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

D. J. Meiklejohn, Mark Adrian Vickers, Elspeth Rona Morrison, R. Dijkhuisen, I. Moore, Stanislaw Urbaniak, Michael Greaves

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54 Citations (Scopus)

Abstract

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 Ib 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.

Original languageEnglish
Pages (from-to)621-631
Number of pages10
JournalBritish Journal of Haematology
Volume112
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • platelet activation
  • glycoprotein polymorphisms
  • thrombotic stroke
  • CORONARY-ARTERY DISEASE
  • INHERITED RISK FACTOR
  • MYOCARDIAL-INFARCTION
  • ISCHEMIC STROKE
  • CEREBROVASCULAR-DISEASE
  • PL(A2) POLYMORPHISM
  • CEREBRAL-ISCHEMIA
  • PL(A1/A2) POLYMORPHISM
  • FIBRINOGEN BINDING
  • GENE POLYMORPHISM

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