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Defective platelet responsiveness to thrombin and protease‐activated receptors agonists in a novel case of gray platelet syndrome: correlation between the platelet defect and the α ‐granule content in the patient and four relatives
Author(s) -
DE CANDIA E.,
PECCI A.,
CIABATTONI G.,
DE CRISTOFARO R.,
RUTELLA S.,
YAOWU Z.,
LAZZARESCHI I.,
LANDOLFI R.,
COUGHLIN S.,
BALDUINI C. L.
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02329.x
Subject(s) - platelet , thrombin , platelet activation , medicine , immunology , biology , endocrinology
Summary. Background: We report a novel case of gray platelet syndrome (GPS). A 14‐year‐old boy had bleeding diathesis, mild thrombocytopenia, giant platelets with severe defect of α ‐granule secretory proteins, myelofibrosis and splenomegaly. Methods and results: Platelet function studies showed a marked reduction of aggregation and Ca 2+ mobilization by thrombin, protease‐activated receptor 1 (PAR1)‐activating peptide (AP) and PAR4‐AP, PAR1 expression at 55% of normal levels, and a more than two hundred fold reduction of in vitro whole‐blood thromboxane B 2 (TXB 2 ) production. Sequencing of coding regions of the PAR1 gene failed to show abnormalities. This patient was initially classified as a sporadic case of GPS, as electron microscopy failed to identify giant platelets and/or α ‐granule deficiency in his relatives. However, further studies on the father and three other relatives showed a relative lack of platelet α ‐granule proteins by immunofluorescence microscopy, a defective platelet response to PAR4‐AP, and severely reduced in vitro whole‐blood TXB 2 production. On this basis, we suggest that in this family, GPS was transmitted in a dominant fashion with highly variable penetrance. Conclusions: Our study suggests that current diagnostic criteria fail to identify some patients with a mild GPS phenotype and that such patients might be identified by the methods cited above. It also better characterizes the pathogenesis of defective platelet responses to thrombin, and raises interesting questions on the correlation between abnormal PAR function and the lack of α ‐granule content in GPS.