Eltrombopag-Induced Falsely Elevated Bilirubin Concentrations in Enzymatic and Vanadate Oxidation Assays: Involvement of High Serum Eltrombopag Concentrations.

BACKGROUND

The administration of eltrombopag, used to restore low blood count, demonstrates a positive interference of blood bilirubin levels when analyzed through the diazo assay. However, research on bilirubin measurements using other methods is limited. Therefore, using an enzymatic assay, this study aimed to investigate the effect of serum eltrombopag on bilirubin measurements in patients with aplastic anemia. It further assessed the concentration-dependent effect of eltrombopag on bilirubin measurements using enzymatic and vanadate oxidation assays.

METHODS

Total and conjugated bilirubin concentrations measured using an enzymatic assay and serum eltrombopag concentrations were examined in 227 serum samples collected from 30 patients with aplastic anemia receiving eltrombopag. Eltrombopag-spiked samples were analyzed using the enzymatic and vanadate oxidation assays for total and conjugated bilirubin to determine its concentration-dependent effects.

RESULTS

A strong positive correlation was observed between total bilirubin and serum eltrombopag concentrations in patients receiving eltrombopag ( r = 0.820). However, the correlation between conjugated bilirubin and serum eltrombopag concentrations was weaker ( r = 0.413). In eltrombopag-spiked serum samples, the enzymatic assay showed significant false elevation of total bilirubin concentrations at ≥6.0 mcg/mL; no interference with conjugated bilirubin measurements was observed. The vanadate oxidation assay showed mild positive biases of 0.2 and 0.1 mg/dL for total and conjugated bilirubin concentrations, respectively, at a high eltrombopag concentration (50 mcg/mL).

CONCLUSIONS

Eltrombopag causes clinically significant concentration-dependent interference in total blood bilirubin, but not in conjugated bilirubin measurements through the enzymatic assay in patients with aplastic anemia. The vanadate oxidation assay may be used as an alternative to measure total blood bilirubin when the eltrombopag concentration is below 50 mcg/mL.