Thrombin-induced Hyperactivity of Platelets of Young Stroke Patients

Kristof Vanschoonbeek; Marion A. H. Feijge; Jeffrey F. W. Keuren; H. Coenraad Hemker; Jan J. Lodder; Karly Hamulyák; Elisabeth C. M. van Pampus; Johan W. M. Heemskerk

doi:10.1055/s-0037-1613336

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 88(06): 931-937
DOI: 10.1055/s-0037-1613336

Involvement of Thrombin Receptors in the Subject-dependent Variability in Ca2+ Signal Generation

Schattauer GmbH

Thrombin-induced Hyperactivity of Platelets of Young Stroke Patients

Kristof Vanschoonbeek

¹Depts. of Human Biology

,

Marion A. H. Feijge

,

Jeffrey F. W. Keuren

,

H. Coenraad Hemker

³Synapse, Cardiovascular Research Institute of Maastricht, University of Maastricht, Maastricht, Depts

,

Jan J. Lodder

,

Karly Hamulyák

⁵Haematology, Academic Hospital of Maastricht, The Netherlands

,

Elisabeth C. M. van Pampus

⁵Haematology, Academic Hospital of Maastricht, The Netherlands

,

Johan W. M. Heemskerk

¹Depts. of Human Biology

› Author Affiliations

Abstract

Summary

Activated platelets are implicated in the development of premature arterial vascular diseases, in particular ischemic stroke. Since elevated cytosolic [Ca²⁺]_i is an integrative marker of platelet activation, we determined the generation of Ca²⁺ signal in stimulated platelets from 26 young patients recuperating from stroke, 20 patients with symptomatic peripheral arterial disease, and 56 healthy volunteers. Even in the presence of aspirin, the platelets from various individuals showed highly different thrombin-induced Ca²⁺ responses. On average, the thrombin-induced Ca²⁺ response was increased for platelets from either patient group in comparison to the controls (P <0.04). Relatively more stroke patients had high-responsive platelets (27%, 7/26) than patients with peripheral arterial disease (10%, 2/20) or healthy subjects (4%, 2/56). The average prothrombinase activities of platelets from patients and controls were similar, but 3 out of 6 patients with increased thrombin-induced Ca²⁺ responses also exhibited high prothrombinase activity. In a follow-up study, the subject-dependent thrombin-induced Ca²⁺ response was found to correlate strongly with the platelet response to protease-activated receptor 1 (PAR1) agonist (r = 0.91), but was not linked to the Pl^A1/2 polymorphism. It is concluded that a significant part of young patients with stroke have platelets with hyperactivity toward thrombin, which is not normalised by aspirin treatment. Furthermore, the subject-dependent variation in thrombin-induced signalling is likely to involve PAR1-mediated platelet activation.

Keywords

Aspirin - calcium - ischemic stroke - platelets - thrombin receptors

Full Text

References

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