#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Consensual guidelines of the Czech National Haemophilia Programme (CNHP) for the diagnosis and treatment of patients with haemophilia, 3rd edition, year 2021


Authors: Pracovní Skupina Čnhp Pro Standardy:;  P. Smejkal 1;  J. Blatný 2;  Z. Hajšmanová 3;  A. Hluší 4;  R. Hrdličková 5;  E. Zápotocká 6;  M. Penka 1;  Rady Koordinační Jménem;  Výkonné Rady Čnhp:;  B. Blažek 7;  Z. Čermáková 5;  Z. Černá 8;  P. Ďulíček 9;  J. Hak 10;  V. Komrska 6;  P. Ovesná 11;  D. Pospíšilová 12;  D. Procházková 13;  P. Timr 14;  J. Ullrychová 15;  I. Vonke 16;  L. Walterová 17
Authors‘ workplace: Oddělení klinické hematologie, FN Brno 1;  Oddělení dětské hematologie, FN Brno 2;  Ústav klinické bio chemie a hematologie, FN Plzeň 3;  Hemato-onkologická klinika, FN Olomouc 4;  Klinika hematoonkologie a Krevní centrum, FN Ostrava 5;  Klinika dětské hematologie a onkologie, FN Motol, Praha 6;  Klinika dětského lékařství, FN Ostrava 7;  Dětská klinika, FN Plzeň 8;  IV. interní hematologická klinika, FN Hradec Králové 9;  Dětská klinika, FN Hradec Králové 10;  Institut bio statistiky a analýz LF MU, Brno 11;  Dětská klinika, FN Olomouc 12;  Dětská klinika, Krajská zdravotní a. s., Masarykova nemocnice v Ústí nad Labem 13;  Dětské oddělení, Nemocnice České Budějovice 14;  Oddělení klinické hematologie, Krajská zdravotní a. s., Masarykova nemocnice v Ústí nad Labem 15;  Oddělení klinické hematologie, Nemocnice České Budějovice 16;  Oddělení klinické hematologie, Krajská nemocnice Liberec 17
Published in: Transfuze Hematol. dnes,27, 2021, No. 1, p. 73-90.
Category: Best Practices
doi: https://doi.org/10.48095/cctahd202173

Overview

The aim of these guidelines is to set-up and standardize dia­gnostic as well as therapeutic approaches to patients with haemophilia according to updated scientific evidence. Update of the original consensual guidelines reflects new available data plus advent of new drugs and recommends the optimal dosage for treatment. The system for haemophilia care in Czech Republic is briefly described.

Keywords:

haemophilia – guidelines – dia­gnosis – treatment – Prophylaxis


Sources

1. Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013; 19: e1–e47.

2. Annual Global Survey. 2018. World Federation of Hemophilia, October. 2019. http: //www1.wfh.org/publications/files/pdf-1731.pdf, přístup 27. 9. 2020.

3. Srivasta A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia 3rd edition. https: //onlinelibrary.wiley.com/doi/abs/10.1111/hae.14046, přístup 27. 9. 2020.

4. White GC, Rozendal F, Aledort L, et al. Definitions in hemophilia. Tromb Haemost. 2001; 85: 560.

5. Maclean RM, Makris M. Hemophilia A and B. In: O’Shaughnessy D, Makris M, Lillicarp D. Practical Hemostasis and Thrombosis. 1st ed. Oxford, Blackwell Publishing. 2005: 41–50.

6. Kemball-Cook G, Gomez K. Molecular basis of hemophilia A. In: Lee CA, Berntorp E, Hoots WK. Textbook of Hemophilia. 2nd ed. Oxford: Blackwell Publishing. 2010: 24–32.

7. Gomez K. Hemophilia B – molecular basis. In: Lee CA, Berntorp E, Hoots WK. Textbook of Hemophilia. 2nd ed. Oxford, Blackwell Publishing. 2010: 88-93.

8. Novotný J, Penka M, Matýšková M, Zavřelová J. Fyziologie krevního srážení. In: Penka M, Tesařová E et al. Hematologie a transfuzní lékařství I, 1. vyd. Praha: Grada Publishing. 2011: 31–59.

