OC 75.3 - Phenotype and genotype characterization of patients with congenital fibrinogen deficiencies: a retrospective analysis of the PRO-RBDD database

Wednesday, June 28, 2023

10:45 – 11:00 ET

Room: 510

Session Available As: On-Demand

Presenting Author(s)

Samin Mohsenian

PhD student
Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy
Milan, Lombardia, Italy

Co-Author(s)

RP

Roberta Palla

Biologist
Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy
MILAN, Lombardia, Italy
Marzia menegatti, PhD

Biologist
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and luigi villa foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
MILAN, Lombardia, Italy
Andrea Cairo

Biologist
Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Milan, Lombardia, Italy
AL

Anna Lecchi

Biologist
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and luigi villa foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milan, Lombardia, Italy
Alessandro Casini, MD

MD
Division of Angiology and Hemostasis, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
Geneva, Geneve, Switzerland
MN

Marguerite Neerman-Arbez

Professor
Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Geneva, Geneve, Switzerland
RA

Rosanna Asselta

Full Professor of Medical Genetics; Deputy Director of the Department of Biomedical Sciences
IRCCS Humanitas Research Hospital, Milan, Italy
GENEVA, Geneve, Switzerland
PD

Philippe De Moerloose

Professor of the Faculty of Medicine
Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
GENEVA, Geneve, Switzerland
Flora Peyvandi, MD, PhD (she/her/hers)

Director
IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy
Milano, Lombardia, Italy

Background: Congenital fibrinogen disorders (CFDs) are classified into quantitative and qualitative fibrinogen defects caused by mutations in the FGA, FGB and FGG.

Aims: To characterize CFD patients based on phenotype and genotype using the PRO-RBDD (prospective rare bleeding disorders database) project. In addition, to explore the correlation between clinical bleeding severity and coagulation factor activity.

Methods: The PRO-RBDD dataset with retrospective and prospective data from 2013-2020 was used to investigate the clinical phenotype, laboratory and genetic features. Patients were classified as asymptomatic and grade I to III based on bleeding severity. The correlation between bleeding severity and factor activity was determined. The analysis was performed using IBM-SPSS-Statistics-26.

Results: A total of 168 CFD patients (from 19 different countries) were included and 114 patients were characterized (Table 1). Considering the median age of diagnosis in different CFD groups, patients with afibrinogenemia were diagnosed at an earlier age (Figure 1). In quantitative CFD patients (afibrinogenemia and hypofibrinogenemia) there was a moderate correlation (r=0.68, p< 0.001) between the age of diagnosis and factor activity. Most of grade III and asymptomatic bleeding severity were observed in afibrinogenemia and dysfibrinogenemia, respectively. We found a moderate correlation (r=-0.6, p< 0.001) between factor activity and bleeding severity in the quantitative CFD patients. 68(60%) patients(23 afibrinogenemia, 17 hypofibrinogenemia, 23 dysfibrinogenemia, 5 hypodysfibrinogenemia) received on-demand treatment of which 43(63%) received fibrinogen-concentrate. Genetic analysis was available in 98 patients with 46 distinct mutations identified (6 novels). Six mutation types were observed: missense (n=24, 52%), nonsense (n=11, 24%), frameshift (n=5, 11%), splicing (n=3, 7%), intronic (n=2, 4%) and deletion (n=1, 2%).

Conclusion(s): A moderately significant correlation between factor activity and age of diagnosis/severity was found in the quantitative CFD patients. Among this large cohort, 30% of patients were asymptomatic while the remainder experienced bleeding (70%) or thrombosis (8%). Missense mutations were the most common variants identified

Learning Objectives:

Upon completion, participants will be able to understand the correlation between the age of diagnosis and factor activity in patients with fibrinogen deficiencies.
Upon completion, participants will be able to understand the correlation between the bleeding severity grades and factor activity in patients with fibrinogen deficiencies.
Upon completion, participants will have an overview of the genetic spectrum of fibrinogen deficiencies.