title: Natural history of patients with congenital dysfibrinogenemia.
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.
authors.affiliation: Division of Angiology and Haemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland;
authors.forename: Alessandro
authors.initials: A
authors.lastname: Casini
authors.affiliation: Division of Angiology and Haemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland;
authors.forename: Marc
authors.initials: M
authors.lastname: Blondon
authors.affiliation: Division of Angiology and Haemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland; Centre Hospitalier Universitaire Clermont-Ferrand, Service d'hématologie biologique, Hôpital Estaing, Clermont-Ferrand, France;
authors.forename: Aurélien
authors.initials: A
authors.lastname: Lebreton
authors.affiliation: Department of Genetic Medicine and Development, University Medical School of Geneva, Geneva, Switzerland;
authors.forename: Jérémie
authors.initials: J
authors.lastname: Koegel
authors.affiliation: Institut Hématologie Transfusion, Pôle Biologie Pathologie Génétique, Centre Hospitalier Regional Universitaire, Lille, France;
authors.forename: Véronique
authors.initials: V
authors.lastname: Tintillier
authors.affiliation: Department of Biology and Haematology, Centre Hospitalier Universitaire Dijon, Dijon, France;
authors.forename: Emmanuel
authors.initials: E
authors.lastname: de Maistre
authors.affiliation: Centre de Traitement Régional de l'Hémophilie, Centre Hospitalier Universitaire Caen, Caen, France; and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gautier
authors.affiliation: Haemostasis Laboratory, Hôpital Saint Eloi, Montpellier, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Biron
authors.affiliation: Department of Genetic Medicine and Development, University Medical School of Geneva, Geneva, Switzerland;
authors.forename: Marguerite
authors.initials: M
authors.lastname: Neerman-Arbez
authors.affiliation: Division of Angiology and Haemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland;
authors.forename: Philippe
authors.initials: P
authors.lastname: de Moerloose
mesh_terms: D000022:Abortion, Spontaneous / Q000453:epidemiology* / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000347:Afibrinogenemia / Q000150:complications* / Q000601:surgery; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D015994:Incidence; D008297:Male; D011183:Postoperative Complications; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000453:epidemiology* / Q000209:etiology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology* / Q000209:etiology; D055815:Young Adult