Fibrinogen

Fibrinogen is a protein composed of 2 Aα-chains, 2 Bβ-chains, and 2 γ-chains that circulates in plasma.  During clotting, fibrinogen is cleaved to fibrin by the enzyme thrombin.  Fibrin monomers then polymerize into fibers, forming a network that reinforces the clot.  Fibrin(ogen) plays a critical role in determining clot formation, structure, and stability, and is thus central to hemostasis and thrombosis.  Elevated levels of fibrinogen in the blood lead to increased risk of venous thrombosis.  Additionally, fibrin network structure affects risk of venous thrombosis.  Multiple factors have been shown to modulate fibrin network structure; the effects of thrombin concentration have been especially well studied.  In the presence of high thrombin concentrations, fibrin networks are dense and resistant to fibrinolysis, and in the presence of low thrombin concentrations, fibrin networks are less dense and are susceptible to fibrinolysis.  We are interested in further elucidating mechanisms leading to altered fibrin structure, as well as investigating the effects of altered fibrin structure on hemostasis and thrombosis.

Fibrinogen synthesis and expression. Fibrinogen synthesis is regulated by both transcriptional and translational mechanisms. After individual fibrinogen chains are translated, fibrinogen assembly occurs stepwise. Single chains assemble first into Aα-γ and Bβ-γ precursors, then into Aα/Bβ/γ half-molecules, and finally into hexameric complexes (Aα/Bβ/γ)2. Once fibrinogen is released into blood, it circulates until thrombin cleaves fibrinopeptides from the Aα and Bβ chains (FpA and FpB, respectively) to form fibrin monomers. These monomers then polymerize in a half-staggered arrangement to form fibrin protofibrils and ultimately the fibrin network at a site of tissue injury.

Fibrinogen synthesis and expression

Kattula S, Byrnes JR, Wolberg AS. Fibrinogen and Fibrin in Hemostasis Thrombosis. Arterioscler Thromb Vasc Biol. 2017;37:e13-e21.


Modifiers of fibrin(ogen) and association with disease. Clot formation, structure, and stability are influenced by conditions present during fibrin generation. Abnormal clot formation is observed in several diseases.

Modifiers of fibrin(ogen) and association with disease

Kattula S, Byrnes JR, Wolberg AS. Fibrinogen and Fibrin in Hemostasis Thrombosis. Arterioscler Thromb Vasc Biol. 2017;37:e13-e21.