In vivo platelet activation in atherothrombotic stroke is not determined by polymorphisms of human platelet glycoprotein IIIa or Ib

Abstract

Summary. Platelet membrane glycoprotein polymorphisms are candidate risk factors for thrombosis, but epidemiological data are conflicting. Thus, demonstration of a genotype-dependent alteration in function is desirable to resolve these inconsistencies. We investigated in vivo platelet activation in acute thrombosis and related this to platelet genotype. Frequencies of the 1b and 2b alleles of the HPA 1a/1b and HPA 2a/2b platelet glycoprotein polymorphisms were determined in 150 (52 men/98 women, mean age 58´3 years) patients with atherothrombotic stroke, and the influence of genotype on markers of platelet activation was assessed. Platelet P-selectin (CD62P) expression and fibrinogen binding was measured using whole blood flow cytometry within 24 h of stroke and 3 months later in 77 patients who provided a repeat blood sample. Results were compared with matched controls. Neither the 1b allele [allele frequency 0´11 vs. 0´13, odds ratio (OR) confidence interval (CI) 0´8 (0´5±1´3)] nor the 2b allele [0´09 vs. 0´07, OR (CI) 1´4 (0´8±2´4)] was significantly over-represented in patients. Increased numbers of activated platelets were found following stroke (acute mean P-selectin expression 0´64% vs. control 0´35%, P , 0´001; acute mean fibrinogen binding 1´6% vs. control 0´9%, P , 0´001). Activation persisted in the convalescent phase (P , 0´001 and P 0´005 vs. controls for P-selectin and fibrinogen respectively). Expression of P-selectin and fibrinogen was not influenced by either the HPA 1a/1b genotype (P . 0´95 for each marker, Scheffe's test) or the 2a/2b genotype (P . 0´95 for each). Although persisting platelet activation is seen in atherothrombotic stroke, it is independent of HPA 1a/1b and 2a/2b genotypes. These data suggest an underlying prothrombotic state, but do not support the polymorphisms studied as risk factors for thrombotic stroke in this population.

Cerebrovascular Events in Patients With Significant Stenosis of the Carotid Artery Are Associated With Hyperhomocysteinemia and Platelet Antigen-1 (Leu33Pro) Polymorphism

“…38 However, other studies failed to demonstrate an association between HPA1a/b and ischemic stroke. 25,37 These conflicting results obtained from various studies can stem from differences in the studied populations and from different specific outcomes that were measured.…”

“…32,33 A polymorphism in the GP IIIa gene (a single nucleotide change T/C, which causes Leu33Pro transition) has also been associated with coronary artery disease in some studies 34 -36 but not in patients with stroke. 26,27,[35][36][37][38] The aim of the present study was to evaluate whether the development of stroke or TIA in patients with significant (Ն50%) carotid artery stenosis is associated with inherited or acquired thrombophilic factors and/or platelet GP polymorphisms.…”

Link between Platelet Activity and Outcomes after an Ischemic Stroke

“…Recent studies [10, 21, 22] have demonstrated that persistent increased platelet activation in stroke patients can, in part, be the result of chronic inflammatory processes [23], vascular risk factors [24], diffuse atherosclerotic lesions [24] or the extent of vascular damage due to a stroke [10]. Interestingly, two recent studies have further demonstrated that substantial interindividual variability is present in platelet reactivity to activation of glycoprotein IIb/IIIa in response to a low concentration of ADP [25, 26].…”

Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: First results from the TRinity AntiPlatelet responsiveness (TrAP) study

“…Platelets are activated in the early, (Grau et al, 1998;Meiklejohn et al, 2001;Marquardt et al, 2002;Garlichs et al, 2003;McCabe et al, 2004a) subacute, (Marquardt et al, 2002) and late phases (Grau et al, 1998;Meiklejohn et al, 2001;Garlichs et al, 2003;McCabe et al, 2004a) after transient ischaemic attack (TIA) or ischaemic stroke. Consequently, antiplatelet agents have the potential to play a key role in the secondary prevention of vascular events in patients with ischaemic cerebrovascular disease (CVD).…”