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38E.P. Mauser-Bunschoten et al.Table 4. Present prophylactic regimen, bleeding frequency, last recovery and half-life time in immune tolerized patients.Pat. Year of birth Prophylactic dose Number of Number of Last inhibitor titer Recovery (percentage) Half-life time (hours)(U FVIII/kg bw) bleeds per year surgical (BU/mL)interventions1 1975 † 1996 0 Neg 80% 12 hrs2 1982 10 U/kg bw 2× week 0-5 0 Neg (0.0) 100% 14 hrs3 1983 15 U/kg bw 3× week 0-5 0 Neg (0.0) 110% 15 hrs4 1984 10-15 U/kg bw 3× week 0-5 1 Neg (0.0) 110% 18 hrs5 1979 10 U/kg bw 3×week 0-5 0 Neg (0.1) 100% 12 hrs6 1984 10-15 U/kg bw 3×week 5-10 0 Neg (0.0) 100% 12 hrs7 1993 25 U/kg bw 3×week 5-10 1 Neg (0.1) 100% 10 hrs8 1989 20 U/kg bw 3×week 5-10 3 Neg (0.1) 110% 6 hrs9 1985 15 U/kg bw 2×week 0-5 0 Neg (0.0) 80% 8 hrs10 1995 25 U/kg bw 3×week 0-5 2 Neg (0.0) 100% 8 hrs11 1996 25 U/kg bw 3×week 0-5 1 Neg (0.1) 100% 6 hrs12 1967 † 1993 1 Neg 100% 12 hrs13 1955 20 U/kg bw 3×week 10-25 5 Neg (0.0) 120% 12 hrs14 1967 † 1993 3 Neg 100% 12 hrs15 1964 10-15 U/kg bw 2×week 0-5 0 Neg (0.0) 120% 12 hrs16 1967 1990 lost for follow-up 0 Neg 60% 7 hrs17 1967 15 U/kg bw 3×week 0-5 1 Neg (0.0) 130% 14 hrs18 1967 10 U/kg bw every other day 0-5 0 Neg (0.0) 90% 12 hrs19 1971 10 U/kg bw 3×week 0-5 0 Neg (0.0) 100% 19 hrs20 1971 10 U/kg bw 3×week 0-5 5 Neg (0.0) 80% 10 hrs21 1975 10-15 U/kg bw 3×week 0-5 0 Neg (0.0) 110% 10 hrs22 1976 10-15 U/kg bw 3×week 0-5 1 Neg (0.0) 100% 8 hrs23 1967 15-20 u/kg bw 3×week 0-5 0 Neg (0.2) 140% 6 hrs24 1974 1985 lost for follow-up 0 Neg 100% 12 hrs25 1987 25 U/kg bw 3×week 0-5 3 Neg (0.0) 100% 9 hrsTable 3. Success of low dose ITT in relation to inhibitor titer.Max titer < 40 BU/mLMax titer > 40 BU/mLNumber of patients 15 12Success 15 6Success after dose adjustment 2Failure 0 2Time needed before success(months)median 6 18range 2-10 12-28ConclusionLow dose ITT (25-50 u FVIII/kg bw 3 × week)is appropriate for patients with low titerinhibitors, for young children in whom aninhibitor just has developed and for patients withhigh titer inhibitors who have a low bleeding frequency.Also for patients in whom ITT has notbeen attempted due to the high costs of otherschedules low dose ITT may be indicated. 18References1. Bloom AL. The treatment of factor VIII inhibitors.Thromb Haemost 1987;58:447-71.2. Lusher JM. Management of patients with factor VIIIinhibitors. Transf Med Rev 1987;1:123-30.3. Brackman HH, Gormesen J. Massive factor VIII infusionin a haemophiliac patient with factor VIII inhibitor,high responder. Lancet 1977;2:933.4. Wensley RT, Burn AM, Redding OM. Induction of toleranceto factor VIII in hemophilia with inhibitors usinglow doses of factor VIII. Thromb Haemost 1985;54:227-30.5. Mauser-Bunschoten EP, Nieuwenhuis HK, RoosendaalR, van den Berg HM. Low-dose immune toleranceinduction in hemophilia A patients with inhibitors.Blood 1995;86:983-8.6. Ewing NP, Sanders NL, Dietrich SL, Kasper CK. Inductionof immune tolerance to factor VIII in hemophiliacswith inhibitors. JAMA 