Factor XIII Deficiency

Excerpt

Factor XIII (FXIII) deficiency is a rare bleeding disorder that presents with symptoms spanning from delayed umbilical cord separation to intracranial hemorrhage. In its activated state, FXIII plays a pivotal role in stabilizing clots and facilitating the cross-linking of the fibrin polymer, thereby ensuring effective hemostasis.

FXIII deficiency can manifest in both congenital and acquired forms, leading to reduced clot stability and abnormal bleeding tendencies. The acquired FXIII deficiency typically arises from factors such as hyperconsumption, hemodilution, and decreased synthesis and is more prevalent than the congenital, autosomal recessive form. In rare instances, individuals with acquired FXIII deficiency may generate autoantibodies targeting FXIII subunits. Conversely, in the congenital variant of FXIII deficiency, which comprises A (FXIII-A) and B (FXIII-B) subunits, most patients typically display a deficiency of the A subunit.

Beyond its role in clotting, FXIII is instrumental in various physiological processes such as wound healing, phagocytosis by macrophages, tissue repair, and bacterial immobilization and clearance. The condition presents a complex genetic landscape with over 100 identified mutations in the FXIII-A gene.

Clinical manifestations of FXIII deficiency include delayed separation of the umbilical cord and bleeding from the umbilical stump in neonates. Moreover, patients may present with intracranial hemorrhage without significant trauma, impaired wound healing, menorrhagia, hemarthrosis, and spontaneous miscarriages in early pregnancy.

Diagnosis of FXIII deficiency involves a stepwise approach, incorporating family history, personal responses to hemostatic challenges, and strategic laboratory testing. Given its rarity, clinicians must remain vigilant in identifying this disorder. Although prophylactic and therapeutic options are available, their restricted availability, high cost, infection risk, and potential administration-related complications present challenges. Clinicians must navigate these complexities to deliver comprehensive care to individuals with FXIII deficiency, highlighting the importance of a multidisciplinary approach for optimal patient management.