Factor XIII Deficiency

Excerpt

Factor XIII is the last factor in the coagulation cascade with unique chemical properties and physiological functions. The history of the discovery of factor XIII can be traced back to 1923, when Barkan and Gasper first demonstrated that fibrin clots formed in the presence of calcium ions (Ca2+) were insoluble in weak bases. In 1948, Laki and Lorand first reported a non-dialyzable, thermolabile serum factor, which made fibrin clots insoluble in concentrated urea solution. They called this serum factor a 'protein fibrin stabilizing factor.' In 1961, Lowey et al. purified the factor from plasma and reported its enzymatic nature. However, the clinical importance of this factor was realized after Duckert et al. (1961) published the report of a pediatric patient with impaired wound healing, abnormal scar formation, and severe bleeding diathesis who was found to be deficient in this factor. The International Committee on Blood Clotting Factors recognized this 'protein fibrin stabilizing factor' as a clotting factor in 1963 and named it factor XIII (FXIII).

The FXIII complex is made up of two subunits FXIIIA and FXIIIB. It plays a significant role in clot stabilization by cross-linking the fibrin and making the clot more dense and stiff. It also plays a crucial role in platelet-dependent clot retraction, wound healing, and tissue repair. FXIII deficiency (mostly FXIIIA subunit deficiency) is an extremely rare bleeding disorder that is inherited in an autosomal recessive mode. Rarely, an acquired deficiency of FXIII has been described, which occurs secondary to either hyperconsumption, hypo-synthesis, or an immune-mediated process. In its severest form, it can present as spontaneous bleeding in the newborn period. Thus, there is a significant mismatch between the severity of FXIII deficiency and clinical presentation. The treatment involves the administration of fresh frozen plasma or cryoprecipitate. However, with the advent of FXIII concentrate and recombinant FXII (rFXIII), prophylaxis strategies in patients with a severe deficiency can be formulated to minimize the bleeding episodes.