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Review
. 2021 Dec;35(6):1197-1217.
doi: 10.1016/j.hoc.2021.07.011. Epub 2021 Aug 14.

Disorders of Fibrinogen and Fibrinolysis

Jori E May  1 , Alisa S Wolberg  2 , Ming Yeong Lim  3
Affiliations
Review

Disorders of Fibrinogen and Fibrinolysis

Jori E May et al. Hematol Oncol Clin North Am. 2021 Dec.

Abstract

Fibrinogen plays a fundamental role in coagulation through its support for platelet aggregation and its conversion to fibrin. Fibrin stabilizes clots and serves as a scaffold and immune effector before being broken down by the fibrinolytic system. Given its importance, abnormalities in fibrin(ogen) and fibrinolysis result in a variety of disorders with hemorrhagic and thrombotic manifestations. This review summarizes (i) the basic elements of fibrin(ogen) and its role in coagulation and the fibrinolytic system; (ii) the laboratory evaluation for fibrin(ogen) disorders, including the use of global fibrinolysis assays; and (iii) the management of congenital and acquired disorders of fibrinogen and fibrinolysis.

Keywords: Afibrinogenemia; Coagulation; D-dimer; Dysfibrinogenemia; Fibrinogen; Fibrinolysis; Hemostasis; Hypofibrinogenemia.

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Conflict of interest statement

Disclosure A.S. Wolberg has received research funding from Bristol Myers Squibb, Takeda, and Stago. M.Y. Lim reports receiving honoraria from American Society of Hematology, and consulting fee from Sanofi Genzyme and Argenx. J.E. May declares no conflict of interests.

Figures

Figure 1.
Figure 1.. Conversion of fibrinogen to fibrin
(A) Thrombin cleaves fibrinopeptides on the N-termini of the Aα and Bβ chains, resulting in fibrin monomers (B) Polymerization of the fibrin monomers occurs between the newly-exposed knobs in the N-termini of the α and β chains (E-domain) of one fibrin monomer and the C-terminal regions of the γ and β chain (in the D-domain) of another fibrin monomer in a half-staggered pattern to form fibrin protofibrils
Figure 2.
Figure 2.. Overview of the coagulation and fibrinolytic pathways
The formation of a fibrin clot is the end-point of the coagulation cascade. Subsequent degradation of the fibrin network into fibrin degradation products (FDPs, e.g., D-dimer) is mediated by the fibrinolytic system. Balance between these two pathways is essential in hemostasis, while abnormalities in these pathways may lead to bleeding and/or thrombosis. FDPs, fibrin degradation products; PAI-1, plasminogen activator inhibitor type 1; TAFI, thrombin activated fibrinolysis inhibitor; TF, tissue factor; tPA, tissue plasminogen activator; uPA, urokinase plasminogen activator
See this image and copyright information in PMC

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