Poor Glycemic Control Is Independently Associated with Fibrinolysis Shutdown in Patients with Peripheral Artery Disease

Objective Fibrinolysis plays a critical role in regulating thrombotic potential by facilitating the breakdown of fibrin-rich thrombi after clot formation. Impaired fibrinolysis, often referred to as hypofibrinolysis or fibrinolytic shutdown, results in reduced clot degradation and promotes thrombus persistence, propagation, and recurrent vascular occlusion. Consequently, impaired fibrinolysis is increasingly recognized as an important contributor to thrombotic risk in patients with peripheral artery disease (PAD). Poor glycemic control has been associated with a prothrombotic milieu through mechanisms including enhanced platelet activation, increased fibrin clot density, and reduced fibrinolytic capacity; however, its relationship with fibrinolytic shutdown in PAD remains poorly defined. Therefore, we aimed to evaluate the association between glycemic control and fibrinolytic shutdown using viscoelastic testing. Methods We performed a retrospective cohort study of 192 patients with PAD who underwent revascularization. Patients were stratified by hemoglobin A1c (HbA1c) <7% and ≥7%. Viscoelastic testing was performed using thromboelastography (TEG). Fibrinolysis was assessed using LY30, and phenotypes were defined as severe shutdown (≤0.3%), partial shutdown (0.3–0.8%), physiologic (0.8–3.0%), and hyperfibrinolysis (>3.0%). Multivariable logistic regression evaluated the association between HbA1c and severe fibrinolysis shutdown, adjusting for demographic, clinical, and treatment variables. Results Patients with HbA1c ≥7% demonstrated lower LY30 values compared with those with HbA1c <7% (0.00 [0.00–0.35] vs 0.30 [0.00–0.90]; p=0.015) and a higher prevalence of severe fibrinolysis shutdown (74.7% vs 51.3%; p=0.009). After adjustment, patients with HbA1c ≥7% had a higher predicted probability of severe shutdown (68.8% [95% CI 51.4–82.2] vs 41.0% [26.3–57.4]; p<0.001). In continuous analysis, each 1% increase in HbA1c was associated with increased odds of severe shutdown (adjusted OR 1.50, 95% CI 1.19–1.93; p=0.001). Severe shutdown was additionally associated with thrombosis-driven reintervention (22.2% vs 8.0%; adjusted OR, 3.60; 95% CI, 1.42–10.54; P=.011). Conclusions Poor glycemic control was independently associated with severe fibrinolysis shutdown in patients with PAD, and severe shutdown was associated with increased thrombosis-driven reintervention. A dose-dependent relationship between HbA1c and impaired fibrinolysis suggests a mechanistic link between hyperglycemia and prothrombotic risk. Hence, patients with higher glucose levels may need increased thromboprophylaxis strategies to mitigate thrombotic risk. These findings may have implications for risk stratification and targeted therapeutic strategies.