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Thromb Haemost 2004; 91(02): 334-344
DOI: 10.1160/TH03-01-0044
Platelets and Blood Cells
Schattauer GmbH

Platelets in patients with acute ischemic stroke are exhausted and refractory to thrombin, due to cleavage of the seven-transmembrane thrombin receptor (PAR-1)

Kerstin Jurk
1   Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University-Hospital of Münster, Münster, Germany
,
Uli-Rüdiger Jahn
1   Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University-Hospital of Münster, Münster, Germany
,
Hugo Van Aken
1   Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University-Hospital of Münster, Münster, Germany
,
Carsten Schriek
1   Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University-Hospital of Münster, Münster, Germany
,
Dirk W. Droste
2   Department of Neurology, University-Hospital of Münster, Münster, Germany
,
Martin A. Ritter
2   Department of Neurology, University-Hospital of Münster, Münster, Germany
,
E.Bernd Ringelstein
2   Department of Neurology, University-Hospital of Münster, Münster, Germany
,
Beate E. Kehrel
1   Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University-Hospital of Münster, Münster, Germany
› Author AffiliationsGrant support: This study was supported by a grant from the Interdisciplinary Center for Clinical Research, project A6, at the University of Münster (Germany).
Further Information

Publication History

Received 22 January 2003

Accepted after resubmission 05 November 2003

Publication Date:
01 December 2017 (online)

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Summary

Platelet activation is involved in the pathogenesis of cerebrovascular ischemia, but the major agonist involved has yet to be identified. To investigate the role of thrombin in platelet activation in patients with acute ischemic stroke, and while thrombin is the most likely candidate for activation of the thrombin receptor PAR-1 in vivo, we assessed its cleavage and internalization using the antibodies SPAN12, binding to uncleaved PAR-1, and WEDE15, recognizing cleaved and uncleaved, but not internalized PAR-1. In contrast to healthy age-matched controls, platelets from stroke patients exhibited significant cleavage and internalization of PAR-1 (P<0.001) and failed to respond to thrombin in vitro. Enhanced surface expression of CD62P, CD63, TSP-1 and less mepacrine uptake showed platelet degranulation during stroke. Platelets from patients with acute cerebral ischemia are exhausted and desensitized to thrombin through cleavage of PAR-1, indicating that high concentrations of thrombin occur with acute cerebrovascular ischemic events in vivo.

Keywords

Thrombin receptor - platelet activation - activation marker - stroke - cerebral ischemia
 

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