Semin Thromb Hemost 2009; 35(8): 814-819
DOI: 10.1055/s-0029-1245114
© Thieme Medical Publishers

Prophylaxis in Congenital Hemophilia with Inhibitors: The Role of Recombinant Activated Factor VII

Massimo Franchini1 , Franco Manzato2 , Gian Luca Salvagno3 , Martina Montagnana3 , Marco Zaffanello4 , Giuseppe Lippi5
  • 1Servizio di Immunoematologia e Medicina Trasfusionale, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Parma
  • 2Laboratorio di Patologia Clinica, Ospedale “Carlo Poma”, Mantova
  • 3Sezione di Chimica Clinica, Dipartimento di Scienze Biomediche e Morfologiche, Università di Verona, Verona
  • 4Dipartimento Materno-Infantile e di Biologia Genetica; Verona
  • 5Unità Operativa di Diagnostica Ematochimica, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Parma; Italy
Further Information

Publication History

Publication Date:
18 February 2010 (online)

ABSTRACT

The development of inhibitors against therapeutically administered factors VIII or IX is actually the most challenging complication of hemophilia patients with inhibitors. The introduction of bypassing agents (i.e., activated prothrombin complex concentrates and recombinant activated factor VII [rFVIIa]) has dramatically improved the management of bleeding episodes in such patients. Over the last decade, there have been increasing reports on the ability of bypassing agents to prevent surgical, joint, or other bleeds in inhibitor patients. The published data on the use of rFVIIa as a prophylactic treatment in hemophilia patients with inhibitors are reviewed in this article.

