Palabras clave
Immune Tolerance
Pediatrics
Cómo citar
Resumen
Brazil has the third highest population of patients diagnosed with hemophilia A in the world and the first in Latin America. Factor VIII (FVIII) replacement prophylaxis is the standard of care currently recommended worldwide. However, about 30% of all patients with severe hemophilia A will develop neutralizing antibodies against FVIII, called inhibitors. The proposed aim of immune tolerance induction (ITI) therapy is to eradicate inhibitors, and several protocol variations are available. In Brazil, ITI treatment follows an escalating rationale, initiating with a low-dose scheme using FVIII 50 IU/kg, three times a week. When the absence of a decline in inhibitor titer with a low-dose regimen of at least 20%, in every six-month period after the beginning of ITI, is observed, it is recommended to initiate high-dose scheme using FVIII 100 IU/kg every day. About one third of all patients with hemophilia A are children and adolescents. Disease management in this population prompts different challenges, potentially leading to chronic and lifelong disabilities, and the age at first treatment also seems to act as a risk factor for inhibitor development. In this narrative review, the authors’ conclusion provides comprehensive knowledge regarding severe congenital hemophilia A with inhibitors (CHAWI) and ITI in children and adolescents, discussing different ITI protocols, with different outcomes, focusing on comparing Brazil's with other global guidelines.
Citas
World Federation of Hemophilia (WFH). Report on the Annual Global Survey 2019. 2020.
Aledort L, Mannucci PM, Schramm W, Tarantino M. Factor VIII replacement is still the standard of care in haemophilia A. Blood Transfus. 2019;17(6):479-86.
Ministério da Saúde (Brasil). Secretaria de Atenção à Saúde. Departamento de Atenção Especializada e Temática. Manual de hemofilia. Brasília: Ministério da Saúde; 2015. 80 p.
Schep SJ, Schutgens REG, Fischer K, Boes ML. Review of immune tolerance induction in hemophilia A. Blood Rev. 2018;32(4):326-38.
van den Berg HM, Fischer K, Carcao M, Chambost H, Kenet G, Kurnik K, et al. Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A. Blood. 2019 Jul 18;134(3):317-20.
Hassan S, Cannavò A, Gouw SC, Rosendaal FR, van der Bom JG. Factor VIII products and inhibitor development in previously treated patients with severe or moderately severe hemophilia A: a systematic review. J Thromb Haemost. 2018;16(6):1055-68.
Peyvandi F, Ettingshausen CE, Goudemand J, JiménezYuste V, Santagostino E, Makris M. New findings on inhibitor development: from registries to clinical studies. Haemophilia. 2017;23:4-13.
Brackmann HH, White GC, Berntorp E, Andersen T, Escuriola-Ettingshausen C. Immune tolerance induction: What have we learned over time? Haemophilia. 2018;24(January):3-14.
Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020 Aug 3;26(S6):1-158.
Giordano P, Franchini M, Lassandro G, Faienza MF, Valente R, Molinari AC. Issues in pediatric haemophilia care. Ital J Pediatr. 2013;39(1):1-5.
Kulkarni R, Soucie JM. Pediatric hemophilia: A review. Semin Thromb Hemost. 2011;37(7):737-44.
Garagiola I, Palla R, Peyvandi F. Risk factors for inhibitor development in severe hemophilia a. Thromb Res. 2018;168(March):20-7.
World Federation of Hemophilia (WFH). Report on the Annual Global Survey 2017. Montréal: World Federation of Hemophilia; 2018. 80 p.
Knight T, Callaghan MU. The role of emicizumab, a bispecific factor IXa- and factor X-directed antibody, for the prevention of bleeding episodes in patients with hemophilia A. Ther Adv Hematol. 2018 Oct 10;9(10):319-34.
Chaves DG, Rodrigues C V. Desenvolvimento de inibidores do fator VIII na hemofilia A. Rev Bras Hematol Hemoter. 2009;31(5):52-8.
Ljung R, Auerswald G, Benson G, Dolan G, Duffy A, Hermans C, et al. Inhibitors in haemophilia A and B: Management of bleeds, inhibitor eradication and strategies for difficult-to-treat patients. Eur J Haematol. 2019;102(2):111-22.
Oldenburg J, Young G, Santagostino E, Escuriola Ettingshausen C. The importance of inhibitor eradication in clinically complicated hemophilia A patients. Expert Rev Hematol. 2018;11(11):857-62.
Hay CRM, DiMichele DM. The principal results of the International Immune Tolerance Study: A randomized dose comparison. Blood. 2012;119(6):1335-44.
Zülfikar B, Aydogan G, Salcioglu Z, Oner AF, Kavakli K, Gursel T, et al. Efficacy of FEIBA for acute bleeding and surgical haemostasis in haemophilia A patients with inhibitors: A multicentre registry in Turkey. Haemophilia. 2012;18(3):383-91.
Franchini M, Coppola A, Tagliaferri A, Lippi G. FEIBA versus NovoSeven in hemophilia patients with inhibitors. Semin Thromb Hemost. 2013;39(7):772-8.
Chai-Adisaksopha C, Nevitt SJ, Simpson ML, Janbain M, Konkle BA. Bypassing agent prophylaxis in people with hemophilia A or B with inhibitors. Cochrane Database Syst Rev. 2017 Sep 25;
Neme D, Ramos Mejía I, Elelhou L, Do Nascimento P, Arrieta ME, Cocca A, et al. A multicentre real-world data study to assess the bleeding rate and management of patients with haemophilia A and factor VIII inhibitors in Argentina. Blood Coagul Fibrinolysis. 2021 Dec;32(8):564-71.