9. Forbes CD, Aledort L, Madhok R. Hemophilia. London, Chapman & Hall. 1997.

10. Raffini L, Manno C. Modern management of haemophilic arthropathy. Br J Haematol. 2007; 136: 777–787.

11. Kulkarni R, Lusher J. Perinatal management of newborns with haemophilia. Br J Haematol. 2001; 112: 264–274.

12. Gray GR, Teasdale JM, Thomas JW. Hemophilia Bm. Canad Med Ass J 1968; 98: 552–554.

13. Verbruggen B, Novakova I, Wessels H, et al. The Nijmegen modification of the Bethesda assay for factor VIII: C inhibitor. Improved specifity and reliability. Thromb Haemost 1995; 73: 247–251.

14. Van den Berg, Fischer K, Carcao M, et al. Timing of inhibitor development in more than 1000 previously untreated patiens with severe hemophilia A. Blood. 2019; 134: 317–320.

15. Gringeri A, Mannucci PM. Italian guidelines for the dia­gnosis and treatment of patiens with haemophilia and inhibitors. Haemophilia. 2005; 11: 611–619.

16. Collins PW, Chlamers E, Hart DP, et al. Dia­g­nosis and treatment of factor VIII and IX inhibitors in congenital haemophilia. 4th ed. Br J Haematol. 2013; 160: 153–170.

17. Bátorová A, Jankovičová D, Žarnovičanová M, et al. Národné štandardné postupy pre liečbu hemofilie a iných vrodených koagulopatií v Slovenskej republike. Lek Obz. 2008; 56: 330–340.

18. De Moerloose P, Fischer K, Lambert T, et al. Recommendations for assessment, monitoring and follow-up of patiens with haemophilia. Haemophilia. 2012; 18: 319–325.

19. Český národní hemofilický program. http: //cnhp.registry.cz.

20. Věstník Ministerstva zdravotnictví České republiky. 2014, částka 3.

21. Colvin BT, Astermark J, Fischer K, et al. European principles of haemophilia care. Haemophilia. 2008; 14: 361–374.

22. Armstrong E, Astermark J, Baghaei F, et al. Nordic Hemophilia Guidelines. Version 1. Printed 23 June. 2015. http: //www.nordhemophilia.org.

23. Den Uijl IE, Mauser-Bunschoten EP, Roosendaal G, et al. Clinical severity of haemophilia A: does the classification of the 1950s still stand? Haemophilia. 2011; 17 (6): 849–853.

24. United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO). Guidelines on the selection and use of therapeutic products to treat haemophilia and other hereditary bleedings disorders. Haemophilia. 2003; 9: 1–23.

25. Santagostino E, Mannucci PM, Bonomi Bianchi A. Guidelines on replacement therapy for haemophilia and inherited coagulation disorders in Italy. Haemophilia. 2000; 6: 1–10.

26. Pabinger I, Heistinger M, Muntean W, et al. Hämophiliebehandlung in Österreich. Wien Klin Wochenschr. 2015; 127 (Suppl 3): 115–130.

27. Věstník Ministerstva zdravotnictví České republiky. 2016, částka 7.

28. Salaj P, Smejkal P, Komrska V, Blatný J, Penka M. Standardy péče o nemocné s hemofilií. Transfuze Hematol dnes. 2013; 13: 96–98.

29. Astermark J, Altisent C, Batorova A, et al. Non-genetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report. Haemophilia. 2010; 16: 747–766.

30. Calvez T, Chambost H, Claeyssens-Donadel S, et al. Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A. Blood. 2014; 124 (23): 3398–3408.

31. Fischer K, Lassila R, Peyvandi F, et al. Inhibitor development in haemophilia according to concentrate. Four-year results from the European Haemophila Safety Surveilance (EUHASS) project. Thromb Haemost. 2015; 113: 968–975.

32. Goudemand J, Rothschild C, Demiguel V, et al. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophila A. Blood. 2006; 107: 46–51.

