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

Abstract

We read with great interest the articles by Grau et al 1 and Marquardt et al, 2 which were from the same institute, concerning the platelet function under antiplatelet therapy and the course of platelet activation markers after acute ischemic stroke. Many studies have shown that activated platelets can be detected in the systemic circulation in patients with stroke, undergoing cardiopulmonary bypass surgery, peripheral artery occlusive disease, acute myocardial infarction, and other thrombotic disorders. However, which marker for activated platelets can most precisely reflect in vivo platelet activation remains uncertain. Besides, it is of great importance whether the marker is useful to predict the recurrence of vascular event and to monitor the antiplatelet therapy. We would like to compare their recent 2 studies 1,2 with previous ones including our study, 3 their previous study 4 and others. [5][6][7][8][9][10] Platelet activation in patients with chronic phase of stroke has been observed using CD62p expression as a marker of platelet activation. [3][4][5] In the previous study by Grau et al, 4 the proportion of platelets expressing activation-dependent antigens (CD62p and CD63) was higher in patients with both acute and previous cerebrovascular ischemia as compared with age-and sex-matched control subjects. In addition, relatively more platelets expressed CD62p than CD63 in most patients in that study. They explained it was because the secretion of lysosomes usually require stronger stimulation than the release of ␣-granules. On the contrary, in the recent study by Marquardt et al, 2 CD62p expression was not significantly different on days 14 and 90 after stroke compared with control groups. We wonder why platelet activation detected by CD62p expression was not observed when compared serially. On the other hand, increased CD63 expression was observed on days 14 and 90 after stroke, which indicates continuously ongoing platelet activation. They explained that in the subacute stage after ischemic stroke, CD63 is a more sensitive marker of platelet activation than CD62p, most likely because of shedding of CD62p. 2 If so, it may be possible to detect the elevation of soluble p-selectin. Then, we would like to know if soluble p-selectin in plasma rather than CD62p on the platelet surface can be a marker of platelet activation in the subacute stage after stroke. Another question is about the course of platelet activation markers in their study. 2 It is considered that platelets are activated more strongly in the acute phase of stroke than in the chronic phase of stroke. 2,5 In the study by Marquardt et al, 2 CD62p expression declined over time after stroke, and 60% of patients showed a decrease in CD62p. However, the percentage of CD63-expressing platelets did not change between days 1 and 90 after stroke, and only 36% of patients showed a decrease in CD63 over time. Moreover, 30% of patients showed an increase in CD63, and in 34% of patients, CD63 expression did not change. If CD63 is a more sensitive marker of ...