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.
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