Congenital Fibrinogen Disorders

Abstract

Congenital fibrinogen disorders (CFD) are rare coagulation disorders. CFD can affect quantity (afibrinogenemia and hypofibrinogenemia), quality (dysfibrinogenemia), or both aspects (hypodysfibrinogenemia) of the fibrinogen molecule. The precise prevalence of CFD is not known, except for afibrinogenemia with an estimated incidence of 1 per 1,000,000 of person. Most patients with hypofibrinogenemia and dysfibrinogenemia are asymptomatic, while hemorrhage is frequent in afibrinogenemia often with umbilical cord bleeding at diagnosis. Thrombotic and obstetrical complications are also a common complication in patients with CFD. Diagnosis is based on the assessment of both antigenic and functional fibrinogen levels. In routine clinical use, the Clauss functional assay is recommended, although a variety of functional and antigenic assays with variable sensitivity are available. Genotype helps to confirm the diagnosis. A wide spectrum of mutations has been discovered in FGA, FGB, and FGG encoding the three chains of fibrinogen molecule. Two hotspot mutations are prevalent in afibrinogenemia and dysfibrinogenemia. Management of patients with congenital fibrinogen disorders is challenging and should always take in account the personal and familial history as well as the genotype in qualitative fibrinogen disorders.