Managing Inhibitors in Hemophilia Treatment: The Importance of Bypassing Agents

Bypassing Agents are a Factor option with a long history of use in treating hemophilia patients with inhibitors

By: Mike Denne

Published: Lifelines for Health, Winter 2017

Treatment of inhibitors is one of the greatest challenges in hemophilia today

Up to 33% of people with severe hemophilia A develop an inhibitor, or antibody, to treatment, while 3% to 13% of patients with moderate to mild hemophilia develop an inhibitor.1,2 (Inhibitors are less common among people with hemophilia B, affecting only 1% to 6% of individuals.1) These inhibitors stop, or block, Factor VIII (FVIII) or Factor IX (FIX) function in your blood-clotting process. Bypassing Agents offer an alternative treatment approach because they go around, or bypass, the need for FVIII or FIX.3

Bypassing Agents supplement other Factors in the blood-clotting process

This chart is a simplified visualization of Bypassing Agent activity in the blood-clotting process.

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REFERENCES:

  1. DiMichele DM. Inhibitor treatment in haemophilias A and B: inhibitor diagnosis. Haemophilia. 2006;12(suppl 6):37-42.

  2. Hay CRM. Factor VIII inhibitors in mild and moderate-severity haemophilia A. Haemophilia. 1998;4(4):558-563.

  3. DiMichele DM. World Federation of Hemophilia website. Inhibitors in hemophilia: a primer.

    http://www1.wfh.org/publication/files/pdf-1122.pdf. Published 2008. Accessed October 5, 2017.

  4. Lenting PJ, van Mourik JA, Mertens K. The life cycle of coagulation factor VIII in view of its structure and function. Blood. 1998;92(11):3983-3996.

  5. Berg JM, Tymoczko JL, Stryer L. Many enzymes are activated by specific proteolytic cleavage. In: Biochemistry.

    5th ed. New York, NY: WH Freeman; 2002. https://www.ncbi.nlm.nih.gov/books/NBK22589/. Accessed September 19, 2017.

  6. Johari V, Loke C. Brief overview of the coagulation cascade. Dis Mon. 2012;58:421-423.

  7. Retzios AD. The new and improved (?) activated factor VII molecules. Bay Clinical R&D Services. 2001:1-41.

  8. Shapiro AD, Hedner U. Advances in bypassing agent therapy for hemophilia patients with inhibitors to close care gaps and improve outcomes. Ther Adv Drug Saf. 2011;2(5):213-225.

  9. Ananyeva NM, Lee TK, Jain N, Shima M, Saenko EL. Inhibitors in hemophilia A: advances in elucidation of inhibitory mechanisms and in inhibitor management with bypassing agents. Semin Thromb Hemost. 2009;35(8):735-751.

  10. Leissinger CA. Prevention of bleeds in hemophilia patients with inhibitors: emerging data and clinical direction. Am J Hematol. 2004;77(2):187-193.

  11. Wolberg AS. Plasma and cellular contributions to fibrin network formation, structure and stability. Haemophilia. 2010;16(suppl 3):7-12.

  12. Colvin BT. Physiology of haemostasis. Vox Sang. 2004;87(suppl 1):S43-S46.

  13. Hoffman M, Monroe DM. A cell-based model of hemostasis. Thromb Haemost. 2001;85:958-965.

  14. Hoffman M, Dargaud Y. Mechanisms and monitoring of bypassing agent therapy. J Thromb Haemost. 2012;10:1478-1485.

  15. Astermark J, Donfield SM, DiMichele DM, et al. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FENOC Study. Blood. 2007;109(2):546-551.

  16. Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016;388:187-197.

  17. Hedner U. Recombinant activated factor VII: 30 years of research and innovation. Blood Rev. 2015;29(suppl1):S4-S8.

  18. Hemophilia Federation of America. Treatment of hemophilia. http://www.hemophiliafed.org/bleeding-disorders/ hemophilia/treatment/. Accessed September 20, 2017.

  19. Santagostino E, Escobar M, Ozelo M, et al. Recombinant activated factor VII in the treatment of bleeds and for the prevention of surgery-related bleeding in congenital haemophilia with inhibitors. Blood Rev. 2015;29(suppl1):S9-S18.

  20. Mehta R, Parameswaran R, Shapiro AD. An overview of the history, clinical practice concerns, comparative studies and strategies to optimize therapy of bypassing agents. Haemophilia. 2006;12(suppl 6):54-61.

  21. National Hemophilia Foundation. Medical and Scientific Advisory Council (MASAC) recommendation regarding the use of bypassing agents in patients with hemophilia A or B and inhibitors. MASAC document #167. 2006.

  22. NIH Clinical Trials Registry. Ongoing and complete clinical trials using bypassing agents in hemophilia patients with inhibitors. https://clinicaltrials.gov/ct2/results/ details?term=hemophilia+a+with+inhibitors%2C+hemophilia+b+with+inhibitors&recr=Closed&cond=hemophilia +a+with+inhibitors%2C+hemophilia+b+with+inhibitors. Accessed September 19, 2017.

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