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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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1437-4331
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Volume 45, Issue 2 (Feb 2007)

Issues

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

Jasper A. Remijn
  • Department of Clinical Chemistry and Laboratory Medicine, Isala Klinieken, Zwolle, The Netherlands
/ Martin J.W. IJsseldijk
  • Department of Haematology, Thrombosis and Haemostasis Laboratory, University Medical Centre, Utrecht, The Netherlands
/ Annuska L.M. Strunk
  • Department of Clinical Chemistry and Laboratory Medicine, Isala Klinieken, Zwolle, The Netherlands
/ Andre P. Abbes
  • Department of Clinical Chemistry and Laboratory Medicine, Isala Klinieken, Zwolle, The Netherlands
/ Henk Engel
  • Department of Clinical Chemistry and Laboratory Medicine, Isala Klinieken, Zwolle, The Netherlands
/ Bert Dikkeschei
  • Department of Clinical Chemistry and Laboratory Medicine, Isala Klinieken, Zwolle, The Netherlands
/ Ellen C. Dompeling
  • Department of Internal Medicine, Isala Klinieken, Zwolle, The Netherlands
/ Philip G. de Groot
  • Department of Haematology, Thrombosis and Haemostasis Laboratory, University Medical Centre, Utrecht, The Netherlands
/ Robbert J. Slingerland
  • Department of Clinical Chemistry and Laboratory Medicine, Isala Klinieken, Zwolle, The Netherlands
Published Online: 2007-02-20 | DOI: https://doi.org/10.1515/CCLM.2007.036

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.

Keywords: adenosine 5′-diphosphate (ADP) receptor; bleeding; mutation; P2Y12; platelet; thrombus

References

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About the article

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,


Received: October 2, 2006

Accepted: November 14, 2006

Published Online: 2007-02-20

Published in Print: 2007-02-01


Citation Information: Clinical Chemical Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2007.036. Export Citation

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