Tertiary prophylaxis in adults: is there a rationale?

There is lack of evidence‐based recommendations or clear‐cut consensus regarding the clinical and economic utility of regular prophylaxis started in adulthood, with the aim of keeping the clinical situation from getting worse by prevention of further bleeds contributing to increasing musculo‐skeletal or other morbidity in haemophilia. Such a prophylaxis program has been shown in relatively small cohorts to be effective in reducing bleeding occurrence, with a variable effect on the joint status, but with significantly higher factor consumption and consequently higher costs than on‐demand therapy. There has been no attempt to identify subsets of patients who may benefit from “tertiary” prophylaxis more than others, for example, due to their bleeding phenotype and/or requirements for product issued on‐demand or to identify the dosage that provides the optimal balance of clinical benefit and cost effectiveness. This article reviews the published literature on prophylaxis started beyond the age of 18 years, the barriers to the uptake of prophylaxis programs particularly in adults and highlights areas in need of further research.

[1]  E. Berntorp,et al.  Quality of life in adult patients with haemophilia – a single centre experience from Sweden , 2012, Haemophilia : the official journal of the World Federation of Hemophilia.

[2]  A. Farrugia,et al.  Health technology assessment and haemophilia , 2012, Haemophilia : the official journal of the World Federation of Hemophilia.

[3]  L. Valentino,et al.  A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management , 2012, Journal of thrombosis and haemostasis : JTH.

[4]  K. Fischer,et al.  Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens , 2010, Journal of thrombosis and haemostasis : JTH.

[5]  M. Morfini,et al.  Efficacy and safety of secondary prophylactic vs. on‐demand sucrose‐formulated recombinant factor VIII treatment in adults with severe hemophilia A: results from a 13‐month crossover study , 2010, Journal of thrombosis and haemostasis : JTH.

[6]  L. Valentino,et al.  Factor VIII prophylaxis for adult patients with severe haemophilia A: results of a US survey of attitudes and practices , 2009, Haemophilia : the official journal of the World Federation of Hemophilia.

[7]  A. Miners,et al.  Revisiting the cost‐effectiveness of primary prophylaxis with clotting factor for the treatment of severe haemophilia A , 2009, Haemophilia : the official journal of the World Federation of Hemophilia.

[8]  J. Astermark,et al.  Break‐through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A , 2009, Journal of thrombosis and haemostasis : JTH.

[9]  J. Stockman Prophylaxis versus Episodic Treatment to Prevent Joint Disease in Boys with Severe Hemophilia , 2009 .

[10]  F. Lafeber,et al.  Haemophilic arthropathy: the importance of the earliest haemarthroses and consequences for treatment , 2008, Haemophilia : the official journal of the World Federation of Hemophilia.

[11]  A. Tagliaferri,et al.  Secondary prophylaxis in adolescent and adult haemophiliacs. , 2008, Blood transfusion = Trasfusione del sangue.

[12]  V. Blanchette,et al.  The use of prophylaxis in 2663 children and adults with haemophilia: results of the 2006 Canadian national haemophilia prophylaxis survey , 2008, Haemophilia : the official journal of the World Federation of Hemophilia.

[13]  P. Mannucci,et al.  Effects of secondary prophylaxis started in adolescent and adult haemophiliacs , 2008, Haemophilia : the official journal of the World Federation of Hemophilia.

[14]  V. Blanchette,et al.  Cost‐utility analysis of Canadian tailored prophylaxis, primary prophylaxis and on‐demand therapy in young children with severe haemophilia A , 2008, Haemophilia : the official journal of the World Federation of Hemophilia.

[15]  J. Astermark,et al.  European principles of haemophilia care , 2008, Haemophilia : the official journal of the World Federation of Hemophilia.

[16]  C. Hermans,et al.  Should prophylaxis be used in adolescent and adult patients with severe haemophilia? An European survey of practice and outcome data , 2007, Haemophilia : the official journal of the World Federation of Hemophilia.

