Measurement of residual platelet thrombogenicity under arterial shear conditions in cerebrovascular disease patients receiving antiplatelet therapy.
Essentials A consensus methodology for assessing the effects of antiplatelet agents has not been established. Measuring platelet thrombus formation (PTF) for evaluating antiplatelet effects was assessed. PTF differentially reflected antiplatelet effects compared to other tests. PTF may be associated with the severity of carotid or intracranial arterial stenosis. Click to hear a presentation on platelet function testing in the clinic by Gresele and colleagues



Background A consensus methodology for assessing the effects of antiplatelet agents has not been established. Objective We investigated the usefulness of directly measuring platelet thrombus formation (PTF) using a microchip-based flow chamber system for evaluating antiplatelet therapy. Patients/Methods Platelet thrombus formation in the whole blood of 94 patients with ischemic cerebrovascular disease treated with clopidogrel and/or aspirin was measured in a flow chamber system at a shear rate of 1500 s(-1) and was compared with the results of assays for agonist-induced platelet aggregability, phosphorylation of vasodilator-stimulated phosphoprotein, platelet p-selectin expression (PS), and platelet-monocyte complexes. Results In all patients tested, area under the flow pressure curve (AUC10), which represents platelet thrombogenicity, showed weak correlation with platelet aggregation induced by either adenosine diphosphate or collagen. In addition, AUC10 was lower in patients treated with dual antiplatelet therapy (median 79.4) compared with patients treated with aspirin or clopidogrel alone (217.7 and 301.0, respectively), whereas the parameters evaluated by the other assays did not reflect the combined treatment efficacy. In clopidogrel monotherapy patients, AUC10 was associated with the severity of arterial stenosis (R(2) = 0.127, β = 1.25), and AUC10 and PS were higher in patients with severe carotid or intracranial arterial stenosis than in those with mild stenosis. Conclusions Platelet thrombus formation measurement using a flow-chamber system was useful for evaluating the efficacy of treatment with aspirin and clopidogrel, both alone and in combination. The present findings indicate that high residual platelet thrombogenicity in patients treated with clopidogrel may be associated with the severity of carotid or intracranial arterial stenosis.
Department of Neurology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan. myamazak@nij.twmu.ac.jp.
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Yamazaki
Research Institute, Fujimori Kogyo Co., Ltd, Yokohama, Kanagawa, Japan.
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Ohnishi
Research Institute, Fujimori Kogyo Co., Ltd, Yokohama, Kanagawa, Japan.
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Hosokawa
Department of Neurosurgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
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Yamaguchi
Department of Neurosurgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
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Yoneyama
Department of Neurosurgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
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Kawashima
Department of Neurosurgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
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Okada
Department of Neurology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
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Kitagawa
Department of Neurology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.|Clinical Research Center for Medicine, International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo, Minato-ku, Japan.
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Uchiyama
D000328:Adult; D000368:Aged; D001158:Arteries / Q000473:pathology; D001241:Aspirin / Q000627:therapeutic use; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000166:cytology*; D002339:Carotid Arteries / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000628:therapy; D000077144:Clopidogrel; D003251:Constriction, Pathologic / Q000097:blood / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests / Q000379:methods; D033081:Shear Strength; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000494:pharmacology; D055815:Young Adult; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D019007:P-Selectin; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
aspirin; blood flow velocity; clopidogrel; microfluidic microchips; platelet function tests