Congenital Fibrinogen Disorders

Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia) or the quality (dysfibrinogenemia) of the circulating fibrinogen or both (hypodysfibrinogenemia). Most often, patients with congenital fibrinogen disorders suffer from a bleeding diathesis but paradoxically may undergo severe thrombotic episodes. Pregnancy loss is another common clinical complication. Even in specialized laboratories, the precise diagnosis of some fibrinogen disorders may be challenging. Characterization of the molecular defect(s) is important as it provides a more accurate diagnosis, may enable prenatal diagnosis, will help elaborate a diagnostic strategy, and may distinguish in some cases those patients at risk of thrombosis rather than bleeding. However, the phenotype-genotype correlation is not easy to establish, and global hemostasis assays may provide a better evaluation of the patient's hemostatic state. Replacement therapy is effective in treating bleeding episodes, but it is important to tailor individual treatments because the pharmacokinetics of fibrinogen after replacement therapy is highly variable among patients. Although the number of cases studied and identified mutations are already quite substantial, the collection and comparison of molecular, biochemical, and clinical data will continue to yield valuable information on the development and course of these diseases, as well as on the choice of the most appropriate treatments.