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Natural history of patients with congenital dysfibrinogenemia
Alessandro Casini1, Marc Blondon1, Aurélien Lebreton2
1Division of Angiology and Haemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland;
Insights
Congenital dysfibrinogenemia (CD) patients face significant risks of major bleeding and thrombotic events throughout their lives. This includes complications during pregnancy, such as postpartum hemorrhage, and after surgery.
Area of Science:
- Hematology
- Genetics
- Clinical Medicine
Background:
- Congenital dysfibrinogenemia (CD) is a rare inherited bleeding disorder.
- Characterizing long-term risks associated with CD is crucial for patient management.
Purpose of the Study:
- To assess the incidence of hemorrhagic and thrombotic events in patients with congenital dysfibrinogenemia.
- To evaluate pregnancy and surgical complications in individuals with CD.
Main Methods:
- A multicenter study involving 101 patients with genotyped CD.
- Long-term follow-up data collection for bleeding and thrombotic events.
- Analysis of pregnancy and surgical complication data.
Main Results:
- At diagnosis, 10.9% experienced major bleeding and 13.9% thrombotic events.
- Long-term cumulative incidences at age 50 were estimated at 19.2% for bleeding and 30.1% for thrombosis.
- Pregnancies were associated with 19.8% spontaneous abortions and 21.4% postpartum hemorrhage; 6.5% of surgeries had bleeding complications.
Conclusions:
- Patients with CD and their relatives face substantial risks of both major bleeding and thrombotic events.
- Postpartum hemorrhage risk is linked to a prior bleeding phenotype.
- Genetic factors like mutation hotspots or fibrinogen levels did not correlate with event risk.
Abstract:
We conducted a multicenter study of 101 patients with congenital dysfibrinogenemia (CD) to characterize the incidence of hemorrhagic and thrombotic events as well as complications of pregnancy and surgery. At the time of diagnosis, 10.9% and 13.9% had experienced major bleeding and thrombotic events, respectively. During a mean follow-up of 8.8 years after CD diagnosis, the incidence of major bleeding and thrombotic events was 2.5 and 18.7 per 1000 patient-years, respectively, with estimated cumulative incidences at age 50 years of 19.2% and 30.1%. We identified 111 pregnancies with an overall incidence of spontaneous abortions and postpartum hemorrhage of 19.8% and 21.4%, respectively. The risk of postpartum hemorrhage was associated with a previously identified bleeding phenotype (odds ratio, 5.8; 95% CI, 1.2 to 28.0). Among 137 surgical procedures analyzed, 9 (6.5%) were complicated by abnormal bleeding. Propositi vs relatives, sex, mutation hotspots, fibrinogen levels, and activity:antigen ratios were not associated with the risk of thrombotic or bleeding outcomes. In conclusion, the results of our study, the largest in genotyped CD and the first including long-term history, indicate that propositi with CD and their relatives carry not only a high risk of major bleeding, including postpartum hemorrhage, but also of thrombotic event.
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