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Are Prothrombotic Variants of Platelet Glycoprotein Receptor Polymorphisms Involved in the Pathogenesis of Thrombotic Microangiopathies?

Departments of Hemostasis and Transfusion Medicine Heinrich Heine University Medical Center, Düsseldorf, sucker{at}med.uni-duesseldorf.de

Michael Schmitz, MD

Department of Nephrology (MS, GRH, BG), Heinrich Heine University Medical Center, Düsseldorf, Germany

Gerd R. Hetzel, MD

Department of Nephrology (MS, GRH, BG), Heinrich Heine University Medical Center, Düsseldorf, Germany

Bernd Grabensee, MD, PhD

Department of Nephrology (MS, GRH, BG), Heinrich Heine University Medical Center, Düsseldorf, Germany

Beate Maruhn-Debowski

Departments of Hemostasis and Transfusion Medicine Heinrich Heine University Medical Center, Düsseldorf

Ljerka Ostojic, MD, PhD

University Medical Center Mostar, Bosnia and Herzegovina Heinrich Heine University Medical Center, Düsseldorf

Rudiger E. Scharf, MD, PhD

Departments of Hemostasis and Transfusion Medicine Heinrich Heine University Medical Center, Düsseldorf

Rainer B. Zotz, MD

Departments of Hemostasis and Transfusion Medicine Heinrich Heine University Medical Center, Düsseldorf

Thrombotic microangiopathies are life-threatening disorders characterized by vascular microthromboses, schistocytic hemolytic anemia, and thrombocytopenia. Although recent research has partially explained the pathogenesis of these rare entities, the determinants contributing to the onset and modulating the severity of thrombotic microangiopathies are largely unknown. The present study assessed the putative role of prothrombotic platelet receptor polymorphisms in thrombotic microangiopathies that have been found to be associated with premature onset of myocardial infarction in predisposed individuals. Thirty-four consecutive patients admitted with the diagnosis of thrombotic microangiopathy and 759 healthy subjects were enrolled. Genotyping of the human platelet antigen (HPA) 2 an the Kozak sequence polymorphism of GP Ib of the platelets’ von Willebrand factor receptor glycoprotein (GP) Ib-V-IX, the HPA-1 and the HPA-3 polymorphism of the fibrinogen receptor GP IIb-IIIa (integrin _IIbβ ₃) and the HPA-5 and GP Ia 807 C/T polymorphism of the collagen receptor GP Ia-IIa (integrin ₂β₁) were determined according to standard procedures. As a result, no significant differences in the prevalence of prothrombotic variants of platelet-receptor polymorphisms between patients and healthy control subjects were observed. However, although not significant, the prothrombotic bb genotype of the HPA-1 polymorphism was more prevalent in the patients. The findings do not provide evidence that platelet receptor polymorphisms are determinants for the onset of thrombotic microangiopathies or predispose to a more severe course. Along with this observation, screening for respective platelet-receptor polymorphisms does not appear to contribute to risk stratification of affected patients.

Key Words: thrombotic microangiopathies • platelet receptor polymorphisms

This version was published on August 1, 2009

Clinical and Applied Thrombosis/Hemostasis, Vol. 15, No. 4, 402-407 (2009)
DOI: 10.1177/1076029608316015


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