Impact of Total Antithrombotic Effect on Bleeding Complications in Patients Receiving Multiple Antithrombotic Agents

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-AUC₁₀and AR₄-AUC₃₀, respectively). Bleeding events occurred in 43 patients during a 22-month follow-up. AR₄-AUC₃₀was 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-AUC₁₀was not significantly related to bleeding events.

Conclusions: A lower AR₄-AUC₃₀level was associated with increasing risk of subsequent bleeding complications in patients with stable coronary artery disease who received multiple antithrombotic agents.