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Targeting Factor Replacement Therapy in Severe Hemophilia: Which Level Is Important?

Fischer, Kathelijn and Berntorp, Erik LU (2015) In Seminars in Thrombosis and Hemostasis 41(8). p.860-863
Abstract
The original aim of prophylactic replacement therapy was to convert the bleeding pattern of severe hemophilia to that of moderate hemophilia through regular infusions of clotting factor concentrates. However, targeting prophylaxis on minimum trough levels does not prevent all bleeding. At the group level, there is a clear association of factor levels with bleeding and outcome. But bleeding phenotype in individual patients shows large variation, independent of trough levels maintained. The association of peak levels with bleeding on prophylaxis is not established. Experience with surgery suggests that certain peak levels need to be achieved during other hemostatic challenges, such as playing sports. Individualization of prophylaxis should... (More)
The original aim of prophylactic replacement therapy was to convert the bleeding pattern of severe hemophilia to that of moderate hemophilia through regular infusions of clotting factor concentrates. However, targeting prophylaxis on minimum trough levels does not prevent all bleeding. At the group level, there is a clear association of factor levels with bleeding and outcome. But bleeding phenotype in individual patients shows large variation, independent of trough levels maintained. The association of peak levels with bleeding on prophylaxis is not established. Experience with surgery suggests that certain peak levels need to be achieved during other hemostatic challenges, such as playing sports. Individualization of prophylaxis should include timing of infusion according to special activities. The clinical relevance of factor levels is even more urgent since the recent introduction of long-acting clotting factor concentrates with their different pharmacokinetic profiles and the prospect of gene therapy resulting in constant factor levels. It should be considered that the success of any prophylactic regimen is also dependent on other factors, such as the age at initiation of prophylaxis, adherence, lifestyle, cartilage susceptibility, and the other components of the clotting system. Factor levels are thus an important but quite small piece in the total picture of treating hemophilia and we currently cannot identify a specific trough or peak level to use for monitoring. At the same time, knowledge of a patients' level during the infusion intervals may help to individualize and adjust treatment according to the clinical symptoms. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Seminars in Thrombosis and Hemostasis
volume
41
issue
8
pages
860 - 863
publisher
Georg Thieme Verlag
external identifiers
  • pmid:26451746
  • wos:000364569900008
  • scopus:84946710809
ISSN
1098-9064
DOI
10.1055/s-0035-1552562
language
English
LU publication?
yes
id
7da50111-1747-4c90-bbb7-e7b89b2fa5ca (old id 8155609)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26451746?dopt=Abstract
date added to LUP
2015-11-03 11:07:54
date last changed
2017-07-02 03:14:56
@article{7da50111-1747-4c90-bbb7-e7b89b2fa5ca,
  abstract     = {The original aim of prophylactic replacement therapy was to convert the bleeding pattern of severe hemophilia to that of moderate hemophilia through regular infusions of clotting factor concentrates. However, targeting prophylaxis on minimum trough levels does not prevent all bleeding. At the group level, there is a clear association of factor levels with bleeding and outcome. But bleeding phenotype in individual patients shows large variation, independent of trough levels maintained. The association of peak levels with bleeding on prophylaxis is not established. Experience with surgery suggests that certain peak levels need to be achieved during other hemostatic challenges, such as playing sports. Individualization of prophylaxis should include timing of infusion according to special activities. The clinical relevance of factor levels is even more urgent since the recent introduction of long-acting clotting factor concentrates with their different pharmacokinetic profiles and the prospect of gene therapy resulting in constant factor levels. It should be considered that the success of any prophylactic regimen is also dependent on other factors, such as the age at initiation of prophylaxis, adherence, lifestyle, cartilage susceptibility, and the other components of the clotting system. Factor levels are thus an important but quite small piece in the total picture of treating hemophilia and we currently cannot identify a specific trough or peak level to use for monitoring. At the same time, knowledge of a patients' level during the infusion intervals may help to individualize and adjust treatment according to the clinical symptoms.},
  author       = {Fischer, Kathelijn and Berntorp, Erik},
  issn         = {1098-9064},
  language     = {eng},
  number       = {8},
  pages        = {860--863},
  publisher    = {Georg Thieme Verlag},
  series       = {Seminars in Thrombosis and Hemostasis},
  title        = {Targeting Factor Replacement Therapy in Severe Hemophilia: Which Level Is Important?},
  url          = {http://dx.doi.org/10.1055/s-0035-1552562},
  volume       = {41},
  year         = {2015},
}