RSS-Feed abonnieren
DOI: 10.1055/s-0038-1642479
Incidence of Factor VIII Inhibitor Development in Hemophilia A Patients Treated with Less Pure Plasma Derived Concentrates
Publikationsverlauf
Received 23. April 1993
Accepted after revision 12. Januar 1994
Publikationsdatum:
06. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199405/lookinside/thumbnails/10-1055-s-0038-1642479-1.jpg)
Summary
Very-high-purity Factor VIII concentrates produced by monoclonal or recombinant technology have been postulated to be more antigenic resulting in an increased risk of inhibitor development in hemophilia A patients. However, previous reports, mainly based on prevalence figures, may have understimated the “true” risk of this complication in patients treated with less pure Factor VIII concentrates. The present study, started in 1975, has been designed to calculate the risk of inhibitor development in patients with severe or moderate hemophilia A, followed since their first exposure to intermediate or high-purity Factor VIII concentrates, produced by conventional technologies. Sixty-four hemophiliacs fulfilled the enrollment criteria. Inhibitors developed in 20.3% (13/64) of all patients and in 23% (11/48) of those with severe Factor VIII deficiency. Eleven patients manifested a strong anamnestic response after exposure to Factor VIII (high responders) and 2 had low inhibitor concenlialions despite repeated Factor Vlll infusions (low responders). The incidence of inhibitor development was 24.6 per 1000 patient yeuis of observalion. The, cumulative! risk of inhibitor formation was 19,9% at age of 6 years, and 20.3% at 5 years after the first exposure. The risk was 19.3% at 70 days of exposure to Factor VIII concentrates, and 17.2% after a total of 50,000 units of Factor VIII given.
Further stuides are needed to confirm the above risk of acquiring an inhibitor, which indicates and under-estimations by previous studies. In addition, more data is needed to demonstrate whether very high purity Factor VIII concentrates may be more antigenie than conventional preparations.
-
References
- 1 Seremetis S, Aledort L, Lusher J, Hilgartner M, Mannucci PM, Mariani G. Highly purified factor VIII concentrates: will we see more inhibitors?. Thromb Haemost 1991; 65: 1160
- 2 Lusher JM, Arkin S, Abilgaard CF, Schwartz RS. and the Kogenate Previously Untreated Patient Group. Recombinant FVIII for the previously untreated patients with Hemophilia A. Safety, efficacy and development of inhibitors. N Engl J Med 1993; 328: 453-9
- 3 Bray GL, Courter S, Lynes M, Lee M, Gomperts E. and the Recombinate Study Group. Safety, efficacy and inhibitor risk of recombinant factor VIII (Recombinate) in a cohort of previously untreated patients (PUPs) with severe hemophilia A. Thromb Haemost 1993; 69: 1205
- 4 Lusher JM, Salzman P. and the Monoclate Study Group. Viral safety and inhibitor development associated with factor VIII: C ultrapurified from plasma in hemophiliacs previously unexposed to factor VIII concentrates. Semin Hematol 1990; 27 (02) 1-7
- 5 Strauss HS. Acquired circulating anticoagulants in hemophilia A. N Engl J Med 1969; 281: 866-73
- 6 Mannucci PM, Ruggeri Z. Circulating anticoagulants in hemophilia. Lancet 1970; 2: 1360
- 7 Ikkala E, Simon O. Factor VIII inhibitors and the use of blood products in patients with hemophilia A. Scand J Haematol 1971; 8: 16
- 8 Brinkhous KM, Roberts HR, Weiss AE. Prevalence of inhibitors in hemophilia A and B. Thromb Diath Haemorrh 1972; 51 (Suppl) 315-321
- 9 Kasper CK. Incidence and course of inhibitors among patients with classic hemophilia. Thromb Diath Haemorrh 1973; 30: 263-271
- 10 Biggs R. Jaundice and antibodies directed against factors VIII and IX in patients treated for hemophilia or Christmas disease in the United Kingdom. Br J Haematol 1974; 26: 313
- 11 Gill FM. The natural history of Factor VIII inhibitors in patients with hemophilia A. Prog Clin Biol Res 1984; 150: 19-29
- 12 Ikkala E, Helsket T, Myllyla G, Nevalinna HR, Pittanen P, Rasi V. Changes in the life expectancy of patients with severe hemophilia in Finland in 1930–1979. Br J Haematol 1982; 52: 7
- 13 Larsson SA. Life expectancy of Swedish hemophiliacs 1831–1980. Br J Haematol 1985; 59: 593
- 14 Rosendaal FR, Varekamp I, Smit C. Mortality and causes of death in Dutch haemophiliacs 1973–1986. Br J Haematol 1987; 24: 241-5
- 15 Schwarzinger I, Pabinger I, Kominger C, Haschke F, Kundi M, Niessner H, Lechner K. Incidence of inhibitors in patients with severe and moderate hemophilia A treated with Factor VIII concentrates. Am J Hematol 1987; 24: 241-5
- 16 Me Millan 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. Observation on the initial development of factor VIII: C inhibitors. N Engl JMed 1988; 71: 344-8
- 17 Rasi V, Ikkala E. Haemophiliacs with factor VIII inhibitors in Finland: prevalence incidence and outcome. Br J Haematol 1990; 76: 369-71
- 18 Kasper CK, Aledort LM, Counts RB, Edson JR, Fratantoni J, Green D, Hampton JW, Hilgartner MW, Lazerson J, Levine PH, Me Millan CW, Pool JG, Shapiro SS, Shulman NR, van Eys J. A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34: 869-72
- 19 Ehrenforth S, Kreuz W, Scharrer I, Linde R, Funk M, Gungor T, Krack- hardt B, Kornhuber B. Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. Lancet 1992; 339: 594-8
- 20 Addiego J, Kasper C, Abilgaard C, Hilgartner M, Lusher J, Glader B, Aledort L. Frequency of inhibitor development in hemophiliacs treated with low-purity factor VIII. Lancet 1993; 342: 462-4