Skip to Main Content




  • Quantitative disorders of fibrinogen may be afibrinogenemia or hypofibrinogenemia, depending on the severity.

  • Normal fibrinogen levels range from 150 to 350 mg/dL. In afibrinogenemia, the fibrinogen concentration is less than 20 mg/dL. In hypofibrinogenemia, the level is less than normal.

  • Mutations resulting in afibrinogenemia or hypofibrinogenemia are presented in Chap. 126, Table 126–1, p. 2055 in Williams Hematology, 8th ed.


Clinical Features


  • Congenital afibrinogenemia is a rare disorder of hepatic biosynthesis of fibrinogen, inherited as an autosomal recessive trait, with low levels of fibrinogen typically found in both parents.

  • Bleeding varies from minimal to severe. Umbilical cord bleeding may occur at birth. Later, bleeding may be from mucosal surfaces, into muscles, or into joints.

  • Spontaneous abortions are frequent.

  • Death is most often a result of intracranial hemorrhage.

  • Hereditary hypofibrinogenemia appears to be caused by abnormal intracellular hepatic storage of fibrinogen.


Laboratory Features


  • All laboratory tests depending on formation of a clot are abnormal in afibrinogenemia or hypofibrinogenemia but can be corrected by mixing with normal plasma or fibrinogen solutions.

  • The diagnosis is established by demonstrating a reduced fibrinogen concentration by immunologic testing.

  • The bleeding time is prolonged and platelet aggregation is abnormal; both can be corrected by infusion of plasma or fibrinogen.


Therapy, Course, and Prognosis


  • Replacement therapy with cryoprecipitate (if available) or fibrinogen concentrate may be required.

  • Cryoprecipitate typically contains 300 mg of fibrinogen per unit. Approximately 50 to 70 percent of the administered fibrinogen circulates posttransfusion, and the biologic half-life of fibrinogen is 3 to 5 days. The recommended initial dose is 1 unit of cryoprecipitate (300 mg of fibrinogen) per 5 kg of body weight to reach hemostatic levels of fibrinogen.

  • Fibrinogen concentrate should be given to increase the plasma concentrations by at least 150 mg/dL. One gram of fibrinogen concentrate raises the plasma fibrinogen level by 20 mg/dL.

  • Patients should receive one-third of the initial loading dose daily as long as is necessary to sustain the fibrinogen level.

  • Cryoprecipitate or fibrinogen concentrate may be given during pregnancy to prevent spontaneous abortion or premature birth.

  • Thrombosis can occur after administration of fibrinogen, and antifibrinogen antibodies may develop.




  • Inherited dysfibrinogenemia is the production of structurally abnormal fibrinogen molecules with altered functional properties. At least 300 families with this fibrinogenemia have been described thus far.

  • Hypodysfibrinogenemia refers to patients with low levels of circulating abnormal fibrinogen.


Etiology and Pathogenesis


  • Dysfibrinogenemia is inherited as an autosomal dominant trait. Most patients are heterozygous but some are homozygous.

  • Fibrinogen abnormalities usually affect one or more phases of fibrin formation:

    — Impaired fibrinopeptide release.

    — Defective fibrin polymerization.

    — Defective cross-linking by factor XIIIa.

  • Biochemical abnormalities do not correlate with clinical expression. For example, the same amino acid substitution can lead to either a familial bleeding tendency ...

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.


About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.