Hedner U
Wallenberg Lab, University Hospital, University of Lund, Malmö, Sweden.
Semin Thromb Hemost. 2000;26(4):363-6. doi: 10.1055/s-2000-8453.
The development of factor VIII and factor IX concentrates markedly improved the management of hemophilia A and B and made home therapy possible. However, treatment of hemophilic patients with acquired inhibitors remained difficult. The preparation of prothrombin complex concentrates, nonactivated or activated, addressed this difficult clinical problem, but their use was associated with serious side effects. Factor VIIa was found to be a safer treatment modality. Factor VIIa per se is inactive and needs tissue factor (TF) to become biologically active. TF serves as the receptor for factor VIIa. TF is expressed from vessel walls only upon injury. Treatment of inhibitor patients with plasma-derived factor VII was found to be successful. This led to the development of recombinant factor VIIa, which was also found to be successful in managing hemophilia patients with inhibitors. Up to this point, large numbers of patients have been treated and few serious side effects have been noted. Because of its unique effects on the hemostasis system, recombinant factor VIIa will be useful for other indications as well, including patients with congenital factor VII deficiency, patients with bleeding and liver function impairment, patients with quantitative and qualitative platelet defects, and individuals who have sustained multiple trauma. The development of recombinant factor VII is reviewed in detail.
凝血因子 VIII 和凝血因子 IX 浓缩剂的研制显著改善了甲型和乙型血友病的治疗，并使家庭治疗成为可能。然而，对获得性抑制剂的血友病患者进行治疗仍然困难重重。非活化或活化的凝血酶原复合物浓缩剂的制备解决了这一棘手的临床问题，但其使用会带来严重的副作用。人们发现凝血因子 VIIa 是一种更安全的治疗方式。凝血因子 VIIa 本身无活性，需要组织因子（TF）才能具有生物活性。TF 作为凝血因子 VIIa 的受体。只有在血管壁受损时 TF 才会表达。研究发现，用血浆源性凝血因子 VII 治疗抑制剂患者是成功的。这促使了重组凝血因子 VIIa 的研制，而且人们发现它在治疗有抑制剂的血友病患者方面也很成功。到目前为止，已有大量患者接受了治疗，且几乎未发现严重的副作用。由于其对止血系统具有独特作用，重组凝血因子 VIIa 也将适用于其他适应症，包括先天性凝血因子 VII 缺乏症患者、有出血和肝功能损害的患者、有血小板数量和质量缺陷的患者以及遭受多处创伤的个体。本文将详细综述重组凝血因子 VII 的研制情况。
