eMedicine Specialties > Emergency Medicine > Hematology & Oncology

Hemophilia, Type B: Treatment & Medication

Author: Brendan R Furlong, MD, Clinical Chief, Department of Emergency Medicine, Georgetown University Hospital
Coauthor(s): Mary A Furlong, MD, Associate Professor and Program/Residency Director, Department of Pathology, Georgetown University School of Medicine
Contributor Information and Disclosures

Updated: Oct 6, 2008

Treatment

Prehospital Care

  • Prehospital providers should address the ABCs while rapidly transporting the patient to a definitive care facility.
  • In the prehospital setting, providers should do the following:
    • Apply aggressive hemostatic techniques.
    • Assist patients capable of self-administered factor therapy.
    • Gather focused historical data if the patient is unable to communicate.

Emergency Department Care

  • Use aggressive hemostatic techniques.
  • Correct coagulopathy immediately. Never delay indicated coagulation correction pending diagnostic testing. However, in cases of previously undiagnosed coagulopathy, collecting blood specimens prior to treatment is important.
  • Perform a diagnostic workup for hemorrhage.
  • If possible, draw blood for the studies listed in Lab Studies, including 2 blue top tubes to be spun and frozen for factor and inhibitor assays.

Consultations

  • Hematologist/blood bank/pathologist
  • Others as indicated by hemorrhagic complications

Medication

Factor IX is the treatment of choice for acute hemorrhage or presumed acute hemorrhage. Recombinant factor IX is the preferred source for replacement therapy. The factor IX activity level should be corrected to 100% of normal for potentially serious hemorrhage (eg, CNS, trauma related, GI, GU, epistaxis) and to 30-50% of normal for minor hemorrhage (eg, hemarthrosis, oral mucosal, muscular). One unit of factor IX is the amount of factor IX in 1 mL of plasma (1 U/mL or 1%). The volume of distribution of factor IX is approximately 100 mL/kg. The difference between the desired factor IX activity level and the patient's native factor IX activity level can be calculated by simple subtraction and expressed as a fraction.

100% - 5% = 95% or 0.95

To find the number of units of factor IX needed to correct the factor IX activity level, use the following:

Units factor IX = (weight in kg)(100 mL/kg)(1 U factor IX/mL)(desired factor IX level minus the native factor IX level)

As an example, an 80-kg person with hemophilia with known 1% factor IX activity level presents to the ED with a serious upper GI bleed. The correct dose of factor IX to administer to the patient would be calculated as follows:

Units factor IX = (80 kg)(100 mL/kg)(1 U factor IX/mL)(.99) = 7920

The next dose should be administered 24 hours after the first and is one half of the initial calculated dose. Minor hemorrhage requires 1-3 doses of factor IX. Major hemorrhage requires many doses and continued factor IX activity monitoring with the goal of keeping the trough activity level at least 50%. Continuous infusions of factor IX may be considered for major hemorrhage.

Factor Ix-containing Products

These agents are used to correct the patient's native deficiency, with the goals of achieving a normal hematologic response to hemorrhage or preventing hemorrhage.


Factor IX recombinant product

Synthetic factor IX. Recombinant product using no human products for stabilization.

Adult

Units factor IX =(weight in kg)(100 mL/kg)(1 U factor IX/mL)(desired factor IX level minus the native factor IX level)

Pediatric

Administer as in adults

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Theoretically no risk for infectious viral transmission; ineffective in patients with high-titer factor IX inhibitors; may induce anamnestic response


Coagulation factor IX concentrates

Pooled plasma product (high purity).

Adult

Units factor IX = (weight in kg)(100 mL/kg)(1 U factor IX/mL)(desired factor IX level minus the native factor IX level)

Pediatric

Administer as in adults

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Viral contamination and infection are remotely possible but unlikely due to prescreening; ineffective in patients with high-titer factor IX inhibitors; can induce an anamnestic response


Factor IX complex concentrates

This pooled plasma product (relatively low purity containing factors II, X, VII) is one treatment option for factor VIII inhibitors.

Adult

U factor IX = (weight in kg)(100 mL/kg)(1 U factor IX/mL)(desired factor IX level minus the native factor IX level)

Pediatric

Administer as in adults

Documented hypersensitivity; ongoing thrombosis (DIC)

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Viral contamination and infection are remotely possible but unlikely due to prescreening; may induce anamnestic response


Fresh frozen plasma (FFP)

Blood product.

Adult

Units factor IX =(weight in kg)(100 mL/kg)(1 U factor IX/mL)(desired factor IX level minus the native factor IX level); 1 mL FFP/U factor IX required

Pediatric

Administer as in adults

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Viral contamination and infection are remotely possible but unlikely due to prescreening; ineffective in patients with factor IX inhibitors; may induce an anamnestic response

Coagulation Factor VIIa (Recombinant)

These agents can activate coagulation factor X to factor Xa as well as coagulation factor IX to IXa.


Coagulation Factor VIIa (Recombinant)1

Recombinant factor VIIa, when complexed with tissue factor, can activate coagulation factor X to factor Xa as well as coagulation factor IX to IXa. Factor Xa in complex with other factors then converts prothrombin to thrombin, which leads to the formation of a hemostatic plug by converting fibrinogen to fibrin and thereby inducing local hemostasis. This process may also occur on the surface of activated platelets.

