Exercise in claudicants is accompanied by excessive thrombin generation

Abstract

Background: Exercise in IC leads to ischaemia-reperfusion injury of leg muscles and a systemic inflammatory response, but the effect of on coagulation is unknown. Objective: To compare the effect of exercise on thrombin formation and fibrin turnover in patients with IC (n = 10), and age and sex matched smokers ([S] n = 5) and non-smokers ([NS] n = 5) without peripheral vascular disease. Methods: Blood was taken from subjects 60 and 30 min before, and 1, 5, 20, 40, 60 and 120 min after, treadmill exercise. Markers of thrombin generation (thrombin-antithrombin complexes [TAT] and prothrombin fragments 1 + 2 [PF1 + 2]) and fibrin turnover (D-dimer and fibrin degradation products [FbDP]) were assayed at each time point. Results: Following exercise, thrombin generation was significantly greater in the claudicant group compared to the control groups (Area Under Curve [AUC] post exercise IC vs S vs NS; TAT 3960 vs 1623 vs 1476 vs=0.007 Kruskal-Wallis [KW]; PF1 + 2 163 vs 107 vs 123 p=0.024 KW). Pre and post-exercise, fibrin turnover in claudicants was similar to smoking controls, but higher than non-smoking controls. (AUC post exercise IC vs NS; D-dimer 6340 vs 2754 p=0.055 Mann-Whitney U[MW]; FbDP 45113 vs 21511 p=0.009 MW). Conclusion: When compared to non-claudicants, exercise in IC is associated with excessive production of thrombin. Despite this, claudicants have a similar level of fibrin turnover suggesting a possible defect in fibrinolysis. This prothrombotic state may contribute to the excess thrombotic morbidity and mortality suffered by claudicants.