Impact of total antithrombotic effect on bleeding complications in patients receiving multiple antithrombotic agents

Abstract

Background: Few reports have evaluated the total antithrombotic effect of multiple antithrombotic agents. Methods and Results: Thrombus formation was evaluated with the Total Thrombus-formation Analysis System (T-TAS®) using 2 types of microchips in 145 patients with stable coronary artery disease receiving oral anticoagulants plus single-or dual-antiplatelet therapy. The PL-chip coated with collagen is designed for analysis of the platelet thrombus formation process under shear stress condition (18 µL/min). The AR-chip coated with collagen and tissue thromboplastin is designed for analysis of the fibrin-rich platelet thrombus formation process under shear stress condition (4 µL/min). The results were expressed as an area under the flow pressure curve (PL18-AUC10 and AR4-AUC30, respectively). Bleeding events occurred in 43 patients during a 22-month follow-up. AR4-AUC30 was significantly lower in patients with bleeding events than in those without (584 [96–993] vs. 1,028 [756–1,252], P=0.0003). Multivariate logistic regression analysis identified AR4-AUC30 (odds ratio 3.18) as a significant predictor of bleeding events, in addition to baseline anemia and usage of the standard dose of direct oral anticoagulants. However, PL18-AUC10 was not significantly related to bleeding events. Conclusions: A lower AR4-AUC30 level was associated with increasing risk of subsequent bleeding complications in patients with stable coronary artery disease who received multiple antithrombotic agents.