Jasper A. Remijn, Martin J.W. IJsseldijk, Annuska L.M. Strunk, Andre P. Abbes, Henk Engel, Bert Dikkeschei, Ellen C. Dompeling, Philip G. de Groot, Robbert J. Slingerland
Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis
Background: The platelet adenosine 5'-diphosphate (ADP) receptor P2Y12 plays a crucial role in haemostasis. Only a few patients with haemorrhagic diathesis due to molecular defects in the P2Y12 receptor have been described so far. We report a novel molecular defect in the gene coding for P2Y12 in a patient with a history of epistaxis, easy bruising and excessive posttraumatic blood loss.
Methods: Platelet aggregation studies, perfusion studies, in which patient blood was perfused over collagen surfaces at arterial shear rates, and PCR and sequencing were used.
Results: Platelet aggregation studies showed impaired ADP and collagen-induced aggregation for patient G.S. Perfusion of patient blood over collagen surfaces showed small thrombi consisting of spread platelets overlayered with non-spread platelets. These thrombi were identical to control thrombi formed in the presence of a P2Y12 antagonist. DNA analysis of the P2Y12 gene revealed a novel heterozygous base pair C?A substitution in exon 3, changing codon 258 from proline to threonine in the third extracellular loop of the P2Y12 receptor.
Conclusions: We conclude that perfusion studies with patient blood are of added value in the diagnostic process, which resulted in identification of a novel molecular defect in the P2Y12 gene of a patient with haemorrhagic diathesis.
Clin Chem Lab Med 2007;45:187–9.
Clinical Chemical Laboratory Medicine, Walter de Gruyter
Print ISSN: 1434-6621
Volume: 45, 02/2007
Pages: 187 - 189
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