Acquired Factor XIII Deficiency Secondary to an Inhibitor: Effect of Factor XIII Replacement and Rituximab Therapy

Abstract

Factor XIII (FXIII) is the last enzyme in the clotting cascade. Its main function is to convert the loose fibrin polymer into a firm, cross-linked structure. FXIII inhibitor is a rare condition, in which three different types of inhibitors have been described usually due to IgG antibodies. We describe two male patients with acquired FXIII deficiency (age; 73 and 69 years), who had a history of significant bleeding. Functional assay using the acetic acid/urea clot solubility test showed residual FXIII levels between 1–2%. Molecular studies by PCR and DNA sequencing excluded an inherited FXIII deficiency. In addition, we demonstrated an inhibitor pattern for FXIII by in vitro mixing studies with both purified FXIII (Fibrogammin, Aventis Behring) and cryoprecipitates as sources of FXIII. Transglutaminase assay of FXIII (Dade Behring) was normal for both patients, consistent with a type III FXIII inhibitor, which believed to be directed against the activated FXIII-fibrin complex. Both patients showed transient correction of clot solubility to normal after infusion of high doses of Fibrogammin. In view of previous reports describing FXIII inhibitors of the IgG class, we attempted a novel treatment with rituximab (chimeric monoclonal anti-CD20 antibody, Roche) to interfere with production of the inhibitor. However, neither patient showed correction of FXIII activity as measured by clot solubility tests during and up to 2 weeks after therapy. Preliminary results suggest that high dose Fibrogammin is required to correct FXIII deficiency due to an acquired type III inhibitor. The role of rituximab or other immunosuppressive therapy requires further investigation.