33. Goudemand J, Peyvandi F, Lacroix-Desmazes S. Key insights to understand the immunogenicity of FVIII products. Thromb Haemost. 2016; 116 (Suppl.1): 52–59.

34. Gouw SC, van der Bom JG, Auerswald G, et al. Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study. Blood. 2007; 109: 4693–4697.

35. Gouw SC, van der Bom JG, van den Berg HM. Treatment-related risk factors of inhibitor development in previously untreated patiens with hemophilia A: the CANAL cohort study. Blood. 2007; 109: 4648–4654.

36. Iorio A, Halimeh S, Holzhauer S, et al. Rate of inhibitor development in previously untreated hemophila A patiens treated with plasma-derived or recombinant factor VIII concentrates: a systematic review. J Thromb Haemost. 2010; 8: 1256–1265.

37. Peerlinck K, Hermans C. Epidemiology of inhibitor formation with recombinant factor VIII replacement therapy. Haemophilia. 2006; 12: 579–590.

38. Xi M, Makris M, Marcuci M, et al. Inhibitor dvelopment in previously treated hemophilia A patients: a systematic review, meta-analysis, and meta-regression. J Thromb Haemost. 2013; 11: 1655–1662.

39. Peyvandi F, Mannucci PM, Garagiola I, et al. A randomized trial od factor VIII and neutralizing antibodies in hemophilia A. N Engl J Med. 2016; 374: 2054–2064.

40. Blatny J, Komrska V, Blazek B, et al. Inhibitors incidence rate in Czech previously untreated patients with haemophilia A has not increased since introduction of recombinant factor VIII treatment in. 2003. Blood Coagul Fibrinolysis. 2015; 26: 673–678.

41. Hay CRM, Palmer BP, Chalmers EA, et al. The incidence of factor VIII inhibitors in severe haemophilia A following a major switch from full-length to B-domain-deleted factor VIII: a prospective cohort comparison. Haemophilia. 2015; 21: 219–226.

42. Giangrande P, Seitz R, Behr-Gross ME, et al. Kreuth III: European consensus proposal for treatment of haemophilia with coagulation factor concentrates. Haemophilia. 2014; 20: 322–325.

43. Collins PW, Fischer K, Morfini M, Blanchette VS, Björkman S. Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia. Haemophilia. 2011; 17: 2–10.

44. Batorova A, Holme P, Gringeri A, et al. Continuous infusion in haemophilia: current practice in Europe. Haemophilia. 2012; 18: 753–759.

45. Eckhardt EL, van Velzen AS, Peters M, et al. Factor VIII gene (F8) mutation risk of inhibitor development in nonsevere hemophilia A. Blood. 2013; 122 (11): 1954-1962.

46. Collins P, Chalmers E, Chowdary P, et al. The use of enhanced half-life coagulation factor concentrates in routine clinical practice: guidance from UKHCDO. Haemophilia. 2016; 22: 487–498.

47. Rayment R, Chalmers E, Forsyth K, et al. Guidelines on the use of prophylactic factor replacement for children and adults with Haemophilia A and B. British Society for Haematology and John Wiley & Sons Ltd. 2020.

48. Königs C, Ozelo MC, Dunn A, et al. Final Results of PUPs A-LONG Study: Evaluating Safety and Efficacy of rFVIIIFc in Previously Untreated Patients with Haemophilia A. [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https: //abstracts.isth.org/abstract/final-resultsof-pups-a-long-study-evaluating-safety-and-efficacy-of-rfviiifc-in-previously-untreated-patients-withhaemophilia-a/. Accessed July 19, 2020.

49. Dodt J, Hubbard AR, Wicks SJ, et al. Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators. Haemophilia. 2015; 21: 543–549.

50. Hubbard AR, Didt J, Lee T, et al. Recommendations on the potency labelling of factor VIII and factor IX concetrates. J Thromb Haemost. 2013; 11: 988–989.

