FIBRIN FORMATION AND DEGRADATION IN PATIENTS WITH ARTERIOSCLEROTIC DISEASE

Background The blood coagulation cascade was reported to be activated in patients with arteriosclerotic disease of the lower limbs (peripher al 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 ou t in the control group. Therefore, markers of the activation of the bl ood coagulation cascade were measured in patients with PAD and in a ca refully defined control group, both groups being subjected to an exerc ise test. Methods and Results Twenty-two patients with angiographicall y documented PAD of grade II (Fontaine classification) and 13 control subjects in whom the presence of arteriosclerotic lesions was ruled ou t by noninvasive means in the carotid arteries, abdominal aorta, leg a rteries, and coronary arteries took part in the study. Before and imme diately after a treadmill stress test, the concentrations of prothromb in fragment F1+2 (F1+2), thrombin-antithrombin III complexes (TAT), fi brinopeptide A (FPA; this peptide was measured in spot urine also), an d 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 m u g/L), and D-dimers (318.2+/-270.1 versus 150.0+/-91.4 mu g/L) were s ignificantly 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 mu g/L) and spot urine were not different, however. F1+2, FPA, a nd D-dimer concentrations correlated with the severity of the PAD as a ssessed by the ankle systolic brood pressure index (ABPI). The symptom -limited stress test did not lead to further activation of the blood c oagulation 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 thr ombin formation in patients with PAD compared with an age- and sex-mat ched control group without clinical and sonographic evidence of arteri osclerosis. The thrombin formed, however, appears to be almost complet ely neutralized by antithrombin III. No direct evidence of fibrin form ation was obtained, since the FPA concentrations were not different. I n the patients with PAD, the higher concentrations of D-dimers are ind icative of invivo fibrinolysis. Thus, some fibrin formation must be po stulated to occur in patients with arteriosclerosis.