Factor XIII and Venous Thromboembolism

Abstract

Plasma factor XIII (FXIII) is a tetrameric zymogen consisting of two potentially active A subunits (FXIII-A) and two carrier/inhibitory B subunits (FXIII-B). In the final phase of the coagulation cascade, FXIII is converted into an active transglutaminase (FXIIIa) by thrombin and Ca (2 + ). FXIIIa strengthens fibrin clot mechanically by cross-linking fibrin chains. In addition, FXIIIa is a key regulator of fibrinolysis, protecting newly formed fibrin from the fibrinolytic machinery by binding α (2)-plasmin inhibitor to the fibrin meshwork. FXIII is essential for maintaining hemostasis; its severe deficiency causes a life-threatening bleeding diathesis. The involvement of FXIII in thrombotic diseases and its association with the risk of these disorders is less clear. The role of FXIII in atherothrombotic diseases has been recently reviewed. This article offers a general overview of the relationship between FXIII and venous thromboembolism (VTE), to collect individual publications on this topic, present conclusions, and examine limitations of published studies. Special attention is given to the association of FXIII-A polymorphism with the risk of VTE, which has provoked considerable interest over the last decade.

Protein biomarkers for incident deep venous thrombosis in critically ill adolescents: An exploratory study

“…The main physiological function of factor XIII is to stabilize the newly formed fibrin clot and protect it from the prompt degradation of the fibrinolytic system . Consistent with our findings, plasma levels of factor XIII were shown to be lower in adults with confirmed pulmonary embolism than in similar adults without pulmonary embolism .…”

Factor XIII activity mediates red blood cell retention in venous thrombi

“…However, the most prevalent F13A coding polymorphism (Val34Leu) has been associated with decreased risk of venous thrombosis in a subset of studies (reviewed in ref. 42). In in vitro assays, the V34L polymorphism results in faster FXIII activation and is associated with denser fibrin structure and decreased permeability in clots made with low fibrinogen, but coarser fibrin structure and increased permeability in clots made with high fibrinogen (43,44).…”

Fibrinogen, red blood cells, and factor XIII in venous thrombosis

“…Genetic studies have associated FXIII polymorphisms with variable risk for VT, suggesting that FXIII activation kinetics and/or function alter clot quality [reviewed in Ref. ]. The FXIII Val34Leu polymorphism has received the most attention.…”