Coagulation factor XIII deficiency

Summary

The 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.

Zusammenfassung

Der plasmatische Blutgerinnungsfaktor XIII (FXIII) ist eine Protransglutaminase, die nach Aktivierung durch Thrombin und Kalzium nicht kovalent vernetzte Fibrindimere verknüpft und zusätzlich durch Einfügen von Fibrinolyse-Inhibitoren dem Blutgerinnsel eine bessere mechanische Stabilität sowie Schutz vor vorzeitiger Fibrinolyse verleiht. Plasma -FXIII ist ein Heterotetramer aus 2 katalytischen FXIII-A- und 2 schützenden FXIII-B-Untereinheiten. Ein angeborener oder erworbener Faktor-XIII-Mangel kann zu Blutungskomplikationen führen. Für einen schweren angeborenen FXIII-Mangel konnte ein breites Mutationspektrum im F13A1- und F13B-Gen ermittelt werden. Trotz der Seltenheit (Prävalenz: 1 in 4 Millionen) stand er vererbbare FXIII-Mangel wegen des Schweregrades an Blutungserscheinungen im Fokus klinischer und genetischer Studien. Mit steigendem Verständnis der pleiotrophen Rolle von FXIII gewinnt der mildere, durch heterozygote Mutationen verursachte FXIII-Mangel zunehmend an Bedeutung in der Forschung. Der erworbene FXIII-Mangel entsteht häufig durch Auto-antikörper oder tritt aufgrund der Verbrauchskoagulation bei anderen Grunder-krankungen (z. B. disseminierte intravasale Koagulopathie) auf.

Diese Übersicht soll aktuelles Wissen zur Pathophysiologie des Faktor-XIII-Mangels und den therapeutischen Optionen vermitteln.

Keywords

Factor XIII - transglutaminase - heterozygous deficiency - heterotetramer

Schlüsselwörter

Blutgerinnungsfaktor XIII - FXIII - Protrans -glutaminase - heterozygote Mutationen

• References

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