title: Alloantibodies against the B subunit of plasma factor XIII developed in its congenital deficiency.
abstract: Factor XIII (FXIII) is a fibrin-stabilising factor consisting of catalytic A subunits (FXIII-A) and carrier B subunits (FXIII-B). FXIII-B prevents the fast clearance of FXIII-A from the circulation. Congenital FXIII-A deficiency is a rare bleeding disorder, and congenital FXIII-B deficiency is even rarer. Through our recent nationwide survey on "acquired haemophilia-like disease due to anti-FXIII autoantibodies," we newly diagnosed severe congenital FXIII-B deficiency in a Japanese man. He developed thrombocytopenia and gingival bleedings at the age of 73, and his FXIII activity was as low as 10% of the normal. When he suddenly developed spontaneous intramuscular haematoma, the bleeding was arrested by infusing FXIII concentrates. However, his FXIII activity remained around 10% of the normal. At the age of 74, ELISA and western blotting assay unexpectedly revealed complete absence of FXIII-B in the patient's plasma. A dot blot assay detected anti-FXIII-B alloantibodies for the first time in this disease, which could be attributed to the infusion of exogenous FXIII. He was found to be homozygous for a Japanese founder-effect mutation of F13B. Repeated infusions of exogenous FXIII for hemostasis increased anti-FXIII-B alloantibodies that resisted FXIII substitution. To the best knowledge of the authors, none of the remaining 10 reported cases of congenital FXIII-B deficiency developed alloantibodies to exogenous FXIII-B of plasma FXIII. An originally mild bleeding phenotype of severe congenital FXIII-B deficiency can be exaggerated by additional acquired conditions. Physicians should consider congenital FXIII-B deficiency when they encounter cases of unexplained bleeding disorders.
authors: Department of Molecular Patho-Biochemistry -Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585 Japan.
authors: Hideho
authors: H
authors: Wada
authors: Masayoshi
authors: M
authors: Souri
authors: Rui
authors: R
authors: Matsumoto
authors: Takashi
authors: T
authors: Sugihara
authors: Akitada
authors: A
authors: Ichinose
mesh_terms: D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D001780:Blood Coagulation Tests; D003029:Coagulants / Q000008:administration & dosage / Q000276:immunology; D005176:Factor XIII / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005177:Factor XIII Deficiency / Q000097:blood / Q000151:congenital / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D009154:Mutation; D010641:Phenotype; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D003029:Coagulants; D007518:Isoantibodies; D005176:Factor XIII; C054380:factor XIIIb