Coagulation
Hereditary thrombophilia / hypercoagulopathies
Dysfibrinogenemia
Author: Jeremy C. Parsons, M.D.
Last author update: 1 June 2016
Last staff update: 23 September 2020
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Dysfibrinogenemia
Cite this page: Parsons JC. Dysfibrinogenemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationdysfibrinogenemiahypercoag.html. Accessed June 3rd, 2023.
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
