Gynecologic and obstetric complications in women with congenital fibrinogen disorders: insights from the Prospective Rare Bleeding Disorders Database

Background: Women and girls with congenital fibrinogen deficiencies (CFDs) face higher hemorrhagic risks during their reproductive years, yet data on gynecologic and obstetric complications remain limited. Objectives: We aimed to rate the prevalence of heavy menstrual bleeding and obstetric complications in women with CFDs and compare our findings with previous reports. Methods: This study analyzed data from the Prospective Rare Bleeding Disorders Database registry, including available fibrinogen activity and antigen levels, as well as clinical phenotype and genotype (2013-2020). Results: A total of 59 women (8 afibrinogenemic, 15 hypofibrinogenemic, and 36 dysfibrinogenemic cases) were investigated, of which 32 patients had 70 pregnancies. The prevalence of heavy menstrual bleeding was comparable between hypofibrinogenemic (27%) and dysfibrinogenemic (36%) cases, with a higher frequency in afibrinogenemic (75%) cases. The rates of postpartum hemorrhage at 36% and miscarriage at 23% were notably higher than those observed in the general population (1%-10% and 10%-20%, respectively). These complications were similarly distributed among patients with dysfibrinogenemia (35% and 37%) and hypofibrinogenemia (36% and 31%). There were only 2 (4%) bleeds during pregnancy, both occurring in dysfibrinogenemic cases. Miscarriage was also observed in 50% of the asymptomatic dysfibrinogenemic patients. No significant difference in miscarriage and postpartum hemorrhage rates was found between dysfibrinogenemic individuals with and without hotspot variants (P = .94). Conclusion: The high rate of obstetric complications in women with CFDs highlights the need for early diagnosis and the potential need for prophylaxis, as pregnancy may also pose risks in asymptomatic cases. Hotspot variants do not appear to increase the risk of obstetric complications.