A NEW PLATELET DISFUNCTION CHARACTERIZED BY SPONTANEOUS PLATELET AGGREGATION AND ENHANCED von WILLEBRAND FACT0R-PLATELET INTERACTION

The proposita is a 48 years old woman who presents mild bleeding tendency and a bleeding time of 7 min. (n. 6 min ± 1.4). Her platelet count is within normal limits and has normal plasma Factor VIII coagulant activity, Ristocetin cofactor activity, von Willebrand Factor (vWF) antigen and vWF multimeric pattern. Spontaneous platelet aggregation (SPA) is observed when citrated PRP is stirred in an aggregometer cuvette. SPA is completely abolished by an anti glycoprotein IIb/IIIa monoclonal antibody and slightly affected by the addition of an anti GPIb monoclonal. The proposita shows an increased ristocetin-induced platelet aggregation although to a lesser extent than that observed in type I IB von Willebrand disease. The distinct feature of this patient, which is also present in two family members studied, is the strong platelet aggregation observed upon the addition of purified vWF at concentrations ranging from 60 to 120 μg/ml f.c. In several normal individuals the addition of vWF up to 300 μg/ml always failed to induce platelet aggregation. The vWF induced platelet aggregation is abolished by anti GPIb and anti GPIIb/IIIa monoclonal antibodies and by EDTA (5 mM). Apyrase (5 ATPase U/ml) inhibits the second wave of aggregation. Patient′s platelets in PRP are 6-6 times more reactive to asialo vWF (AS vWF) induced platelet aggregation than normal platelets. We were not able to demostrate any increased binding of vWF to the patient′s platelets in the presence or in the absence of ristocetin, while we have demonstrated enhanced binding of As vWF, compared to normal, to platelets in PRP. Patient′s platelets do not show an abnormality of GPIb as detected by SDS page and immunoblot analysis using antibody LJIb 10 which reacts with denaturated and reduced GPIb alfa chain. The number of GPIb molecules detected by monoclonal antibody is 17,870 (n. 19,796 ± 3,791). Unlike the previous reported patients with pseudo or platelet type von Willebrand disease, our patient has normal vWF parameters.