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

Abstract

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 AUC 10 (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). AUC 10 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 (rs >0.59, p<0.01). In contrast, AUC 10 in dual antiplatelet therapy patients was significantly correlated with ADP-induced platelet aggregation at all examined shear rates (rs >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.

Assessment of platelet‐derived thrombogenicity with the total thrombus‐formation analysis system in coronary artery disease patients receiving antiplatelet therapy

“…These features allowed us to broaden the use of this system to assess blood samples without any reference to the drugs used. The utility of the T-TAS for evaluating clotting status has been reported in experimental animals [31], healthy subjects [32][33][34], and a small population of patients [19,35]. The present study confirmed its usefulness in CAD patients.…”

A novel quantitative assessment of whole blood thrombogenicity in patients treated with a non-vitamin K oral anticoagulant

“…e l s e v i e r . c o m / l o c a t e / i j c a r d thrombogenic surfaces [4,5,8]. One chip, the platelet (PL)-chip, contains 25 capillary channels (40 μm wide × 40 μm deep) coated with type I collagen.…”

Use of a microchip flow-chamber system as a screening test for platelet storage pool disease

“…The microchip flow-chamber system, T-TAS ® (Fujimori Kogyo, Kanagawa, Japan) was utilized with a minor modification according to the protocol proposed by Hosokawa et al [7,9] to analyze the flow-based thrombus formation. Evaluation of platelet thrombus formation was performed with type 1 collagen-coated PL (platelet)-chips (Nitta Gelatin, Osaka, Japan).…”

“…In particular, a newly automated microchip flow-chamber system (total thrombus-formation analysis system, T-TAS ® ) has been recently developed, and some groups have already reported on the comprehensive assessment for hemostatic functions of anti-thrombotic or anti-platelet drugs [7][8][9], hemodilution at cardiopulmonary bypass [10], coagulant bleeding disorder such as hemophilia [11] and von Willebrand disease [12]. This automated device has advantages in evaluating thrombus formation quantitatively in whole blood.…”