Clinical characteristics and genetic variant spectrum of 27 patients with coagulation factor XI deficiency.

Hereditary factor XI (FXI) deficiency is a rare bleeding disorder characterized by diminished plasma FXI activity (FXI: C) due to F11 gene mutations. Clinical manifestations are often asymptomatic or involve mild-to-moderate bleeding, typically occurring after trauma or surgery involving tissue with high fibrinolytic activity. The molecular basis of FXI deficiency is widely heterogeneous across different populations. This study aimed to characterize the spectrum of clinical features and the underlying genetic landscape of this disorder in a cohort of Han Chinese individuals from Shanxi province. We investigated the clinical characteristics and underlying molecular variants in 27 unrelated patients with FXI deficiency, who exhibited significantly low FXI: C levels (median, 4 [< 2–31.6]%), with 21 having severe deficiency (FXI: C, < 2–13.5%) and 6 having partial deficiency (FXI: C, 20.9–31.6%). Most patients presented for coagulation abnormalities found during laboratory testing. Twenty patients were asymptomatic, and seven exhibited minor bleeding manifestations. Genetic variants were identified by direct sequencing. Genetic analysis revealed 19 cases with compound heterozygous variants, one with a homozygous variant, and seven with heterozygous variants. A total of 23 different variants were detected, including six novel variants (three missense variants, two deletion variants and one nonsense variant). Bioinformatic analysis predicted that these novel variants could impair the function and structure of the FXI protein. To investigate the pathogenic mechanisms of the three novel missense variants, we performed in vitro cellular experiments, which demonstrated that these variants resulted in reduced FXI: C. In conclusion, coagulation factor XI deficiency exhibits high heterogeneity in clinical presentation and genetic variation.