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Immune tolerance induction in patients with hemophilia A

Astermark, Jan LU (2011) In Thrombosis Research 127. p.6-9
Abstract
Replacement therapy with factor VIII (FVIII) concentrates has become the mainstay of treatment for hemophilia, but about 30% of patients with a severe disease develop neutralizing antibodies against FVIII, which can lead to treatment resistance and an increased risk of bleeding. Immune tolerance induction (ITI) overcomes the immune response to FVIII concentrates in the majority of patients. Several factors may influence the efficacy of ITI, including disease-related factors (e. g. peak inhibitor titer and pre-ITI titer), and genetic factors (e. g. type of mutation). Treatment-related factors, such as the type of FVIII concentrate used in ITI will also potentially influence the outcome. Specifically, higher success rates with von Willebrand... (More)
Replacement therapy with factor VIII (FVIII) concentrates has become the mainstay of treatment for hemophilia, but about 30% of patients with a severe disease develop neutralizing antibodies against FVIII, which can lead to treatment resistance and an increased risk of bleeding. Immune tolerance induction (ITI) overcomes the immune response to FVIII concentrates in the majority of patients. Several factors may influence the efficacy of ITI, including disease-related factors (e. g. peak inhibitor titer and pre-ITI titer), and genetic factors (e. g. type of mutation). Treatment-related factors, such as the type of FVIII concentrate used in ITI will also potentially influence the outcome. Specifically, higher success rates with von Willebrand factor (VWF)-containing factor VIII concentrates than with high-purity FVIII concentrates have been reported, but further studies are needed. Potential mechanisms involved include steric hindrance, inhibition of FVIII degradation, or immunomodulatory effects. However, the exact mechanism by which immune tolerance is induced remains unclear. High-dose FVIII ITI appears to induce immune tolerance more rapidly than low-dose protocols and with a reduced risk of bleeding episodes. The addition of immunosuppressive therapy, such as rituximab, to ITI may improve outcomes, although the optimal approach to combined ITI/immunosuppression has not been established. Ongoing studies are likely to provide further insight into the role of genetic features and the type of FVIII concentrate on the success rate of ITI. (C) 2010 Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Hemophilia, Immune tolerance, Factor VIII (FVIII), von Willebrand, factor (VWF), FVIII/VWF concentrate
in
Thrombosis Research
volume
127
pages
6 - 9
external identifiers
  • wos:000286134600003
  • scopus:78651406684
ISSN
1879-2472
DOI
10.1016/j.thromres.2010.10.006
language
English
LU publication?
yes
id
9173e509-7c5f-4559-b68e-e5b92204cdf7 (old id 1790672)
date added to LUP
2011-03-02 14:42:52
date last changed
2017-01-01 03:46:07
@article{9173e509-7c5f-4559-b68e-e5b92204cdf7,
  abstract     = {Replacement therapy with factor VIII (FVIII) concentrates has become the mainstay of treatment for hemophilia, but about 30% of patients with a severe disease develop neutralizing antibodies against FVIII, which can lead to treatment resistance and an increased risk of bleeding. Immune tolerance induction (ITI) overcomes the immune response to FVIII concentrates in the majority of patients. Several factors may influence the efficacy of ITI, including disease-related factors (e. g. peak inhibitor titer and pre-ITI titer), and genetic factors (e. g. type of mutation). Treatment-related factors, such as the type of FVIII concentrate used in ITI will also potentially influence the outcome. Specifically, higher success rates with von Willebrand factor (VWF)-containing factor VIII concentrates than with high-purity FVIII concentrates have been reported, but further studies are needed. Potential mechanisms involved include steric hindrance, inhibition of FVIII degradation, or immunomodulatory effects. However, the exact mechanism by which immune tolerance is induced remains unclear. High-dose FVIII ITI appears to induce immune tolerance more rapidly than low-dose protocols and with a reduced risk of bleeding episodes. The addition of immunosuppressive therapy, such as rituximab, to ITI may improve outcomes, although the optimal approach to combined ITI/immunosuppression has not been established. Ongoing studies are likely to provide further insight into the role of genetic features and the type of FVIII concentrate on the success rate of ITI. (C) 2010 Elsevier Ltd. All rights reserved.},
  author       = {Astermark, Jan},
  issn         = {1879-2472},
  keyword      = {Hemophilia,Immune tolerance,Factor VIII (FVIII),von Willebrand,factor (VWF),FVIII/VWF concentrate},
  language     = {eng},
  pages        = {6--9},
  series       = {Thrombosis Research},
  title        = {Immune tolerance induction in patients with hemophilia A},
  url          = {http://dx.doi.org/10.1016/j.thromres.2010.10.006},
  volume       = {127},
  year         = {2011},
}