eMedicine Specialties > Pediatrics: General Medicine > Hematology

Inherited Abnormalities of Fibrinogen: Treatment & Medication

Author: Sara J Israels, MD, FRCPC, Professor of Pediatric Hematology/Oncology, Section Head of Pediatric Hematology/Oncology/BMT, Department of Pediatrics and Child Health, University of Manitoba
Contributor Information and Disclosures

Updated: Feb 12, 2009

Treatment

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. The usual starting dose for adults is 1-2 g intravenously administered. The pediatric dose is 30-100 mg/kg intravenously administered, depending on the severity and site of bleeding. Cryoprecipitate has been used as a source of fibrinogen; each bag of cryoprecipitate contains 100-250 mg of fibrinogen.
  • Thrombosis: Patients presenting 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.

Surgical Care

To prevent excessive bleeding during surgical procedures, prophylactic treatment to raise fibrinogen levels to 1.0-1.5 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.

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.

Medication

Plasma sources of fibrinogen

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 (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.

Adult

1-2 g IV qd; adjust dose to maintain fibrinogen levels at or above 0.5-0.8 g/L for moderate bleeding episodes; above 1.5 g/L for CNS hemorrhage or in preparation for major surgery.

Pediatric

30-100 mg/kg IV qd; adjust dose to maintain fibrinogen levels at or above 0.5-0.8 g/L for moderate bleeding episodes; above 1.5 g/L for CNS hemorrhage or in preparation for major surgery.

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause allergic reactions or antifibrinogen antibody development; may increase thrombosis risk


Cryoprecipitate

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.

Adult

1 bag per 5 kg/d IV initially, then 1 bag per 15 kg/d IV; monitor fibrinogen levels to maintain >0.5-0.8 g/L

Pediatric

Administer as in adults

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause allergic reactions or fibrinogen antibody development; may increase thrombosis risk; increases risk of transfusion-transmitted viral infection


Fibrinogen concentrate, human (RiaSTAP)

Orphan drug for replacement of absent or deficient coagulation factor in patients with congenital fibrinogen deficiency during acute bleeding episodes. 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.

Adult

Administer IV, not to exceed injection rate of 5 mL/min
Dose (mg/kg) = (Target level [mg/dL] - measured level [mg/dL]) divided by 1.7; if fibrinogen level unknown, use 70 mg/kg
Maintain target fibrinogen level of 100 mg/dL until hemostasis obtained

Pediatric

Data limited; clinical trials included 4 children <16 y
Children exhibited shorter half-life and faster clearance than adults, but limited number of children restricts statistical interpretation of these data

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects include fever and headache; monitor for signs of allergic or hypersensitivity reaction; may cause thrombotic events; as with all pooled plasma products, risk of infection exists (eg, viral, Creutzfeldt-Jakob disease)

Antifibrinolytics

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)

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

Adult

30 g/d PO/IV divided q3-6h; not to exceed 30 g/d

Pediatric

50 mg/kg PO/IV tid/qid; not to exceed 200 mg/kg/d

Coadministration with estrogens may increase levels of clotting factors, leading to hypercoagulable state

Documented hypersensitivity; evidence of active intravascular clotting process; because aminocaproic acid can be fatal in patients with disseminated intravascular coagulation (DIC), differentiating between hyperfibrinolysis and DIC is important

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not administer unless diagnosis of hyperfibrinolysis confirmed; caution in patients with a personal or family history of thrombosis; caution in cardiac, hepatic, or renal disease


Tranexamic acid (Cyklokapron)

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

Adult

25 mg/kg PO tid/qid
10 mg/kg IV tid/qid in patients unable to take PO

Pediatric

Administer as in adults

Limited data available; none reported

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment; caution in patients with a personal or family history of thrombosis

More on Inherited Abnormalities of Fibrinogen

Overview: Inherited Abnormalities of Fibrinogen
Differential Diagnoses & Workup: Inherited Abnormalities of Fibrinogen
Treatment & Medication: Inherited Abnormalities of Fibrinogen
Follow-up: Inherited Abnormalities of Fibrinogen
Multimedia: Inherited Abnormalities of Fibrinogen
References
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References

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

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

  3. 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. Sep 2004;10(5):593-628. [Medline].

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

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

  6. 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. Nov 2000;6(6):705-8. [Medline].

  7. Peyvandi F, Haertel S, Knaub S, Mannucci PM. Incidence of bleeding symptoms in 100 patients with inherited afibrinogenemia or hypofibrinogenemia. J Thromb Haemost. Jul 2006;4(7):1634-7. [Medline].

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

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Further Reading

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Keywords

afibrinogenemia, congenital afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, congenital dysfibrinogenemia, fibrinogen deficiency, fibrinogen abnormalities, clotting disorder, blood disorder, inherited abnormalities of fibrinogen, defective fibrinogen synthesis, venous thrombosis, factor XIII deficiency

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Contributor Information and Disclosures

Author

Sara J Israels, MD, FRCPC, Professor of Pediatric Hematology/Oncology, Section Head of Pediatric Hematology/Oncology/BMT, Department of Pediatrics and Child Health, University of Manitoba
Sara J Israels, MD, FRCPC is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, Canadian Medical Association, Children's Oncology Group, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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; Assistant Clinical Professor, Department of Pediatrics, Creighton University; 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 Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Executive Director, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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