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Dysfibrinogenemia

  • Author: Russell Burgess, MD; Chief Editor: Perumal Thiagarajan, MD  more...
 
Updated: Oct 21, 2015
 

Background

Congenital dysfibrinogenemia is a term used to describe a relatively rare condition wherein an inherited abnormality in the fibrin molecule results in defective fibrin clot formation. The complications associated with abnormal clot formation range from asymptomatic to life threatening. Fortunately, 40% of patients with congenital dysfibrinogenemia are asymptomatic; however, 50% of patients have a bleeding disorder and the remaining 10% have a thrombotic disorder or combined thrombotic and bleeding tendencies. Acquired dysfibrinogenemias, often called dysfibrinogenemia of liver disease, are the most common causes. Up to 50% of patients with severe liver disease secondary to cirrhosis, hepatoma, or hepatitis exhibit bleeding complications.[1]

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Pathophysiology

In the clotting cascade, the various blood coagulation factors function in concert to produce a balance between fibrin clot formation and its subsequent degradation. When any factor in the cascade is absent, decreased, or abnormal, the delicate balance is disrupted, possibly leading to bleeding or thrombotic disorders. The clinical manifestations range from no symptoms to life-threatening events depending on which coagulation factor is affected and the degree to which it is affected.

In normal fibrin clot formation, a fibrin monomer forms after thrombin cleaves fibrinopeptide A and B from the alpha and beta chains of the fibrinogen molecule. Factor XIIIa then catalyzes the cross-linkage between different fibrin chains, forming a stabilized fibrin polymer or clot. Eventually, plasmin lyses the fibrin clot.

Acquired dysfibrinogenemia occurs most often in patients with severe liver disease. The impairment of the fibrinogen, which is manufactured in the liver, is due to a structural defect caused by an increased carbohydrate content impairing the polymerization of the fibrin, depending on the degree of abnormality of the fibrinogen molecule. Rarely, dysfibrinogenemia may also be associated with malignancies, most commonly primary or secondary liver tumors, but acquired dysfibrinogenemia has also been reported in patients with renal cell carcinoma.

One of the rarer disorders of coagulation is congenital dysfibrinogenemia, a qualitative abnormality of the fibrin molecule. Multiple variations of these dysfibrinogenemias are elucidated. Each is named for the city where it was first discovered. With only rare exceptions, the congenital dysfibrinogenemias are inherited in an autosomal dominant or codominant fashion. Depending on the fibrinogen abnormality, defects may occur in one or more of the steps in fibrin clot formation, although the most common defect involves polymerization of the fibrin monomer.[2]

Bleeding may ensue when a fibrin clot forms that cannot be effectively stabilized. Bleeding in patients with congenital dysfibrinogenemia tends to be relatively mild or even absent; it is only a laboratory curiosity and is not life threatening. In contrast to the bleeding experienced by approximately half of the patients with congenital dysfibrinogenemia, one subset of patients (diagnosed with fibrinogen Oslo I) has an abnormal fibrinogen that is associated with thromboembolic complications that are often relatively mild. The abnormal fibrinogen in these patients forms a fibrin clot that is resistant to fibrinolysis by plasmin.[3]

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Epidemiology

Frequency

International

Only 200-300 families are reported to have congenital dysfibrinogenemia. Hereditary transmission is autosomal dominant or codominant except in a few cases that appear to be transmitted recessively. Approximately 50% of patients with severe liver disease exhibit bleeding secondary to abnormal fibrinogen molecules.

Mortality/Morbidity

While many patients with congenital dysfibrinogenemias are asymptomatic, those who experience symptoms commonly have only mild bleeding or thrombotic events, although these are extremely rare. Severe hemorrhagic episodes may characterize a few abnormal fibrinogen variants (eg, Imperate, Dettori, Detroit).

Patients with dysfibrinogenemia of liver disease often have a more severe bleeding disorder than patients with an inherited disorder. The condition tends to worsen as the liver disease worsens.

A multicenter study of 101 patients with congenital dysfibrinogenemia found that, over a mean 8.8 year follow-up period after diagnosis, the incidence of major bleeding and of thrombotic events was 2.5 and 18.7 per 1000 patient-years, respectively. At 50 years of age, those incidences were estimated at 19.2% and 30.1%. In addition, of 111 pregnancies identified, the incidence of spontaneous abortions and postpartum hemorrhage were 19.8% and 21.4%, respectively. Abnormal bleeding was a complication in nine of 137 surgical procedures analyzed.[4]

Race

Prevalence is not increased in any race.

