Seminars in Hematology
Volume 45 , Pages S38-S41 , April 2008

Single-Dose Recombinant Activated Factor VII Therapy in Hemophilia Patients With Inhibitors

  • Gili Kenet

      Affiliations

    • Corresponding Author InformationAddress correspondence to Gili Kenet, MD, Director, Thrombosis Unit, The Israeli National Hemophilia Center, Sheba Medical Center, Tel-Hashomer, 52621, Israel.
    • ,
  • Uri Martinowitz

References 

  1. Santagostino E, Mancuso ME, Rocino A, Mancuso G, Mazzucconi MG, Tagliaferri A, et al. Environmental risk factors for inhibitor development in children with haemophilia A: A case-control study. Br J Haematol. 2005;130:422–427
  2. White GC, Kempton CL, Grimsley A, Nielsen B, Roberts HR. Cellular immune responses in hemophilia: Why do inhibitors develop in some, but not all hemophiliacs?. J Thromb Haemost. 2005;3:1676–1681
  3. Lusher JM. Inhibitor antibodies to factor VIII and factor IX: Management. Semin Thromb Hemost. 2000;26:179–188
  4. Erhardtsen E. Pharmacokinetics of recombinant activated factor VII (rFVIIa). Semin Thromb Hemost. 2000;26:385–391
  5. Key NS, Aledort LM, Beardsley D, Cooper HA, Davignon G, Ewenstein BM, et al. Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors. Thromb Haemost. 1998;80:912–918
  6. Ingerslev J, Thykjaer H, Kudsk Jensen O, Fredberg U. Home treatment with recombinant activated factor VII: Results from one centre. Blood Coagul Fibrinolysis. 1998;9(suppl 1):S107–S110
  7. Proulle V, Hugel B, Guillet B, Trichet C, Rafowicz A, Lambert T, et al. Injection of recombinant activated factor VII can induce transient increase in circulating procoagulant microparticles. Thromb Haemost. 2004;91:873–878
  8. Carr ME, Martin EJ, Kuhn JG, Seremetis SV. Effects of recombinant factor VIIa on platelet function and clot structure in blood with deficient prothrombin conversion. Thromb Haemost. 2003;89:803–811
  9. He S, Ekman GJ, Hedner U. The effect of platelets on fibrin gel structure formed in the presence of recombinant factor VIIa in hemophilia plasma and in plasma from a patient with Glanzmann thrombasthenia. J Thromb Haemost. 2005;3:272–279
  10. Erhardtsen E, Nony P, Dechavanne M, Ffrench P, Boissel JP, Hedner U. The effect of recombinant factor VIIa (NovoSeven) in healthy volunteers receiving acenocoumarol to an international normalized ratio above 2.0. Blood Coagul Fibrinolysis. 1998;9:741–748
  11. Sumner WT, Monroe DM, Hoffman M. Variability in platelet procoagulant activity in healthy volunteers. Thromb Res. 1996;81:533–543
  12. Schulman S, d'Oiron R, Martinowitz U, Pasi J, Briquel ME, Mauser-Bunschoten E, et al. Experiences with continuous infusion of recombinant activated factor VII. Blood Coagul Fibrinolysis. 1998;9(suppl 1):S97–S101
  13. Villar A, Aronis S, Morfini M, Santagostino E, Auerswald G, Thomsen HF, et al. Pharmacokinetics of activated recombinant coagulation factor VII (NovoSeven) in children vs. adults with haemophilia A. Haemophilia. 2004;10:352–359
  14. Abshire TC. Dose optimization of recombinant factor VIIa for control of mild to moderate bleeds in inhibitor patients: Improved efficacy with higher dosing. Semin Hematol. 2004;41(suppl 1):3–7
  15. Kenet G, Lubetsky A, Luboshitz J, Martinowitz U. A new approach to treatment of bleeding episodes in young hemophilia patients: A single bolus megadose of recombinant activated factor VII (NovoSeven). J Thromb Haemost. 2003;1:450–455
  16. Cooper HA, Jones CP, Campion E, Roberts HR, Hedner U. Rationale for the use of high dose rFVIIa in a high-titre inhibitor patient with haemophilia B during major orthopaedic procedures. Haemophilia. 2001;7:517–522
  17. Kenet G, Lubetsky A, Luboshitz J, Ravid B, Tamarin I, Martinowitz U. High dose recombinant activated factor VII for treatment of patients with haemophilia and inhibitors. Haemophilia. 2004;10:53–66(abstr)
  18. Parameswaran R, Shapiro AD, Gill JC, Kessler CM HTRS Registry Investigators. Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with inhibitors: Analysis from the Hemophilia and Thrombosis Research Society Registry. Haemophilia. 2005;11:100–106
  19. Kavakli K, Makris M, Zulfikar B, Erhardtsen E, Abrams ZS, Kenet G, et al. Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors (A multi-centre, randomised, double-blind, cross-over trial). Thromb Haemost. 2006;95:600–605
  20. Santagostino E, Mancuso ME, Rocino A, Mancuso G, Scaraggi F, Mannucci PM. A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of haemarthroses in hemophiliacs with inhibitors. J Thromb Haemost. 2006;4:367–371
  21. Young G, Shafer FE, Rojas P, Seremetis S. Single 270 μg/kg-dose rFVIIa versus standard 90 μg/kg-dose rFVIIa and APCC for home treatment of joint bleeds in haemophilia patients with inhibitors: A randomised comparison. Haemophilia. 2008;14:287–294
  22. Abshire T, Kenet G. Recombinant factor VIIa: Review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors. J Thromb Haemost. 2004;2:899–909
  23. Aledort LM. Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity. J Thromb Haemost. 2004;2:1700–1708
  24. O'Connell KA, Wood JJ, Wise RP, Lozier JN, Braun MM. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA. 2006;295:293–298
  25. Konkle BA, Ebbesen LS, Erhardtsen E, Bianco RP, Lissitchkov T, Rusen L, et al. Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors. J Thromb Haemost. 2007;5:1904–1913

 STATEMENT OF CONFLICT OF INTEREST: Both authors have received honoraria from, and served on advisory boards for, Novo Nordisk.

PII: S0037-1963(08)00051-6

doi: 10.1053/j.seminhematol.2008.03.011

Seminars in Hematology
Volume 45 , Pages S38-S41 , April 2008

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