Characterization and management of patients with hereditary factor X deficiency: A case series

Hereditary factor X deficiency (HFXD) is an ultra-rare, autosomal recessive bleeding disorder that results in reduced factor X coagulant activity (FX:C). HFXD is traditionally classified by severity as severe (FX:C <1%), moderate (FX:C = 1%-5%), or mild (FX:C = 6%-10%). Treatment aims to replace the deficient factors, but there are no standardized guidelines for management.

This multicenter retrospective chart review examined the diagnostic features, bleeding patterns, and current management strategies for HFXD patients in the United States. Patients were classified based on the revised European Network of Rare Bleeding Disorders (EN-RBD) criteria: severe (FX:C <10%), moderate (FX:C = 10%-40%), and mild (FX:C >40%). Data, including demographics, bleeding symptoms, laboratory analyses, and treatments, were collected.

Twenty-four patients were included, with diagnoses based on family history or significant bleeding history; most were diagnosed in childhood (n = 10) or adolescence (n = 6). All patients had FX:C >5%, with 2 and 12 patients classified as EN-RBD mild and moderate, respectively. Twenty patients experienced bleeding episodes requiring treatment. Bleeding episodes were heterogeneous, ranging from epistaxis to spontaneous subdural hematoma; treatments included antifibrinolytics, hormonal therapy, and factor replacement. Seven patients with FX:C >40% had bleeding episodes that required treatment, and 3 of them experienced multiple bleeding episodes.

HFXD presents with variable bleeding phenotypes that may not correlate with FX:C levels. This analysis demonstrates that while bleeding phenotypes generally align with the revised EN-RBD classification, patients with mild or moderate HFXD can experience significant bleeding. Future work should focus on correlating genotype with phenotype and refining management guidelines for mild and moderate HFXD.