Factor VII Deficiency in China: The Genotype-Phenotype Analysis and Current Status of Management

Abstract

Introduction: Congenital factor VII (FVII) deficiency is one of the rare bleeding disorders characterized by a wide molecular and clinical heterogeneity. Aim: This study aimed to investigate the correlations among the F7 genotype, FVII activity (FVII:C) and bleeding phenotype of patients with FVII deficiency throughout China and to show their current status and management. Methods: We retrospectively analyzed demographics, patient characteristics, clinical history and manifestation, gene mutation and treatment strategy of 193 patients with FVII deficiency registered across China. Results: The most frequent bleeding symptoms were epistaxis (44.6%), cutaneous (38.9%), oral cavity (40.4%) bleeding and menorrhagia (44.3% of females in fertile age). Fatal central nervous system bleeding and joint deformity hemarthrosis occurred in 3 and 3 patients, respectively. The majority of patients (89.6%) belonged to the FVII:C ≤10% group and the proportion of symptomatic patients in this group (79.8%) was significantly higher than that in 10%<FVII:C≤25% (41.7%) and 25%<FVII:C≤50% group (37.5%) (Chi2=13.641, P=0.001). Major bleeds just occurred in patients with FVII:C≤10%. Most mutations were missense (62.5%) and most patients were detected with homozygous (10.9%) or compound heterozygous (74.5%) mutations. Prothrombin complex concentrates (72.4%) was the most frequently used on-demand replacement therapy. Prophylaxis before delivery could decrease the risk of postpartum bleeding in women (Chi2=69.243, P=0.000). Conclusion: Our study provided useful information on the relationship among F7 genotype, FVII:C, clinical phenotype and current status of patient management, and may promote further exploration of FVII deficiency in the future as well as care of this population in China.