L.G. Melton, C.M. Thompson, D.A. Gabriel.

Hemorrhage associated with uremia remains a significant clinical problem. Although guanidinosuccinic acid has been implicated in the platelet dysfunction, other factors such as the hematocrit and platelet count are also important. Current therapeutic intervention includes transfusion of red blood cells and platelets, which may enhance the rheophoretic effect and increase the platelet number at the vessel surface. Alternatively, fresh frozen plasma, cryoprecipitate and DDAVP are sometimes infused to improve platelet adhesion. These therapies have disadvantages of volume expansion, allo-immunization, and the risk of viral exposure. In this pilot study, we have examined the efficacy of rhFVIIa on improving hemostasis in uremic patients as evaluated by a flow device (Clot Signature Analyzer). rhFVIIa may be effective in improving platelet activation through thrombin generation since rhFVIIa has the advantage of activating both zymogens FIX and FX. The CSA flow device can assess the effects of rhFVIIa on functional hemostasis with three quantitative parameters, Platelet Hemostasis Time (PHT), Clotting (CT), and Collagen-Induced Thrombus Formation (CITF). These parameters are determined using unanticoagulated whole blood under a defined shear field with minimal manipulation of blood. Unanticoagulated whole blood from four dialysis patients was doped with increasing concentrations of rhFVIIa (0, 75, 150 and 300 nM) and then immediately examined on the flow device. As expected the baseline parameters (PHT, CT and CITF) were prolonged compared to normal blood donors. The concentration effect of rhFVIIa on uremic blood (oDonor 1, Donor 2, Donor 3 and Donor 4) is shown below. The addition of 150 nM rhFVIIa to uremic blood corrects all three parameters to normal values, except for Donor 4 who had a more severe coagulopathy that required higher concentrations of rhFVIIa for correction. These preliminary data show a potential benefit of rhFVIIa infusion in the treatment of hemorrhage in patients.

XVIII th Congress of the I.S.T.H.- Paris.