Pathogenesis of a Bleeding Disorder Characterized by Platelet Unresponsiveness to Thromboxane A₂

ABSTRACT

A platelet disorder characterized by the absence of thromboxane A₂ (TXA₂)-induced platelet aggregation is a new clinical entity of platelet dysfunction. The platelets of three patients had the ability to bind exogenous TXA₂, but synthetic TXA₂ mimetic-induced postreceptor biochemical events, such as IP₃ formation, Ca²⁺ mobilization, phosphatidic acid formation, and GTPase activities, were selectively defective, suggesting impaired coupling between the TXA₂ receptor and phospholipase C activation. Gene analysis of the TXA₂ receptor showed a substitution of Leu for Arg⁶⁰ in the first cytoplasmic loop in all patients, and this mutation seemed to be responsible for this platelet disorder.

Platelet unresponsiveness to thromboxane A₂ (TXA₂) - G-protein - phospholipase C - TXA₂ receptor - point mutation

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