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


CONCLUSIONS
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.
Pamukcu
Burak
B
Department of Cardiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. burakpamukcu@istanbul.edu
Oflaz
Huseyin
H
Nisanci
Yilmaz
Y
D000368:Aged; D000483:Alleles; D016824:Antigens, Human Platelet / Q000235:genetics*; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D023903:Coronary Restenosis / Q000150:complications / Q000235:genetics*; D023921:Coronary Stenosis / Q000628:therapy; D004252:DNA Mutational Analysis; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D039661:Integrin beta3 / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015607:Stents; D019851:Thrombophilia / Q000188:drug therapy* / Q000209:etiology
D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors; C083451:human platelet antigen 1b; D001241:Aspirin