Factor XIIIa

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Factor XIIIa is a transglutaminase that plays a key role in the final phase of the coagulation cascade. Its activation leads to the formation of covalent bonds between fibrin molecules, resulting in the stabilization of the blood clot. In addition to its involvement in hemostasis, Factor XIIIa has been implicated in various physiological and pathological processes, including wound healing, tissue repair and certain diseases. This article will give you an overview of Factor XIIIa, highlighting its structure, function, activation mechanisms, clinical significance, and potential therapeutic applications.

Figure 1. Structure of Factor XIII.

Structure

Factor XIII is a proenzyme that consists of two A subunits and two B subunits. Under normal conditions, Factor XIII circulates in the blood in an inactive form (Factor XIII). Activation occurs through proteolysis of the activating peptide by thrombin, which subsequently releases the active enzyme, factor XIIIa. Once activated, factor XIIIa forms a tetrameric complex (2A2B) that exhibits transglutaminase activity. the A-subunit confers enzymatic activity, while the B-subunit provides structural stability and assists the substrate.

Functions

The main function of factor XIIIa is to cross-link fibrin, strengthen the clot and enhance its resistance to fibrinolysis (the process of blood clot breakdown). By forming covalent bonds between fibrin monomers, Factor XIIIa promotes fibrin polymerization and stabilizes the fibrin network. This stabilizing effect is essential to prevent premature clot lysis and ensure durable clot formation. In addition to its role in coagulation, Factor XIIIa has become a key player in wound healing and tissue repair. Through its transglutaminase activity, Factor XIIIa supports the deposition and organization of extracellular matrix proteins, contributing to connective tissue integrity and remodeling. In addition, it is involved in the regulation of re-epithelialization, angiogenesis, and immune response, all of which are essential processes for efficient wound healing.

Clinical significance

• Hereditary Factor XIII Deficiency: Inherited defects or mutations in the A-subunit or B-subunit genes can lead to Factor XIII deficiency. This rare disorder results in impaired clot stability and an increased risk of bleeding. Prompt diagnosis and specific replacement therapy with recombinant Factor XIII or cryoplasm are key to managing Factor XIII deficiency and preventing bleeding complications.
• Acquired Factor XIII deficiency: Several acquired disorders, such as liver disease, disseminated intravascular coagulation (DIC), or certain medications, can lead to acquired Factor XIII deficiency. Identifying and addressing the underlying cause is important in the management of acquired deficiencies, along with supportive therapy to restore Factor XIII levels.
• Diagnostic and Prognostic Implications: Factor XIIIa measurement is useful in evaluating patients suspected of having coagulation disorders, identifying subtypes of Von Willebrand disease (VWD), and monitoring disease progression in certain malignancies. It can also be used as a prognostic marker for cardiovascular disease, indicating an increased risk of adverse outcomes.

Conclusion

Factor XIIIa is a key transglutaminase that plays a critical role in coagulation, wound healing and tissue repair. Its ability to cross-link fibrin and stabilize blood clots ensures effective hemostasis, prevents excessive bleeding and supports wound closure. Defects in Factor XIIIa can lead to bleeding disorders, emphasizing the importance of accurate diagnosis and proper management. In addition, factor XIIIa is involved in tissue repair and remodeling, opening avenues for potential therapeutic interventions and paving the way for the development of wound healing and regenerative medicine.