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Published on: November 8, 2024
Platelet function under aspirin, clopidogrel, and both after ischemic stroke: a case-crossover study
Armin J Grau1, Sven Reiners, Christoph Lichy
1Neurology Department, University of Heidelberg, Germany. graua@klilu.de
Insights
Combined aspirin and clopidogrel did not reduce platelet activation markers compared to single drugs in stroke patients. However, combination therapy significantly prolonged collagen-ADP closure times in some patients, suggesting potential benefits and risks.
Area of Science:
- Cardiovascular Medicine
- Neurology
- Hematology
Background:
- Dual antiplatelet therapy with aspirin and clopidogrel is considered for stroke prevention.
- The comparative effect of combined versus single antiplatelet agents on platelet activation after stroke is not fully understood.
Purpose of the Study:
- To investigate if combined aspirin and clopidogrel reduce platelet activation more effectively than either drug alone in patients with a history of atherothrombotic or lacunar stroke.
Main Methods:
- A case-crossover study involving 31 stroke patients treated sequentially with aspirin, clopidogrel, and both agents for 4 weeks each.
- Platelet function was assessed using flow cytometry for activation-dependent antigens (CD62p, CD63) and the Platelet Function Analyzer (PFA-100) for collagen/epinephrine (CEPI-CT) and collagen/ADP (CADP-CT) closure times.
- Comparisons were made between treatment regimens and with healthy control subjects.
Main Results:
- No significant differences in CD62p or CD63 expression were observed between the three antiplatelet treatment regimens.
- CD63 expression was higher in stroke patients than in controls, irrespective of treatment.
- Collagen/epinephrine closure time (CEPI-CT) was prolonged by aspirin and combination therapy compared to clopidogrel alone. Collagen/ADP closure time (CADP-CT) was significantly prolonged by combination therapy compared to monotherapy or controls, particularly in a subgroup of patients.
Conclusions:
- Platelet activation, indicated by CD63 expression, remains elevated after stroke and is only partially suppressed by aspirin, clopidogrel, or their combination.
- The pronounced prolongation of CADP-CT with dual therapy in a subset of patients may suggest reduced thrombotic risk but potentially increased bleeding risk.
- Further prospective studies are needed to determine the clinical significance and predictive value of these platelet activation parameters.
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.
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