Impact of Factor Xa Inhibition on Coagulation, Platelet Reactivity, and Thrombosis in Patients with Peripheral Artery Disease

Objective The role of thrombin in vascular pathology is a focus of investigation. The incorporation of direct Factor-Xa inhibition into practice patterns is based on its theoretical dual-pathway attenuation of both thrombin generation and platelet aggregation. However, quantification of the effect of direct anti-Xa medications on platelet function is not established. Thromboelastography with Platelet Mapping (TEG-PM) leverages dual-pathway metrics to provide comprehensive coagulation profiles. We evaluated the effects of direct oral anticoagulants (DOACs) on coagulation and platelet function profiles and correlate these data with post-operative Major Adverse Limb Events (MALE) in patients with PAD. Methods We conducted a prospective study of patients undergoing lower extremity revascularization with serial perioperative TEG-PM analysis. Patients on DOACs were compared to those not on DOACs, and stratified by concurrent mono- or dual-antiplatelet regimens (MAPT/DAPT). Post-operative MALE was recorded and difference in antithrombotic regimens and TEG-PM analysis compared between groups. Results 471 samples from 141 patients were analyzed. 29.5% were reflective of circulating DOAC therapy. Compared to MAPT alone, patients on DOAC+MAPT exhibited longer time to clot formation (R-time) [7.4(±2.4) vs. 6.7(±2.7); p<.02], but less platelet inhibition. Patients on DAPT exhibited greater platelet inhibition compared to either group [23.7(±26.9) vs. 31.0(±28.3) vs. 42.2(±31.2); p<.01]. Patients who experienced MALE were more likely to be on DOAC therapy [43.8% vs. 22.0% p=.02]. TEG-PM analysis from patients who experienced MALE also demonstrated longer R-time [8.6(±3.9 vs. 7.3(±3.0); p=.05] and increased Maximum Clot Amplitude (MA) [66.7(±4.2) vs. 61.8(±8.2); p=0.001]. Conclusion DOAC therapy resulted in a prolonged R-time but had no impact on platelet inhibition. Patients who experienced MALE were more often on DOACs and demonstrated an increased R-time, but also showed greater platelet reactivity evident by increased MA, suggesting DOACs may not be effective at protecting against MALE. Further research comparing DOAC therapy to a dual-antiplatelet approach may add clarity to emerging multimodal antithrombotic recommendations.