REFERENCES

  • 1 Haya S, Moret A, Cid A R et al.. Inhibitors in haemophilia A: current management and open issues.  Haemophilia. 2007;  13(Suppl 5) 52-60
  • 2 Wight J, Paisley S. The epidemiology of inhibitors in haemophilia A: a systematic review.  Haemophilia. 2003;  9(4) 418-435
  • 3 Lee C A, Lillicrap D, Astermark J. Inhibitor development in hemophiliacs: the roles of genetic versus environmental factors.  Semin Thromb Hemost. 2006;  32(Suppl 2) 10-14
  • 4 DiMichele D M, Hoots W K, Pipe S W, Rivard G E, Santagostino E. International workshop on immune tolerance induction: consensus recommendations.  Haemophilia. 2007;  (13 Suppl 1) 1-22
  • 5 DiMichele D M, Kroner B L. North American Immune Tolerance Study Group . The North American Immune Tolerance Registry: practices, outcomes, outcome predictors.  Thromb Haemost. 2002;  87(1) 52-57
  • 6 Franchini M, Zaffanello M, Veneri D. Recombinant factor VIIa. An update on its clinical use.  Thromb Haemost. 2005;  93(6) 1027-1035
  • 7 Lloyd Jones M, Wight J, Paisley S, Knight C. Control of bleeding in patients with haemophilia A with inhibitors: a systematic review.  Haemophilia. 2003;  9(4) 464-520
  • 8 Hedner U. Treatment of patients with factor VIII and factor IX inhibitors with special focus on the use of recombinant factor VIIa.  Thromb Haemost. 1999;  82(2) 531-539
  • 9 Leissinger C A. Prophylaxis in haemophilia patients with inhibitors.  Haemophilia. 2006;  12(Suppl 6) 67-73
  • 10 Hedner U, Erhardtsen E. Potential role for rFVIIa in transfusion medicine.  Transfusion. 2002;  42(1) 114-124
  • 11 Hedner U, Glazer S, Pinkel K et al.. Successful use of rFVIIa in a patient with severe haemophilia A during synovectomy.  Lancet. 1988;  2 1193
  • 12 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(6) 899-909
  • 13 Shapiro A D, Gilchrist G S, Hoots W K, Cooper H A, Gastineau D A. Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in haemophilia patients with inhibitors undergoing surgery.  Thromb Haemost. 1998;  80(5) 773-778
  • 14 Lusher J, Ingerslev J, Roberts H, Hedner U. Clinical experience with recombinant factor VIIa.  Blood Coagul Fibrinolysis. 1998;  9(2) 119-128
  • 15 Scharrer I. Recombinant factor VIIa for patients with inhibitors to factor VIII or IX or factor VII deficiency.  Haemophilia. 1999;  5(4) 253-259
  • 16 Ingerslev J, Freidman D, Gastineau D et al.. Major surgery in haemophilic patients with inhibitors using recombinant factor VIIa.  Haemostasis. 1996;  26(Suppl 1) 118-123
  • 17 DiMichele D. The use of recombinant factor VIIa (Novoseven) for central catheter insertion: an international experience.  Thromb Haemost. 1997;  22(suppl) 167-172
  • 18 Ingerslev J. Efficacy and safety of recombinant factor VIIa in the prophylaxis of bleeding in various surgical procedures in hemophilic patients with factor VIII and factor IX inhibitors.  Semin Thromb Hemost. 2000;  26(4) 425-432
  • 19 Santagostino E, Morfini M, Rocino A, Baudo F, Scaraggi F A, Gringeri A. Relationship between factor VII activity and clinical efficacy of recombinant factor VIIa given by continuous infusion to patients with factor VIII inhibitors.  Thromb Haemost. 2001;  86(4) 954-958
  • 20 Smith M P, Ludlam C A, Collins P W et al.. Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII: plasma factor VII activity of 10 IU/ml is associated with an increased incidence of bleeding.  Thromb Haemost. 2001;  86(4) 949-953
  • 21 Ludlam C A, Smith M P, Morfini M, Gringeri A, Santagostino E, Savidge G F. A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: a pharmacokinetic and efficacy evaluation.  Br J Haematol. 2003;  120(5) 808-813
  • 22 Pruthi R K, Mathew P, Valentino L A et al.. Haemostatic efficacy and safety of bolus and continuous infusion of recombinant factor VIIa are comparable in haemophilia patients with inhibitors undergoing major surgery. Results from an open-label, randomized, multicenter trial.  Thromb Haemost. 2007;  98(4) 726-732
  • 23 Laurian Y D, Tagariello G, Jimenez-Yuste V et al.. Primary knee arthroplasty using recombinant factor VIIa (rFVIIa) as first-line therapy in haemophilia patients with high responding inhibitors.  J Thromb Haemost. 2007;  5(Suppl 2) , Abstract PM140
  • 24 Rodriguez-Merchan E C, Hedner U, Heijnen L et al.. Prevention of haemophilic arthropathy during childhood. May common orthopaedic management be extrapolated from patients without inhibitors to patients with inhibitors?.  Haemophilia. 2008;  14(Suppl 6) 68-81
  • 25 Fischer K, Valentino L, Ljung R, Blanchette V. Prophylaxis for severe haemophilia: clinical challenges in the absence as well as in the presence of inhibitors.  Haemophilia. 2008;  14(Suppl 3) 196-201
  • 26 Goldstein B, Geldziler B, Bjerre J, Seremetis S. Evidence-based use of recombinant FVIIa (NovoSeven, NiaStase) for the treatment of hemophilia with inhibitors in children and adolescents.  Transfus Apher Sci. 2008;  38 25-32
  • 27 Hedner U. Prevention of arthropathy: may it be extrapolated from patients without inhibitors to patients with inhibitors?.  Haemophilia. 2008;  14(Suppl 6) 23-27
  • 28 Brackmann H H, Effenberger E, Hess L, Schwaab R, Oldenburg J. NovoSeven in immune tolerance therapy.  Blood Coagul Fibrinolysis. 2000;  11(11 Suppl 1) S39-44
  • 29 Saxon B R, Shanks D, Jory C B, Williams V. Effective prophylaxis with daily recombinant factor VIIa (rFVIIa-Novoseven) in a child with high titre inhibitors and a target joint.  Thromb Haemost. 2001;  86 1126-1127
  • 30 Cooper H A, Jones C P, Campion E, Roberts H R, 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(5) 517-522
  • 31 Bryant P, Carr M, Martin E, Sutton J. High dose recombinant activated factor VII in a pediatric patient with factor VIII deficiency and high titer inhibitor.  , [abstract] Blood. 2003;  102 104b-105b
  • 32 Young G, McDaniel M, Nugent D J. Prophylactic recombinant factor VIIa in haemophilia patients with inhibitors.  Haemophilia. 2005;  11(3) 203-207
  • 33 Morfini M, Auerswald G, Kobelt R A et al.. Prophylactic treatment of haemophilia patients with inhibitors: clinical experience with recombinant factor VIIa in European Haemophilia Centres.  Haemophilia. 2007;  13(5) 502-507
  • 34 Konkle B A, Ebbesen L S, Erhardtsen E et al.. Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors.  J Thromb Haemost. 2007;  5(9) 1904-1913
  • 35 Hoots W K, Ebbesen L S, Konkle B A Novoseven (F7HAEM-1505) Investigators et al. Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of haemophilia patients with inhibitors.  Haemophilia. 2008;  14(3) 466-475
  • 36 Marques-Verdier A, Chaleteix C, Souliè B, Bay J O. Secondary prophylaxis with recombinant activated factor VII (RFVIIA) in a severe haemophilia A patient with anti-factor VIII inhibitors.  J Thromb Haemost. 2007;  5(Suppl 2) , Abstract PT168
  • 37 Lopez Fernandez M, Saavedra A, Amor Otero M A, Batlle J. Primari prophylactic treatment with recombinant activated factor VII (RFVIIA) during immune tolerance in a haemophilic child.  J Thromb Haemost. 2007;  5(Suppl 2) , Abstract PT161
  • 38 Blatny J, Kohlerova S, Zapletal O, Fiamoli V, Penka M. RFVIIA is effective alternative to APCC in prophylaxis of bleeding during immune tolerance protocol in haemophiliac with inhibitor.  J Thromb Haemost. 2007;  5(Suppl 2) , Abstract PT166
  • 39 Jimenez-Yuste V, Quintana M, Alvarez M T, Martin-Salces M, Hernandez-Navarro F. “Primary prophylaxis” with rFVIIa in a patient with severe haemophilia A and inhibitor.  Blood Coagul Fibrinolysis. 2008;  19(7) 719-720
  • 40 Brophy D F, Martin E J, Nolte M E, Kuhn J G, Carr Jr M E. Effect of recombinant factor VIIa variant (NN1731) on platelet function, clot structure and force onset time in whole blood from healthy volunteers and haemophilia patients.  Haemophilia. 2007;  13(5) 533-541
  • 41 Møss J, Scharling B, Ezban M, Møller Sørensen T. Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects.  J Thromb Haemost. 2009;  7(2) 299-305

Dr. Massimo FranchiniM.D. 

Servizio di Immunoematologia e Medicina Trasfusionale, Dipartimento di Patologia e Medicina di Laboratorio

Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

Email: massimo.franchini@azosp.vr.it

    >