Adult

Bleeding episodes for patients with hemophilia A or B with inhibitors: 90 mcg/kg IV q2h until hemostasis achieved or until treatment judged to be inadequate; interval and duration of further doses are based on specific clinical scenario

Surgical or invasive procedures in patients with hemophilia A or B with inhibitors: 90 mcg/kg IV bolus infusion q2h for duration of procedure and for days thereafter; interval and duration of further doses are based on specific clinical scenario

Pediatric

Administer as in adults

Documented hypersensitivity to product, mouse, hamster, or bovine proteins

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Patients should be monitored for clinical signs and symptoms of inappropriate thrombosis; avoid simultaneous use of activated prothrombin complex or prothrombin complex concentrates (although specific drug interaction was not studied in a clinical trail, there have been more than 50 episodes of concomitant use of antifibrinolytic therapies and recombinant coagulation factor VIIa

Antifibrinolytics

These agents are used in addition to factor IX replacement for oral mucosal hemorrhage and prophylaxis, as the oral mucosa is rich in native fibrinolytic activity.


Epsilon aminocaproic acid (Amicar)

Lysine analog that binds to natively produced plasmin, reducing its fibrinolytic activity.

Adult

200 mg/kg PO/IV initial dose followed by 100 mg/kg q6h; not to exceed 5 g

Pediatric

Newborns: Not indicated
Children: Not established

Estrogens may cause increase in clotting factors leading to hypercoagulable state

Documented hypersensitivity; intravascular clotting; complex concentrates; ventricular arrhythmias; hypotension; hypokalemia

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

Not for use in patients with ventricular arrhythmias, hypotension, or hypokalemia

More on Hemophilia, Type B

Overview: Hemophilia, Type B
Differential Diagnoses & Workup: Hemophilia, Type B
Treatment & Medication: Hemophilia, Type B
Follow-up: Hemophilia, Type B
References
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References

  1. Coagulation Factor VII a (Recombinant) [package insert]. Denmark: Novo Nordisk; 2006. [Full Text].

  2. Adamson S, Charlebois T, O'Connell B, Foster W. Viral safety of recombinant factor IX. Semin Hematol. Apr 1998;35(2 Suppl 2):22-7. [Medline].

  3. Bell B, Canty D, Audet M. Hemophilia: an updated review. Pediatr Rev. Aug 1995;16(8):290-8. [Medline].

  4. Bolan CD, Alving BM. Pharmacologic agents in the management of bleeding disorders. Transfusion. Jul-Aug 1990;30(6):541-51. [Medline].

  5. Brettler DB, Levine PH. Clinical manifestations and therapy of inherited coagulation factor deficiencies. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice, Third Edition. 1994:169-83.

  6. Brinkhous KM, Sigman JL, Read MS, et al. Recombinant human factor IX: replacement therapy, prophylaxis, and pharmacokinetics in canine hemophilia B. Blood. Oct 1 1996;88(7):2603-10. [Medline].

  7. DiMichele D, Neufeld EJ. Hemophilia. A new approach to an old disease. Hematol Oncol Clin North Am. Dec 1998;12(6):1315-44. [Medline].

  8. Dunn AL, Abshire TC. Recent advances in the management of the child who has hemophilia. Hematol Oncol Clin North Am. Dec 2004;18(6):1249-76, viii. [Medline].

  9. Furie B, Limentani SA, Rosenfield CG. A practical guide to the evaluation and treatment of hemophilia. Blood. Jul 1 1994;84(1):3-9. [Medline].

  10. Goldsmith JC. Hemophilia: Current Medical Management. The National Hemophilia Foundation; 1994:1-30.

  11. Ludlam CA. Treatment of haemophilia. Br J Haematol. May 1998;101 Suppl 1:13-4. [Medline].

  12. Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Found. Recommendations concerning prophylaxis. Medical Bulletin #193. 1994;1-3.

  13. Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Found. Recommendations regarding the use of recombinant factor VIII in the treatment of hemophilia A. Medical Bulletin # 232. 1995;1-2.

  14. Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Found. Revised recommendations regarding hepatitis A vaccination in individuals with hemophilia and other congenital bleeding disorders. Medical Advisory # 277. 1997;1-2.

  15. Soucie JM, Evatt B, Jackson D. Occurrence of hemophilia in the United States. The Hemophilia Surveillance System Project Investigators. Am J Hematol. Dec 1998;59(4):288-94. [Medline].

  16. Thompson A. Recombinant factor IX for the treatment of hemophilia B. Introduction. Semin Hematol. Apr 1998;35(2 Suppl 2):1-3. [Medline].

  17. White G, Shapiro A, Ragni M. Clinical evaluation of recombinant factor IX. Semin Hematol. Apr 1998;35(2 Suppl 2):33-8. [Medline].

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Further Reading

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Keywords

hemophilia type B, hemophilia type B, blood disorder, deficiency of factor IX, factor IX deficiency, dysfunctional factor IX, factor IX inhibitors, hemorrhage, bleeding, bleeding disorder, factor IX activity, plasma coagulation

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Contributor Information and Disclosures

Author

Brendan R Furlong, MD, Clinical Chief, Department of Emergency Medicine, Georgetown University Hospital
Brendan R Furlong, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Mary A Furlong, MD, Associate Professor and Program/Residency Director, Department of Pathology, Georgetown University School of Medicine
Mary A Furlong, MD is a member of the following medical societies: United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Medical Editor

William G Gossman, MD, Associate Clinical Professor of Emergency Medicine, Creighton University School of Medicine; Consulting Staff, Department of Emergency Medicine, Creighton University Medical Center
William G Gossman, MD is a member of the following medical societies: American Academy of Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center
Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Steven C Dronen, MD, FAAEM, Director of Emergency Services, Director of Chest Pain Center, Department of Emergency Medicine, Ft Sanders Sevier Medical Center
Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

 
 
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