Human Fibrinogen: Molecular and Genetic Aspects of Congenital Disorders

Abstract

Congenital fibrinogen disorders can be quantitative (afibrinogenemia, hypofibrinogenemia) or functional (dysfibrinognemia). To date, several genetic variants have been identified in individuals with fibrinogen disorders. The complexity of the fibrinogen molecules, formed by three non-identical chains and with a trinodal organization, renders the identification of molecular causes and of clinical and biochemical phenotypes very challenging. However, the acknowledgement of the type of molecular defect is crucial for a safer therapy, which is going to improve the clinical management of these patients. In this review, some aspects concerning molecular and clinical findings available on congenital fibrinogen disorders will be discussed.

Keywords: afibrinogenemia; dysfibrinogenemia; hypofibrinogenemia.

Figure 1

A sketch representing the physiologic role of fibrinogen in the clot formation. The fibrinogen molecule links activated platelets together (white clot) through the alphaIIb–beta3integrin that serves as the fibrinogen receptor. In addition, it is transformed in fibrin by the action of activated thrombin (FIIa), which further stabilizes the fibrin clot by activating FXIII.

Figure 2

Graphic schematic representation of possible clinical phenotype following a genetic impairment of the fibrinogen molecule.