PATHOGENETIC ANALYSIS OF 5 CASES WITH A PLATELET DISORDER CHARACTERIZED BY THE ABSENCE OF THROMBOXANE A(2) (TXA(2))-INDUCED PLATELET-AGGREGATION IN SPITE OF NORMAL TXA(2) BINDING-ACTIVITY

Five patients with mild bleeding tendencies characterized by defective thromboxane A(2) (TXA(2))-induced platelet aggregation are reported. The platelets of all the patients had the ability to bind exogenous TX A(2). Bleeding time was markedly prolonged in one patient. In three of the five patients, synthetic TXA(2) mimetic (STA(2))-induced platelet responses, including IP3 formation, Ca2+ mobilization, phosphatidic a cid formation and GTPase activities were selectively defective, sugges ting impaired coupling between the TXA(2) receptor and phospholipase C activation. However, in the remaining two patients, these responses w ere all within normal limits. This suggests that the defective site of this type of platelet disorder is heterogenous and that signaling mec hanisms other than the TXA(2) receptor-phospholipase C pathway are als o involved in TXA(2)-induced platelet aggregation.