Download PDF
Thromb Haemost 2006; 96(04): 433-440
DOI: 10.1160/TH06-02-0125
Review Article
Schattauer GmbH

Evidence for the benefits of prophylaxis in the management of hemophilia A

W. Keith Hoots
1   Department of Pediatrics and Internal Medicine, University of Texas Medical School, Houston, Texas, USA
2   Department of Pediatrics, University of Texas – M.D. Anderson Cancer Center, Houston, Texas, USA
,
Diane J. Nugent
3   Department of Hematology, Children’s Hospital of Orange County, Orange, California, USA
4   Department of Pediatric Hematology Oncology, Mattel Children’s Hospital, UCLA Medical School, Los Angeles, California, USA
› Author Affiliations
Further Information

Publication History

Received 28 February 2006

Accepted after resubmission 31 July 2006

Publication Date:
29 November 2017 (online)

    Permissions and Reprints

Summary

The optimal treatment of hemophilia has been evolving since the advent of factor VIII concentrates, continues to vary geographically, and remains a source of debate. There now exists an extensive clinical literature that demonstrates clear benefits of prophylaxis for patients with hemophilia A compared to on-demand treatment, including a reduction in the number of bleeding episodes, improved joint function, and greater patient well-being. However, the value of these benefits must be weighed against the heavier economic burden of increased factor use. This paper reviews the literature that compares the benefits of prophylaxis with that of on-demand treatment, compares varying prophylaxis dose and administration frequency protocols, and considers the long-term cost-benefit of prophylactic therapy.