Sex

Prevalence is not increased in either sex.

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Contributor Information and Disclosures
Author

Russell Burgess, MD (Retired) Chief, Division of Hematology/Oncology, Eastern Carolina Internal Medicine, PA

Russell Burgess, MD is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Guy B Faguet, MD Retired Professor, Department of Medicine, Section of Hematology and Oncology, Georgia Regents University

Guy B Faguet, MD is a member of the following medical societies: American Association of Immunologists, American Society of Hematology, International Society of Hematology, New York Academy of Sciences, Southern Medical Association, Southern Society for Clinical Investigation, American Federation for Clinical Research, Southeastern Cancer Research Association, Polycythemia Vera Study Group

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Society for Clinical Investigation, Association of American Physicians, American Society for Biochemistry and Molecular Biology, American Heart Association, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Acknowledgements

Wendy Brick, MD Consulting Staff, Department of Internal Medicine, Division of Hematology and Oncology, Mecklenburg Medical Group

Wendy Brick, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, and American Society of Hematology

Disclosure: Nothing to disclose.

References
  1. Acharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia. 2008 Nov. 14(6):1151-8. [Medline].

  2. Kotlin R, Reicheltova Z, Maly M, et al. Two cases of congenital dysfibrinogenemia associated with thrombosis - Fibrinogen Praha III and Fibrinogen Plzen. Thromb Haemost. 2009 Sep. 102(3):479-86. [Medline].

  3. Morris TA, Marsh JJ, Chiles PG, et al. High prevalence of dysfibrinogenemia among patients with chronic thromboembolic pulmonary hypertension. Blood. 2009 Aug 27. 114(9):1929-36. [Medline]. [Full Text].

  4. Casini A, Blondon M, Lebreton A, Koegel J, Tintillier V, de Maistre E, et al. Natural history of patients with congenital dysfibrinogenemia. Blood. 2014 Oct 15. [Medline].

  5. Miesbach W, Schenk J, Alesci S, Lindhoff-Last E. Comparison of the fibrinogen Clauss assay and the fibrinogen PT derived method in patients with dysfibrinogenemia. Thromb Res. 2010 Dec. 126(6):e428-33. [Medline].

  6. Miesbach W, Galanakis D, Scharrer I. Treatment of patients with dysfibrinogenemia and a history of abortions during pregnancy. Blood Coagul Fibrinolysis. 2009 Jul. 20(5):366-70. [Medline].

  7. Bornikova L, Peyvandi F, Allen G, Bernstein J, Manco-Johnson MJ. Fibrinogen replacement therapy for congenital fibrinogen deficiency. J Thromb Haemost. 2011 Sep. 9(9):1687-704. [Medline].

  8. Bazzan M, Tamponi G, Vaccarino A, et al. Natural and acquired inhibitors of hemostasis in selected symptomatic outpatients with venous thromboembolic disease. Haematologica. 1997 Jul-Aug. 82(4):420-2. [Medline].

  9. Galanakis DK. Inherited dysfibrinogenemia: emerging abnormal structure associations with pathologic and nonpathologic dysfunctions. Semin Thromb Hemost. 1993. 19(4):386-95. [Medline].

  10. Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen. Thromb Haemost. 1995 Jan. 73(1):151-61. [Medline].

  11. Martinez J. Congenital dysfibrinogenemia. Curr Opin Hematol. 1997 Sep. 4(5):357-65. [Medline].

  12. Martinez J. Quantitative and qualitative disorders of fibrinogen. In: Hoffman, et al, eds. Hematology: Basic Principles and Procedures. 2nd ed. Philadelphia, Pa: Churchill Livingstone. 1995:1703-13, 2011-13.

  13. Mori T, Ikeda Y. [Acquired dysfibrinogenemia]. Ryoikibetsu Shokogun Shirizu. 1998. (21 Pt 2):529-31. [Medline].

  14. Mosesson MW. Dysfibrinogenemia and thrombosis. Semin Thromb Hemost. 1999. 25(3):311-9. [Medline].

  15. Rodgers GM, Greenberg CS. Inherited coagulation disorders. In: Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM, eds. Wintrobe's Clinical Hematology. 10th ed. Baltimore, Md: Williams & Wilkins. 1999:1702-3.

  16. Schorer AE, Singh J, Basara ML. Dysfibrinogenemia: a case with thrombosis (fibrinogen Richfield) and an overview of the clinical and laboratory spectrum. Am J Hematol. 1995 Nov. 50(3):200-8. [Medline].

 
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