What is Fibrinolysis?

Fibrinolysis is the break-down of blood clots, which is a crucial part of wound healing. If fibrinolysis is not properly regulated it can lead to numerous different diseases.

Fibrin and blood clots

A blood clot (Thrombus) is made up of aggregated platelets, red blood cells, and a mesh of cross-linked fibrin proteins. A thrombus naturally occurs as a response to an injury, as a means to prevent bleeding. Thrombi can become harmful if they form in healthy blood vessels and block the flow of blood.

Blood clot Illustration. Image Credit: Adike / Shutterstock
Blood clot Illustration. Image Credit: Adike / Shutterstock

Fibrinogen is a soluble protein that circulates in the blood at relatively small concentrations and is comprised of three separate polypeptide chains (Aα, Bβ, and γ) that are linked by disulfide bonds. Fibrinogen is converted into fibrin monomers when the protein thrombin removes the A and B fibrinopeptides.

The fibrin monomers can now be assembled one at a time, which is a crucial process for the formation of a thrombus. The release of fibrinopeptide A initiates the aggregation of fibrin fibers, which leads to the formation of a semi-staggered, overlapping pattern of fibrin within the developing thrombus. Factor XIIIa allows for further crosslinking of fibrin, which acts with platelets and red blood cells to provide strength to the structure of the growing thrombus.

The strength of the thrombus is very important as weak clots are susceptible to unwanted fibrinolysis, and firmer clots may promote thrombosis. Many factors affect the stability of a thrombus, including the fibrin fiber diameter, local fibrin concentration, and the structure of the fibrin network. Other factors such as thrombin generation and platelet reactivity also affect the structure of a thrombus.

What is fibrinolysis?

Fibrinolysis is the breakdown of fibrin within blood clots. There are two types of fibrinolysis, being primary and secondary fibrinolysis. Primary fibrinolysis occurs naturally and secondary fibrinolysis occurs due to an external cause such as medicine or a medical disorder.

Fibrinolysis is tightly controlled by the actions of various cofactors, inhibitors, and receptors. Plasmin is the main protein that activates fibrinolysis. Plasmin is converted from plasminogen by tissue plasminogen activator (tPA) and urokinase (up A). tPA is synthesized by endothelial cells, whereas uPA is synthesized by monocytes, macrophages, and urinary epithelium cells. uPA has a lower affinity to plasminogen than tPA, also uPA does not require fibrin as a cofactor to initiate plasmin formation. Plasmin activates tPA and uPA, creating a positive feedback loop where the activation of plasminogen leads to more activation of plasminogen. This positive feedback loop is crucial as clearing blood clots that have served their purpose is extremely important.

Medcalf R (2018): Fibrinolysis - blood clot busting and well beyond

The role of fibrinolysis in disease

Dysregulation and faults with the fibrin/fibrinogen proteins can lead to a multitude of disorders relating to bleeding and clot formation. Dysfibrinogenemias are caused by rare autosomal dominant mutations in any one of the three fibrinogen polypeptide chains. There are multiple different mutations that can occur, each with different changes to the structure of fibrinogen.

Fibrinogen Dusard is a γ-dysfibrinogenemia that results in impairment of tPA and fibrin binding, which results in reduced activation of plasminogen, impaired fibrinolysis, and increased likelihood of thrombosis. Afibrinogenemia is caused by a congenital absence of fibrinogen, which leads to symptoms such as umbilical bleeding and thrombosis.

Hyperfibrinolysis causes excessive bleeding. One theory suggests that hyperfibrinolysis is caused by systemic inflammation resulting in increased consumption of fibrin within microthrombi, which results in a deficiency of circulating fibrin. Hyperfibrinolysis can also be caused by the loss of fibrinolytic inhibitors due to deficient synthesis caused by a disease, such as chronic liver disease.

Hypofibrinolysis causes impaired clot break-down, leading to thrombosis. This can be caused by the production of auto-antibodies against plasminogen activators (such as tPA and uPA), or against fibrinolytic receptor components (such as annexin). Hypothyroidism has been associated with hypofibrinolysis as decreased levels of crucial fibrinolysis proteins (such as A2AP, tPA, and PAI-1) occur with this disease.

The treatment of fibrinolysis disorders varies by type and cause. Disorders of impaired clot formation and structure can be treated using hemostatic treatments such as recombinant factor VIIa. For disorders caused by external factors, removing this external factor can treat the disorder. For example, treating hypothyroidism can alleviate hypofibrinolysis symptoms.

Further Reading

Last Updated: Mar 27, 2019

Written by

Samuel Mckenzie

Sam graduated from the University of Manchester with a B.Sc. (Hons) in Biomedical Sciences. He has experience in a wide range of life science topics, including; Biochemistry, Molecular Biology, Anatomy and Physiology, Developmental Biology, Cell Biology, Immunology, Neurology  and  Genetics.


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Mckenzie, Samuel. (2019, March 27). What is Fibrinolysis?. News-Medical. Retrieved on November 29, 2023 from https://www.news-medical.net/health/What-is-Fibrinolysis.aspx.

  • MLA

    Mckenzie, Samuel. "What is Fibrinolysis?". News-Medical. 29 November 2023. <https://www.news-medical.net/health/What-is-Fibrinolysis.aspx>.

  • Chicago

    Mckenzie, Samuel. "What is Fibrinolysis?". News-Medical. https://www.news-medical.net/health/What-is-Fibrinolysis.aspx. (accessed November 29, 2023).

  • Harvard

    Mckenzie, Samuel. 2019. What is Fibrinolysis?. News-Medical, viewed 29 November 2023, https://www.news-medical.net/health/What-is-Fibrinolysis.aspx.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.