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Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia

Collins, Peter William, Fischer, K., Morfini, M., Blanchette, V. S. and Borkman, S. 2011. Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia. Haemophilia 17 (1) , pp. 2-10. 10.1111/j.1365-2516.2010.02370.x

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Abstract

The pharmacokinetic (PK) response to factor VIII (FVIII) and factor IX varies between patients and this has important clinical implications for treatment. Although PK is affected by patient characteristics, this relationship is too weak to infer a result for an individual and, if required, PK must be measured. An important determinant of the efficacy of prophylaxis is the length of time an individual spends with a low level of coagulation factor. This time is more dependent on the patient's coagulation factor half-life and the frequency of dosing than in vivo recovery and dose infused. Improved understanding of the effect of PK and dose frequency on factor levels in patients on prophylaxis will help tailor regimens to individuals better and allow more cost effective use of coagulation factor concentrates. Calculations suggest that adults need less FVIII per kg body weight than children. The effect of half-life on trough levels questions the logic of Monday, Wednesday, Friday dosing and suggests a role for innovative regimens including low-dose daily treatment which leads to either higher trough levels or decreased FVIII requirement. This may expand access to prophylaxis in healthcare systems with limited resources and potentially improve patient outcomes. The ideal trough level will vary between individuals and at different times of their lives and may be <1 IU dL)1. If PK is to be used in routine clinical practice, a simplified method for its measurement is required and this methodology is becoming available.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: break through bleeding, half-life, pharmacokinetics, prophylaxis, trough
Publisher: Wiley-Blackwell
ISSN: 1351-8216
Last Modified: 04 Jun 2017 03:46
URI: http://orca.cf.ac.uk/id/eprint/26445

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