Tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in patients with symptomatic lower extremity artery disease.

Background: Lower extremity artery disease (LEAD) involves progressive arterial narrowing manifested by intermittent claudication (IC). LEAD entails endothelial dysfunction and fibrinolytic disorders. In the current study, we analyze the selected parameters of the fibrinolytic system in the blood of patients with symptomatic LEAD depending on clinical parameters.

Methods: The test group was comprised of 80 patients with diagnosis of LEAD based on Ankle-Brachial Index (ABI) test (27 female/53 male) with an average age of 63.5±9 years. The control group included 30 healthy, non-smoking volunteers (10 female/20 male), with the median age of 56±6 years. The research material - venous blood - was sampled to determine the concentrations of tissue-type plasminogen activator (t-PA Ag), plasminogen activator inhibitor type 1 (PAI-1 Ag), D-dimer, fibrinogen, and platelet count (PLT).

Results: We found elevated concentrations of t-PA Ag, PAI-1 Ag, D-dimer, and fibrinogen in the plasma of subjects with symptomatic LEAD. Various stages of the Fontaine classification demonstrated a gradual, statistically significant increase in the concentrations of fibrinogen and PLT count as the disease progressed. More so, in the subgroup of LEAD patients aged ≥65 years, we observed significantly higher levels of D-dimer than in the group of younger subjects. In addition to that, the LEAD group demonstrated negative correlations of IC distance, fibrinogen concentrations, and PLT count, negative correlations of ABI at rest and concentrations of D-dimer and PLT count, as well as positive correlations between age and D-dimer levels.

Conclusions: High t-PA Ag concentrations in LEAD patients suggest damage to the endothelium which comprises the main source of this factor. With high PAI-1 Ag levels, inactive fibrinolytic t-PA-PAI-1 complexes are formed. Increasing fibrinogen concentrations at the subsequent stages in accordance with the Fontaine classification, indicate increasing inflammation. Moreover, heightened values of D-dimer reflect an increased secondary fibrinolysis activation as patients get older and impaired extremity vascularization, manifested by the decreasing ABI, progresses.