Semin Thromb Hemost 2000; Volume 26(Number 01): 043-046
DOI: 10.1055/s-2000-9802
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4663)

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

Ichiro Fuse, Wataru Higuchi, Yoshifusa Aizawa
  • First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan
Further Information

Publication History

Publication Date:
31 December 2000 (online)

 

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.

KEYWORD

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

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