Fibrin formation and degradation in patients with arteriosclerotic disease.

Abstract

BACKGROUND The blood coagulation cascade was reported to be activated in patients with arteriosclerotic disease of the lower limbs (peripheral arterial disease, PAD). There is more thrombin and fibrin formation compared with healthy control subjects. In many studies, however, the presence of arteriosclerotic disease had not been thoroughly ruled out in the control group. Therefore, markers of the activation of the blood coagulation cascade were measured in patients with PAD and in a carefully defined control group, both groups being subjected to an exercise test. METHODS AND RESULTS Twenty-two patients with angiographically documented PAD of grade II (Fontaine classification) and 13 control subjects in whom the presence of arteriosclerotic lesions was ruled out by noninvasive means in the carotid arteries, abdominal aorta, leg arteries, and coronary arteries took part in the study. Before and immediately after a treadmill stress test, the concentrations of prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA; this peptide was measured in spot urine also), and D-dimers were measured. Before exercise, the concentrations of F1 + 2 (1.0 +/- 0.6 versus 0.7 +/- 0.3 nmol/L), TAT (2.9 +/- 2.1 versus 1.9 +/- 0.8 micrograms/L), and D-dimers (318.2 +/- 270.1 versus 150.0 +/- 91.4 micrograms/L) were significantly higher in the patients with PAD compared with the healthy control subjects. FPA concentrations in plasma (1.9 +/- 1.0 versus 1.4 +/- 0.6 micrograms/L) and spot urine were not different, however. F1 + 2, FPA, and D-dimer concentrations correlated with the severity of the PAD as assessed by the ankle systolic blood pressure index (ABPI). The symptom-limited stress test did not lead to further activation of the blood coagulation cascade. However, concentrations of F1 + 2 (P < .001) and TAT (P < .01) after exercise correlated with the presence of ischemic changes in the stress-test ECG. CONCLUSIONS There is evidence of enhanced thrombin formation in patients with PAD compared with an age- and sex-matched control group without clinical and sonographic evidence of arteriosclerosis. The thrombin formed, however, appears to be almost completely neutralized by antithrombin III. No direct evidence of fibrin formation was obtained, since the FPA concentrations were not different. In the patients with PAD, the higher concentrations of D-dimers are indicative of in vivo fibrinolysis. Thus, some fibrin formation must be postulated to occur in patients with arteriosclerosis.