Serial changes in platelet activation in patients after ischemic stroke: role of pharmacodynamic modulation.
OBJECTIVE
Enhanced platelet activity has previously been reported in the acute phase after ischemic stroke. We tested the hypothesis that activated platelets (expressed by CD62p) are substantially increased in the acute stage after a stroke and decrease thereafter, and that antiplatelet therapies can suppress CD62p expression.


METHODS
We serially examined platelet CD62p expression using flow cytometry after acute ischemic stroke in 87 consecutive patients. The CD62p expression was also evaluated in 20 healthy volunteers and 33 at-risk control subjects.


RESULTS
CD62p expression was significantly higher in the acute phase after ischemic stroke than in normal and at-risk control subjects (both P<0.0001). CD62p expression decreased to a significantly lower level on day 21, and to a substantially lower level on day 90. CD62p expression was not significantly suppressed by warfarin. However, CD62p expression was significantly suppressed by aspirin treatment (P=0.024) and more substantially suppressed by clopidogrel (P<0.0001) on day 90. Furthermore, only clopidogrel treatment (P=0.0016) was significantly independently associated with decreased CD62p expression on day 90.


CONCLUSIONS
Platelet activation was significantly increased in acute ischemic stroke and substantially decreased thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.
Yip
Hon-Kan
HK
Division of Cardiology, Chang Gung Memorial Hospital, Niao Sung Hsiang, Kaohsiung Hsien, Taiwan, Republic of China.
Chen
Shun-Sheng
SS
Liu
Josef S
JS
Chang
Hsueh-Wen
HW
Kao
Yi-Fen
YF
Lan
Min-Yu
MY
Chang
Yung-Yee
YY
Lai
Shung-Lon
SL
Chen
Wei-Hsi
WH
Chen
Mien-Cheng
MC
D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis* / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D020521:Stroke / Q000097:blood* / Q000188:drug therapy*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014859:Warfarin / Q000494:pharmacology / Q000627:therapeutic use
D000925:Anticoagulants; D019007:P-Selectin; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin