Regular Article Lack of uniform platelet activation in patients after ischemic stroke and choice of antiplatelet therapy Victor L. Serebruany a, * , Alex I. Malinin a , Benjamin R. Oshrine a , David C. Sane b , Aviv Takserman c , Dan Atar c , Charles H. Hennekens d a Internal Medicine, Johns Hopkins University, 7600 Osler drive, ste. 307, Baltimore, MD 21204, USA b Wake Forest University School of Medicine, Winston Salem, NC, USA c Aker University Hospital, Oslo, Norway d University of Miami School of Medicine, Miami, FL, USA Received 15 January 2004; received in revised form 26 February 2004; accepted 4 March 2004 Available online 12 April 2004 ABSTRACT Introduction: Platelets play an important role in the natural history of ischemic stroke, and are known to be activated in the acute phase. Although aspirin reduces risks of myocardial infarction, stroke and cardiovascular death, the extent of platelet action and the effect of aspirin on platelet function in patients recovering from stroke remain unclear. Methods: We studied 120 individuals divided into three equal groups: aspirin-free patients after ischemic stroke, post-stroke patients receiving aspirin (81 – 650 mg/daily), and aspirin-free subjects with multiple risk factors for vascular disease. Conventional platelet aggregation induced by 5 AM ADP and 5 AM epinephrine, cartridge-based analyzers (UltegraR, and PFA-100k) readings, and expression of CD31, CD41a, CD42b, GPIIb/IIIa activity, CD51/CD61, CD62p, CD63, CD107a, CD154, CD165, formation of platelet – monocyte aggregates, intact (SPAN12), and cleaved (WEDE15) PAR-1 thrombin receptors by flow cytometry were analyzed. Results: There were no differences between aspirin-free post- stroke patients and aspirin-free controls. Although aggregation was slightly higher, 12 out of the 14 receptor analyses, were surprisingly lower in the post-stroke cohort. Aspirin-treated patients exhibited highly significant inhibition of epinephr- ine-induced aggregation ( p = 0.0001), prolongation of the closure time ( p = 0.03), and reduction of the aspirin reactive units ( p = 0.02) measured by the UltegraR device. In addition, surface platelet expression of thrombospondin ( p = 0.001), GPIIb/IIIa activity ( p = 0.04), P-selectin ( p = 0.03), CD40-ligand ( p = 0.04), CD165 0049-3848/$ - see front matter A 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2004.03.002 Abbreviations: ADP, adenosine diphosphate; ARU, aspirin response unit; ASA, aspirin; CD, cluster of differentiations; GP, platelet glycoprotein; LAMP, lyzosome associated membrane protein; NSAIDS, non-steroids anti-inflammatory drugs; PECAM, platelet/ endothelial cell adhesion molecule; PETA, platelet/endothelial tetraspan antigen; PFA, platelet function analyzer; RPFA, rapid platelet-function assay; TIA, transient ischemic attack. * Corresponding author. Tel.: +1-410-847-9490; fax: +1-443-583-0205. E-mail address: Heartdrug@aol.com (V.L. Serebruany). intl.elsevierhealth.com/journals/thre KEYWORDS Stroke; Platelets; Aspirin Thrombosis Research (2004) 113, 197 – 204