Patients with congenital bleeding disorders due to primary platelet defects are currently managed during bleeding episodes and surgical procedures with administration of platelet transfusions.
Our specific aims are to study: 1) the effect of intravenously administered 1-desamino-8-D-arginine vasopressin (DDAVP) on the bleeding time, platelet counts, platelet volume, in vitro platelet function, and plasma levels of factor VIII activity, factor VIII-related antigen, factor VIII-von Willebrand factor/ristocetin cofactor activity and tissue plasminogen activator (t-PA) in well-characterized patients with congenital platelet function defects, excluding vWD, and 2) the efficacy of DDAVP in providing adequate hemostasis during surgical procedures and bleeding episodes in the above group of patients. DDAVP, a synthetic vasopressin analog, induces a rise in plasma levels of FVIII:C, FVIII:RAg and FVIII:RCo on intravenous administration in normal subjects and patients with milder vWD and hemophilia A and has been approved recently by FDA for treatment of such patients. Preliminary studies suggest that infusion of cryoprecipitate or DDAVP shortens the bleeding time in patients with platelet defects. We will perform a double-blind randomized trial using DDAVP and placebo in 25-30 patients with congenital platelet function defects, carefully characterized in our laboratory with respect to the underlying abnormalities, and determine the effect on bleeding time and the above mentioned parameters, measured before, at 45 minutes and 4 hours after DDAVP infusion. In addition, we will assess the effect of DDAVP in providing hemostasis in selected patients presenting with bleeding episodes or undergoing surgery. If a beneficial effect is established, this study will have a major impact on management of patients with congenital platelet function abnormalities during bleeding episodes and surgical procedures. It will reduce the blood transfusions and the risks of hepatitis, febrile reactions, alloimmunization and the acquired immune deficiency syndrome (AIDS). We will correlate the effect on the bleeding time with the underlying mechanisms of platelet dysfunction in these patients. We will examine the relationship between the plasma levels of FVIII:Ag and t-PA. These studies will provide valuable insights into the mechanisms operating in normal hemostasis particularly on the vessel wall- factor VIII- platelet interaction.
