Researchers have reported that a personalized approach to estimating factor VIII (FVIII) half-life led to fewer errors and better accuracy and published their findings in the Journal of Thrombosis and Hemostasis.

Hemophilia A is characterized by a deficiency in FVIII, which can result in spontaneous bleeds, some of which can be life-threatening. The most common remedy for this disease is factor replacement therapy, which aims to keep FVIII levels above a target threshold.

Studies indicate that considerable interindividual variability exists in FVIII pharmacokinetics. Hence, physicians are increasingly turning towards a personalized treatment approach by tailoring dosing according to pharmacokinetic data. Population pharmacokinetic modeling and Bayesian methods are often used to estimate pharmacokinetic parameters from sparse samples in personalized prophylaxis. 


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Guidelines from the International Society on Thrombosis and Hemostasis recommend that samples be taken during specific time windows to estimate FVIII half-lives. However, the recommended time window may not be optimal at an individual level, considering that pharmacokinetics differ between individuals.

The authors of the study hence proposed evaluating a personalized limited sampling approach that can suggest a next sampling time point that provides for a more accurate estimate of FVIII half-lives.

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They evaluated the personalized limited sampling approach by extracting rich sampling pharmacokinetic data on standard half-life and extended half-life FVIII concentrates from the Web-Accessible Population Pharmacokinetic Service — Hemophilia. Two evaluation sets were created: one using the personalized limited sampling approach and another using the random sampling approach.

“The evaluation of this [personalized limited sampling] approach showed that half-life could be accurately estimated with an error always lower than 20% using only 2 samples,” the authors said.

A personalized limited sampling approach can also reduce clinic visits if physicians obtain 1 sampling at trough shortly before the infusion of FVIII, and another at peak shortly after FVIII infusions. Both of these samples can be taken during the same clinic visit, preventing unnecessary hassle for patients with hemophilia.

Reference

Chelle P, Iorio A, Edginton AN. A personalized limited sampling approach to better estimate terminal half-life of FVIII concentratesJ Thromb Haemost. Published online June 26, 2022. doi:10.1111/jth.15803