Clinical phenotype and laboratory characteristics of 93 patients with congenital fibrinogen disorders from unrelated 36 families

Background Congenital fibrinogen disorders (CFDs) are rare bleeding disorders (RBDs) caused by mutations in one of the three fibrinogen genes (FGA, FGB, and FGG). Objectives To investigate the clinical phenotype, laboratory features, diagnosis, treatment and prognosis of CFDs. Methods Clinical data of 93 subjects with CFDs identified from June 2018 to December 2023 were retrospectively analyzed. Results Among the 93 patients, there were 46 males (49.5%) and 47 females (50.5%) , with a median age of 23 years. 53/93(57%) subjects experienced bleeding , 3/93(3.2%) thrombosis and 37/93(39.8%) were asymptomatic. Females were more prone to experience bleeding (P < .0001). The 93 patients exhibited prolonged thrombin time (TT), significantly decreased fibrinogen activity (Fg:C), and normal or decreased fibrinogen antigen (Fg:Ag). The 93 patients included 3 with hypofibrinogenemia (Hypo-), 16 with hypodysfibrinogenemia (Hypodys-), and 74 with dysfibrinogenemia (Dys-). Among the 53 patients with bleeding, bleeding episodes were identified in 3.8% (2/53), 20.8% (11/53), 75.5% (40/53) patients with Hypo-, Hypodys-, and Dys-, respectively. Genetic analysis was performed on 22 cases from 8 pedigrees, revealing 10 mutations, including one novel splice mutation. 28 (30.1%) subjects received replacement therapy to treat or prevent bleeding, consisted of 8 fresh frozen plasma (FFP) transfusions, 3 packing and suture treatment, and 61 fibrinogen infusions. Conclusions Most patients with CFDs have mild or no bleeding symptoms. Fg:C combined with Fg:Ag and pedigree investigation can improve the feasibility and accuracy of diagnosis of CFDs. And, the severity of bleeding symptoms was negatively correlated with Fg:C.