Published Online
on March 13, 2003

A more recent version of this article appeared on April 1, 2003

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Submitted on September 30, 2002
Accepted on November 5, 2003

Platelet Function Under Aspirin, Clopidogrel, and Both After Ischemic Stroke. A Case-Crossover Study

Armin J. Grau MD, PhD^*; Sven Reiners Cand Med; Christoph Lichy MD; Florian Buggle MD; and Andreas Ruf MD, PhD

From the Neurology Department, University of Heidelberg, Heidelberg, and Center for Laboratory Medicine, Microbiology, Transfusion Medicine, Klinikum Karlsruhe (A.R.), Karlsruhe, Germany.

^* To whom correspondence should be addressed. E-mail: graua{at}klilu.de.

Background and Purpose--Combined antiplatelet agents may offer additive protection over single drugs after stroke. We investigated whether platelet activation is reduced under combined aspirin and clopidogrel compared with each drug alone.

Methods--In a case-crossover study, 31 patients with previous atherothrombotic or lacunar stroke who were treated with aspirin (100 to 300 mg/d) received clopidogrel (75 mg/d) and both aspirin and clopidogrel for 4 weeks. Platelet function in whole blood was studied after each treatment period and in healthy control subjects to assess activation-dependent antigens CD62p and CD63 by flow cytometry and collagen/epinephrine (CEPI-CT) and collagen/ADP (CADP-CT) closure times with the platelet function analyzer PFA-100, which investigates platelet-related function under shear stress.

Results--CD62p expression and CD63 expression were not different under the 3 treatment regimens. CD63 but not CD62p expression was lower in control subjects than in stroke patients regardless of the antiplatelet treatment (P<0.05). CEPI-CT was prolonged under aspirin and aspirin plus clopidogrel compared with clopidogrel monotherapy (P<0.0001). CADP-CT was longer under combination therapy than under aspirin (P=0.0009) or clopidogrel (P=0.0074) or in control subjects (P=0.0010), mainly because of strong prolongation in a patient subgroup (28%).

Conclusions--CD63 expression reflecting the release of platelet lysosomes is consistently increased after stroke and incompletely suppressed by treatment with aspirin, clopidogrel, or both. The strong prolongation of CADP-CT under combined aspirin and clopidogrel in a patient subgroup may indicate a lower risk of thrombosis but also a higher risk of hemorrhage. The predictive value of platelet activation parameters requires investigation in prospective studies.

Key words: inflammation • platelet aggregation inhibitors • platelets • secondary prevention

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