ACTIVATION OF PROTHROMBIN IN WHOLE HUMAN BLOOD

在过去的一年中，619号协议已被用于监测全血模型系统中的血液凝固。 患者队列根据研究所需的参数而变化。 我们广泛研究了因子VIII（fVIII）缺陷者（血友病A）和因子IX（fIX）缺陷者（血友病C），以更好地了解这些缺陷在凝血事件期间如何在凝血酶产生、血小板活化、纤维蛋白肽产生方面表现出来。、因子V（fV）和凝血酶原活化。 从收集的数据中，我们可以看到，与正常人相比，两组血友病患者的凝血时间延长，凝血酶生成曲线降低。 纤维蛋白肽的产生在反应的时间过程中被延迟，但在定量上没有显著影响。 因子V活化也显著受损。 患者血液中fIX和fVIII的替代导致与正常对照相当的曲线。在治疗期间同样监测了接受化疗的患者，以研究血小板减少症对凝血的影响。 该患者在化疗周期的不同时间点进行了几个月的研究。在每个时间点，血小板计数变化，通过时间过程监测凝血，并分析凝血酶生成、纤维蛋白肽生成和血小板活化。 直到血小板计数达到低于10，000 K/cm的水平，才影响凝血时间。 数据显示，当患者接近血小板减少状态（血小板计数降低）时，凝血酶生成与血小板计数直接相关地显著受损。 因此，血小板活化同样依赖于血小板群体。 然而，纤维蛋白肽释放在血小板减少状态下不受影响。未来的计划包括对血友病患者进行更多的研究，以确定因子VIIa替代疗法是否与因子VIII或因子IX替代疗法一样有效，以及因子VIIa升高对凝血的影响。

Protocol 619 has been used during the past year to monitor blood coagulation in a whole blood model system. The patient cohort has been varied depending on the parameters desired for study. We have looked extensively at both factor VIII (fVIII) deficient persons (hemophilia A) and factor IX (fIX) deficient persons (hemophilia C) to better understand how these deficiencies manifest themselves during a coagulation event in terms of thrombin generation, platelet activation, fibrinopeptide production, factor V (fV) and prothrombin activation. From the data gathered, we can see an extended clot time, and depressed thrombin generation profile in both sets of hemophiliac patients as compared to normal persons. Fibrinopeptide production is delayed over the time course of the reaction, but is not significantly effected quantitatively. Factor V activation was also significantly impaired. Replacement of fIX and fVIII in patient blood resulted in profiles equivalent to the normal controls. A patient on chemotherapy was likewise monitored during treatment to study the effects of thrombocytopenia on blood coagulation. The patient was studied over several months at different points in the chemotherapy round. At each time, platelet count varied and coagulation was monitored via a time course and analyzed for thrombin generation, fibrinopeptide production and platelet activation. Clot time was not effected until the platelet count reached levels below 10, 000 K/cmm. The data have shown that as the patient approaches a thrombocytopenic state (lowering platelet count), thrombin generation is significantly impaired in direct relation to platelet count. Consequently, platelet activation is equally dependent on the platelet population. Fibrinopepetide release, however, was not affected in a thrombocytopenic state. Future plans include more studies of hemophiliac patients to determine if factor VIIa replacement therapy is as effective as replacement with factor VIII or factor IX and what effects elevated factor VIIa have on blood coagulation.