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 P2Y ₁₂ 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 P2Y ₁₂ gene of a patient with haemorrhagic diathesis.

Clin Chem Lab Med 2007;45:187–9.