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. 2019 Mar 4;3(2):161–172. doi: 10.1002/rth2.12191

Fibrinogen and fibrin: An illustrated review

Marlien Pieters 1, Alisa S Wolberg 2,✉
PMCID: PMC6462751  PMID: 31011700

Abstract

Since its discovery over 350 years ago, studies of fibrinogen have revealed remarkable characteristics. Its complex structure as a large (340 kDa) hexameric homodimer supports complex roles in hemostasis and homeostasis. Fibrinogen synthesis is regulated at the transcriptional and translational levels, undergoing both constitutive (basal) secretion from liver, and inducible upregulation in response to inflammatory events. In addition, alternative splicing yields fibrinogen variants with unique properties and contributions to coagulation biochemistry. During coagulation, fibrinogen conversion to fibrin occurs via thrombin‐mediated proteolytic cleavage that produces intermediate protofibrils and then mature fibers that provide remarkable biochemical and mechanical stability to clots. Fibrin formation, structure, and stability are regulated by various genetic, biochemical, and environmental factors, allowing for dynamic kinetics of fibrin formation and structure. Interactions between fibrinogen and/or fibrin and plasma proteins and receptors on platelets, leukocytes, endothelial cells, and other cells enable complex functions in hemostasis, thrombosis, pregnancy, inflammation, infection, cancer, and other pathologies. Disorders in fibrinogen concentration and/or function increase risk of bleeding, thrombosis, and infection. This illustrated review covers fundamental aspects of fibrinogen and fibrin biology, biochemistry, biophysics, epidemiology, and clinical applications. Continued efforts to enhance our understanding of fibrinogen and fibrin in these processes are likely to advance treatment and prevention of many human diseases.

Keywords: factor XIII, fibrin, fibrinogen, fibrinolysis, hemostasis, infection, thrombosis

Essentials.

  • Fibrinogen is a complex glycoprotein present in high concentrations in plasma.

  • Fibrinogen is converted to fibrin, which stabilizes blood clots and promotes hemostasis.

  • Fibrin structure and mechanical properties are modified by genetic and environmental factors.

  • Fibrin(ogen) also contributes to thrombosis, host defense, inflammation, and wound healing.

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RELATIONSHIP DISCLOSURE

The authors report no conflicts of interest to disclose.

AUTHOR CONTRIBUTION

M. Pieters and A.S. Wolberg developed the concepts and images, wrote the manuscript, and approved the final content.

ACKNOWLEDGEMENTS

We thank the following colleagues for providing information and/or images: Drs. John Weisel (history of fibrinogen discovery), Richard Fish and Marguerite Neerman‐Arbez (fibrinogen gene expression), Michael Falvo (fibrinogen ribbon drawing and atomic force microscope schematic), Martin Guthold (protofibril packing structure), and Robert Ariëns (scanning electron micrographs of γA/γA and γA/γ‘ fibrinogen). We also thank DréVon Dobson for helpful suggestions.

Pieters M, Wolberg AS. Fibrinogen and fibrin: An illustrated review. Res Pract Thromb Haemost. 2019;3:161–172. 10.1002/rth2.12191

Funding information

M. Pieters is supported by funding from the South African Medical Research Council and the Academy of Medical Sciences UK (Newton Fund Advanced Fellowship Grant). A.S. Wolberg is supported by funding from the National Institutes of Health (R01HL126974)

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