Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Inherited Abnormalities of Fibrinogen Treatment & Management

  • Author: Suchitra S Acharya, MBBS, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
 
Updated: Aug 15, 2016
 

Approach Considerations

A study by Nagler et al looking at the long-term clinical course and laboratory data associated with four patients with congenital afibrinogenemia indicated that regular fibrinogen replacement or orthotopic liver transplantation can produce long-term remission. Arterial thrombi were found to have resolved after 6-12 months in the two patients who underwent such treatment, while the two who received infrequent fibrinogen replacement had recurrent thromboembolic events.[18]

Next

Medical Care

Hemorrhage

For patients with clinical bleeding associated with afibrinogenemia or dysfibrinogenemia, replacement of fibrinogen to a level of more than 0.8 g/L is usually adequate to maintain hemostasis, although levels greater than 1 g/L have been recommended for CNS hemorrhage. Plasma-derived fibrinogen concentrates have the advantage of virus inactivation. Plasma recovery of fibrinogen with the use of fibrinogen concentrate is 1.8 mg/mL per mg/kg infused. Replacement with 70 mg/kg is recommended prior to surgical procedures and severe bleeding episodes, and 40 mg/kg for mild to moderate bleeding.

The half-life of fibrinogen is approximately 3.5 days, and afibrinogenemic patients can usually be managed postoperatively with infusion of replacement therapy every 2-3 days for major surgery.

Children have more rapid plasma fibrinogen clearance and may require higher and more frequent dosing for surgery and major bleeding. The therapeutic goal is to achieve a plasma fibrinogen activity level of 100-150 mg dL-1 prior to surgery that is maintained until hemostasis is achieved and wound healing is complete.[19]

Cryoprecipitate has been used as a source of fibrinogen; each bag of cryoprecipitate contains 100-250 mg of fibrinogen. The guidelines for dysfibrinogenemia are not standardized due to a lack of sufficient data in bleed management.

Fibrinogen dosage calculation [11]

Dose (g) = desired increment in g/L x plasma volume (plasma volume is 0.07 x (1-hematocrit) x weight (kg)

The patient's personal and family history of bleeding and thrombosis should be taken into consideration for appropriate dosing of replacement therapy. In addition, the pharmacokinetics of fibrinogen after replacement therapy widely varies, and individual dose adjustment is recommended.

Thrombosis

Patients who present with thrombosis associated with dysfibrinogenemia should receive anticoagulation therapy. The duration of therapy has not been established for this particular group of patients; the decision depends on the clinical situation and the presence of other contributing factors. If the patient has had multiple thromboembolic events, a single life-threatening event, or has additional inherited risk factors, protracted anticoagulation therapy is recommended.

Spontaneous abortion

Recurrent spontaneous abortion may be prevented by routine prophylaxis with fibrinogen concentrates starting early in pregnancy.

Acquired inhibitors

Acquired inhibitors have been reported after replacement therapy and should be considered in previously treated patients who demonstrate poor hemostasis with usual therapies.

Previous
Next

Surgical Care

To prevent excessive bleeding during surgical procedures, prophylactic treatment to raise fibrinogen levels to 1-1.5 g/L during the procedure is recommended. Replacement should be continued for 4-14 days following surgery, depending on the nature of the surgical procedure and time to complete healing.

Previous
Next

Consultations

Consultation with a hematologist/hemostasis specialist is advisable for patients who require fibrinogen replacement therapy. Genetic counseling and family studies should be part of a complete evaluation.

Previous
 
 
Contributor Information and Disclosures
Author

Suchitra S Acharya, MBBS, MD Program Head, Bleeding Disorders and Thrombosis Program, Cohen Children's Medical Center of New York; Associate Professor of Pediatrics and Pediatrics in Medicine, Hofstra North Shore-LIJ School of Medicine at Hofstra University

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

Disclosure: Nothing to disclose.

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

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

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.

References
  1. 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. [Medline].

  2. Roberts HR, Stinchcombe TE, Gabriel DA. The dysfibrinogenaemias. Br J Haematol. 2001 Aug. 114(2):249-57. [Medline].

  3. Asselta R, Duga S, Tenchini ML. The molecular basis of quantitative fibrinogen disorders. J Thromb Haemost. 2006 Oct. 4(10):2115-29. [Medline].

  4. 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. [Medline].

  5. 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. [Medline].

  6. 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. [Medline].

  7. 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. [Medline].

  8. 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].

  9. 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. [Medline].

  10. 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. [Medline].

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

  12. 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. [Medline].

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

  14. Verhovsek M, Moffat KA, Hayward CP. Laboratory testing for fibrinogen abnormalities. Am J Hematol. 2008 Dec. 83(12):928-31. [Medline].

  15. 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. [Medline].

  16. Cunningham MT, Brandt JT, Laposata M, Olson JD. Laboratory diagnosis of dysfibrinogenemia. Arch Pathol Lab Med. 2002. 126:499-505. [Medline].

  17. Peyvandi F, Cattaneo M, Inbal A, De Moerloose P, Spreafico M. Rare bleeding disorders. Haemophilia. 2008 Jul. 14 Suppl 3:202-10. [Medline].

  18. 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 Jul 7. 116 (4):[Medline].

  19. 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. [Medline].

 
Previous
Next
 
The conversion of soluble fibrinogen to insoluble fibrin.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.