Keularts I M, Hamulyak K, Hemker H C, Béguin S
Department of Biochemistry, Cardiovascular Research Institute Maastricht, The Netherlands.
Thromb Haemost. 2000 Oct;84(4):638-42.
In von Willebrand disease (vWD) type 1 and mild haemophilia A patients we studied the effect of an infusion of DDAVP (0.3 microg/kg body weight) on thrombin generation in platelet-rich plasma (PRP) and platelet-poor plasma (PPP). Baseline thrombin generation in PRP was diminished both in the haemophilia A and vWD patients. It was normal in vWD plasma when sufficient procoagulant phospholipids were present, either via adding phospholipid vesicles to PPP or via scrambling of the platelet membrane with ionomycin in PRP. In haemophilia A plasma, thrombin generation did not normalize by providing procoagulant phospholipids. Treatment with DDAVP temporarily restored thrombin generation in PRP to normal in both diseases. To investigate the individual roles of von Willebrand factor (vWF) and factor VIII, we also studied the effect of factor VIII infusion on thrombin generation in a severe haemophilia patient. It appears that at a fixed normal vWF concentration, <25% factor VIII is sufficient for normal thrombin generation in PRP. At a sufficient factor VIII concentration, however, thrombin generation is still lower than normal in vWD patients; approximately 40% of vWF is required for half-normal thrombin generation in PRP. It thus appears that vWF is also a clotting factor, in the sense that it is required for normal thrombin generation. This underlines the importance of the interaction between coagulation and the platelets in normal haemostasis. Thrombin generation in PRP appears to be a suitable test to reflect the combined function.
在1型血管性血友病（vWD）患者和轻度甲型血友病患者中，我们研究了输注去氨加压素（DDAVP，0.3微克/千克体重）对富血小板血浆（PRP）和贫血小板血浆（PPP）中凝血酶生成的影响。甲型血友病患者和vWD患者PRP中的基线凝血酶生成均减少。当存在足够的促凝磷脂时，vWD血浆中的凝血酶生成正常，这可以通过向PPP中添加磷脂囊泡或通过在PRP中用离子霉素扰乱血小板膜来实现。在甲型血友病血浆中，提供促凝磷脂并不能使凝血酶生成恢复正常。DDAVP治疗可使两种疾病的PRP中的凝血酶生成暂时恢复正常。为了研究血管性血友病因子（vWF）和凝血因子VIII的各自作用，我们还研究了输注凝血因子VIII对一名重度血友病患者凝血酶生成的影响。结果显示，在vWF浓度正常且固定的情况下，<25%的凝血因子VIII足以使PRP中的凝血酶生成正常。然而，在凝血因子VIII浓度足够时，vWD患者的凝血酶生成仍低于正常水平；PRP中凝血酶生成达到正常水平的一半大约需要40%的vWF。因此，从正常凝血酶生成需要vWF这一意义上来说，vWF也是一种凝血因子。这突出了凝血与血小板之间的相互作用在正常止血过程中的重要性。PRP中的凝血酶生成似乎是反映综合功能的合适检测方法。
