eMedicine Specialties > Emergency Medicine > Hematology & Oncology

Hemophilia, Type A: 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

  • Rapid transport to definitive care is the mainstay of prehospital care.
  • Prehospital care 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.
  • Include a diagnostic workup for hemorrhage.
  • If possible, draw blood for the studies listed above, 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 VIII is the treatment of choice for acute or potential hemorrhage. Recombinant factor VIII concentrate is the preferred source of factor VIII. The factor VIII activity level should be corrected to 100% of normal for potentially serious hemorrhage (eg, CNS, trauma related, GI, genitourinary [GU], epistaxis) and to 30-50% of normal for minor hemorrhage (eg, hemarthrosis, oral mucosal, muscular). One unit of factor VIII is the amount of factor VIII in 1 mL of plasma (1 U/mL or 1%). The volume of distribution of factor VIII is that of plasma, approximately 50 mL/kg. The difference between the desired factor VIII activity level and the patient's native factor VIII activity level can be calculated by simple subtraction and expressed as a fraction (eg, 100% - 5% = 95% or 0.95).

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

Units factor VIII=(weight in kg)(50 mL plasma/kg)(1 U factor VIII/mL plasma)(desired factor VIII level minus the native factor VIII level)

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

Units factor VIII = (80 kg)(50 mL/kg)(1 U factor VIII/mL)(.99) = 3960

The next dose should be administered 12 hours after the initial dose and is one half the initial calculated dose. Minor hemorrhage requires 1-3 doses of factor VIII. Major hemorrhage requires many doses and continued factor VIII activity monitoring with the goal of keeping the trough activity level at least 50%. Continuous infusions of factor VIII may be considered for major hemorrhage.

The specific factor product which patients use is often part of their individualized treatment plan.  Patient's will usually be well educated on their dosing/products.  This information also can be found on institutional treatment center/blood bank data bases.

Prophylactic administration of factor VIII is often recommended for pediatric patients with severe disease.

Other medicinal adjuncts to factor VIII (eg, DDAVP, antifibrinolytics) often are useful in achieving hemostasis and can lessen the need for factor VIII infusion.

Factor VIII 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 VIII pooled plasma (ultrapure preparations recommended)

Pooled plasma product (high purity).

Adult

U factor VIII=(weight in kg)(50 mL plasma/kg)(1 U factor VIII/mL plasma)(desired factor VIII level minus native factor VIII level); administer IV

Pediatric

Administer as in adults

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Viral contamination and infections are remotely possible but unlikely due to prescreening; ineffective in patients with factor VIII inhibitors; can induce an anamnestic response


Factor VIII recombinant products

Synthetic products; the most commonly used treatment when administration of factor is indicated.

Adult

U factor VIII=(weight in kg)(50 mL plasma/kg)(1 U factor VIII/mL plasma)(desired factor VIII level minus native factor VIII level); administer IV

Pediatric

Administer as in adults

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Ineffective in patients with factor VIII inhibitors; can induce an anamnestic response


Fresh frozen plasma (FFP)

Blood product.

Adult

U factor VIII=(weight in kg)(50 mL plasma/kg)(1 U factor VIII/mL plasma)(desired factor VIII level minus native factor VIII level); administer 1 mL FFP/U factor VIII needed; administer IV

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

Antifibrinolytics

These agents are used in addition to factor VIII 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
Alternatively, consider 10 g slow IV (over 2 h), followed by 1 g/h continuous infusion

Pediatric

Infants: Not indicated
Children: Not established

Estrogens may increase clotting factors, leading to hypercoagulable state

Documented hypersensitivity; active intravascular clotting process; ventricular arrhythmias; hypotension; hypokalemia

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Do not administer unless definite diagnosis of hyperfibrinolysis has been made; caution in cardiac, hepatic, or renal disease

Antihemophilic Agent

These agents raise plasma levels of factor VIII.


1-deamino-8-D-arginine vasopressin (desmopressin acetate, DDAVP)

Causes transient increase (up to 4-fold) in factor VIII plasma levels of those patients with mild disease but useful in patients with minor hemorrhage episodes only. Ineffective after several doses and may be useful in patients with factor VIII inhibitors.

Adult

0.3 mcg/kg in 30-50 mL 0.9% isotonic saline IV over 15-20 min, peak effect 30-60 min
150 mcg intranasal (1 metered dose) for weight 50 kg, peak effect 60-90 min

Pediatric

<3 months: Not indicated
3 months to 12 years: 5-30 mcg/d intranasal qd or divided bid
>12 years: Administer as in adults

Demeclocycline and lithium decrease effects; fludrocortisone and chlorpropamide increase effects

Documented hypersensitivity; platelet-type von Willebrand disease

Pregnancy

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

Precautions

Avoid overhydration when being used for its hemostatic effects, may result in hyponatremia; critical hyponatremia with seizures secondary to water intoxication has been reported, particularly in the very young; use extreme caution when administering to children

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

More on Hemophilia, Type A

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

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

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

  4. Brettler DB, Levine PH. Clinical manifestations and therapy of inherited coagulation factor deficiencies. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd ed. 1994:169-83.

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

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

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

  8. Luck JV, Silva M, Rodriguez-Merchan EC, et al. Hemophilic arthropathy. J Am Acad Orthop Surg. Jul-Aug 2004;12(4):234-45. [Medline].

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

  10. Manco-Johnson M. Hemophilia management: optimizing treatment based on patient needs. Curr Opin Pediatr. Feb 2005;17(1):3-6. [Medline].

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

  12. 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.

  13. 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.

  14. Mudad R, Kane WH. DDAVP in acquired hemophilia A: case report and review of the literature. Am J Hematol. Aug 1993;43(4):295-9. [Medline].

  15. Schneiderman J, Nugent DJ, Young G. Sequential therapy with activated prothrombin complex concentrate and recombinant factor VIIa in patients with severe haemophilia and inhibitors. Haemophilia. Jul 2004;10(4):347-51. [Medline].

  16. 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].

  17. von Depka M. Immune tolerance therapy in patients with acquired hemophilia. Hematology. Aug 2004;9(4):245-57. [Medline].

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Further Reading

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Keywords

hemophilia type A, hemophilia A, deficiency of functional plasma coagulation factor VIII, factor VIII deficiency, dysfunctional factor VIII, factor VIII inhibitors, disruption of the normal intrinsic coagulation cascade

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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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