The Impact of Common Thromboprophylactic Regimens on Thrombin Generation in Patients with Peripheral Artery Disease...

Antithrombotic therapy reduces thrombotic risk in patients with peripheral artery disease (PAD) by targeting thrombin generation, a key hypercoagulability factor. However, the specific effects of different antithrombotic combinations on thrombin generation dynamics remain poorly understood. This study uses calibrated automated thrombogram (CAT) to objectively measure and compare patient responses to various common thromboprophylactic regimens.

We prospectively enrolled patients with PAD aged 60+ years who underwent revascularization between January 2021 and December 2022. Whole blood samples were collected preoperatively and at 1, 3, and 6 months postintervention, with 1-year clinical follow-up. Analysis focused on 1-month samples using CAT to quantify thrombin generation parameters: lag time, peak thrombin concentration, endogenous thrombin potential, and thrombin generation rate. Patients were stratified by antithrombotic regimen: mono antiplatelet therapy (MAPT), dual antiplatelet therapy (DAPT), MAPT + direct oral anticoagulant (DOAC), and DAPT + DOAC. Statistical analysis used Mann-Whitney U and t-tests.

Among 56 PAD patients analyzed, DOAC addition produced notable thrombin generation changes, with more pronounced effects in patients on MAPT. MAPT + DOAC showed significant reductions in thrombin generation rate (-38.2 nM/min, P = 0.014), increased lag time (+5.4 min, P = 0.019), and decreased peak thrombin (-111 nM, P = 0.013). DAPT + DOAC produced smaller, nonsignificant reductions. One-year adverse events occurred in 38.5% of DAPT patients, 20.0% DAPT + DOAC, 17.6% MAPT + DOAC, and 0% MAPT patients. Large standard deviations indicated substantial interpatient variability.

PAD patients demonstrate marked thrombin generation variability, with DOAC addition to MAPT producing the most significant thrombin generation changes. These findings highlight biological response heterogeneity in PAD and support individualized antithrombotic strategies.