Weeterings Cees, Lisman Ton, de Groot Philip G
Department of Clinical Chemistry and Hematology, University Medical Center, Utrecht, The Netherlands.
Semin Hematol. 2008 Apr;45(2 Suppl 1):S12-5. doi: 10.1053/j.seminhematol.2008.03.018.
The molecular mechanisms responsible for the hemostatic efficacy of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) in platelet-related bleeding disorders remain unclear. The general concept is that rFVIIa locally enhances thrombin generation at the site of injury, where tissue factor (TF) has become exposed. However, a growing amount of evidence shows that rFVIIa is also able to exert its activity in a manner independent of TF. Using an in vitro flow model, we recently showed that TF-independent thrombin generation is responsible for increased platelet deposition onto injured vessels following rFVIIa administration. Furthermore, it has been shown that rFVIIa can restore platelet aggregation in Glanzmann's thrombasthenia (GT) patients via TF-independent thrombin generation. However, the mechanism behind TF-independent thrombin generation remains to be elucidated. It is postulated that, in vivo, both the TF-dependent and TF-independent thrombin generation induced by rFVIIa contribute to the control of hemorrhage in patients with platelet-related bleeding disorders and, perhaps, other causes of hemorrhagic diatheses.
重组活化凝血因子VII（rFVIIa；诺其，丹麦诺和诺德公司， Bagsvaerd）在血小板相关出血性疾病中止血疗效的分子机制仍不清楚。一般观点认为，rFVIIa在组织因子（TF）暴露的损伤部位局部增强凝血酶生成。然而，越来越多的证据表明，rFVIIa也能够以独立于TF的方式发挥其活性。我们最近使用体外血流模型表明，rFVIIa给药后，不依赖TF的凝血酶生成导致血小板在损伤血管上的沉积增加。此外，已表明rFVIIa可通过不依赖TF的凝血酶生成恢复血小板无力症（GT）患者的血小板聚集。然而，不依赖TF的凝血酶生成背后的机制仍有待阐明。据推测，在体内，rFVIIa诱导的依赖TF和不依赖TF的凝血酶生成均有助于控制血小板相关出血性疾病患者以及或许其他出血性素质病因患者的出血。