51. Pruthi RK. Laboratory monitoring of new hemostatik agents for hemophilia. Semin Hematol. 2016; 53: 28-34.

52. Workshop report: Characterisation of new clotting factor concentrates (FVIII, FIX) with respect to potency assays used for labelling and testing of post infusion samples. 26 June. 2014. http: //www.ema.europa.eu/docs/en_GB/document_library/Report/2014/07/WC500169760.pdf, přístup 22. 6. 2020

53. Young GA, Perry DJ and for The International Prophylaxis Studfy Group (IPSG). Laboratory assay measurement of modified clotting factor concetrates: a review of the literature and recommendations for practice. J Thromb Haemost. 2019; 17: 567–573.

54. Gray E, Kitchen S, Bowyer A, et al. Laboratoty measurement of factor replacement therapies in the treatment of congenital haemophilia: A United Kingdom Haemophilia Centre Doctors’Organisation guideline. Haemophilia. 2020; 26: 6–16.

55. Shima M, Hanabusa H, Taki M, et al. Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med. 2016; 374 (21): 2044–2053.

56. Lenting PJ, Denis CV, Christophe OD. Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII? Blood. 2017; 130 (23): 2463–2468.

57. https: //www.ema.europa.eu/en/documents/product-information/hemlibra-epar-product-information_cs.pdf, přístup 22. 6. 2020

58. Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017; 377 (9): 809–818.

59. Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia a without inhibitors. N Engl J Med. 2018; 379 (9): 811–822.

60. Pipe SW, Shima M, Lehle M, et al. Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study. Lancet Haematol. 2019; 6 (6): e295–e305.

61. MASAC document #258. Recommendation on the use and management of emicizumab- KXWH (HEMLIBRA®) for hemophilia A with and without inhibitors. https: //www.hemophilia.org/sites/default/files/document/files/258_emicizumab.pdf, přístup 22. 6. 2020.

62. Müller J, Pekrul I, Pötzsch B, et al. Laboratory monitoring in emicizumab-treated persons with hemophilia A. Thromb Haemost. 2019; 119: 1384–1393.

63. Kruse-Jarres R, Callaghan MU, Croteau SE, et al. Surgical experience in two multicenter, open-label phase 3 studies of Emicizumab in person with hemophilia A with inhibitors (HAVEN 1 and HAVEN 2). Blood. 2017; 130 (Supplement 1): 89.

64. Peyvandi F, Garagiola I. Clinical advances in gene therapy updates on clinical trials of gene therapy in haemophilia. Haemophilia. 2019; 25: 738–746.

65. Hemophilia of Georgia, U.S.A. Protocol for the treatment of haemophilia and von Willebrand Disease. Haemophilia. 2000; 6 (Suppl. 1): 84–93.

66. Mahlangu JN, Gilham A. Guideline for the treatment of haemophilia in South Africa. S Afr Med J. 2008; 98: 1296–1311.

67. Rodriguez-Merchan EC. Articular bleeding (hemarthrosis) in hemophilia. http: //www.wfh.org/2/docs/Publications/Musculoskeletal_Physiotherapy/TOH-23-Hermarthrosis-Revised2008.pdf, přístup 22. 6. 2020.

68. Hanley J, McKernan A, Greagh MD, et al. Guidelines for the management of acute joint bleeds and chronic synovitis in haemophilia. UKHCDO guideline. Haemophilia. 2017; 23: 5121–520.

69. Fernandez-Palazzi F. Treatment of acute and chronic synovitis by non-surgical means. Haemophilia 1998; 4: 518–523.

70. Dunn AL, Busch MT, Wyly JB, Abshire TC. Radionuclide synovectomy for hemophilic arthropathy: a comprehensive review of safety and efficacy and recommendation for a standardized treatment protocol. Thromb Haemost. 2002; 87: 383–393.

71. Rodriguez-Merchan EC, Quintana M, de la Corte-Rodriguez H, Coyas J. Radioactive synoviorthesis for the treatment of haemophilic synovitis. Haemophilia. 2007; 13 (Suppl. 3): 32–37.

72. Rodrigez-Merchan EC, Valentino LA. Safety of radiation exposure after radiosynovectomy in paediatric patients with haemophilia. Haemophilia. 2015; 21: 411–418.

