Tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in patients with symptomatic lower
Radosław Wieczór1,2, Anna Maria Wieczór3, Danuta Rość3
1Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland - wieczorcmumk@tlen.pl.
Insights
This study found elevated fibrinolytic factors like tissue-type plasminogen activator (t-PA Ag) and PAI-1 Ag in patients with lower extremity artery disease (LEAD). These markers, along with fibrinogen and D-dimer, correlate with disease severity and progression.
Area of Science:
- Vascular Biology
- Hematology
- Clinical Medicine
Background:
- Lower extremity artery disease (LEAD) is characterized by arterial narrowing and intermittent claudication (IC).
- LEAD is associated with endothelial dysfunction and disruptions in the fibrinolytic system.
- Understanding fibrinolytic parameters is crucial for managing symptomatic LEAD.
Purpose of the Study:
- To investigate specific fibrinolytic system parameters in patients with symptomatic LEAD.
- To correlate these parameters with clinical manifestations and disease progression.
- To analyze the relationship between fibrinolytic markers and patient age and Ankle-Brachial Index (ABI).
Main Methods:
- Analysis of venous blood samples from 80 LEAD patients and 30 healthy controls.
- Measurement of tissue-type plasminogen activator (t-PA Ag), PAI-1 Ag, D-dimer, fibrinogen, and platelet count (PLT).
- Correlation of biomarker levels with Fontaine classification, IC distance, ABI, and age.
Main Results:
- Elevated plasma concentrations of t-PA Ag, PAI-1 Ag, D-dimer, and fibrinogen were observed in LEAD patients.
- Fibrinogen and PLT count increased significantly with disease progression (Fontaine stages).
- Higher D-dimer levels were found in LEAD patients aged ≥65 years; D-dimer and PLT count correlated negatively with ABI.
Conclusions:
- High t-PA Ag suggests endothelial damage in LEAD patients.
- Elevated PAI-1 Ag contributes to fibrinolysis inhibition.
- Increasing fibrinogen and D-dimer levels reflect inflammation, secondary fibrinolysis, and disease severity in LEAD.
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.
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