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Non-genetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report.

Astermark, Jan LU ; Altisent, C; Batorova, A; Diniz, M J; Gringeri, A; Holme, P A; Karafoulidou, A; Lopez-Fernández, M F; Reipert, B M and Rocino, A, et al. (2010) In Haemophilia May 4. p.747-766
Abstract
Summary. The development of inhibitors to the infused factor in patients with haemophilia is a serious clinical problem. Recent evidence suggests that alongside the strong genetic contribution to inhibitor formation, there are a number of non-genetic factors - perceived by the immune system as danger signals - which promote formation of inhibitors. This study provides a comprehensive review of clinical studies relating to these factors and also presents a survey of opinion concerning their importance and clinical influence, conducted among the members of the European Haemophilia Treatment Standardisation Board (EHTSB). Taken together, this information highlights the lack of robust data concerning the influence of several non-genetic risk... (More)
Summary. The development of inhibitors to the infused factor in patients with haemophilia is a serious clinical problem. Recent evidence suggests that alongside the strong genetic contribution to inhibitor formation, there are a number of non-genetic factors - perceived by the immune system as danger signals - which promote formation of inhibitors. This study provides a comprehensive review of clinical studies relating to these factors and also presents a survey of opinion concerning their importance and clinical influence, conducted among the members of the European Haemophilia Treatment Standardisation Board (EHTSB). Taken together, this information highlights the lack of robust data concerning the influence of several non-genetic risk factors on inhibitor development, and an urgent need for prospective, well-conducted studies that adhere to recommendations made by the European Medicines Agency (EMEA) for studying inhibitors. Based on current literature, the EHTSB formulated consensus recommendations. It is desirable to minimize intensive treatment wherever possible, given the clinical situation. Prophylaxis should be offered to all children, although we still need to determine optimal dosing with respect to inhibitor development, and age for starting treatment. Vaccinations should be given subcutaneously and concomitant factor concentrate infusions avoided. According to the board, there is no evidence in the literature supporting suggestions that the type of concentrate influences inhibitor risk; but all patients should be monitored during their first exposures. Furthermore, there is no evidence to support an association between pregnancy-related issues, breast feeding and treatment-related factors (e.g. route of administration, or use of blood components) and inhibitor development. (Less)
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Contribution to journal
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published
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Haemophilia
volume
May 4
pages
747 - 766
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000281218400006
  • pmid:20398077
  • scopus:77955928309
ISSN
1351-8216
DOI
10.1111/j.1365-2516.2010.02231.x
language
English
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yes
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5df5bd9f-515a-488c-a18d-0af3bce09042 (old id 1595156)
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http://www.ncbi.nlm.nih.gov/pubmed/20398077?dopt=Abstract
date added to LUP
2010-05-04 17:15:04
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2018-07-15 04:20:02
@article{5df5bd9f-515a-488c-a18d-0af3bce09042,
  abstract     = {Summary. The development of inhibitors to the infused factor in patients with haemophilia is a serious clinical problem. Recent evidence suggests that alongside the strong genetic contribution to inhibitor formation, there are a number of non-genetic factors - perceived by the immune system as danger signals - which promote formation of inhibitors. This study provides a comprehensive review of clinical studies relating to these factors and also presents a survey of opinion concerning their importance and clinical influence, conducted among the members of the European Haemophilia Treatment Standardisation Board (EHTSB). Taken together, this information highlights the lack of robust data concerning the influence of several non-genetic risk factors on inhibitor development, and an urgent need for prospective, well-conducted studies that adhere to recommendations made by the European Medicines Agency (EMEA) for studying inhibitors. Based on current literature, the EHTSB formulated consensus recommendations. It is desirable to minimize intensive treatment wherever possible, given the clinical situation. Prophylaxis should be offered to all children, although we still need to determine optimal dosing with respect to inhibitor development, and age for starting treatment. Vaccinations should be given subcutaneously and concomitant factor concentrate infusions avoided. According to the board, there is no evidence in the literature supporting suggestions that the type of concentrate influences inhibitor risk; but all patients should be monitored during their first exposures. Furthermore, there is no evidence to support an association between pregnancy-related issues, breast feeding and treatment-related factors (e.g. route of administration, or use of blood components) and inhibitor development.},
  author       = {Astermark, Jan and Altisent, C and Batorova, A and Diniz, M J and Gringeri, A and Holme, P A and Karafoulidou, A and Lopez-Fernández, M F and Reipert, B M and Rocino, A and Schiavoni, M and von Depka, M and Windyga, J and Fijnvandraat, K},
  issn         = {1351-8216},
  language     = {eng},
  pages        = {747--766},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {Non-genetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report.},
  url          = {http://dx.doi.org/10.1111/j.1365-2516.2010.02231.x},
  volume       = {May 4},
  year         = {2010},
}