Congenital fibrinogen abnormalities are rare orphan diseases. They are classified as quantitative abnormalities, defined by a total deficit (afibrinogenemia) or low level (hypofibrinogenemia) of circulating fibrinogen, and as qualitative abnormalities characterized by a discrepancy between the level of circulating fibrinogen measured by a functional method and the antigenic level (dysfibrinogenemia or hypodysfibrinogenemia). Laboratory diagnosis is based on conventional hemostasis testing and is usually confirmed by genetic testing. Clinical presentation varies based on the level of coagulant activity of fibrinogen and its structural abnormality.
Our research on congenital fibrinogen abnormalities is focused on three main areas: genetics, functional analysis, and epidemiology. With regard to the genetic part, we carry out the diagnosis by sequencing 3 fibrinogen genes as part of a research project on the molecular defects of fibrinogen, in collaboration with the team of the Prof. Marguerite Neerman-Arbez. Expression of the recombinant protein can complement the genetic exploration in selected cases. Other abnormalities, including fibrinogen deficiencies, are studied in zebrafish (Danio rerio). With regard to functional analyses, they are carried out by Dr. Alessandro Casini and performed primarily for dysfibrinogenemias and hypodysfibrinogenemias in order to identify the structural abnormality and thus better defined the clinical phenotype of the patient.As part of this study, we analyze the turbidity (fibrin polymerization and lysis), viscoelasticity, and ultrastructure of the fibrin clot (permeability, fiber density, and network architecture). Finally, for the epidemiology, we participate in several international studies aiming to better define the prevalence, incidence of complications, treatment, and quality of life of patients with congenital fibrinogen abnormalities.