Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Database.

Autor:	Mohsenian S; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy., Palla R; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy., Menegatti M; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy., Cairo A; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy., Lecchi A; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy., Casini A; Division of Angiology and Hemostasis, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland., Neerman-Arbez M; Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Asselta R; Department of Biomedical Sciences, Humanitas University, Milan, Italy.; IRCCS Humanitas Research Hospital, Milan, Italy., Scardo S; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy., Siboni SM; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy., Blatny J; Department of Paediatrics Haematology and Biochemistry, University Hospital Brno and Masaryk University, Brno, Czech Republic., Zapletal O; Department of Paediatrics Haematology and Biochemistry, University Hospital Brno and Masaryk University, Brno, Czech Republic., Schved JF; Department of Biological Hematology, CHU Montpellier, Université de Montpellier, Montpellier, France., Giansily-Blaizot M; Department of Biological Hematology, CHU Montpellier, Université de Montpellier, Montpellier, France., Halimeh S; Coagulation Centre Rhein-Ruhr, Duisburg, Germany., Daoud MA; Coagulation Centre Rhein-Ruhr, Duisburg, Germany., Platokouki H; Haemophilia-Centre-Haemostasis Unit, Aghia Sophia Children's Hospital, Athens, Greece., Pergantou H; Haemophilia-Centre-Haemostasis Unit, Aghia Sophia Children's Hospital, Athens, Greece., Schutgens REG; Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Van Haaften-Spoor M; Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Brons P; Department of Pediatric Hematology, Radboud University Medical Center, Nijmegen, The Netherlands., Laros-van Gorkom B; Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands., Van Pinxten E; Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands., Borhany M; Clinical Hematology, National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan., Fatima N; Clinical Hematology, National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan., Mikovic D; Hemostasis Department, Blood Transfusion Institute of Serbia, Belgrade, Serbia., Saracevic M; Hemostasis Department, Blood Transfusion Institute of Serbia, Belgrade, Serbia., Özdemir GN; Pediatric Hematology Department, Istinye University, Istanbul, Turkey., Ay Y; University of Health Sciences Kartal Health Application and Research Center, Pediatric Hematology and Oncology Clinic, Istanbul, Turkey., Makris M; Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, United Kingdom., Lockley C; Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, United Kingdom., Mumford A; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom., Harvey A; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom., Austin S; Department of Haematology, Guys and St Thomas' NHS Foundation Trust, London, United Kingdom., Shapiro A; Indiana Hemophilia and Thrombosis Center, Indianapolis, IN., Williamson A; Indiana Hemophilia and Thrombosis Center, Indianapolis, IN., McGuinn C; Indiana Hemophilia and Thrombosis Center, Indianapolis, IN., Goldberg I; Division of Pediatric Hematology Oncology, Department of Pediatrics, Weill Cornell Medicine, New York, NY., De Moerloose P; Division of Angiology and Hemostasis, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland., Peyvandi F; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Mar 26; Vol. 8 (6), pp. 1392-1404.
DOI:	10.1182/bloodadvances.2023012186
Abstrakt:	Abstract: Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB, and FGG. We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory, and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade 3 based on their bleeding severity. In addition, FGA, FGB, and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, and 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of the cases. The rates of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%, respectively) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. Eighty-six patients received treatment (69 on-demand and/or 17 on prophylaxis), with fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants (FGG, p.Arg301Cys/His and FGA, p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory, and genetic history of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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