1988;259:65-8.7. Oldenburg J, Schwaab R, Brackmann HH. Induction ofimmune tolerance in haemophilia A inhibitor patientsby the “Bonn protocol”: Predictive parameter for therapyduration and outcome. Vox Sang 1999;77 Suppl1:49-54.8. Kreuz W, Mentzer D, Auerswald G. Successful immunetolerance therapy of FVIII-inhibitor in children afterchanging from high to intermediate purified FVIII concentrate.Haemophilia 1996;2 Suppl 1:19a[abstract].haematologica vol. 88(supplement n. 12):september 2003
IV International Workshop on Immune Tolerance in Hemophilia399. Aznar JA, Jorquera JI, Peiro A, Garcia I. The importanceof corticoids added to continued treatment with factorVIII concentrates in the suppression of inhibitors inhaemopihilia A. Thromb Haemost 1984;51:217-21.10. Nilsson IM, Berntorp E, Zetterval O. Induction ofimmune tolerance to factor VIII in hemophiliacs withinhibitors, N Eng J Med 1988;318:947-50.11. Van Leeuwen EF, Mauser-Bunschoten EP, van DijkenPJ, Kok AJ, Sjamsoedin-Visser EJ, Sixma JJ. Low doseimmune tolerance induction in hemophilia A patientswith inhibitors. Br J Haematol 1986;64:291-7.12. Van den Berg HM, Fischer K, Mauser-Bunschoten EP,Beek FJA, Roosendaal G, van der Bom JG, et al. Longtermoutcome of individulized prophylactic treatment ofchildren with severe haemophilia. Br J Haematol 2001;112:561-5.13. Rosendaal FR, Nieuwenhuis HK, van den Berg HM, HeijboerH, Mauser-Bunschoten EP, van der Meer J, et al.A sudden increase in factor VIII development in multitransfusedhemophilia A patients in the Netherlands.Blood 1993;81:2180-6.14. Kasper CK, Aledort LM, Counts RB, Edson JG, FratnatoniJ, Green D, et al. A more uniform measurement offactor VIII inhibitors. Thromb Diath Haemorrh 1975;43: 469.15. Verbruggen B, Novakova I, Wessels H, Boezeman J, vanden Berg M, Mauser-Bunschoten E. The Nijmegen modificationof the Bethesda assay for factor VIII:cinhibitors: Improved specificity and reliability. ThrombHaemost 1995;73:247-51.16. Bouma BN, Starkenborg AE. Dilution of haemophilicplasma used as reagent in the determination of antihaemophilicfactor A (factor VIII). Haemostasis 1974;3:94-7.17. Lee ML, Gomperts ED, Kingdom HS. A note on the calculationof recovery for factor VIII infusions. ThrombHaemost 1993; 69:87.18. El Alfy MS, Tnatawy AAG, Ahmed MH, Abdin IA. Frequencyof inhibitor development in severe haemophiliaA children treated with cryoprecipitate and low-doseimmune tolerance induction. Haemophilia 2000; 6:635-8.19. Dimichele DM. Immune tolerance: a synopsis of internationalexperience. Haemophilia 1998; 4:568-73.20. Haya S, Lopez MF, Aznar JA, Battle J. Immune tolerancetreatment in haemophilia patients with inhibitors: theSpanish registry. The Spanish immune tolerance group.Haemophilia 2001; 7:154-9.21. Hay CR. Immune tolerance induction: prospective trials.Haematologica 2000; 85 Suppl:52-6.haematologica vol. 88(supplement n. 12):september 2003
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Index of authorsAhmad, R.U., 56Albe
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