Sex Differences in Thrombin Generation Using Calibrated Automated Thrombogram in Patients With Peripheral Artery Disease.

INTRODUCTION

The influence of thromboprophylaxis on thrombin generation in patients with peripheral artery disease (PAD) following revascularization, including potential sex-based variation in physiological response, remains poorly defined. This study examined sex-specific differences in thrombin generation following lower extremity revascularization.

METHODS

In this single-center, observational prospective cohort study, 93 PAD patients aged ≥60 y undergoing lower extremity revascularization were enrolled at baseline, of whom 49 provided samples at the 1-mo primary analysis time point (17 females and 32 males). Thrombin generation was quantified using calibrated automated thrombogram, measuring lag time, peak thrombin, thrombin generation rate, and endogenous thrombin potential. Patients were stratified by sex, and cross-sectional and longitudinal analyses were conducted using Mann-Whitney U or unpaired t-tests as appropriate.

RESULTS

At baseline (n = 49), TEG parameters were similar between sexes. At 1 mo postintervention, females demonstrated significantly accelerated and higher thrombin generation compared to males, including increased thrombin generation rate (63.3 versus 40.8 nM/min, P = 0.022), higher peak thrombin (275.4 versus 141.9 nM, P = 0.004), and shorter lag time (9.0 versus 12.0 min, P = 0.037). Endogenous thrombin potential trended higher but was not statistically significant (P = 0.066). Thrombin generation rate was strongly associated with major adverse limb events (r = 0.409, P = 0.004), with affected patients demonstrating higher rates (90.3 versus 46.1 nM/min, P = 0.002). Females demonstrated inadequate thrombin suppression across antithrombotic regimens. This pattern persisted at 3 and 6 mo, with thrombin generation rate again significantly higher in females at 6 mo (P = 0.024).

CONCLUSIONS

Females with PAD demonstrate persistently accelerated thrombin generation following revascularization, supporting the need for sex-specific evaluation of antithrombotic strategies.