Congenital afibrinogenemia

Abstract

Congenital afibrinogenemia is a rare disorder with unusual clinical manifestations. The disease is inherited as an autosomal recessive trait and consanguinity is common among affected families. Clinical manifestations range from minimal bleeding to catastrophic hemorrhage. Congenitally afibrinogenemic patients seem to be peculiarly susceptible to spontaneous rupture of the spleen. Coagulation tests which depend on clot formation as an end point may be infinitely prolonged and abnormalities of platelet function are usually present. The diagnosis is established by demonstrating trace or no immunoreactive fibrinogen. The disease is caused by markedly reduced or absent synthesis of fibrinogen by liver cells, but the genetic defect remains unknown. Bleeding episodes can be effectively treated with cryoprecipitate. Purified virally inactivated fibrinogen concentrates have been used in Europe and may soon be widely available.

Mutations in the fibrinogen gene cluster accounting for congenital afibrinogenemia: an update and report of 10 novel mutations

“…Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system [Acharya et al, 2004;al-Mondhiry and Ehmann, 1994;Awidi, 1992;Fried and Kaufman, 1980;Peyvandi and Mannucci, 1999], with intracranial hemorrhage the major cause of death. In comparison with patients suffering from hemophilia, bleeding in skeletal muscle is not as frequent: in a series of 55 patients with afibrinogenemia, hemarthrosis and muscle hematomas were reported in 54% and 72% of the patients, respectively [Lak et al, 1999].…”

Fibrinogen Stabilizes Placental-Maternal Attachment During Embryonic Development in the Mouse

“…Later in life, spontaneous intracerebral bleeding and splenic rupture may occur. 17 Fg deficiencies also result in spontaneous miscarriage in the early gestational period. 18 -20 Although reasons for fetal loss in pregnant females homozygous for the FGG deletion, which results in a total deficiency of Fg (FG Ϫ/Ϫ ), are primarily uncertain, protection against premature bleeding, offered in part by Fg, is most likely involved in allowing pregnancy to advance.…”

Management of Congenital Afibrinogenemia: Report of Two Cases

“…The normal level of fibrinogen in the blood is from 2 to 4 g/L. A few case reports have revealed that thrombosis is associated with afibrinogenemia [1]. In congenital afibrinogenemia, the bleeding varies in severity, from mild to life-threatening.…”

“…Its structure is composed of three polypeptide chains, i.e., alpha, beta, and gamma chains that interact with each other to form the hexametric structure [1]. A separate gene encodes each polypeptide; α polypeptide is encoded by FGA, a β polypeptide is encoded by FGB, γ polypeptide is encoded by FGG [2].…”

“…In turn, thrombin converts fibrinogen to fibrin, which is the end target of both extrinsic and intrinsic pathways. A deficiency in fibrinogen results in the tendency to bleed [1]. …”