The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment
Abstract
:1. Introduction
2. Historical Discovery of the Fibrinolytic System and Current Concepts
Our Current Understanding of Fibrinolysis
3. Measuring Fibrinolysis
3.1. Early Observations and Methods
3.2. Dynamic Assays
3.2.1. Euglobulin Lysis Time and Plasma-Based Clot Formation and Lysis Assays
3.2.2. Plasmin Generation
3.2.3. Fibrin Clot Structure
3.2.4. Viscoelastic Tests
3.3. Measurement of Circulating Factors
3.3.1. Circulating Pro- and Antifibrinolytic Proteins
3.3.2. Fibrin Degradation Products
4. Fibrinolysis in Specific Clinical Settings
4.1. Fibrinolysis in Trauma
4.1.1. Major Trauma
4.1.2. Brain Trauma
4.2. Fibrinolysis in Coronary Artery Disease
4.3. Fibrinolysis in Sepsis
4.4. Venous Thromboembolism
Pulmonary Embolism
4.5. Fibrinolysis in Liver Disease
4.5.1. Cirrhosis
4.5.2. Acute Liver Failure and Liver Transplantation
4.6. Beyond Bleeding and Thrombosis Risk: Hereditary Angioedema
5. The Fibrinolytic System as a Treatment Target
6. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical Setting | Changes in the Fibrinolytic System |
---|---|
Liver disease | |
Stable cirrhosis | Alcoholic cirrhosis: increased fibrinolysis due to release and defective clearance of tPA Non-alcoholic steatohepatitis cirrhosis: hypofibrinolysis due to increased levels of PAI-1 |
Decompensated cirrhosis and acute-on-chronic liver failure | Highly variable, ranging from severely hypofibrinolytic to hyperfibrinolytic |
Acute liver failure | Profound hypofibrinolysis, uncertain clinical relevance |
Liver transplantation | Hyperfibrinolysis due to defective clearance of tPA in the anhepatic state and increased release from the donor liver. Antifibrinolytic therapy is recommended during surgery |
Trauma | |
Major trauma | Hyperfibrinolysis, hypofibrinolysis, and fibrinolytic shutdown. Antifibrinolytic therapy increases survival after major trauma with haemorrhagic shock if administered less than 3 h after trauma |
Brain trauma | Variable, both hyperfibrinolysis and hypofibrinolysis. Early antifibrinolytic therapy may be beneficial in mild-to-moderate brain injury |
Sepsis | Consistent findings of hypofibrinolysis in correlation with organ failure. Increased levels of PAI-1, TAFIa/TAFIa, and fibrinogen, decreased levels of plasminogen |
Cardiovascular disease | Both stable atherosclerosis and ACS are associated with decreased fibrin clot permeability and prolonged lysis times. Clot structure and lysis time may be prognostic marker for reinfarction or cardiovascular mortality in ACS patients |
Venous thromboembolism (VTE) | |
DVT | A high PAI-1 level predisposes to VTE. Patients with recurrent DVT have higher PAI-levels than patients without recurrence of DVT. |
PE | Patients with PE may have looser clot structure than patients with isolated DVT. In high-risk PE patients, systemic thrombolysis is indicated. In cases of contraindications, catheter-based thrombo-aspiration is an alternative. |
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Hvas, C.L.; Larsen, J.B. The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment. Int. J. Mol. Sci. 2023, 24, 14179. https://doi.org/10.3390/ijms241814179
Hvas CL, Larsen JB. The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment. International Journal of Molecular Sciences. 2023; 24(18):14179. https://doi.org/10.3390/ijms241814179
Chicago/Turabian StyleHvas, Christine Lodberg, and Julie Brogaard Larsen. 2023. "The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment" International Journal of Molecular Sciences 24, no. 18: 14179. https://doi.org/10.3390/ijms241814179