Enhanced thrombin generation in diabetic elderly patients with peripheral arterial disease.

Abstract

Diabetic patients with peripheral arterial disease (PAD) experience higher rates of revascularization failure and major adverse limb events compared with nondiabetics. This disparity persists despite modern surgical techniques and optimal therapy. Although diabetes induces endothelial dysfunction and inflammation, specific coagulation abnormalities contributing to adverse surgical outcomes remain inadequately defined. This study evaluated thrombin generation profiles in elderly patients with PAD to identify diabetes-specific coagulation patterns that could influence surgical decisions and assessed their correlation with 12-month clinical outcomes. We prospectively enrolled 85 symptomatic elderly (≥60 years) patients with PAD scheduled for revascularization (44 diabetic, 41 nondiabetic) between January 2021 and December 2022. Both male and female patients were included, with sex determined by self-identification. Whole blood samples were collected prior to revascularization and analyzed by calibrated automated thrombinography to assess lag time (time until initial thrombin formation), peak thrombin concentration, endogenous thrombin potential, and thrombin generation rate. Parameters between groups were compared using the Mann-Whitney U test after confirming that the distributions were non-normal. Patients were followed for 12 months to assess clinical outcomes, including stent/bypass patency and limb salvage. All procedures received institutional review board approval, and written informed consent was obtained from all participants. Among 85 elderly patients with PAD (51% diabetic), those with diabetes exhibited significantly enhanced thrombin generation compared with nondiabetics, with a 48.7% higher thrombin generation rate (83.7 vs 56.3 nM/min; P = .018) and a 42.3% higher peak thrombin concentration (249 vs 175 nM; P = .041). Within the diabetic cohort, patients with hemoglobin A1c ≥7.5% demonstrated more pronounced prothrombotic profiles than those with better glycemic control (peak thrombin: 287.5 vs 218.3 nM; P = .032; endogenous thrombin potential: 1436.0 vs 1155.0 nM×min; P = .042). At 12-month follow-up, diabetic patients experienced significantly higher rates of revascularization failure (stent occlusion: 9.8% nondiabetic vs 29.5% diabetic, P = .031; bypass occlusion: 0% nondiabetic vs 20.5% diabetic; P = .002) and limb loss (above-knee amputation: 0% nondiabetic vs 18.2% diabetic; P = .006; below-knee amputation: 4.9% nondiabetic vs 25.0% diabetic; P = .021). Elderly diabetic patients with PAD exhibited a pronounced hypercoagulable state characterized by significantly enhanced thrombin generation, with greater severity observed in patients with poorer glycemic control. Diabetes was associated with substantially worse clinical outcomes at 12-month follow-up, including higher rates of revascularization failure and amputation. These findings suggest that the hypercoagulable state observed in diabetic patients with PAD may represent both a marker of disease severity and a potentially modifiable therapeutic target for improving outcomes in this high-risk population.