Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients

Background: Factor XIII (FXIII) deficiency is a challenge in the diagnosis of rare bleeding disorders with inherited and acquired causes. Objectives: We evaluated consecutive cases tested for FXIII deficiency for insights on diagnosis. Methods: With ethics approval, we retrospectively reviewed FXIII tests performed between 2013 and 2023 and local patient records for insights into causes and presentations of FXIII deficiency. Results: Two thousand one hundred ninety-one samples from 1915 patients (ages: 0-90 years; 38% local) were tested. The FXIII activity (FXIII:Act; Berichrom FXIII, Siemens Healthcare) was low in 14%/9.7% of tested samples/patients. FXIII subunit A antigen (FXIII-A:Ag; Werfen HemosIL FXIII antigen; low in 45% of 251 samples) helped characterize FXIII deficiency severity and identify type 2 deficiencies from acquired FXIII inhibitors. Urea clot solubility tests (18.2% requested without FXIII:Act) were largely noninformative as all abnormal samples (n = 7) had undetectable FXIII-A:Ag levels. Excluding FXIII inhibitor patients, FXIII:Act showed strong correlation with FXIII-A:Ag (R ² = 0.84, P < .001) and weak correlation with plasma fibrinogen (R ² = .005, P < .001). Some patients had combined acquired FXIII and fibrinogen deficiencies from consumption or major bleeding. FXIII-deficient and nondeficient patients had similar bleeding except for more umbilical and gastrointestinal bleeding among deficient patients (P < .05). Most FXIII deficiencies were acquired (92%), and although several were autoimmune, most were from consumption, major bleeds, or severe infections or had uncertain significance, with bleeding sometimes attributable to other causes. Conclusion: Congenital and acquired FXIII deficiency are associated with bleeding. Local practices were changed to ensure that FXIII:Act is used to screen for FXIII deficiency and that deficient patients have FXIII:Act and FXIII-A:Ag quantified and compared.