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Sections Inherited Abnormalities of Fibrinogen
Overview
Presentation
DDx
Workup
Treatment
Medication
Follow-up
References

Medication

Plasma sources of fibrinogen

Class Summary

Fibrinogen concentrates and cryoprecipitate are both derived from human plasma. The advantage of fibrinogen concentrates is that virus inactivation is incorporated into the preparation of this product. More precise dosing can be achieved with concentrates, as the fibrinogen concentration in cryoprecipitate may vary.

Fibrinogen concentrate, human (RiaSTAP)

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Approved by the FDA in 2009. Indicated for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. Not indicated for dysfibrinogenemia. Available as single-use vials containing 900-1300 mg lyophilized fibrinogen concentrate powder for reconstitution. Actual fibrinogen potency for each lot is printed on vial label and carton.

Fibrinogen concentrate (Haemocomplettan P, Clottagen, Fibrinogen HT)

Fibrinogen concentrates are derived from human plasma and have been virus-inactivated to improve their safety. In the United States, human fibrinogen is available as an orphan drug from Alpha Therapeutics.

Cryoprecipitate

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Can be used when fibrinogen concentrates are not available. Unlike fibrinogen concentrates, it does not undergo virus inactivation. The precipitate formed when fresh frozen plasma (FFP) is slowly thawed. It contains factor VIII, factor XIII, fibrinogen, von Willebrand factor (vWF), and fibronectin. Each bag provides 100-250 mg fibrinogen.

Class Summary

These are useful in conjunction with fibrinogen replacement for the treatment of mucosal bleeding, particularly bleeding involving the oronasopharynx. Inhibition of local fibrinolysis allows maintenance of the clot and decreases the frequency of rebleeding.

Aminocaproic acid (Amicar)

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Lysine analogue that inhibits fibrinolysis by blocking binding of plasmin or plasminogen activators to lysine residues on fibrin.

Tranexamic acid (Cyklokapron)

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Alternative to aminocaproic acid. Inhibits fibrinolysis by displacing plasminogen from fibrin.

Follow-up

Bolton-Maggs PH, Perry DJ, Chalmers EA, et al. The rare coagulation disorders--review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia. 2004 Sep. 10(5):593-628. [QxMD MEDLINE Link].
Roberts HR, Stinchcombe TE, Gabriel DA. The dysfibrinogenaemias. Br J Haematol. 2001 Aug. 114(2):249-57. [QxMD MEDLINE Link].
Tiscia GL, Margaglione M. Human Fibrinogen: Molecular and Genetic Aspects of Congenital Disorders. Int J Mol Sci. 2018 May 29. 19 (6):[QxMD MEDLINE Link]. [Full Text].
Neerman-Arbez M, Casini A. Clinical Consequences and Molecular Bases of Low Fibrinogen Levels. Int J Mol Sci. 2018 Jan 8. 19 (1):[QxMD MEDLINE Link]. [Full Text].
Casini A, Neerman-Arbez M, Ariens RA, de Moerloose P. Dysfibrinogenemia: from molecular anomalies to clinical manifestations and management. J Thromb Haemost. 2015 Jun. 13 (6):909-19. [QxMD MEDLINE Link]. [Full Text].
Asselta R, Duga S, Tenchini ML. The molecular basis of quantitative fibrinogen disorders. J Thromb Haemost. 2006 Oct. 4(10):2115-29. [QxMD MEDLINE Link].
Parameswaran R, Dickinson JP, de Lord S, et al. Spontaneous intracranial bleeding in two patients with congenital afibrinogenaemia and the role of replacement therapy. Haemophilia. 2000 Nov. 6(6):705-8. [QxMD MEDLINE Link].
Peyvandi F, Haertel S, Knaub S, Mannucci PM. Incidence of bleeding symptoms in 100 patients with inherited afibrinogenemia or hypofibrinogenemia. J Thromb Haemost. 2006 Jul. 4(7):1634-7. [QxMD MEDLINE Link].
Acharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia. 2008 Nov. 14(6):1151-8. [QxMD MEDLINE Link]. [Full Text].
Martinez J. Congenital dysfibrinogenemia. Curr Opin Hematol. 1997 Sep. 4(5):357-65. [QxMD MEDLINE Link].
Kirihara T, Fujikawa Y, Takeda W, Kurihara T, Sato K, Ueki T, et al. Congenital dysfibrinogenemia coincidentally diagnosed at the onset of chronic myelogenous leukemia. Rinsho Ketsueki. 2014 May. 55(5):541-5. [QxMD MEDLINE Link].
Sumitha E, Jayandharan GR, Arora N, Abraham A, David S, Devi GS, et al. Molecular basis of quantitative fibrinogen disorders in 27 patients from India. Haemophilia. 2013 Jul. 19(4):611-8. [QxMD MEDLINE Link].
Zhou J, Ding Q, Chen Y, et al. Clinical features and molecular basis of 102 Chinese patients with congenital dysfibrinogenemia. Blood Cells Mol Dis. 2015 Dec. 55 (4):308-15. [QxMD MEDLINE Link].
Acharya SS, Coughlin A, Dimichele DM,. Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias. J Thromb Haemost. 2004 Feb. 2(2):248-56. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Casini A, Blondon M, Lebreton A, et al. Natural history of patients with congenital dysfibrinogenemia. Blood. 2015 Jan 15. 125 (3):553-61. [QxMD MEDLINE Link]. [Full Text].
Kaur M, Kumar N, Bose SK, Rajendran A, Trehan A, Ahluwalia J. Congenital afibrinogenemia in a new born: a rare cause for bleeding. Blood Coagul Fibrinolysis. 2014 Feb 6. [QxMD MEDLINE Link].
Verhovsek M, Moffat KA, Hayward CP. Laboratory testing for fibrinogen abnormalities. Am J Hematol. 2008 Dec. 83(12):928-31. [QxMD MEDLINE Link].
Jacquemin M, Vanlinthout I, Van Horenbeeck I, et al. The amplitude of coagulation curves from thrombin time tests allows dysfibrinogenemia caused by the common mutation FGG-Arg301 to be distinguished from hypofibrinogenemia. Int J Lab Hematol. 2017 Jun. 39 (3):301-7. [QxMD MEDLINE Link].
Van Cott EM, Smith EY, Galanakis DK. Elevated fibrinogen in an acute phase reaction prolongs the reptilase time but typically not the thrombin time. Am J Clin Pathol. 2002 Aug. 118(2):263-8. [QxMD MEDLINE Link].
Cunningham MT, Brandt JT, Laposata M, Olson JD. Laboratory diagnosis of dysfibrinogenemia. Arch Pathol Lab Med. 2002. 126:499-505. [QxMD MEDLINE Link].
Peyvandi F, Cattaneo M, Inbal A, De Moerloose P, Spreafico M. Rare bleeding disorders. Haemophilia. 2008 Jul. 14 Suppl 3:202-10. [QxMD MEDLINE Link].
Nagler M, Kremer Hovinga JA, Alberio L, et al. Thromboembolism in patients with congenital afibrinogenaemia. Long-term observational data and systematic review. Thromb Haemost. 2016 Sep 27. 116 (4):722-32. [QxMD MEDLINE Link].
Peyvandi F. Epidemiology and treatment of congenital fibrinogen deficiency. Thromb Res. 2012 Dec. 130 Suppl 2:S7-11. [QxMD MEDLINE Link].
Ross C, Rangarajan S, Karimi M, et al. Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency. J Thromb Haemost. 2018 Feb. 16 (2):253-61. [QxMD MEDLINE Link].
Lissitchkov T, Madan B, Djambas Khayat C, et al. Efficacy and safety of a new human fibrinogen concentrate in patients with congenital fibrinogen deficiency: an interim analysis of a Phase III trial. Transfusion. 2018 Feb. 58 (2):413-22. [QxMD MEDLINE Link].
Manco-Johnson MJ, Dimichele D, Castaman G, Fremann S, Knaub S, Kalina U. Pharmacokinetics and safety of fibrinogen concentrate. J Thromb Haemost. 2009 Dec. 7(12):2064-9. [QxMD MEDLINE Link].
Khayat C, Marchi R, Durual S, Lecompte T, Neerman-Arbez M, Casini A. Impact of Fibrinogen Infusion on Thrombin Generation and Fibrin Clot Structure in Patients with Inherited Afibrinogenemia. Thromb Haemost. 2022 Sep. 122 (9):1461-8. [QxMD MEDLINE Link].

