The role of platelet glycoprotein IIIa polymorphism in the high prevalence of in vitro aspirin resistance in patients with intracoronary stent restenosis

Am Heart J. 2005 Apr;149(4):675-80. doi: 10.1016/j.ahj.2004.10.007.

Abstract

Objectives: The aim of our study was to determine the relation between platelet glycoprotein IIIa (Pl A ) polymorphism and aspirin resistance in patients with intracoronary stent restenosis.

Background: Clinically, aspirin resistance is defined as having thrombotic and embolic cardiovascular events despite regular aspirin therapy. Platelet glycoprotein IIIa polymorphism is said to be a possible mechanism of aspirin resistance.

Methods: We studied the prevalence of aspirin resistance in 204 previously intracoronary stent-implanted patients with stable coronary artery disease. In 102 of these patients, intracoronary stent restenosis was present. Platelet functions were analyzed in a platelet function analyzer (PFA-100, Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and collagen and/or adenosine diphosphate cartridges. Closure time <186 seconds was defined as aspirin resistance with Col/Epi cartridges of PFA-100. The Pl A polymorphisms of 43 aspirin-resistant and 51 aspirin-sensitive subjects were determined with polymerase chain reaction and restriction fragments length polymorphism.

Results: A total of 31.3% (n = 32) of patients with intracoronary stent restenosis and 10.7% (n = 11) of patients with patent intracoronary stents were resistant to aspirin by PFA-100. The Pl A1,A1 allele of glycoprotein IIIa was present in 36 subjects (83.7.%) and the Pl A1,A2 allele was present in 7 subjects (16.2.%) in the aspirin-resistant patients group. The Pl A1,A1 allele of glycoprotein IIIa was present in 37 subjects (72.5%) and the Pl A1,A2 allele was present in 14 subjects (27.5%) in the aspirin-sensitive patients group ( P = .195).

Conclusion: Our results suggest that platelets of patients with intracoronary stent restenosis with or without Pl A2 heterozygosity of glycoprotein IIIa are more likely to be resistant to low-dose aspirin therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Antigens, Human Platelet / genetics*
  • Aspirin / pharmacology*
  • Aspirin / therapeutic use
  • Coronary Restenosis / complications
  • Coronary Restenosis / genetics*
  • Coronary Stenosis / therapy
  • DNA Mutational Analysis
  • Drug Resistance / genetics*
  • Female
  • Genotype
  • Humans
  • Integrin beta3 / chemistry
  • Integrin beta3 / genetics*
  • Integrin beta3 / physiology
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Function Tests
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Stents
  • Thrombophilia / drug therapy*
  • Thrombophilia / etiology

Substances

  • Antigens, Human Platelet
  • ITGB3 protein, human
  • Integrin beta3
  • Platelet Aggregation Inhibitors
  • human platelet antigen 1b
  • Aspirin