Introduction: Haemophilia A patients require perioperative clotting factor replacement to limit excessive bleeding. Weight-based dosing of Factor VIII (FVIII) does not account for inter-individual pharmacokinetic (PK) variability, and may lead to suboptimal FVIII exposure. Aim: To perform an external validation of a previously developed population PK (popPK) model of perioperative FVIII in haemophilia A patients. Methods: A retrospective chart review identified perioperative haemophilia A patients at the University of North Carolina (UNC) between April 2014 and November 2019. Patient data was used to externally validate a previously published popPK model proposed by Hazendonk. Based on these validation results, a modified popPK model was developed to characterize FVIII PK in our patients. Dosing simulations were performed using this model to compare FVIII target attainment between intermittent bolus (IB) and continuous infusion (CI) administration methods. Results: A total of 521 FVIII concentrations, drawn from 34 patients, were analysed. Validation analyses revealed that the Hazendonk model did not fully capture FVIII PK in the UNC cohort. Therefore, a modified one-compartment model, with weight and age as covariates on clearance (CL), was developed. Dosing simulations revealed that CI resulted in improved target attainment by 16%, with reduced overall FVIII usage by 58 IU/kg, compared to IB. Conclusion: External validation revealed a previously published popPK model of FVIII did not adequately characterize UNC patients, likely due to differences in patient populations. Future prospective studies are needed to evaluate our model prior to implementation into clinical practice.
|Number of pages||10|
|Early online date||17 Aug 2021|
|Publication status||Published - Nov 2021|
Bibliographical noteFunding Information:
JZ is funded by the National Heart, Lung, and Blood Institute (NHBLI), grant number 5T32HL007149-44. RJB was funded by the National Institute of General Medical Sciences (NIGMS), grant number T32GM086330. WS was funded by a UNC-Nuventra PK/PD Fellowship.
JZ is funded by the National Heart, Lung, and Blood Institute (NHBLI), grant number 5T32HL007149‐44. RJB was funded by the National Institute of General Medical Sciences (NIGMS), grant number T32GM086330. WS was funded by a UNC‐Nuventra PK/PD Fellowship.
© 2021 John Wiley & Sons Ltd.