Congenital
fibrinogen disorders are diseases associated with a
bleeding tendency; however, there are also reports of thrombotic events.
Fibrinogen plays a role in the pathogenesis of
thrombosis due to altered plasma concentrations or modifications to
fibrinogen's structural properties, which affect clot permeability, resistance to lysis, and its stiffness. Several distinct types of genetic change and pathogenetic mechanism have been described in patients with
bleeding and a thrombotic phenotype, including mutations affecting synthesis or processing in three
fibrinogen genes. In this paper, we focused on familial hypofibrinogenemia, a rare inherited quantitative
fibrinogen disorder characterized by decreased
fibrinogen levels with a high phenotypic heterogeneity. To begin, we briefly review the basic information regarding
fibrinogen's structure, its function, and the clinical consequences of low
fibrinogen levels. Thereafter, we introduce 15 case reports with various gene mutations derived from the
fibrinogen mutation database GFHT (French Study Group on Hemostasis and
Thrombosis), which are associated with
congenital hypofibrinogenemia with both
bleeding and
thrombosis. Predicting clinical presentations based on genotype data is difficult. Genotype-phenotype correlations would be of help to better understand the pathologic properties of this
rare disease and to provide a valuable tool for the identification of patients who are not only at risk of
bleeding, but also at risk of a thrombotic event.