Several
disorders in the quantity and/or quality of fibrinogen cause pathological bleeding, pathological blood clotting, and/or the deposition of fibrinogen in the liver, kidneys, and other tissues.
Congenital afibrinogenemia Congenital afibrinogenemia is a rare and generally
autosomal recessive inherited disorder in which blood does not clot due to a lack of fibrinogen (plasma fibrinogen levels typically) but sometimes detected at extremely low levels, e.g. 150 mg/dl) but are c. 50% lower when measured by clot formation methods. The disorder exhibits
reduced penetrance, with only some individuals with the abnormal gene showing symptoms of abnormal bleeding and thrombosis.
Hereditary fibrinogen Aα-Chain amyloidosis Hereditary fibrinogen Aα-Chain amyloidosis is an autosomal dominant extremely rare inherited disorder caused by a mutation in one of the two copies of the
FGA gene. It is a form of congenital dysfibrinogenemia in which certain mutations lead to the production of an abnormal fibrinogen that circulates in the blood while gradually accumulating in the kidney. This accumulation leads over time to one form of
familial renal amyloidosis. Plasma fibrinogen levels are similar to that seen in other forms of congenital dysfibrinogenemia. Fibrinogen Aα-Chain amyloidosis has not associated with abnormal bleeding or thrombosis.
Acquired dysfibrinogenemia Acquired dysfibrinogenemia is a rare disorder in which circulating fibrinogen is composed at least in part of a dysfunctional fibrinogen due to various acquired diseases. One well-studied cause of the disorder is severe
liver disease including
hepatoma, chronic active
hepatitis,
cirrhosis, and
jaundice due to
biliary tract obstruction. The diseased liver synthesizes a fibrinogen which has a normally functional
amino acid sequence but is incorrectly
glycosylated (i.e. has a wrong amount of sugar residues) added to it during its passage through the Golgi. The incorrectly glycosalated fibrinogen is dysfunctional and may cause pathological episodes of bleeding and/or blood clotting. Other, less well understood, causes are
plasma cell dyscrasias and
autoimmune disorders in which a circulating abnormal immunoglobulin or other protein interferes with fibrinogen function, and rare cases of cancer and medication (
isotretinoin,
glucocorticoids, and
antileukemic drugs) toxicities.
Cryofibrinogenemia Cryofibrinogenemia is an acquired disorder in which fibrinogen precipitates at cold temperatures and may lead to the intravascular precipitation of fibrinogen,
fibrin, and other circulating proteins, thereby causing the
infarction of various tissues and bodily extremities. Cryoglobulonemia may occur without evidence of an underlying associated disorders, i.e. primary cryoglobulinemia (also termed essential cryoglobulinemia) or, far more commonly, with evidence of an underlying disease, i.e. secondary cryoglobulonemia. Secondary cryofibrinoenemia can develop in individuals with infection (% of cases),
malignant or
premalignant disorders (21%),
vasculitis (25%), and
autoimmune diseases (42%). In these cases, cryofibinogenema may or may not cause tissue injury and/or other symptoms and the actual cause-effect relationship between these diseases and the development of cryofibrinogenmia is unclear. Cryofibrinogenemia can also occur in association with the intake of certain drugs.
Acquired hypofibrinogenemia Acquired hypofibrinogenemia is a deficiency in circulating fibrinogen due to excessive consumption that may occur as a result of
trauma, certain phases of
disseminated intravascular coagulation, and
sepsis. It may also occur as a result of hemodilution as a result of blood losses and/or transfusions with
packed red blood cells or other fibrinogen-poor whole blood replacements. The low fibrinogen level in
hemorrhagic fever caused by
crimean-congo hemorrhagic fever virus is associated with high mortality rate. == Laboratory tests ==