Physical Exertion Induces Thrombin Formation and Fibrin Degradation in Patients With Peripheral Atherosclerosis

From the Wihuri Research Institute (P.M., R.L.) and the Department of Surgery (M.L.), Helsinki University Central Hospital, Helsinki, Finland.

Correspondence to Riitta Lassila, MD, PhD, Wihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, Finland.

Abstract—Sudden extreme physical stress is associated with an increased risk of myocardial infarction mainly in people with preexisting atherosclerosis. In this study we compared the effect of submaximal exercise on coagulation and fibrinolysis in patients with peripheral arterial occlusive disease (PAOD) with that in healthy control subjects. Fifteen PAOD patients with intermittent claudication and 15 healthy control subjects, matched for age, sex, medication use, smoking habit, and conditioning, were studied. Thrombin–antithrombin III complex (TAT), D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI)-1 antigens (Ag), t-PA activity, and plasmin-₂–antiplasmin complex (PAP), as well as plasma catecholamines, were measured before and after a treadmill exercise test. At rest, fibrinogen (3.3±0.5 versus 2.9±0.5 g/L [mean±SD]; P<.05), D-dimer (392±128 versus 271±113 ng/mL; P<.05), t-PA Ag (9.1±5.1 versus 5.5±1.2 ng/mL; P<.02), and PAI-1 Ag (14.9±7.1 versus 7.6±3.8 ng/mL; P<.002) levels in plasma were markedly higher in the patient group than in the control group. In patients but not in control subjects, exercise of similar intensity elevated circulating concentrations of TAT (from 3.43±1.45 to 4.83±2.27 ng/mL; P<.05). Exercise caused a parallel increase in D-dimer, t-PA Ag, t-PA activity, PAP, and catecholamines in both groups, whereas PAI-1 Ag remained stable. Plasma lactic acid was significantly higher in patients after exercise and was associated with lower-limb ischemia. Compared with healthy control subjects, patients with PAOD showed higher t-PA Ag, PAI-1 Ag, and D-dimer levels both at rest and after exercise. Notably, submaximal exercise on a treadmill enhanced thrombin formation in patients with PAOD but not in the control subjects. Sudden catecholamine release and local ischemia during exercise may accelerate the preexisting prothrombotic potential of the atherosclerotic vessel wall.

Key Words: atherosclerosis • exercise • coagulation • fibrinolysis • catecholamines

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