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Licensed Unlicensed Requires Authentication Published by De Gruyter February 20, 2007

Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis

  • 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 and Robbert J. Slingerland

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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Corresponding author: J.A. Remijn, PhD, Department of Clinical Chemistry and Laboratory Medicine, Isala Klinieken Zwolle, Postbus 10.500, 8000 GM Zwolle, The Netherlands Phone: +31-38-4242903, Fax: +31-38-4242676,

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Published Online: 2007-02-20
Published in Print: 2007-02-01

©2007 by Walter de Gruyter Berlin New York

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