Optimizing Perioperative Management of Haemophilia B With rFIX-FP: Pharmacokinetic Validation of the Hemoptidose Tool

Surgical management of haemophilia B requires precise factor IX replacement to ensure adequate haemostasis while optimizing factor consumption. Extended half-life rFIX-FP simplifies perioperative management but exhibits substantial pharmacokinetic variability. PK-guided dosing is recommended by WFH guidelines, yet validated tools for perioperative rFIX-FP individualization are lacking.

To validate a population PK model under perioperative conditions and evaluate Hemoptidose, a model-informed precision dosing (MIPD) platform, for individualizing rFIX-FP therapy during surgery.

We retrospectively analyzed 24 surgeries in haemophilia B patients treated with rFIX-FP. Predictive performance was assessed at population level and after Bayesian individualization with varying numbers of FIX samples. Actual perioperative consumption was retrospectively compared with Hemoptidose-recommended doses.

The population PK model demonstrated robust perioperative performance. Population predictions yielded a mean absolute error (MAE) of 20.6%; after Bayesian updating, accuracy improved with MAE of 10.0%. Prediction error decreased from 20.6% without monitoring to 14% with three samples. Retrospective analysis indicated a potential 49% reduction in factor consumption with model-guided dosing compared to empirical regimens (p < 0.001).

The population PK model retains valid predictive performance in surgical settings. Two to three FIX measurements enable reliable individualization. The substantial discrepancy between empirical and model-guided dosing highlights major optimization potential. Hemoptidose provides accessible MIPD implementation for perioperative rFIX-FP management.