Keywords

Hemophilia - prophylaxis - on-demand - factor VIII - arthropathy - cost-benefit
 

  • References

  • 1 Berntorp E, Astermark J, Bjorkman S. et al. Consensus perspectives on prophylactic therapy for haemophilia: summary statement. Haemophilia 2003; May; 09 (Suppl. 01) 1-4.
    PubMedGoogle Scholar
  • 2 Nilsson IM, Hedner U, Ahlberg A. Haemophilia prophylaxis in Sweden. Acta Paediatr Scand 1976; 65: 129-35.
    CrossrefPubMedGoogle Scholar
  • 3 Nilsson IM, Berntorp E, Lofqvist T. et al. Twentyfive years’ experience of prophylactic treatment in severe haemophilia A and B. J Intern Med 1992; 232: 25-32.
    CrossrefPubMedGoogle Scholar
  • 4 Lofqvist T, Nilsson IM, Berntorp E. et al. Haemophilia prophylaxis in young patients--a long-term follow-up. J Intern Med 1997; 241: 395-400.
    CrossrefPubMedGoogle Scholar
  • 5 Kreuz W, Escuriola CEttingshausen, Funk M. et al. [Prevention of joint damage in hemophilic children with early prophylaxis]. Orthopade 1999; 28: 341-6.
    CrossrefPubMedGoogle Scholar
  • 6 Plug I, van der Bom JG, Peters M. et al. Thirty years of hemophilia treatment in the Netherlands, 1972–2001. Blood 2004; 104: 3494-500.
    CrossrefPubMedGoogle Scholar
  • 7 Geraghty S, Dunkley T, Harrington C. et al. Practice patterns in haemophilia A therapy -- global progress towards optimal care. Haemophilia 2006; 12: 75-81.
    PubMedGoogle Scholar
  • 8 Stobart K, Iorio A, Wu JK. Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B. Cochrane Database Syst Rev 2005; 02: CD003429.
    PubMedGoogle Scholar
  • 9 More on: are randomized clinical trials the only truth? Not always. J Thromb Haemost 2006; 04: 1167-8.
    CrossrefPubMedGoogle Scholar
  • 10 Aledort L, Ljung R, Blanchette V. Are randomized clinical trials the only truth? Not always. J Thromb Haemost 2006; 04: 503-4.
    CrossrefPubMedGoogle Scholar
  • 11 Iorio A, Stobart K, Bolton-Maggs P. Can evidence harm? Certainly not hemophilia treatment and community. J Thromb Haemost 2006; 04: 505-6.
    CrossrefPubMedGoogle Scholar
  • 12 Mannucci PM. Need for randomized trials in hemophilia. J Thromb Haemost 2006; 04: 501-2.
    CrossrefPubMedGoogle Scholar
  • 13 Abshire TC, Brackmann HH, Scharrer I. et al. Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy--International Kogenate-FS Study Group. Thromb Haemost 2000; 83: 811-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Lusher JM, Lee CA, Kessler CM. et al. The safety and efficacy of B-domain deleted recombinant factor VIII concentrate in patients with severe haemophilia A. Haemophilia 2003; 09: 38-49.
    PubMedGoogle Scholar
  • 15 Aledort LM, Haschmeyer RH, Pettersson H. A longitudinal study of orthopaedic outcomes for severe factor-VIII-deficient haemophiliacs. The Orthopaedic Outcome Study Group. J Intern Med 1994; 236: 391-9.
    CrossrefPubMedGoogle Scholar
  • 16 Panicker J, Warrier I, Thomas R. et al. The overall effectiveness of prophylaxis in severe haemophilia. Haemophilia 2003; 09: 272-8.
    CrossrefPubMedGoogle Scholar
  • 17 Manco-Johnson MJ, Blanchette VS. North American prophylaxis studies for persons with severe haemophilia: background, rationale and design. Haemophilia 2003; May; 09 (Suppl. 01) 44-8 discussion 9.
    CrossrefPubMedGoogle Scholar
  • 18 Manco-Johnson MJA, Brown TC, Buchanan D. et al. Initial results of a randomized, prospective trial of prophylaxis to prevent joint disease in young children with factor VIII (FVIII) deficiency. Blood. 2005 106. Abstract 3.
    PubMedGoogle Scholar
  • 19 Lundin B, Ljung R, Pettersson H. MRI scores of ankle joints in children with haemophilia--comparison with clinical data. Haemophilia 2005; 11: 116-22.
    CrossrefPubMedGoogle Scholar
  • 20 Morado M, Villar A, Jimenez VYuste. et al. Prophylactic treatment effects on inhibitor risk: experience in one centre. Haemophilia 2005; 11: 79-83.
    CrossrefPubMedGoogle Scholar
  • 21 Santagostino E, Mancuso ME, Rocino A. et al. Environmental risk factors for inhibitor development in children with haemophilia A: a case-control study. BrJ Haematol 2005; 130: 422-7.
    CrossrefPubMedGoogle Scholar
  • 22 Steen KCarlsson, Hojgard S, Glomstein A. et al. On-demand vs. prophylactic treatment for severe haemophilia in Norway and Sweden: differences in treatment characteristics and outcome. Haemophilia 2003; 09: 555-66.
    CrossrefPubMedGoogle Scholar
  • 23 Fischer K, van der Bom JG, Molho P. et al. Prophylactic versus on-demand treatment strategies for severe haemophilia:a comparison of costs and long-term outcome. Haemophilia 2002; 08: 745-52.
    CrossrefPubMedGoogle Scholar
  • 24 van den Berg HM, Fischer K, Mauser-Bunschoten EP. et al. Long-term outcome of individualized prophylactic treatment of children with severe haemophilia. Br J Haematol 2001; 112: 561-5.
    CrossrefPubMedGoogle Scholar
  • 25 Miners AH, Sabin CA, Tolley KH. et al. Cost-utility analysis of primary prophylaxis versus treatment ondemand for individuals with severe haemophilia. Pharmacoeconomics 2002; 20: 759-74.
    CrossrefPubMedGoogle Scholar
  • 26 Lippert B, Berger K, Berntorp E. et al. Cost effectiveness of haemophilia treatment:a cross-national assessment. Blood Coagul Fibrinolysis 2005; 16: 477-85.
    CrossrefPubMedGoogle Scholar
  • 27 Bohn RL, Schramm W, Bullinger M. et al. Outcome measures in haemophilia: more than just factor levels. Haemophilia 2004; 10 (Suppl. 01) 2-8.
    CrossrefPubMedGoogle Scholar
  • 28 Bullinger M, von Mackensen S. Quality of life assessment in haemophilia. Haemophilia 2004; 10 (Suppl. 01) 9-16.
    PubMedGoogle Scholar
  • 29 Gringeri A, von Mackensen S, Auerswald G. et al. Health status and health-related quality of life of children with haemophilia from six West European countries. Haemophilia 2004; 10 (Suppl. 01) 26-33.
    CrossrefPubMedGoogle Scholar
  • 30 Shapiro AD, Donfield SM, Lynn HS. et al. Defining the impact of hemophilia: the Academic Achievement in Children with Hemophilia Study. Pediatrics 2001; 108: E105.
    CrossrefPubMedGoogle Scholar
  • 31 Schramm W, Berger K. Economics of prophylactic treatment. Haemophilia 2003; 09 (Suppl. 01) 111-5 discussion 6.
    CrossrefPubMedGoogle Scholar
  • 32 Fischer K, Astermark J, van der Bom JG. et al. Prophylactic treatment for severe haemophilia: comparison of an intermediate-dose to a high-dose regimen. Haemophilia 2002; 08: 753-60.
    CrossrefPubMedGoogle Scholar
  • 33 Astermark J, Petrini P, Tengborn L. et al. Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized. Br J Haematol 1999; 105: 1109-13.
    CrossrefPubMedGoogle Scholar
  • 34 Fischer K, van der Bom JG, Mauser-Bunschoten EP. et al. The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia. Blood 2002; 99: 2337-41.
    CrossrefPubMedGoogle Scholar
  • 35 Brackmann HH, Eickhoff HJ, Oldenburg J. et al. Long-term therapy and on-demand treatment of children and adolescents with severe haemophilia A: 12 years of experience. Haemostasis 1992; 22: 251-8.
    PubMedGoogle Scholar
  • 36 Ahnstrom J, Berntorp E, Lindvall K. et al. A 6-year follow-up of dosing, coagulation factor levels and bleedings in relation to joint status in the prophylactic treatment of haemophilia. Haemophilia 2004; 10: 689-97.
    CrossrefPubMedGoogle Scholar
  • 37 Feldman BM, Pai M, Rivard GE. et al. Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study. J Thromb Haemost 2006; 04: 1228-36.
    CrossrefPubMedGoogle Scholar
  • 38 Fischer K, Van Der Bom JG, Prejs R. et al. Discontinuation of prophylactic therapy in severe haemophilia: incidence and effects on outcome. Haemophilia 2001; 07: 544-50.
    CrossrefPubMedGoogle Scholar
  • 39 World Health Organization HDPDoND. Report of a joint WHO/WFH meeting on the control of haemophilia: modern treatment of haemophilia: World Health Organization. 1994: 21-23 March.
    PubMedGoogle Scholar
  • 40 Ewenstein BM, Valentino LA, Journeycake JM. et al. Consensus recommendations for use of central venous access devices in haemophilia. Haemophilia 2004; 10: 629-48.
    CrossrefPubMedGoogle Scholar