Congenital factor XIII deficiency is an autosomal recessive inherited coagulation disorder caused by a decreased amount of factor XIII (FXIII). This rare coagulation disorder affects both sexes equally. The estimated prevalence of FXIII deficiency is approximately 1:2.5 million. Symptoms can occur at any age, but the diagnosis is often made in infancy due to umbilical cord stump bleeding. Other symptoms include delayed wound healing, postoperative bleeding, subcutaneous or tissue hemorrhage, life-threatening cerebral hemorrhage, and recurrent abortions in women.


Factor XIII is a transglutaminase consisting of two catalytic A subunits and two non-catalytic B subunits. Activated factor XIII (aFXIII) is necessary for cross-linking and stabilization of fibrin, and it plays an important role in blood clotting through its hemostatic and reparative functions. In most cases, mutations in the gene encoding the A subunit (F13A1 gene) are causative for FXIII deficiency. In rare cases, mutations in the gene encoding the B subunit (F13B gene) have been observed. A severe bleeding tendency is found in homozygous or combined heterozygous carriers of pathogenic variants, and factor XIII activity is often less than 5% in these cases. Heterozygous carriers do not usually show an increased bleeding tendency and have a reduced FXIII activity of 30-60%. In most cases, the bleeding tendency correlates with the measured factor XIII activity.


Factor XIII deficiency is difficult to diagnose biochemically because it cannot be detected by the screening coagulation parameters prothrombin time, partial thromboplastin time, and thrombin time. These tests show inconspicuous values despite a massive bleeding tendency. Therefore, a factor XIII functionality test is recommended as a first-line screening test for the diagnosis of factor XIII deficiency. Molecular genetic testing can confirm the diagnosis.


Factor XIII deficiency can also be acquired. Causes include liver synthesis disorders, inflammatory bowel disease, consumption coagulopathy, or factor XIII inhibition (e.g., caused by medication).


Substitution therapy with factor XIII concentrates is possible.



Tahlan et Ahluwalia 2014, Arch Pathol Lab Med 138:278 / Bolton-Maggs 2013, Pediatr Blood Cancer 60:37 / Levy et Greenberg 2013, Transfusion 53:1120 / Eshghi et al. 2012, IJBC 2:85 / Biswas et al. 2011, Blood Reviews 25:193 / Kohler et al. 2011, J Thromb Haemost 9:1404 / Wells et al. 2006, Am J Epidemiol 164:101

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