Rare Congenital Fibrinogen Deficiencies

Differential Diagnosis

Acquired causes of hypofibrinogenemia and dysfibrinoegenemia need to be ruled out. The most common cause of acquired dysfibrinogenemia is advanced liver disease.33 Fibrinogen abnormalities are observed in the majority of patients with cirrhosis, acute or chronic hepatitis, and in individuals with metastatic hepatoma34 or renal carcinoma.35 Acquired hypofibrinogenemia can occur with disseminated intravascular coagulation, and with L-asparaginase and valproate therapy.36,37{Gralnick, 1971 #5307;Hauser, 1996 #5308;Gralnick, 1971 #40}

Conditions Mimicking Congenital Fibrinogen Disorders

Fetal fibrinogen, which transitions to the adult form of the molecule approximately 3 weeks after birth,38 is characterized by increased sialic acid content and phosphorylation with decreased sulfation. These fetal posttranslational modifications result in a fibrin molecule that is more translucent and has reduced tensile strength compared to the adult fibrinogen form.

Fibrinogen synthesized in some individuals with liver disease also exhibits altered carbohydrate content, causing a condition mimicking dysfibrinogenemia in certain laboratory tests.34,39

Elevated fibrinogen levels due to an acute phase reaction can be associated with prolonged reptilase times, possibly due to increased sialation and/or phosphorylation.40

Conditions associated with a prolonged thrombin time and not related to fibrinogen deficiency include the following:

  • Presence of heparin, a direct thrombin inhibitor, or a heparin-like compound in the blood sample
  • Presence of fibrin/fibrinogen degradation products
  • Presence of bovine thrombin antibodies from prior exposure to bovine thrombin
  • High concentrations of serum proteins (eg, multiple myeloma)