Hemophilia

Hemofil M 

Hemophilia therapy Hemofil M is a sterile, dried, monoclonal purified preparation of human antihemophilic factor (AHF) obtained using the Method M process. Method M involves using immunoaffinity chromatography utilizing a murine monoclonal antibody to factor VIII:C to obtain AHF (factor VIII) from pooled human plasma. The risk of virus transmission is reduced by the addition of an organic solvent (tri-n-butyl phosphate) and a detergent (octoxynol 9) followed by an additional nanofiltration step.¹ 

Factor VIII/AHF is missing in patients with hemophilia A, predisposing them to bleeding, and the addition of exogenous AHF corrects the hemostatic imbalance. Hemofil M is indicated for the prevention and control of hemorrhagic events in hemophilia A. It is not indicated for patients with von Willebrand disease. Hemofil M is available in single-dose bottles that come in 250-, 500-, 1000-, and 1700-IU doses. It is administered exclusively via the intravenous route, and the dose administered is dependent on the required peak postinfusion AHF activity required.¹ The unit for peak post-AHF-infusion activity is represented as “% of normal” or “IU/dL plasma,” and this value is calculated by multiplying the dose administered per kilogram of body weight (IU/kg) by 2.² Dosages for hemorrhagic events are outlined below: 

• Early hemarthrosis, muscle bleed, or oral bleed: Begin infusion of 20 to 40 IU/kg every 12 to 24 hours for 1 to 3 days until bleeding episode (as indicated by pain) is resolved or healing is achieved
• More extensive hemarthrosis, muscle bleed, or hematoma: Repeat infusion of 30 to 60 IU/kg for 3 days or more until pain and disability are resolved
• Life-threatening bleeds such as head injury, throat bleed, or severe abdominal pain: Repeat infusion of 60 to 100 IU/kg every 8 to 24 hours until resolved

 Table 1. Recommended dosing schedule for Hemofil M prior to surgery¹ 

Type of operation	Required peak postinfusion AHF activity*	Frequency of infusion
Minor surgery, including tooth extraction	60-80	A single infusion plus oral antifibrinolytic therapy within 1 hour is sufficient in approximately 70% of cases.
Major surgery	80-100 (pre- and postoperative)	Repeat infusion every 8 to 24 hours, depending on state of healing.

*Value represented as % of normal or IU/dL plasma. 

Adverse events include hypersensitivity reactions, including anaphylaxis, and the development of neutralizing antibodies. There is also a theoretical risk of transmission of viruses and prion diseases. The safety of Hemofil M has not been established in pregnant or lactating persons. 

Get full prescribing information for Hemofil M at MPR

Koate-DVI 

Koate®-DVI is a sterile, stable, purified, dried concentrate of AHF that has been treated with tri-n-butyl phosphate and polysorbate 80 and heated in lyophilized form in the final container at 80 °C for 72 hours. It is indicated for the treatment of hemophilia A. Although Koate-DVI contains small amounts of von Willebrand factor, it is not recommended for use in treating this condition. 

The in vivo elevation in factor VIII level (% of normal) can be estimated by multiplying the dose of AHF (human) per kilogram of body weight (IU/kg) by 2% as seen in the equation below.  

Expected % factor VIII increase % of normal= # of units administered × 2%/IU/kgbody weight (kg)

The dose required can be obtained by rearranging the equation:

For mild hemorrhage, a single dose of 10 IU/kg is administered, and repeat doses may be given if there is evidence of further bleeding. For more serious bleeding episodes, factor VIII level should be raised to 30% to 50% of normal by administering 15 to 25 IU/kg, with repeated doses of 10 to 15 IU/kg every 8 to 12 hours as needed. In patients with life-threatening bleeding or possible hemorrhage involving vital structures (eg, central nervous system, retropharyngeal and retroperitoneal spaces, iliopsoas sheath), the factor VIII level should be raised to 80% to 100% of normal to achieve hemostasis, requiring an initial dose of 40 to 50 IU/kg and maintenance doses of 20 to 25 IU/kg every 8 to 12 hours. Factor VIII levels should also be raised to 100% of normal prior to surgical procedures and confirmed before commencing surgery.³ For prophylaxis, a dose of 24 to 40 IU/kg is recommended.⁴ 

Studies have not been conducted in pregnant persons or in children, however, Koate-DVI has been used in these patient populations under the supervision of experienced clinicians. 

References

1. Hemofil M. Drugs.com. Updated May 24, 2021. Accessed December 24, 2021.

2. Abildgaard CF, Simone JV, Corrigan JJ, et al. Treatment of hemophilia with glycine-precipitated factor VIII. N Engl J Med. 1966;275:471-475. doi:10.1056/NEJM196609012750904

3. Antihemophilic factor (human): Koate-DVI. Package insert. Grifols Therapeutics Inc.; 2012. Accessed December 24, 2021.

4. Nilsson IM, Berntorp E, Löfqvist T, Pettersson H. Twenty-five years’ experience of prophylactic treatment in severe haemophilia A and B. J Intern Med. 1992;232(1):25-32. doi:10.1111/j.1365-2796.1992.tb00546.x

Reviewed by Hasan Avcu, MD, on 12/26/2021.

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Kyle Habet, MD

Kyle Habet, MD, is a physician at Belize International Institute of Neuroscience where he is a member of a multidisciplinary group of healthcare professionals involved in the care of patients with an array of neurological and psychiatric diseases. He is a published author, researcher and instructor of neuroscience and clinical medicine at Washington University of Health and Science.