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The Effect of Glycoprotein IIIa PIA1/A2 Polymorphism on the PFA-100 Response to GP IIbIIIa Receptor Inhibitors—The Importance of Anticoagulants Used

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Abstract

Antithrombotic drugs including glycoprotein (GP) IIbIIIa receptor inhibitors have significantly reduced ischaemic events in coronary disease. Variability in the response to GP receptor inhibitors has been observed both with healthy individuals and in clinical studies. One single nucleotide polymorphism on GP IIIa (PIA1/A2) correlates with increased risk for cardiovascular events in many studies. In this study we investigated whether this polymorphism associates with individual differences in the response to GP IIbIIIa receptor inhibitors in healthy individuals. Fresh blood samples were collected randomly from individuals without a history of coronary disease. Blood samples were anticoagulated with either sodium citrate or with PPACK. The ability of different GP IIbIIIa receptor inhibitors (tirofiban, eptifibatide and abciximab) to inhibit platelet aggregation was investigated using a commercial PFA-100 analyser. At baseline, the function of platelets with different PIA genotypes did not differ from each other. With sodium citrate anticoagulated samples, tirofiban prolonged the closure time slightly more rapidly when platelets with PIA2A2 genotype were used than with other genotypes (p < 0.05) both on epinephrine-collagen and ADP-collagen coated membranes. With eptifibatide or abciximab no differences were observed. If an anticoagulant not affecting Ca2+ concentration (PPACK) was used, no differences were observed between different GP IIIa genotypes and the ability of any of the GP IIbIIIa receptor inhibitors to prolong the closure time. The effect of tirofiban and eptifibatide was significantly affected by the anticoagulant used (p < 0.001), whereas abciximab functioned equally regardless of the anticoagulant.

Abbreviated Abstract

Glycoprotein IIIa PIA2 allele has been found in many studies to associate with risk of thrombosis. In healthy controls the function of GP IIbIIIa receptor inhibitors on platelets with different PIA genotypes was modified by anticoagulants used. PIA polymorphism does not explain the interindividual variance in the response to GP IIbIIIa receptor inhibitors in healthy individuals. The study, however, demonstrates the importance of the anticoagulant used in in vitro studies and the important role of Ca2+ concentration with tirofiban and eptifibatide, but not with abciximab.

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Abbreviations

GP:

glycoprotein

SNP:

single nucleotide polymorphism

PPACK:

Phe-Pro-Arg chloromethylketone

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Authors and Affiliations

  1. Tampere University Hospital, Heart Center, P.O. Box 2000, Tampere, Fin-33521, Finland

    Katriina Aalto-Setälä & Kari Niemelä

  2. Department of Forensic Medicine, Tampere University and Research Unit of Laboratory Centre, Tampere University Hospital, Tampere, Finland

    Pekka J. Karhunen & Jussi Mikkelsson

Authors
  1. Katriina Aalto-Setälä
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  2. Pekka J. Karhunen
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  3. Jussi Mikkelsson
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  4. Kari Niemelä
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Correspondence to Katriina Aalto-Setälä.

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Aalto-Setälä, K., Karhunen, P.J., Mikkelsson, J. et al. The Effect of Glycoprotein IIIa PIA1/A2 Polymorphism on the PFA-100 Response to GP IIbIIIa Receptor Inhibitors—The Importance of Anticoagulants Used. J Thromb Thrombolysis 20, 57–63 (2005). https://doi.org/10.1007/s11239-005-2912-2

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