Relationship between bleeding time, aspirin and the PlA1/A2 polymorphism of platelet glycoprotein IIIa

Szczeklik, Andrzej; Undas, Anetta; Sanak, Marek; Frołow, Marzena; Wegrzyn, Wojciech

doi:10.1046/j.1365-2141.2000.02267.x

Cited by 118 publications

(77 citation statements)

References 14 publications

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“…Concerning platelet membrane glycoproteins, it has been reported that genetic polymorphisms of GPIa, 10 GPIba, 11 GPIIIa 12,13 and GPVI 14 influence the efficacy of aspirin or platelet responsiveness. Furthermore, Halushka et al 15 reported the association of platelet aggregation with genetic mutation of COX-1, Papafili et al 16 the association with genetic mutation of COX-2, Higuchi et al 17 the association with genetic mutation of TXA 2 receptors (TP), Stafforini et al 18 the association with genetic mutation of platelet activating factor acetylhydrolase (PAFAH) and Undas et al 19 the association with genetic mutation of coagulation factor XIII (FXIII).…”

Section: Introductionmentioning

confidence: 99%

Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity

et al. 2007

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Section: Introductionmentioning

confidence: 99%

Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity

et al. 2007

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“…Several investigators have reported that carriers of the PlA2 polymorphism appeared to be more resistant to aspirin than did noncarriers; in particular, PlA2 homozygosity has been associated with an inadequate response to aspirin (40)(41)(42). However, due to the retrospective nature of the study and the low number of patients included in the analysis, the results of the present study should be interpreted cautiously.…”

Section: Discussionmentioning

confidence: 40%

PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA and risk of cranial ischemic complications in giant cell arteritis

Salvarani¹,

Casali²,

Farnetti³

et al. 2007

Arthritis & Rheumatism

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Objective. To investigate potential associations of the PlA1/A2 polymorphism of the platelet glycoprotein IIIa (GPIIIa) gene with susceptibility to, and clinical expression of, giant cell arteritis (GCA).Methods. One hundred forty patients with biopsyproven GCA who were residents of Reggio Emilia, Italy, and 241 population-based healthy controls from the same geographic area were genotyped for the PlA1/A2 polymorphism of the platelet GPIIIa gene by molecular methods. The patients were divided into subgroups according to the presence or absence of polymyalgia rheumatica and cranial ischemic complications. The distribution of the PlA1/A2 genotype was investigated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.Results. The distribution of the PlA1/A2 genotype differed significantly between GCA patients with and those without visual loss caused by anterior ischemic optic neuritis (P ‫؍‬ 0.016, corrected P [P corr ] ‫؍‬ 0.048). The PlA2 allele was found significantly more frequently in GCA patients with anterior ischemic optic neuritis than in those without anterior ischemic optic neuritis (P ‫؍‬ 0. Conclusion. Our findings show that A2/A2 homozygosity is associated with an increased risk of visual loss due to anterior ischemic optic neuritis in GCA patients. Antiplatelet therapy, however, was not effective in reducing the risk of ischemic events in this population of GCA patients.

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“…18 Finally, carriers of Pl A2 receiving aspirin have a blunted bleeding time response. 19 However, other studies have failed to show any enhanced effect. [20][21][22] Patients, materials, and methods…”

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confidence: 94%

Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes

O'Connor

Shields

Fitzgerald

et al. 2001

Blood

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This study examined the influence of the Pl A polymorphism of glycoprotein IIIa (GPIIIa) in determining the response to an oral GPIIb/IIIa antagonist, orbofiban, in patients with unstable coronary syndromes. Genotyping for the Pl A polymorphism was performed in 1014 patients recruited into the OPUS-TIMI-16 (orbofiban in patients with unstable coronary syndromes-thrombolysis in myocardial infarction 16) trial, in which patients were randomized to low-or high-dose orbofiban or placebo for 1 year. The primary end point (n ‫؍‬ 165) was a composite of death, myocardial infarction (MI), recurrent ischemia requiring rehospitalization, urgent revascularization, and stroke.Overall, orbofiban failed to reduce ischemic events when compared with placebo, but increased the rate of bleeding. In the whole population, Pl A2 carriers had a significant increase in MI (n ‫؍‬ 33) during follow up, with a relative risk (RR) of 2.71 (95% CI, 1.37 to 5.38; P ‫؍‬ .004). There was a significant interaction between treatment (placebo and orbofiban) and the Pl A polymorphism for bleeding (n ‫؍‬ 187; P ‫؍‬ .05). Thus, while orbofiban increased bleeding in noncarriers (RR ‫؍‬ 1.87, 1.29 to 2.71; P < .001) in a dose-dependent fashion, it did not increase bleeding events in Pl A2 carriers (RR ‫؍‬ 0.87, 0.46 to 1.64). There was no interaction between treatment (placebo and orbofiban) and the Pl A polymorphism for the primary end point (P ‫؍‬ .10). However, in the patients receiving orbifiban there was a higher risk of a primary event (RR ‫؍‬ 1.55, 1.03 to 2.34; P ‫؍‬ .04) and MI (RR 4.27, 1.82 to 10.03; P < .001) in Pl A2 carriers compared with noncarriers. In contrast, there was no evidence that Pl A2 influenced the rate of recurrent events in placebo-treated patients. In patients presenting with an acute coronary syndrome, the Pl A polymorphism of GPIIb/IIIa may explain some of the variance in the response to an oral GPIIb/IIIa antagonist. IntroductionPlatelet activation and subsequent aggregation play major roles in initiating coronary thrombosis, the underlying event in acute coronary syndromes such as unstable angina and myocardial infarction (MI). Platelet aggregation is mediated by glycoprotein (GP) IIb/IIIa, the receptor for fibrinogen and von Willebrand factor (vWf). GPIIb/IIIa antagonists bind to the receptor and prevent platelet aggregation to all known agonists. Yet oral GPIIb/IIIa antagonists have proven ineffective and may be harmful when administered chronically to patients presenting with acute coronary syndromes. 1 Three large-scale clinical trials have reported an increase in death and MI in patients on active treatment compared with placebo. In the OPUS-TIMI-16 (orbofiban in patients with unstable coronary syndromes-thrombolysis in myocardial infarction 16) trial of orbofiban, the study was terminated due to an increase in mortality. 2 In the SYMPHONY II (sibrafiban versus aspirin to yield maximum protection from ischemic heart events post-acute coronary syndromes II) trial, 3 there was an increase in MI and death in patien...

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Relationship between bleeding time, aspirin and the PlA1/A2 polymorphism of platelet glycoprotein IIIa

Cited by 118 publications

References 14 publications

Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity

Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity

PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA and risk of cranial ischemic complications in giant cell arteritis

Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes

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