospholipid antibodies

  • Heparin, at subanticoagulant doses, and low-dose aspirin regimens are thought to reduce the risk of spontaneous pregnancy loss in patients with antiphospholipid syndrome

  • In a mouse model of antiphospholipid syndrome, pregnancy complications are initiated by complement-mediated inflammation, rather than by thrombosis

  • Treatment with heparin prevents complement activation and protects mice from pregnancy complications induced by antiphospholipid antibodies, whereas other anticoagulants are not protective

  • Heparins might prevent obstetric complications in women with antiphospholipid syndrome because of their anti-inflammatory effects

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Figure 1: Proposed mechanism for the pathogenic effects of antiphospholipid antibodies on tissue injury
Figure 2: Potential mechanisms by which heparin prevents fetal and placental injury by antiphospholipid antibodies

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Authors and Affiliations

  1. JE Salmon is a Director of the Mary Kirkland Center for Lupus Research, Collette Kean Research Chair and Professor of Medicine, G Girardi is an Associate Scientist and Assistant Professor, and MD Lockshin is Director of the Barbara Volcker Center for Women and Rheumatic Disease, a Director of the Mary Kirkland Center for Lupus Research and Professor of Medicine at the Hospital for Special Surgery-Weill Medical College, Cornell University, New York, NY, USA.,

    Jane E Salmon, Guillermina Girardi & Michael D Lockshin

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  1. Jane E Salmon
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Correspondence to Jane E Salmon.

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Salmon, J., Girardi, G. & Lockshin, M. The antiphospholipid syndrome as a disorder initiated by inflammation: implications for the therapy of pregnant patients. Nat Rev Rheumatol 3, 140–147 (2007). https://doi.org/10.1038/ncprheum0432

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