Mertens K, Briët E, Giles A R
Department of Blood Coagulation, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Thromb Haemost. 1990 Aug 13;64(1):138-44.
The role of factor VIIa in haemostasis has been studied using a canine model of factor VIII deficiency. Highly purified human factor VIIa was administered to dogs at a dosage of 0.5 microgram/kg. At selected times pre- and post-infusion, haemostasis was evaluated by the cuticle bleeding time. Plasma was collected for the assay of various parameters, including fibrinopeptide A (FPA) as a marker for thrombin generation in vivo. Factor VIIa infusion resulted in a 6-fold increase of factor VII clotting activity with a t1/2 of 2 h. FPA levels, which were 1.4 ng/ml before infusion, did not increase significantly in haemophilic dogs. In normal dogs, however, FPA levels rose to a mean value of 190 ng/ml 30 min post-infusion. It appeared that thrombin generation by factor VIIa infusion had occurred mainly via the intrinsic, factor VIII-dependent pathway. In factor VIII-deficient dogs, factor VIIa infusion did not correct cuticle bleeding, but an inconsistent haemostatic effect was observed 15-30 min post-infusion. Similar results were obtained in haemophilic dogs with circulating antibodies against factor VIII. The haemostatic effectivity could not be improved by increasing the factor VIIa dosage up to 40-fold. Although these data suggest that the extrinsic, factor VII-dependent factor X activation provides only a minor pathway of thrombin generation in vivo, it is possible that the suboptimal haemostatic effect noted may be promoted in bleeding situations where tissue factor availability is less limited. As such, factor VIIa may prove useful in the treatment of haemophilia A patients with acquired inhibitors to factor VIII.
已使用犬类VIII因子缺乏模型研究了VIIa因子在止血中的作用。将高度纯化的人VIIa因子以0.5微克/千克的剂量给予犬类。在输注前和输注后的选定时间，通过表皮出血时间评估止血情况。收集血浆用于测定各种参数，包括纤维蛋白肽A（FPA）作为体内凝血酶生成的标志物。输注VIIa因子导致VII因子凝血活性增加6倍，半衰期为2小时。在血友病犬中，输注前为1.4纳克/毫升的FPA水平没有显著增加。然而，在正常犬中，输注后30分钟FPA水平升至平均190纳克/毫升。似乎输注VIIa因子产生凝血酶主要是通过内源性、依赖VIII因子的途径。在VIII因子缺乏的犬中，输注VIIa因子并未纠正表皮出血，但在输注后15 - 30分钟观察到不一致的止血效果。在患有抗VIII因子循环抗体的血友病犬中也获得了类似结果。将VIIa因子剂量增加至40倍也无法提高止血效果。尽管这些数据表明外源性、依赖VII因子的X因子激活在体内仅提供了一条次要的凝血酶生成途径，但在组织因子可用性限制较小的出血情况下，可能会促进所观察到的次优止血效果。因此，VIIa因子可能被证明对治疗患有VIII因子获得性抑制剂的甲型血友病患者有用。
