Measuring Factor XIII Inhibitors in Patients with Factor XIII Deficiency: A Case Report and Systematic Review of Current Practices in Japan

Abstract

Factor XIII (FXIII) deficiency is a rare but serious coagulopathy. FXIII is critical in blood coagulation, and FXIII deficiencies can lead to uncontrolled or spontaneous bleeding. FXIII deficiencies can be congenital or acquired; acquired FXIII deficiency can be categorized as autoimmune and non-autoimmune. Immunological tests to measure FXIII inhibitors are required to diagnose acquired FXIII deficiency; however, appropriate test facilities are limited, which increases the turnaround time of these tests. In the case of critical bleeding, delayed test results may worsen prognosis due to delayed treatment. Here, we report a case of acquired FXIII deficiency, followed by a review of FXIII deficiency cases in Japan. We performed a systematic review to investigate the present conditions of the diagnosis and treatment of FXIII deficiency, including the measurement of FXIII inhibitors in Japan. FXIII inhibitor testing was only performed in 29.7 of acquired FXIII deficiency cases. Clinical departments other than internal medicine and pediatrics were often involved in medical treatment at the time of onset. Therefore, it is important for doctors in clinical departments other than internal medicine and pediatrics to consider FXIII deficiency and perform FXIII inhibitor testing when examining patients with prolonged bleeding of unknown cause or persistent bleeding after trauma.

Factor XIII deficiency, a rare coagulopathy: case reports

“…Hereditary Factor XIII Deficiency (FXIIID) is a rare disorder of hemostasis, autosomal recessive, and, with a prevalence of about one per 1 million people, with a higher prevalence in descendents of consanguineous relationships. [1][2][3] Data from the Ministry of Health publication indicates that Brazil had 96 cases of FXIIID registered in 2022, a value that corresponds to a 2.97 % prevalence of rare coagulopathies in the country. 4 In the previous year (2021), Brazil had 90 cases of FXIIID documented, representing a prevalence of 3.02% for rare coagulopathies in the country.…”

“…6 Umbilical stump bleeding is very suggestive of this clotting disorder, occurring in 80% of cases and IH is the main cause of death. 2 Coagulation Factor XIII (FXIII) is a pro transglutaminase formed by two A subunits (FXIII-A) and two B subunits (FXIII-B) that circulates as a heterotetramer (FXIII-A2B2), catalyzing the formation of cross-links between the monomers of fibrin and between α2-antiplasmin and fibrin. [1][2][3] FXIII-A is produced in the bone marrow, while FXIII-B is produced by hepatocytes.…”

“…2 Coagulation Factor XIII (FXIII) is a pro transglutaminase formed by two A subunits (FXIII-A) and two B subunits (FXIII-B) that circulates as a heterotetramer (FXIII-A2B2), catalyzing the formation of cross-links between the monomers of fibrin and between α2-antiplasmin and fibrin. [1][2][3] FXIII-A is produced in the bone marrow, while FXIII-B is produced by hepatocytes. 1 Activated FXIII promotes stabilization and protection of newly formed fibrin against premature fibrinolysis, with an extremely relevant role in hemostasis, pregnancy maintenance, wound healing, and angiogenesis.…”

“…1 Activated FXIII promotes stabilization and protection of newly formed fibrin against premature fibrinolysis, with an extremely relevant role in hemostasis, pregnancy maintenance, wound healing, and angiogenesis. 2,6 FXIIID is due to a mutation in the gene that encodes the A subunit of FXIII or the B subunit. FXIII-A deficiency is more frequent and severe.…”

“…FXIII-A deficiency is more frequent and severe. 2 Over 200 genetic mutations have been recognized since the initial instance of inherited FXIII deficiency was documented. A newly discovered and probably pathogenic mutation in the F13A1 gene was reported, expanding the range of gene mutations associated with inherited FXIII deficiency.…”