Bedoya MA, Raffini L, Durand R, Acord MR, Srinivasan A, Krishnamurthy G, et al. Implantable venous access devices in children with severe hemophilia: a
tertiary pediatric institutional experience. Pediatr Radiol. 2020 Jul 11;50(8):1148-55.
Soto A. V, Cortez S. D, González S. M. Efectividad de inducción de tolerancia inmune en niños con hemofilia A y aloanticuerpos neutralizantes. Rev Chil Pediatría. 2020 Apr 22;91(2):232.
Valentino LA, Kempton CL, Kruse-Jarres R, Mathew P, Meeks SL, Reiss UM. US Guidelines for immune tolerance induction in patients with haemophilia a and inhibitors. Haemophilia. 2015;21(5):559-67.
AHCDO - Australian Haemophilia Centre Directors’ Organisation. Guidelines for the management of haemophilia in Australia | National Blood Authority. 2016.
Sociedad Argentina de Hematología. Hemofilia. Guías de diagnóstico y tratamiento. 2017. p. 167-78.
Gobierno de Chile. Ministerio de Salud. Guía Clínica AUGE - Hemofilia [Internet]. 2013. Available from: http://library1.nida.ac.th/termpaper6/sd/2554/19755.pdf
Gobierno de El Salvador. Ministerio de Salud. Guía clínica para la atención integral de la persona con hemofilia. 2018.
Neme D, Elhelou L, Coca A, Honorat E. Guía para el manejo de la Hemofilia Congénita. 3rd ed. Buenos Aires: Fundación de la Hemofilia; 2021.
Bianco RP, Ozelo MC, Villaça PR, Solano MH, Cruz GJ, Murillo CM, et al. Diagnosis and treatment of congenital hemophilia with inhibitors. A Latin American perspective. Medicina (B Aires). 2008;68(3):227-42.
Porras-Moreno A, Ugalde-Solera D. Immunotolerance induction in a pediatric hemophilic patient in Costa Rica. Acta Med Costarric. 2018;60(3):139-41.
Armstrong EP, Malone DC, Krishnan S, Wessler MJ. Costs and utilization of hemophilia A and B patients with and without inhibitors. J Med Econ. 2014;17(11):798-802.
Rocha P, Carvalho M, Lopes M, Araújo F. Costs and utilization of treatment in patients with hemophilia. BMC Health Serv Res. 2015;15(1):1-7.
Messori A. Inhibitors in Hemophilia A: A Pharmacoeconomic Perspective. Semin Thromb Hemost. 2018;44(6):561-7.
Kenet G, Oladapo A, Epstein JD, Thompson C, Novack A, Nugent DJ. Estimating the potential cost of a high dose immune tolerance induction (ITI) therapy relative to the cost of a combined therapy of a low dose ITI therapy with bypassing agent prophylaxis. Haemophilia. 2017;23(5):e394-402.
Sayago M, Lorenzo C. O acesso global e nacional ao tratamento da hemofilia: reflexões da bioética crítica sobre exclusão em saúde. Interface - Comun Saúde, Educ. 2020;24:1-15.
Thorat T, Neumann PJ, Chambers JD. Hemophilia Burden of Disease: A Systematic Review of the Cost-Utility Literature for Hemophilia. J Manag Care Spec Pharm. 2018 Jul;24(7):632-42.
Paim J, Travassos C, Almeida C, Bahia L, MacInko J. The Brazilian health system: History, advances, and challenges. Lancet. 2011;377(9779):1778-97.
Athale AH, Marcucci M, Iorio A. Immune tolerance induction for treating inhibitors in people with congenital haemophilia A or B. Cochrane Database Syst Rev. 2014 Apr 24;
Ministério da Saúde (Brasil). Secretaria de Atenção à Saúde. Departamento de Atenção Especializada e Temática. Imunotolerância. Protocolo de uso de indução de imunotolerância para pacientes com hemofilia e inibidor. 2015.
Camelo R, Magalhaes LP, Jardim LL, Zuccherato LW, Oliveira AG, Franco VKB, et al. Immune Tolerance Induction in Patients with Hemophilia A and Inhibitors: Extended Results of the Brazilian Immune Tolerance (BrazIT) Study. Res Pract Thromb Haemost. 2019;3:322-3.
Camelo R, Magalhaes L, Jardim L, Werneck L, Gonçalves A, Roberti MR, et al. Immune Tolerance Induction in Patients with Hemophilia A and Inhibitors: Preliminary Results of the Brazilian Immune Tolerance (BrazIT) Study. Res Pract Thromb Haemost. 2018;2:97-8.
Carcao M, Escuriola‐Ettingshausen C, Santagostino E, Oldenburg J, Liesner R, Nolan B, et al. The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab. Haemophilia. 2019;25(4):676-84.
Todo el material publicado en la revista Hematología (versión electrónica y versión impresa), será cedido a la Sociedad Argentina de Hematología. De conformidad con la ley de derecho de autor (ley 11723) se les enviara a los autores de cada trabajo aceptado formulario de cesión de derechos de autor que deberá ser firmado por todos los autores antes de la publicación. Los autores deberán retener una copia del original pues la revista, no acepta responsabilidad por daños o pérdidas del material enviado. Los autores deberán remitir una versión electrónica al correo: revista@sah.org.ar