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Implications of Hemostasis Disorders in Patients with Critical Limb Ischemia-An In-Depth Comparison of Selected
Radosław Wieczór1,2, Arleta Kulwas1, Danuta Rość1
1Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland.
Insights
Patients with critical limb ischemia (CLI) show significant coagulation activation, with higher levels of tissue factor (TF) and thrombin-antithrombin complex (TAT). This indicates a prothrombotic state with increased fibrinolysis in CLI patients.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Vascular Surgery
Background:
- Peripheral arterial disease (PAD) and critical limb ischemia (CLI) are associated with high mortality.
- Blood coagulation disorders significantly contribute to PAD/CLI pathogenesis.
- Tissue factor (TF) plays a crucial role in the coagulation cascade.
Purpose of the Study:
- To investigate the activation of the coagulation system, specifically via tissue factor (TF), in patients with CLI.
- To compare coagulation parameters in CLI patients versus those with intermittent claudication (IC).
Main Methods:
- Blood samples were collected from 65 CLI patients, 15 IC patients, and 30 healthy controls.
- Assayed parameters included TF (antigen and activation), TFPI (antigen and activation), TAT, fibrinogen, platelet count, t-PA, PAI-1, and D-dimer.
- Hemostasis parameters were measured before initiating treatment.
Main Results:
- PAD patients exhibited significantly higher levels of most hemostasis parameters compared to healthy subjects.
- CLI patients showed significantly higher TF antigen, TAT, fibrinogen, and D-dimer levels compared to IC patients.
- CLI patients had decreased TF activation, lower TFPI antigen, and slightly increased TFPI activation compared to IC patients.
Conclusions:
- Patients with CLI demonstrate activated coagulation and a prothrombotic balance.
- Elevated D-dimer levels in CLI patients suggest secondary fibrinolysis activation.
- The findings confirm a prothrombotic condition with heightened fibrinolysis in CLI.
Background:
Atherosclerosis is a systemic disease. Among patients with atherosclerosis, those suffering from peripheral arterial disease (PAD) represent a group of individuals with particularly high death risk, especially during the course of critical limb ischemia (CLI). In the pathogenesis of PAD/CLI complications, blood coagulation disorders play a significant role. The study aim was to examine the activation of the coagulation system depending on tissue factor (TF) in patients with CLI as compared with those with intermittent claudication (IC).
Methods:
Before initiating proper treatment (invasive or maintenance), blood samples were collected from 65 patients with CLI and 15 with IC to measure the following selected hemostasis parameters: concentrations and activation of tissue factor (TF Ag and TF Act) and tissue factor pathway inhibitor (TFPI Ag and TFPI Act), concentrations of thrombin-antithrombin complex (TAT Ag) and fibrinogen, platelet count (PLT), and concentrations of tissue-plasminogen activator (t-PA Ag), plasminogen activator inhibitor 1 (PAI-1), and D-dimer. The control group included 30 healthy volunteers (10 female/20 male).
Results:
The values of all analyzed parameters (except for lower TFPI Act) were significantly higher in the blood of PAD patients (with respect to PLT only in the CLI subgroup) in comparison with healthy subjects. The blood of patients with CLI as compared to the IC subgroup revealed much higher concentrations of TF Ag (p < 0.001), with slightly decreased TF Act, significantly lower concentrations of TFPI Ag (p < 0.001), slightly increased TFPI Act, and significantly higher levels of TAT Ag (p < 0.001), fibrinogen (p = 0.026), and D-dimer (p < 0.05).
Conclusions:
In patients with CLI, we can observe coagulation activation and a shifting balance toward prothrombotic processes. Furthermore, increased concentrations of D-dimer suggest a secondary activation of fibrinolysis and confirm the phenomenon as a prothrombotic condition with heightened fibrinolysis.
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