Nationwide Study on Factor V Deficiency in China: Clinical Characteristics, Genotype, and Treatment Approaches.

Introduction: Congenital factor V (FV) deficiency is a rare bleeding disorder caused by recessive variants in the F5 gene.

Aim: To investigate the phenotype and genotype of patients with congenital FV deficiency throughout China.

Methods: Based on data from the Chinese National Haemophilia Registry, we analysed the clinical and genetic characteristics of 45 congenital FV deficiency patients.

Results: The study cohort comprised 45 patients with confirmed FV:C reductions (undetectable to 48%), including six mild (FV:C >10%), 31 moderate (FV:C 1%-10%), and eight severe (FV:C <1%) patients. Of 39 patients with medical history, nine were asymptomatic. Major bleeding (Grade III) occurred in six patients with FV:C <10%. The most common symptoms included gingival (n = 15, 38.5%) and cutaneous bleeding (n = 13, 33.3%) in 39 patients. Menorrhagia (n = 7) was observed in 38.9% of 18 female patients of reproductive age. Gene sequencing identified 33 distinct variants in 20 patients, including 12 novel pathogenic/likely pathogenic variants and one novel variant of uncertain significance. Variants affecting the light chain (vs. heavy chain) were associated with lower FV:C (p = 0.002). Fresh frozen plasma served as the primary on-demand therapy, administered to 19 patients for active bleeding management and to two asymptomatic patients as preoperative prophylaxis.

Conclusion: This study characterizes China's largest FV-deficient cohort, identifying 13 novel F5 variants. Light chain variants predicted severe coagulation disorder, while on-demand FFP achieved effective haemostasis. High prevalences of menorrhagia (38.9%) and ovarian cysts (22.2%) in reproductive-age females highlight urgent needs for gender-specific interventions and management of this rare disorder.