[17]  S. Darby,et al.  Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV. , 2007, Blood.

[18]  M. Franchini,et al.  Experience of secondary prophylaxis in 20 adolescent and adult Italian hemophiliacs , 2006, Thrombosis and Haemostasis.

[19]  S. Donadel-Claeyssens Current co‐ordinated activities of the PEDNET (European Paediatric Network for Haemophilia Management) , 2006, Haemophilia : the official journal of the World Federation of Hemophilia.

[20]  U. Siebert,et al.  Cost effectiveness of haemophilia treatment: a cross-national assessment , 2005, Blood Coagulation and Fibrinolysis.

[21]  F. Rosendaal,et al.  Chronic venous abnormalities in symptomatic and asymptomatic protein C deficiency , 2005, Journal of thrombosis and haemostasis : JTH.

[22]  F. Rosendaal,et al.  Thirty years of hemophilia treatment in the Netherlands, 1972-2001. , 2004, Blood.

[23]  S. Darby,et al.  The incidence of factor VIII and factor IX inhibitors in the hemophilia population of the UK and their effect on subsequent mortality, 1977–99 , 2004, Journal of thrombosis and haemostasis : JTH.

[24]  English Only Delivery of treatment for haemophilia , 2003, Haemophilia : the official journal of the World Federation of Hemophilia.

[25]  J. Astermark,et al.  Consensus perspectives on prophylactic therapy for haemophilia: summary statement , 2003, Haemophilia : the official journal of the World Federation of Hemophilia.

[26]  L. Aledort Orthopedic outcome studies and cost issues. , 2003, Seminars in thrombosis and hemostasis.

[27]  Guidelines on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders , 2003, Haemophilia : the official journal of the World Federation of Hemophilia.

[28]  A. Mackay Health technology assessment and mental health , 2002 .

[29]  P. Giangrande,et al.  Quality‐of‐life differences between prophylactic and on‐demand factor replacement therapy in European haemophilia patients , 2002, Haemophilia : the official journal of the World Federation of Hemophilia.

[30]  P. Giangrande,et al.  Clinical outcomes and resource utilization associated with haemophilia care in Europe , 2002, Haemophilia : the official journal of the World Federation of Hemophilia.

[31]  Mannucci,et al.  Guidelines on replacement therapy for haemophilia and inherited coagulation disorders in Italy , 2000, Haemophilia : the official journal of the World Federation of Hemophilia.

[32]  J. Bijlsma,et al.  Articular cartilage is more susceptible to blood induced damage at young than at old age. , 2000, The Journal of rheumatology.

[33]  F R Rosendaal,et al.  Risk Factors for Venous Thrombotic Disease , 1999, Thrombosis and Haemostasis.

[34]  C. Sabin,et al.  Assessing the effectiveness and cost‐effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease , 1998, Journal of internal medicine.

[35]  Mannucci Pm Haemophilia treatment protocols around the world: Towards a consensus , 1998 .

[36]  C. Kessler,et al.  Guidelines on treatment of haemophilia in Sweden , 1998, Haemophilia : the official journal of the World Federation of Hemophilia.

[37]  H. Pettersson,et al.  A longitudinal study of orthopaedic outcomes for severe factor‐VIII‐deficient haemophiliacs , 1994, Journal of internal medicine.

[38]  H. Pettersson Radiographic scores and implications. , 1993, Seminars in hematology.

[39]  M. Gilbert Prophylaxis: musculoskeletal evaluation. , 1993, Seminars in hematology.

[40]  C. Sherbourne,et al.  The MOS 36-Item Short-Form Health Survey (SF-36) , 1992 .

[41]  H. Pettersson,et al.  A radiologic classification of hemophilic arthropathy. , 1980, Clinical orthopaedics and related research.

[42]  Å. Ahlberg,et al.  HAEMOPHILIA PROPHYLAXIS IN SWEDEN , 1976, Acta paediatrica Scandinavica.

[43]  Eric F. Gardner,et al.  Summary Statement , 1946 .