Acquired autoimmune coagulation factor XIII/13 deficiency

Abstract

Coagulation factor XIII/13 (FXIII) is a transglutaminase that cross-links fibrin monomers, provides clot stabilization and resistance to fibrinolysis and proteolysis, and ultimately contributes to hemostasis and wound healing. FXIII is a hetero-tetramer formed by two catalytic A subunits (FXIII-A) and two noncatalytic B subunits (FXIII-B). Autoimmune acquired factor XIII/13 deficiency secondary to anti-FXIII antibodies (AH13) is a severe bleeding disorder that occurs mainly in the elderly. While AH13 is a very rare disease, with only about 100 cases reported worldwide, more than 60 of these cases have been identified in Japan. AH13 is somewhat difficult to diagnose because the abnormalities are not detected by routine coagulation testing. Anti-FXIII autoantibodies have been sub-classified into three types, including: (1) type Aa autoantibodies that mainly inhibit the thrombin-mediated proteolytic cleavage of FXIII-A, preventing its activation, (2) type Ab autoantibodies that inhibit the enzymatic activity of activated FXIII-A, and (3) type B autoantibodies that bind to and remove noncatalytic FXIII-B subunits from the circulation. We have encountered four cases of AH13 (three of type Aa and one of type B) in the past decade. This review outlines the diagnosis and treatment of AH13, with a focus on recent experience at our hospital.