Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis
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Jasper A. Remijn
Abstract
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.
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©2007 by Walter de Gruyter Berlin New York
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- Hyperhomocysteinemia and cardiovascular risk in postmenopausal women: the role of folate supplementation
- Association of vitamin B12, folate and homocysteine with functional and pathological characteristics of the elderly in a mountainous village in Sicily
- Association of thyroid dysfunction with vitamin B12, folate and plasma homocysteine levels in the elderly: a population-based study in Sicily
- Desmond (Des) Kenny MSc MCB FICI FRCPath Eur Clin Chem, 1941–2006
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