Incidence of Factor VIII Inhibitor Development in Severe Hemophilia A Patients Treated only with One Brand of Highly Purified Plasma-Derived Concentrate

Summary

The incidence of factor VIII inhibitor was studied in a cohort of 56 previously untreated patients with severe hemophilia A (factor VIII below 1 U/dl). They received only one brand of highly purified factor VIII concentrate (HPSD-VIII) prepared by conventional chromatography with a solvent-detergent step for viral inactivation. Followup since the first infusion of HPSD-VIII was from 1 to 76 months (mean = 29) and cumulative exposure days (CED) from 1 to over 100 (median = 26). Five patients (9%) developed an inhibitor after 6 to 19 CED, only one being a high responder (2%), showing a low incidence of inhibitor compared with previous studies using high purity plasma- derived or recombinant products.

• References

• 1 Mannucci PM. Modern treatment of hemophilia: From the shadows towards the light. Thromb Haemost 1993; 70: 17-23
• 2 Lusher JM. Viral safety and inhibitor development associated with monoclonal antibody-purified FVIIIC. Ann Hematol 1991; 63: 138-141
• 3 Addiego JE, Gomperts E, Liu SL, Bailey P, Courter SG, Lee ML, Neslund GG, Kingdon HS, Griffith MJ. Treatment of hemophilia A with a highly purified factor VIII concentrate prepared by anti-FVIIIC immunoaffinity chromatography. Thromb Haemost 1993; 67: 19-27
• 4 Lusher JM, Arkin S, Abildgaard CF, Schwartz RS. the Kogenate previously untreated patients study group. Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. N Engl J Med 1993; 328: 453-459
• 5 Lusher JM, Arkin S, Abildgaard CF, Inwood M, Zimmermann R, Hiltgartner M, Hurst D. And the Kogenate PUP study group. Inhibitor development in previously untreated patients (PUPS) with hemophilia receiving Kogenate: 4.5 year follow-up data, including response to immune tolerance with Kogenate Blood 1993; 82 Suppl (Suppl. 01) 153 abstract
• 6 Bray GL, Gomperts E, Courter S, Gruppo EM, Manco-Johnson M, Shapiro A, Scheibel M, White G, Lee M. And the Recombinate Study Group. A multicenter study of recombinant factor VIII (Recombinate): Safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A Blood 1994; 83: 2428-2435
• 7 Ehrenforth S, Kreuz W, Scharrer I, Linde R, Funk M, Giingor T, Krackhardt B, Kornhuber B. Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. Lancet 1992; 339: 594-598
• 8 Ljung R, Petrini P, Lindgren AC, Tengbom L, Nilsson IM. Factor VIII and factor IX inhibitors in haemophiliacs. Lancet 1992; 339: 1550
• 9 Addiego J, Kasper C, Abildgaard C, Hiltgartner M, Lusher J, Glader B, Aledort L. Frequency of inhibitor development in haemophiliacs treated with low-purity factor VIII. Lancet 1993; 342: 462-464
• 10 de Biasi R, Rocino A, Papa ML, Salerno E, Mastrullo L, De Blasi D. Incidence of factor VIII inhibitor development in hemophilia A patients treated with less pure plasma derived concentrates. Thromb Haemost 1994; 71: 544-547
• 11 Aledort LM. World registry on factor VIII inhibitor patients: Why. Sem Hematol 1993; 30 (02) Suppl (Suppl. 01) 7-9
• 12 Scharrer I, Neutzling O. Incidence of inhibitors in haemophiliacs. A review of the literature Blood Coag Fibrinol 1993; 4: 753-758
• 13 Burnouf T, Bumouf-Radosevich M, Huart JJ, Goudemand M. A highly purified factor VIII :C concentrate prepared from cryoprecipitate by ion- exchange chromatography. Vox Sang 1991; 60: 8-15
• 14 Guérois C, Parquet A, Vicariot M, Ferrer-Lecoeur F, Maisonneuve P, Couroucé AM, Dubois F, Laurian Y. Efficacité de 1’inactivation virale des concentrés de facteur VIII et IX par procédé solvant-détergent. Presse Méd 1991; 20: 1163-1166
• 15 Goudemand J, Parquet A, d’Oiron R, Stieltjes N, Guérois C, Fonlupt J, Alcalay M, Négrier C, Cazenave JP, Briquel ME, Fressinaud E. Hepatitis A in French hemophiliacs. Vox Sang 1994; 67 Suppl (Suppl. 01) 9-13
• 16 Langdell RD, Wagner RH, Brinkhous KM. Effect of antihemophilic factor on one-stage clotting test. J Lab Clin Med 1953; 41: 637-647
• 17 Kasper CK, Aledort LM, Counts RB, Edson JR, Fratantoni J, Green D, Hampton JW, Hilgartner MW, Lazerson J, Levine PH, McMillan CW, Pool JG, Shapiro SS, Shulman NR, van Eys J. A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34: 869-872
• 18 Goldsmith JC. Diagnosis of factor VIII versus nonspecific inhibitors. Sem Hematol 1993; 30 (02) Suppl (Suppl. 01) 3-6
• 19 Commercial clinical documentation from Armour Pharmaceutical Company. 1994
• 20 McMillan CW, Shapiro SS, Whitehurst D, Hoyer LW, Rao AV, Lazerson J. And the Hemophilia Study Group. The natural history of factor VIII inhibitors in patients with hemophilia A: A national cooperative study.II Observations on the initial development of factor VIII: C inhibitors Blood 1988; 71: 344-348
• 21 Macik BG. Treatment of factor VIII inhibitors. Sem Thromb Haemost 1993; 19: 13-24
• 22 Peerlinck K, Arnout J, Gilles JG, Saint-Remy JM, Vermylen J. A higher than expected incidence of factor VIII inhibitors in multitransfused haemophilia A patients treated with an intermediate purity pasteurized factor VIII concentrate. Thromb Haemost 1993; 69: 115-118
• 23 Rosendaal FR, Nieuwenhuis HK, van den Berg HM, Heijboer H, Mauser-Bunschoten EP, van der Meer J, Smit C, Strengers PF W, Briet E. And the Dutch Hemophilia Study Group. A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands Blood 1993; 81: 2180-2186