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. 2023 Feb 17;7(2):100081. doi: 10.1016/j.rpth.2023.100081

Fibrinolysis: an illustrated review

Rebecca A Risman 1, Nicholas C Kirby 2, Brittany E Bannish 3, Nathan E Hudson 4, Valerie Tutwiler 1,∗
PMCID: PMC10024051  PMID: 36942151

Abstract

In response to vessel injury (or other pathological conditions), the hemostatic process is activated, resulting in a fibrous, cellular-rich structure commonly referred to as a blood clot. Succeeding the clot’s function in wound healing, it must be resolved. This illustrated review focuses on fibrinolysis—the degradation of blood clots or thrombi. Fibrin is the main mechanical and structural component of a blood clot, which encases the cellular components of the clot, including platelets and red blood cells. Fibrinolysis is the proteolytic degradation of the fibrin network that results in the release of the cellular components into the bloodstream. In the case of thrombosis, fibrinolysis is required for restoration of blood flow, which is accomplished clinically through exogenously delivered lytic factors in a process called external lysis. Fibrinolysis is regulated by plasminogen activators (tissue-type and urokinase-type) that convert plasminogen into plasmin to initiate fiber lysis and lytic inhibitors that impede this lysis (plasminogen activator inhibitors, alpha 2-antiplasmin, and thrombin activatable fibrinolysis inhibitor). Furthermore, the network structure has been shown to regulate lysis: thinner fibers and coarser clots lyse faster than thicker fibers and finer clots. Clot contraction, a result of platelets pulling on fibers, results in densely packed red blood cells (polyhedrocytes), reduced permeability to fibrinolytic factors, and increased fiber tension. Extensive research in the field has allowed for critical advancements leading to improved thrombolytic agents. In this review, we summarize the state of the field, highlight gaps in knowledge, and propose future research questions.

Keywords: blood, blood coagulation, blood clot, clot lysis time, fibrinolysis, fibrin

Essentials

  • •

    Fibrinolysis is the degradation of the fibrin network of a blood clot.

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    Fibrinolysis is required to achieve hemostatic balance.

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    Fibrinolysis can occur naturally in the body or with delivery of pharmacological agents.

  • •

    Rate of fibrinolysis is affected by the fibrin structure and the clot’s cellular components.

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Acknowledgments

NIH R00HL148646-01 (V.T.), New Jersey Commission for Cancer Research COCR22PRF010

(R.R.), NIH T32 GM135141 (R.R.), NIH R15HL148842 (N.E.H.), and R15HL150666 (N.E.H.)

Author contributions

R.A.R., N.C.K., B.B., N.H., and V.T. contributed to creating all illustrations and writing the manuscript. All authors read and approved the final version of the paper.

Relationship Disclosure

There are no competing interests to disclose.

Footnotes

Funding information NIH R00HL148646-01 (V.T.), New Jersey Commission for Cancer Research COCR22PRF010 (R.R.), NIH T32 GM135141 (R.R.), NIH R15HL148842 (N.E.H.), and R15HL150666 (N.E.H.)

Handling Editor: M Sholzberg

Rebecca A. Risman and Nicholas C. Kirby contributed equally to this study.

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