Hereditary bleeding disorder due to a primary defect in platelet release reaction.

A large family with a hereditary bleeding disorder was investigated. Easy bruising, epistaxis and menorrhagia were noted in seven members of three generations and at least one member in each generation was affected. Platelet function abnormalities were characterized by reduced 14C-serotonin release, absent second wave aggregation in response to ADP or epinephrine and reduced aggregation in response to collagen. Bleeding time was prolonged in three individuals and platelet factor 3 availability was abnormal in four. Platelet count, morphology, adhesiveness and clot retraction were normal in all. Platelet ADP and ATP as well as ATP to ADP ratio were normal. This family probably represents the first documented instance of hereditary platelet primary release disorder. To elucidate the pathogenetic mechanism, further functional studies were performed. No appreciable shape change, 14C-serotonin release of aggregation was observed when the propositus' platelets were stimulated with sodium arachidonate or a PGH2 analogue. By contrast, platelets responded normally to ionophore A23187, thrombin and ristocetin. The findings indicate that the hereditary primary release disorder is probably due to a reduced thromboxane A2 production secondary to thromboxane synthetase deficiency. Alternatively, it may be due to platelet membrane abnormalities which render platelets unresponsive to thromboxane A2.