Factor XIII Deficiency: A Review of Biology, Testing, and Treatment

Authors: Jacobs, JW; Booth, GS; Costa, V; Figueroa Villalba, CA; Savani, BN; Adkins, BD

Affiliations: Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, USA. Special Coagulation Laboratory, Vanderbilt Medical Laboratories, Nashville, TN, USA. Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, USA. Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. Department of Laboratory Medicine and Pathology, Seattle Children’s Hospital, Seattle, WA, USA. Division of Transfusion Medicine and Hemostasis, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Publication: Clinical hematology international; 2026; 8. 10–25

ABSTRACT: Factor XIII (FXIII) deficiency is a rare bleeding disorder characterized by unstable hemostatic clots due to defective fibrin cross‑linking. Congenital FXIII deficiency arises from variants in the F13A1 (FXIII-A subunit) or F13B (FXIII-B subunit) genes, and classically presents with delayed umbilical stump hemorrhage, soft‑tissue and intracranial bleeding, impaired wound healing, and recurrent pregnancy loss. Acquired deficiency stems from inhibitory autoantibodies or from reduced synthesis or consumption in critical illness and surgery. Routine coagulation screening tests are normal and diagnosis relies on quantitative FXIII activity assays with or without antigenic phenotyping and, when indicated, inhibitor testing and molecular confirmation. Plasma‑derived FXIII concentrate reduces spontaneous and intracranial bleeding; recombinant FXIII‑A2 is appropriate for F13A1 defects but not patients with F13B variants. Perioperative and obstetric care target activity thresholds suited to procedural risk and individual pharmacokinetics. This review synthesizes the molecular biology, epidemiology, clinical features, diagnostic methods, and evidence‑based management of FXIII deficiency, with practical guidance for assay selection, validation, and result interpretation.