Analysing responses to aspirin and clopidogrel by measuring platelet thrombus formation under arterial flow conditions

Kazuya Hosokawa; Tomoko Ohnishi; Hisayo Sameshima; Naoki Miura; Takashi Ito; Takehiko Koide; Ikuro Maruyama

doi:10.1160/TH12-06-0441

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 109(01): 102-111
DOI: 10.1160/TH12-06-0441

Platelets and Blood Cells

Schattauer GmbH

Analysing responses to aspirin and clopidogrel by measuring platelet thrombus formation under arterial flow conditions

Authors

Kazuya Hosokawa

¹Research Institute, Fujimori Kogyo Co., Ltd., Yokohama, Kanagawa, Japan

³Department of System Biology in Thromboregulation, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Tomoko Ohnishi

¹Research Institute, Fujimori Kogyo Co., Ltd., Yokohama, Kanagawa, Japan
Hisayo Sameshima

¹Research Institute, Fujimori Kogyo Co., Ltd., Yokohama, Kanagawa, Japan
Naoki Miura

²Department of Veterinary Medicine, Faculty of Agriculture, Kagoshima University, Kagoshima, Japan
Takashi Ito

³Department of System Biology in Thromboregulation, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Takehiko Koide

³Department of System Biology in Thromboregulation, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Ikuro Maruyama

³Department of System Biology in Thromboregulation, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

Abstract

Summary

High residual platelet aggregability and circulating platelet-monocyte aggregates in patients administered aspirin and clopidogrel are associated with ischaemic vascular events. To determine the relevance of these factors with residual thrombogenicity, we measured platelet thrombus formation using a microchip-based flow-chamber system in cardiac patients receiving aspirin and/or clopidogrel, and evaluated its correlation with agonist-inducible platelet aggregation and platelet-monocyte aggregates. Platelet thrombus formation was analysed by measuring flow pressure changes due to the occlusion of micro-capillaries and was quantified by calculating AUC₁₀ (area under the flow pressure curve). The growth and stability of platelet thrombi that formed inside microchips at shear rates of 1000, 1500, and 2000 s^-1 were markedly reduced in patients receiving aspirin and/or thienopyridine compared to healthy controls (n=33). AUC₁₀ values of aspirin therapy patients (n=20) were significantly lower and higher than those of healthy controls and dual antiplatelet therapy patients (n=19), respectively, and showed relatively good correlations with collagen-induced platelet aggregation and platelet-monocyte aggregates at 1000 and 1500 s^-1 (r _s>0.59, p<0.01). In contrast, AUC₁₀ in dual antiplatelet therapy patients was significantly correlated with ADP-induced platelet aggregation at all examined shear rates (r _s>0.59, p<0.01), but did not correlate with collagen-induced aggregation. Aspirin monotherapy patients with high residual platelet thrombogenicity also exhibited significant elevations in both collagen-induced platelet aggregation and platelet-monocyte aggregates. Our results, although preliminary, suggest that residual platelet thrombogenicity in aspirin-treated patients is associated with either collagen-induced platelet aggregation or circulating platelet-monocyte aggregates, but it is predominantly dependent on ADP-induced platelet aggregation in patients receiving dual antiplatelet therapy.

Keywords

Antiplatelet therapy - aspirin - clopidogrel - platelet thrombus - blood flow

Full Text

References

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