Expression of platelet glycoprotein VI is associated with transient ischemic attack and stroke

Eur J Neurol. 2010 Jan;17(1):111-7. doi: 10.1111/j.1468-1331.2009.02754.x. Epub 2009 Jul 21.

Abstract

Background and purpose: Platelet collagen receptor glycoprotein VI (GPVI) contributes significantly to platelet adhesion and thrombus formation. We aimed to investigate GPVI in patients presenting with symptoms of acute cerebrovascular disease and to define GPVI as biomarker for acute stroke.

Methods: We consecutively evaluated 205 patients, who admitted the stroke unit with symptoms for stroke. Surface expression of the platelet activation markers (GPVI, CD62P, GPIb) was determined by two-color whole blood flow cytometry.

Results: Patients with transient ischemic attack (TIA) (n = 18; 8.8%) as well as with stroke (n = 133; 64.9%) showed a significantly enhanced GPVI expression (mean fluorescence intensity +/- SD) on admission compared to patients with non-ischemic (NI) events (n = 54; 26.3%) (TIA: 20.9 +/- 7.1 vs. NI: 16.2 +/- 3.9; P = 0.002; stroke: 20.4 +/- 5.7 vs. NI; P = 0.002). Neither CD62P nor GPIb surface expression showed a significant difference. Logistic regression analysis revealed that on admission GPVI was associated with stroke independent of conventional laboratory markers such as C-reactive protein, blood glucose, and creatine kinase. Using a receiver operating characteristic curve on GPVI, we have determined the cut off value of 18.2 for stroke. Thus, patients with enhanced GPVI expression levels (>or=18.2) had a 2.4-fold relative risk for stroke. Patients with elevated platelet GPVI expression level had a poorer clinical outcome in cumulative event-free survival for stroke, myocardial infarction, and cerebro-/cardiovascular death at 3-month follow-up (log rank; P = 0.045).

Conclusions: These findings indicate that platelet GPVI surface expression is significantly enhanced in patients with TIA and stroke compared to patients with NI events. Determination of platelet-specific GPVI may be useful as an early biomarker for cerebral ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Intracranial Thrombosis / diagnosis
  • Intracranial Thrombosis / metabolism*
  • Intracranial Thrombosis / physiopathology
  • Ischemic Attack, Transient / diagnosis*
  • Ischemic Attack, Transient / mortality
  • Ischemic Attack, Transient / physiopathology
  • Male
  • Middle Aged
  • Platelet Adhesiveness / physiology
  • Platelet Membrane Glycoproteins / analysis
  • Platelet Membrane Glycoproteins / metabolism*
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Sensitivity and Specificity
  • Stroke / diagnosis*
  • Stroke / mortality
  • Stroke / physiopathology
  • Up-Regulation / physiology

Substances

  • Biomarkers
  • Platelet Membrane Glycoproteins
  • platelet membrane glycoprotein VI