Coagulation
Hereditary thrombophilia / hypercoagulopathies
Dysfibrinogenemia

Author: Jeremy Parsons, M.D. (see Authors page)

Revised: 27 April 2016, last major update June 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Dysfibrinogenemia

Definition / General
  • Disorders of fibrinogen structure (over 350 described)
  • Have variable effects on function (25% associated with bleeding, 20% associated with thrombosis, 55% have no symptoms or prolonged thrombin time)
  • Bleeding due to defective fibrin clot formation (impaired release of fibrinopeptides A or B and impaired fibrin monomer polymerization)

  • Thrombosis due to:
    • defective thrombin binding to fibrin, causing increased thrombin in circulation and more thrombosis
    • defective binding of tPA or plasminogen to fibrin or fibrin resistance to plasmin; includes Dusart (Paris V) and Chappel Hill III dysfibrinogens that are resistant to degradation by plasmin

  • Congenital (hereditary) dysfibrinogenemia is a rare cause of hypercoagulability (350 reported cases, 0.8% of patients with venous thrombosis); usually due to single amino acid substitutions in fibrinogen Aalpha, Bbeta or gamma genes
  • Recommended to use only as a second-line test in patients with thrombosis since dysfibrinogenemia is so rare
  • Autosomal dominant inheritance, but higher incidence in women due to pregnancy related thrombosis, particularly post-partum and in venous lower extremities, at mean age 27 years
  • Also associated with spontaneous abortions
Laboratory
  • Primary screening test is thrombin time (prolonged except for fibrinogens Oslo I and Valhalla - shortened)
  • Prolongation may also be due to heparin, heparin - like inhibitors, fibrin degradation products, hypofibrinogenemia, excess fibrinogen, paraproteins, excess protamine, anti - fibrinogen antibodies, anti - bovine thrombin antibodies, systemic amyloidosis, acquired dysfibrinogenemia
  • The sensitivity of thrombin time assays varies for dysfibrinogenemia because many assays are designed primarily to detect heparin contamination
  • Some labs use the reptilase time, which is not affected by heparin

  • Confirmatory test (if thrombin time or reptilase time is prolonged):
    • Fibrinogen activity-antigen ratio below reference range
    • Activity measured by Clauss method (rate of clot formation after adding high concentration of thrombin to citrated plasma
    • Use standard curve relating clotting time to plasma of known fibrinogen activity)
    • Antigen concentration determined by ELISA, radial immunodiffusion, precipitation or thrombin clotting methods
    • Perform both tests on same sample in same laboratory and using method-specific reference ranges

  • Diagnosis:
    • Similar laboratory test abnormalities in family members
    • If necessary, demonstrate abnormal structure or function of fibrinogen

  • Diagnosis of acquired dysfibrinogenemia:
    • Abnormal liver function tests, no dysfibrinogenemia in family members