Coagulation factor XIII deficiency

Abstract

SummaryThe plasma circulating zymogenic coagulation factor XIII (FXIII) is a protransglutaminase, which upon activation by thrombin and calcium cross-links preformed fibrin clots/fibrinolytic inhibitors making them mechanically stable and less susceptible to fibrinolysis. The zymogenic plasma FXIII molecule is a heterotetramer composed of two catalytic FXIII-A and two protective FXIII-B subunits. Factor XIII deficiency resulting from inherited or acquired causes can result in pathological bleeding episodes. A diverse spectrum of mutations have been reported in the F13A1 and F13B genes which cause inherited severe FXIII deficiency. The inherited severe FXIII deficiency, which is a rare coagulation disorder with a prevalence of 1 in 4 million has been the prime focus of clinical and genetic investigations owing to the severity of the bleeding phenotype associated with it. Recently however, with a growing understanding into the pleiotropic roles of FXIII, the fairly frequent milder form of FXIII deficiency caused by heterozygous mutations has become one of the subjects of investigative research. The acquired form of FXIII deficiency is usually caused by generation of autoantibodies or hyperconsumption in other disease states such as disseminated intravascular coagulation. Here, we update the knowledge about the pathophysiology of factor XIII deficiency and its therapeutic options.

Effects of factor XIII deficiency on thromboelastography. Thrombelastography with calcium and lysis by addition of streptokinase is more sensitive than solubility tests

“…On the other hand, congenital deficiency in the FXIII-B subunit is a relatively rare cause of FXIII deficiency, and levels of the B subunit are usually reduced, and very rarely both A and B subunits are absent. Bleeding symptoms in patients with FXIII-B deficiencies are relatively milder than FXIII-A deficiencies 4–6…”

“…The clot solubility test is an inexpensive procedure that has been used in hemostasis laboratories, but it has the limitation of detecting only homozygous or double heterozygous FXIII deficiency 6,9,13. Quantitative assays of FXIII activity and antigen are now recommended by experts because they can detect heterozygous congenital as well as mild acquired deficiencies, automate instruments can be used and then they can be better standardized 6.…”

“…Quantitative assays of FXIII activity and antigen are now recommended by experts because they can detect heterozygous congenital as well as mild acquired deficiencies, automate instruments can be used and then they can be better standardized 6. Furthermore, viscoelastic and lysis characteristics of the clot in patients with FXIII deficiency could also be important to explain clinical manifestation, even in patients with heterozygous congenital or mild acquired deficiencies.…”

Structural and functional influences of coagulation factor XIII subunit B heterozygous missense mutants

“…2011; Biswas et al. 2014a,b). Only recently, focus has shifted to the mild/heterozygous form of this deficiency that is associated with mild or even an asymptomatic phenotype (unless the affected individual is exposed to some kind of a trauma, for example, perioperative settings, accident etc.).…”

“…2010a,b; Biswas et al. 2014a,b). One key observation from these articles is that the FXIIIB subunit mutations, which are rarely reported in the severe homozygous form of FXIII deficiency, occur at almost equal proportion when compared with the frequency of FXIIIA subunit mutations in mild heterozygous FXIII deficiency (Ivaskevicius et al.…”