73. Sorensen B, Benson GM, Bladen M, et al. Management of muscle haematoma in patiens with severe haemophilia in an evidence-poor world. Haemophila. 2012; 18: 598–606.

74. Richards M, Williams M, Chalmers E, et al. A United Kingdom Haemophilia Centre Doctors’ Organization guidelines approved by the British Committee for Standards in Haematology: guideline on the use of prophylactic factor VIII concentrate in children and adults with severe haemophilia A. Br J Haematol. 2010; 149: 498–507.

75. Pipe SW, Valentino LA. Optimizing outcomes for patients with severe haemophilia A. Haemophilia. 2007; 13 (Suppl. 4): 1–16.

76. Auerswald G, Bidlingmaier C, Kurnik K. Early prophylaxis/FVIII tolerization that avoids immunological ganger signals is still effective in minimizing FVIII inhibitor developments in previously untreated patients – long-term follow-up and continuing experience. Haemophilia. 2012; 18: e18–e20.

77. Auerswald G, Kutnik K, Aledort LM, et al. The EPIC study: a lesson to learn. Haemophilia. 2015; 21: 622–628.

78. Ljung R, Auerswald G, Benson G, et al. Novel coagulation factor concentrates: Issues relating to their clinical implementation and pharmacokinetic assessment for optimal prophylaxis in haemophilia patients. Haemophilia. 2013; 19: 481–486.

79. Hay CRM. Prophylaxis in adults with haemophilia. Haemophilia. 2007; 13 (Suppl. 2): 10–15.

80. Nijdam A, Foppen W, de Kleijn P, et al. Discontinuing early prophylaxis in severe haemophilia leads to deterioration of joint status despite low bleeding rates. Thromb Haemost. 2016; 115: 931–938.

81. Manco-Johnson MJ, Kempton CL, Reding MT, et al. Randomized, controlled, parallel-group trial of routine prophylaxis vs on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART). J Thromb Haemost. 2013; 11: 1119–1127.

82. Tagliaferri A, Feola G, Molinari AC, et al. Benefits of prophylaxis versus on-demand treatment in adolescents and adulkts with severe haemophilia A: the POTTER study. Thromb Haemost. 2015; 114: 35–45.

83. Fischer K, Collins P, Björkman S, et al. Trends in bleeding patterns during prophylaxis for severe haemophilia: observation from a series of prospective clinical trials. Haemophilia. 2011; 17: 433–438.

84. Ljung R, Fischer K, Carcao M, et al. Practical considerations in choosing a factor VIII prophylaxis regimen: Role of clinical phenotype and trough levels. Thromb Haemost. 2016; 115: 913–920.

85. Iorio A, Iserman E, Blanchette V, et al. Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement. Haemophilia. 2017; 23: e170–e179.

86. Bojar M. Metodický návod o komplexní péči o nemocné s hemofilií a dalšími poruchami hemostázy. Č.j.: PKP/2-2713-1.4. 92 (Věstník MZ ČR č. 3/1992).

87. Brewer A, Correa ME. Guidelines for dental treatment of patients with inherited bleeding disorders. World Federation of Hemophilia. 2006. http: //www.wfh.org/2/docs/Publications/Dental_Care/TOH-40_Dental_treatment.pdf, přístup 22. 6. 2020.

88. EASL Recommendations on Treatment of Hepatitis C. 2016 SUMMARY. Journal of Hepatology, September. 2016. http: //www.easl.eu/medias/cpg/HCV2016/Summary.pdf, přístup 22. 6. 2020.

89. Staritz P, De Moerloose P, Schutgens R, Dolans G. Applicability of the European Society of kardiology guidelines on management of acute coronary syndromes to people with haemophilia – an assessment by the ADVANCE Working Group. Haemophilia. 2013; 19: 833–840.

90. Schutgens REG, Klamroth R, Pabinger I, et al. Management of atrial fibrilation in people with haemophilia – a concensus view by the ADVANCE Working Group. Haemophilia. 2014; 20: e399–e443.

