Hedner Ulla
University of Lund, Malmö, Sweden.
Semin Thromb Hemost. 2006 Apr;32 Suppl 1:77-85. doi: 10.1055/s-2006-939557.
Recombinant factor VIIa (rFVIIa) has been developed for treatment of bleeding in patients with hemophilia who have inhibitors against factor VIII (FVIII) or FIX, and has been found to induce hemostasis during major orthopedic surgery. The use of rFVIIa treatment for hemophilia is a new concept and is based on the low-affinity binding of FVIIa to the surface of thrombin-activated platelets. Administration of pharmacologic doses of exogenous rFVIIa enhances thrombin generation on the platelet surface at the site of injury independently of the presence of FVIII or FIX. Pharmacologic doses of rFVIIa induce hemostasis not only in hemophilia patients, but also in patients with thrombocytopenia, functional platelet defects, and with profuse bleeding triggered by extensive surgery or trauma. The general mechanism of action of rFVIIa to induce hemostasis under these conditions may be its capacity to generate a tight fibrin hemostatic plug through increased thrombin generation. A tight fibrin plug will aid in resisting the overwhelming local release of fibrinolytic activity triggered by vast tissue damage occurring in extensive trauma. Local fibrinolytic activity also occurs in the gastrointestinal tract as well as during profuse postpartum bleeding. Pharmacologic doses of rFVIIa induce hemostasis in these cases also.
重组凝血因子VIIa（rFVIIa）已被开发用于治疗患有针对凝血因子VIII（FVIII）或FIX抑制剂的血友病患者的出血，并且已发现在大型骨科手术期间可诱导止血。rFVIIa用于治疗血友病是一个新概念，其基于FVIIa与凝血酶激活的血小板表面的低亲和力结合。给予药理剂量的外源性rFVIIa可在损伤部位的血小板表面增强凝血酶生成，而与FVIII或FIX的存在无关。药理剂量的rFVIIa不仅可在血友病患者中诱导止血，还可在血小板减少症、功能性血小板缺陷以及由广泛手术或创伤引发的大量出血患者中诱导止血。在这些情况下，rFVIIa诱导止血的一般作用机制可能是其通过增加凝血酶生成来产生紧密纤维蛋白止血栓的能力。紧密的纤维蛋白栓将有助于抵抗由广泛创伤中发生的巨大组织损伤引发的压倒性局部纤溶活性释放。局部纤溶活性也发生在胃肠道以及产后大出血期间。药理剂量的rFVIIa在这些情况下也可诱导止血。
