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

Few reports have evaluated the total antithrombotic effect of multiple antithrombotic agents.

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.

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.