Subscribe to RSS
DOI: 10.1055/s-0037-1613376
Age at first treatment and immune tolerance to factor VIII in severe hemophilia
Publication History
Received
12 November 2002
Accepted after revision
30 December 2002
Publication Date:
09 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200303/lookinside/thumbnails/10-1055-s-0037-1613376-1.jpg)
Summary
Findings from a recent study suggest that earlier start of treatment with factor VIII in patients with severe hemophilia is associated with a higher risk to develop inhibitors.
We set out to assess the association between age of first administration of clotting factor VIII and the risk to develop inhibitors in infants with severe hemophilia A.
This work was a cohort study, carried out in the national hemophilia treatment center. The study included eighty-one consecutive patients with severe hemophilia A who received their first dose of factor VIII between 1975 and 1998. Patients were followed until their last visit in 2001 or 2002.
The average follow-up was 16 years (range 3-26). Persistent inhibitory antibodies developed in 12 of 81 patients (15%).
Cumulative incidence at 100 exposure days was 34% (95% confidence interval 7-61%) in patients starting therapy before the age of 6 months, 20% (4-36%) in patients starting therapy between 6 months and 1 year, 13% (0-27%) in those starting therapy between 1 and 1.5 years, and 0% in those who started therapy beyond 1.5 years of age (p for trend 0.03).
Our findings confirm that age of first factor VIII administration in children with severe hemophilia A is inversely associated with the risk to develop antibodies against factor VIII. The role of confounding factors such as the type of factor VIII mutation and environmental factors needs to be evaluated.
-
References
- 1 Scharrer I, Bray GL, Neutzling O. Incidence of inhibitors in haemophilia A patients – a review of recent studies of recombinant and plasma-derived factor VIII concentrates. Haemophilia 1999; 5 (03) 145-54.
- 2 Briet E, Rosendaal FR, Kreuz W, Rasi V, Peerlinck K, Vermylen J. et al High titer inhibitors in severe haemophilia A. A meta-analysis based on eight long-term follow-up studies concerning inhibitors associated with crude or intermediate purity factor VIII products [letter]. Thromb Haemost 1994; 72 (01) 162-4.
- 3 Gilles JG, Jacquemin MG, Saint RJ. Factor VIII inhibitors. Thromb Haemost 1997; 78 (01) 641-6.
- 4 Kaplan J, Genyea C, Secord E. Factor VIII inhibitors. Potential for prevention of inhibitor formation by immune tolerance. Semin Thromb Hemost 2000; 26 (02) 173-8.
- 5 Holt PG, Jones CA. The development of the immune system during pregnancy and early life. Allergy 2000; 55 (08) 688-97.
- 6 Murphy MS, Harrison R, Davies P, Buckels JA, Mayer AD, Hubscher S. et al Risk factors for liver rejection: evidence to suggest enhanced allograft tolerance in infancy. Arch Dis Child 1996; 75 (06) 502-6.
- 7 Lorenzo I J, Lopez A, Altisent C, Aznar JA. Incidence of factor VIII inhibitors in severe haemophilia: the importance of patient age. Br J Haematol 2001; 113 (03) 600-3.
- 8 Mauser-Bunschoten EP, Van Der Bom JG, Bongers M, Twijnstra M, Roosendaal G, Fischer K. et al Purity of factor VIII product and incidence of inhibitors in previously untreated patients with haemophilia A. Haemophilia 2001; 7 (04) 364-8.
- 9 World Medical Association declaration of Helsinki Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997; 277 (11) 925-6.
- 10 Kasper CK, Aledort LM, Counts RB, Edson JR, Fratantoni J, Green D.. et al A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34: 869
- 11 Mauser-Bunschoten EP, Rosendaal FR, Nieuwenhuis HK, Roosendaal G, Briet E, van den Berg HM. Clinical course of factor VIII inhibitors developed after exposure to a pasteurised Dutch concentrate compared to classic inhibitors in hemophilia A. Thromb Haemost 1994; 71 (06) 703-6.
- 12 Oldenburg J, Brackmann HH, Schwaab R. Risk factors for inhibitor development in hemophilia A. Haematologica 2000; 85 (Suppl. 10) 7-13.
- 13 Mauser-Bunschoten EP, Nieuwenhuis HK, Roosendaal G, van den Berg HM. Low-dose immune tolerance induction in hemophilia A patients with inhibitors. Blood 1995; 86 (03) 983-8.