91. Franchini M, Mannucci PM. Co-morbidities and quality of life in elderly persons with haemophilia. Br J Haematol. 2009; 148: 522–533.

92. Mannucci PM, Schutgens REG, Santagostino E, Mauser-Bunschoten EP. How I treat age-related morbidities in elderly persons with hemophilia. Blood. 2009; 114: 5256–5263.

93. Martin K and Key NS. How I treat patients with inherited bleeding disorders who need anticoagulant therapy. Blood. 2016; 128 (2): 178–184.

94. Jabbar AY, Baydoun H, Janbain M, Ferdinand KC. Current concepts in the management of stable ischemic heart disease and acute coronary syndrome in patients with hemophilia. Ann Transf Med. 2018; 6 (15): 299–305.

95. Schutgens REG, van der Heijden JF, Mauser-Bunschoten EP, Mannucci PM. New concept for anticoagulant therapy in persons with hemophilia. Blood. 2016; 128: 2471–2474.

96. Mannucci PM, Mauser-Bunschoten EP. Cardiovascular disease in haemophilia patients: a contemporary issue. Haemophilia. 2010; 16 (Suppl. 3): 58–66.

97. Wight J, Paisley S. The epidemiology of inhibitors in haemophilia A: a systematic review. Haemophilia. 2003; 9: 418–435.

98. Astermark J, Morado M, Rocino A, et al. Current European practise in immune tolerance induction therapy in patiens with haemophilia and inhibitors. Haemophilia. 2006; 12: 363–371.

99. DiMichele DM, Hoots WK, Pipe SW, et al. International workshop on immune tolerance induction: consensus recommendations. Haemophilia. 2007; 13 (Suppl. 1): 1–22.

100. Astermark J. Overview of inhibitors. Semin Hematol. 2006; 43 (Suppl. 4): 3–7.

101. Darby SC, Keeling DM, Spooner RJD, 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. J Thromb Haemost. 2004; 2: 1047–1054.

102. Peerlinck K, Jacquemin M. Characterictics of inhibitors in mild/moderate haemophilia A. Haemophilia. 2006; 12 (Suppl. 6): 43–47.

103. Abbonizio F, Giampaolo A, Coppola A, et al. Therapeutic management and cost of severe haemophilia A patients with inhibitors in Italy. Haemophilia. 2014; 20: e243–e250.

104. Hay CRM. The epidemiology of factor VIII inhibitors. Haemophilia. 2006; 12 (Suppl. 6): 23–29.

105. Astermark J. Why do inhibitors develop? Principles of and factors influencing the risk for inhibitor development in haemophilia. Haemophilia. 2006; 12 (Suppl. 3): 52–60.

106. Castaman G, Fijnvandraat K. Molecular and clinical predictors of inhibitor risk and its prevetion and treatment in mild hemophiliaA. Blood. 2014; 124 (15): 2333–2336.

107. Oldenburg J, Pavlova A. Genetic risk factors for inhibitors to factors VIII and IX. Haemophilia. 2006; 12 (Suppl. 6): 15–22.

108. EHC response to the Publication of the SIPPET Study. June 3, 2016. http: //static.ehc.eu/wp-content/uploads/EHC-SIPPET-Position-3-June-2016-WEB.pdf

109. Cormier M, Batty P, Tarrant J, Lillicrap D. Advances in knowledge of inhibitor formation in severe haemophilia A. Br J Haematol. 2020; 189: 39–53.

110. Platokouki H, Fischer K, Gouw SC, et al. Vaccinations are not associated with inhibitor development in boys with severe haemophilia A. Haemophilia. 2018; 24: 283–290.

111. Fischer K, Collins PW, Ozelo MC, et al. When and how to start prophylaxis in boys with severe hemophilia without inhibitors: Communication from SSc of the ISTH. J Thromb Haemost. 2016; 14: 1105–1109.

112. http: //www.euhanet.org/, přístup 22. 6. 2020.

Labels
Haematology Internal medicine Clinical oncology

Article was published in

Transfusion and Haematology Today

Issue 1

2021 Issue 1

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#