Presented in abstract form at the 29th meeting of the World Federation of Haemophilia, Buenos Aires, Argentina, 13 July 2010 [†].
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ORIGINAL ARTICLE
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Surgery and inhibitor development in hemophilia A: a systematic review
Article first published online: 29 SEP 2011
DOI: 10.1111/j.1538-7836.2011.04467.x
© 2011 International Society on Thrombosis and Haemostasis
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How to Cite
ECKHARDT, C. L., van der BOM, J. G., VAN DER NAALD, M., PETERS, M., KAMPHUISEN, P. W. and FIJNVANDRAAT, K. (2011), Surgery and inhibitor development in hemophilia A: a systematic review. Journal of Thrombosis and Haemostasis, 9: 1948–1958. doi: 10.1111/j.1538-7836.2011.04467.x
Publication History
- Issue published online: 29 SEP 2011
- Article first published online: 29 SEP 2011
- Accepted manuscript online: 12 AUG 2011 06:03PM EST
- Received 20 April 2011, accepted 2 August 2011
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Keywords:
- antibody;
- hemophilia A;
- intensive FVIII exposure;
- risk factor;
- surgery;
- systematic review
Summary. Background: Although the association between intensive treatment and the formation of inhibiting antibodies towards factor VIII (FVIII) in hemophilia A has been demonstrated, the contributing effect of surgery is presently unclear. The release of immunological danger signals resulting from tissue damage during surgery in the presence of a high FVIII antigen load may elicit the formation of FVIII antibodies. The aim of this systematic review was to investigate the role of surgery in the inhibitor risk associated with intensive treatment as compared with treatment for bleeding and prophylactic administration of FVIII. Methods: A comprehensive literature search was performed that identified four cohort studies and three case control studies, comprising 342 inhibitor patients among a total of 957 hemophilia A patients. Results: Intensive treatment increased the inhibitor risk, most pronounced with intensive treatment of ≥ 5 exposure days (EDs) compared with < 3 EDs (OR, 4.1; 95% confidence interval, 2.6–6.5). Pooled odds ratio for inhibitor development in severe hemophilia patients that received intensive treatment for surgery at first exposure was 4.1 (95% confidence interval, 2.0–8.4) compared with treatment for bleeding or prophylaxis. Information on continuous infusion, previously treated patients and non-severe hemophilia A was insufficient for valid meta-analyses. Conclusions: Intensive FVIII treatment for surgery at first exposure leads to a higher inhibitor risk in hemophilia A patients compared with intensive treatment for bleeding.