Factor XIII deficiency: an updated approach to diagnosis and management

Factor XIII deficiency (FXIIID) is a rare bleeding disorder that may be congenital or acquired and is associated with significant morbidity, particularly in its congenital form, including intracranial hemorrhage, impaired wound healing, and adverse pregnancy outcomes. Unlike other coagulation factor deficiencies, FXIIID is not detected by routine coagulation screening tests, contributing to delayed diagnosis and underrecognition. This review provides an updated overview of the epidemiology, molecular biology, clinical manifestations, laboratory diagnosis, and management of FXIIID. Particular emphasis is placed on contemporary diagnostic strategies, including the advantages and limitations of functional, antigen, inhibitor, and genetic assays, as well as preanalytical and analytical pitfalls that may affect test interpretation. Special attention is given to acquired FXIIID, emerging diagnostic challenges, and complex clinical scenarios, including pregnancy, neonatal care, surgery, and anticoagulation. Persistent knowledge gaps, including assay standardization and limited evidence supporting current recommendations for managing special scenarios, are also highlighted. Continued international collaboration and prospective data collection are needed to improve diagnosis, refine treatment strategies, and strengthen future evidence-based guidance.