Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation
Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation
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DOI：
10.1038/nm1121
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发表时间：
2004-11-01
期刊：
影响因子：
82.9
通讯作者：
Salmon, JE
中科院分区：
文献类型：
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作者：
Girardi, G;Redecha, P;Salmon, JE
抗磷脂综合征（APS）的定义是在存在抗磷脂（aPL）抗体的情况下血栓形成和复发性妊娠丢失，通常采用抗凝治疗。由于补体激活在aPL抗体诱导的胎儿损伤中是必要的和致病的，我们假设肝素通过抑制补体保护妊娠APS患者免受并发症的影响。用肝素（未分离或低分子量）治疗可在体内和体外阻止补体活化，并保护小鼠免受aPL抗体诱导的妊娠并发症。其他抗凝剂fondaparinux和水水定都不能抑制补体分裂产物的产生或防止妊娠丢失，这表明抗凝治疗不足以保护aps相关性流产。我们的数据表明，肝素可以预防APS妇女的产科并发症，因为它们阻断了针对单个组织的aPL抗体诱导的补体活化，而不是通过其抗凝作用。
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.