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Semin Thromb Hemost 2015; 41(08): 860-863
DOI: 10.1055/s-0035-1552562
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Kathelijn Fischer
1   Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands
2   Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
,
Erik Berntorp
3   Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, Malmö, Sweden
4   Malmö Centre for Thrombosis and Haemostasis, Skåne University Hospital, Malmö, Sweden
› Author Affiliations
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Publication History

Publication Date:
09 October 2015 (online)

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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.

Keywords

prophylaxis - pharmacokinetics - trough level - peak level
 

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