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Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
Activation of coagulation and fibrinolytic systems in patients with CLI is not normalized after surgical
H Pärsson1, A Holmberg, A Siegbahn
1Institution for Surgical Science, Uppsala, Sweden.
Insights
Surgical revascularisation for critical limb ischemia (CLI) causes significant coagulation and fibrinolysis disturbances, alongside inflammatory mediator release. These prothrombotic and hyperfibrinolytic states persist for 30 days post-surgery.
Area of Science:
- Vascular Surgery
- Hematology
- Critical Limb Ischemia (CLI)
- Coagulation and Fibrinolysis
Background:
- Critical limb ischemia (CLI) is a severe manifestation of peripheral artery disease, often requiring surgical revascularization.
- Understanding the hemostatic and inflammatory changes associated with revascularization is crucial for managing CLI patients.
Purpose of the Study:
- To investigate the activation of coagulation and fibrinolysis pathways.
- To assess inflammatory mediator levels before, during, and after surgical revascularization in CLI patients.
Main Methods:
- Prospective clinical study involving 40 CLI patients undergoing femoro-popliteal or femoro-distal reconstruction.
- Assessed coagulation activation via prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT).
- Measured fibrinolysis using tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), and D-dimer; analyzed inflammatory mediators IL-2-rec, IL-6, IL-10, and MCP-1.
Main Results:
- Patients exhibited a preoperative prothrombotic state (high TAT) and ongoing fibrinolysis (high t-PA, D-dimer).
- Post-reperfusion, a prothrombotic state persisted for the first week, with defective fibrinolysis (increased tPA/D-dimer unopposed by PAI-1) at one week and 30 days.
- Elevated inflammatory mediators (IL-6, IL-10, MCP-1) were observed post-reperfusion, normalizing by 30 days.
Conclusions:
- Surgical revascularization for CLI leads to significant, persistent disturbances in both coagulation and fibrinolytic systems.
- These hemostatic changes are accompanied by the release of inflammatory mediators.
- A prothrombotic state and increased fibrinolysis remain evident even 30 days after successful revascularization.
Objective:
To study the activation of coagulation and fibrinolysis before, during and after surgical revascularisation in patients with critical limb ischemia (CLI).
Design:
Prospective clinical study.
Materials And Methods:
Forty patients with CLI underwent femoro-popliteal or femoro-distal reconstruction and were compared to a control-group. Measurements of prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) assessed activation of coagulation. Fibrinolysis was determined by tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) and fibrin degradation product (D-dimer). The inflammatory mediators: Interleukin 2 receptor (IL-2-rec), Interleukin 6 (IL-6), Interleukin 10 (IL-10) and Monocyte chemoattractant protein 1 (MCP-1) was also analysed.
Results:
Patients (in 35 of the 40 reconstruction was possible) were operated upon using either vein (n=23) or ePTFE (n=12) grafts. Patients with CLI had a preoperative prothrombotic state as indicated by high TAT-levels and also ongoing fibrinolysis with high levels of t-PA and D-dimer. After reperfusion an ongoing prothrombotic state for the first week was demonstrated. A significant as well as defective fibrinolysis was also seen with increased levels of tPA and D-dimer unopposed by PAI-1 after one week and also after 30 days. Increased levels of inflammatory mediators IL-6, IL-10 and MCP-1 was observed after reperfusion and normalised after 30 days.
Conclusion:
This study demonstrates significant disturbances of both the coagulation and fibrinolytic systems before, during and after revascularisation for CLI. This was accompanied by release of inflammatory mediators. A prothrombotic state and increased fibrinolysis were evident also 30 days after successful revascularisation.
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