Abstract
Coagulation factor XIII (FXIII) is an essential protein that stabilizes the hemostatic
plug formed in the final stage of the coagulation reaction and controls its dissolution.
In the blood, it exists as a heterotetramer consisting of A subunit dimers and B subunit
dimers. Genetic defects in each subunit result in a congenital deficiency, which causes
fatal or mild bleeding symptoms. Acquired FXIII deficiency can develop owing to reduced
production or increased consumption of FXIII, and its severe form can cause various
bleeding symptoms. In particular, autoimmune FXIII deficiency (AiF13D) causes fatal
bleeding symptoms due to the suppression of FXIII activity by anti-FXIII autoantibodies
and/or accelerated clearance of FXIII. AiF13D is characterized by extremely severe
FXIII deficiency and severe bleeding symptoms. It is associated with the highest hemorrhagic
mortality rate among autoimmune coagulation factor deficiencies, making it essential
to differentiate it from other non-immune FXIII deficiencies (NiF13D), such as those
arising from liver cirrhosis or leukemia. The probable and definitive diagnosis of
AiF13D require the presence of FXIII inhibitors and anti-FXIII autoantibodies, respectively.
FXIII inhibitors can be detected by a general FXIII activity assay in the mixed plasma
of patients and healthy controls, and can be measured in a regular laboratory. In
contrast, immunological assays are conducted in limited research facilities because
they are not commercially available. NiF13D is usually treated by hemostatic therapy
with FXIII concentrates, but AiF13D requires hemostatic therapy plus autoantibody
eradication therapy with immunosuppressants. Since the disease often becomes resistant
to treatment, long-term follow-up is strongly recommended.
Keywords anti-factor XIII autoantibody - factor XIII inhibitor - hyper-clearance - hypo-production
- hyper-consumption
