Pathogenetic analysis of three cases with a bleeding disorder characterized by defective platelet aggregation induced by Ca2+ ionophores

We report three cases of platelet dysfunction characterized by defective Ca 2+ ionophore-induced platelet aggregation without impaired production of th romboxane A(2) (TXA(2)), The patients had mild to moderate bleeding tendenc ies, and their platelet aggregation and secretion induced by ADP, collagen, arachidonic acid, stable TXA(2) (STA(2)) and Ca2+ ionophore A23187 was def ective or much reduced, However, ristocetin- or thrombin-induced platelet a ggregation was normal. The analysis of second messenger formation showed th at inositol 1,4,5-triphosphate formation or Ca2+ mobilization induced by th rombin, STA(2) or A23187 was normal. Furthermore, the phosphorylation of 47 kDa protein (pleckstrin) and 20 kDa protein (myosin light chain, MLC) in r esponse to those agonists was normal. These findings suggest that the defec tive site in the patients' platelets lies in the process distal to or indep endent of protein kinase C activation, Ca2+ mobilization and MLC phosphoryl ation.