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Heparin prevents antiphospholipid antibody–induced fetal loss by inhibiting complement activation

Nature Medicine volume 10, pages 1222–1226 (2004)Cite this article

Abstract

The antiphospholipid syndrome (APS) is defined by thrombosis and recurrent pregnancy loss in the presence of antiphospholipid (aPL) antibodies and is generally treated with anticoagulation therapy. Because complement activation is essential and causative in aPL antibody–induced fetal injury, we hypothesized that heparin protects pregnant APS patients from complications through inhibition of complement. Treatment with heparin (unfractionated or low molecular weight) prevented complement activation in vivo and in vitro and protected mice from pregnancy complications induced by aPL antibodies. Neither fondaparinux nor hirudin, other anticoagulants, inhibited the generation of complement split products or prevented pregnancy loss, demonstrating that anticoagulation therapy is insufficient protection against APS-associated miscarriage. Our data indicate that heparins prevent obstetrical complications in women with APS because they block activation of complement induced by aPL antibodies targeted to decidual tissues, rather than by their anticoagulant effects.

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Figure 1: Heparins protect mice from aPL-IgG induced pregnancy loss.
Figure 2: UFH and LMWH prevent complement deposition in deciduas of mice treated with aPL antibodies.
Figure 3: Heparin does not inhibit aPL-antibody binding to deciduas.

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Acknowledgements

We thank M. Holers, R. Silverstein and M. Lockshin for discussions, P. Casali for providing human monoclonal antibodies and M. Guerra for help in preparing the manuscript. This research was supported in part by the Alliance for Lupus Research (J.E.S.), the Mary Kirkland Center for Lupus Research at Hospital for Special Surgery (G.G. and J.E.S.), and the S.L.E. Foundation, Inc. (G.G.).

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  1. Department of Medicine, Hospital for Special Surgery and Weill Medical College, Cornell University, 535 East 70th Street, New York, 10021, New York, USA

    Guillermina Girardi, Patricia Redecha & Jane E Salmon

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  1. Guillermina Girardi
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Correspondence to Jane E Salmon.

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Girardi, G., Redecha, P. & Salmon, J. Heparin prevents antiphospholipid antibody–induced fetal loss by inhibiting complement activation. Nat Med 10, 1222–1226 (2004). https://doi.org/10.1038/nm1121

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