Pathogenetic Analysis of Five Cases with a Platelet Disorder Characterized by the Absence of Thromboxane A₂(TXA₂)-Induced Platelet Aggregation in Spite of Normal TXA₂ Binding Activity

Summary

Five patients with mild bleeding tendencies characterized by defective thromboxane A₂ (TXA₂)-induced platelet aggregation are reported. The platelets of all the patients had the ability to bind exogenous TXA₂. Bleeding time was markedly prolonged in one patient. In three of the five patients, synthetic TXA₂ mimetic (STA₂)-induced platelet responses, including IP3 formation, Ca²⁺ mobilization, phosphatidic acid formation and GTPase activities were selectively defective, suggesting impaired coupling between the TXA₂ receptor and phospholipase C activation. However, in the remaining two patients, these responses were all within normal limits. This suggests that the defective site of this type of platelet disorder is heterogenous and that signaling mechanisms other than the TXA₂ receptor-phospholipase C pathway are also involved in TXA₂-induced platelet aggregation.

• References

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