Media Gallery

The conversion of soluble fibrinogen to insoluble fibrin.

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Author

Suchitra S Acharya, MD, MBBS Associate Professor of Pediatrics and Pediatrics in Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Program Head, Bleeding Disorders and Thrombosis Program, Cohen Children's Medical Center of New York

Suchitra S Acharya, MD, MBBS is a member of the following medical societies: American Society of Hematology, Hemophilia and Thrombosis Research Society, International Society on Thrombosis and Haemostasis, World Federation of Hemophilia

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Novonordisk, Shire <br/>Received research grant from: Bayer Pharmaceuticals .

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Cameron K Tebbi, MD Director, Children's Cancer Research Group Laboratories

Cameron K Tebbi, MD is a member of the following medical societies: International Society of Pediatric Oncology

Disclosure: Nothing to disclose.

Acknowledgements

Vinod V Balasa, MD Associate Professor of Pediatrics, Director of Hemophilia and Thrombosis Clinic, Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Louisville School of Medicine

Vinod V Balasa, MD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, Hemophilia and Thrombosis Research Society, Indian Medical Association, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Gary R Jones, MD Associate Medical Director, Clinical Development, Berlex Laboratories

Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Sections Inherited Abnormalities of Fibrinogen
Overview
Presentation
DDx
Workup
Treatment
Medication
Follow-up
References

Inherited Abnormalities of Fibrinogen Medication

Plasma sources of fibrinogen

Class Summary

Fibrinogen concentrate, human (RiaSTAP)

Fibrinogen concentrate, human (RiaSTAP)

Fibrinogen concentrate (Haemocomplettan P, Clottagen, Fibrinogen HT)

Cryoprecipitate

Cryoprecipitate

Antifibrinolytics

Class Summary

Aminocaproic acid (Amicar)

Aminocaproic acid (Amicar)

Tranexamic acid (Cyklokapron)

Tranexamic acid (Cyklokapron)

Inherited Abnormalities of Fibrinogen Medication

Plasma sources of fibrinogen

Class Summary

Fibrinogen concentrate, human (RiaSTAP)

Fibrinogen concentrate, human (RiaSTAP)

Fibrinogen concentrate (Haemocomplettan P, Clottagen, Fibrinogen HT)

Cryoprecipitate

Cryoprecipitate

Antifibrinolytics

Class Summary

Aminocaproic acid (Amicar)

Aminocaproic acid (Amicar)

Tranexamic acid (Cyklokapron)

Tranexamic acid (Cyklokapron)

References

Tables

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