The bleeding tendency of renal dysfunction patients is a poorly understood phenomenon which appears to be related in part to abnormalities of factor VIII/von Willebrand factor (vWF). To elucidate the relationship between these plasma proteins and uremic bleeding we propose to: 1) Analyze changes in factor VIII and vWF form and function which occur as a result of kidney transplantation. These changes will be related to bleeding time, and indicators of prothrombin and platelet activation with the objective of determining the temporal relationship among these entities. 2) Examine the effect of deamino-8-D-arginine vassopressin (DDAVP) on factor VIII/vWF related activities and bleeding time in renal dysfunction patients. We will test the hypothesis that the effectiveness of DDAVP on bleeding time correction can be predicted by knowledge of the patient's plasma vWF concentration and molecular weight distribution of factor VIII antigen. 3) Examine the content and form of vWF in renal dysfunction patients' platelets as well as the interaction of these platelets with vWF. Potential abnormalities of platelet release or binding of vWF will be demonstratd in these studies. 4) Examine the interaction of patient plasma vWF with collagen fibrils and heparin sepharose. Renal dysfunction patients may have substances in their plasma which inhibit the binding of vWF to platelets or to the subendothelial matrix. This investigation will determine if these inhibitory substances interact with discrete domains on vWF.
