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Pathogenetic analysis of three cases with a bleeding disorder characterized by defective platelet aggregation induced by Ca 2+ ionophores
Author(s) -
Fuse Ichiro,
Higuchi Wataru,
Uesugi Yumiko,
Aizawa Yoshifusa
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02637.x
Subject(s) - platelet , chemistry , thrombin , myosin light chain kinase , ristocetin , ionophore , platelet activation , phosphorylation , thromboxane , thromboxane a2 , clot retraction , second messenger system , thromboxane b2 , endocrinology , medicine , biochemistry , platelet aggregation , receptor , membrane
We report three cases of platelet dysfunction characterized by defective Ca 2+ ionophore‐induced platelet aggregation without impaired production of thromboxane A 2 (TXA 2 ). The patients had mild to moderate bleeding tendencies, and their platelet aggregation and secretion induced by ADP, collagen, arachidonic acid, stable TXA 2 (STA 2 ) and Ca 2+ ionophore A23187 was defective or much reduced. However, ristocetin‐ or thrombin‐induced platelet aggregation was normal. The analysis of second messenger formation showed that inositol 1,4,5‐triphosphate formation or Ca 2+ mobilization induced by thrombin, STA 2 or A23187 was normal. Furthermore, the phosphorylation of 47 kDa protein (pleckstrin) and 20 kDa protein (myosin light chain, MLC) in response to those agonists was normal. These findings suggest that the defective site in the patients' platelets lies in the process distal to or independent of protein kinase C activation, Ca 2+ mobilization and MLC phosphorylation.