Eltrombopag interferes with the measurement of plasma total bilirubin in pediatric patients in an automated colorimetric method

Kutasz, Ezequiel; Barbieri, Alejandra; D'Isa, Gabriela; Toscano, Agostina; Chilelli, Carla; Jurado, Virginia; Chaler, Eduardo

doi:10.1515/cclm-2018-0789

Cited by 1 publication

(1 citation statement)

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“…There have been multiple small-scale reports of highdose eltrombopag (200-300 mg daily in adults [7,8,11], 75-150 mg daily in children [12]) causing a reddish-brown discoloration of plasma/serum and discrepant total bilirubin results by automated colorimetric assays. For example, two groups have demonstrated that the Beckman Coulter DxC 800 analyzer is susceptible to producing undetectable levels of total bilirubin in patients on high-dose eltrombopag [7,8].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive characterization and resolution of discrepant spectrophotometric bilirubin results in patients on eltrombopag therapy

Cheng

Tsui

Kwok

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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BackgroundEltrombopag is a thrombopoietin receptor agonist used for the treatment of thrombocytopenic conditions. It can cause pH-dependent discoloration of plasma/serum. Eltrombopag is potentially hepatotoxic. It can affect the assessment of hyperbilirubinemia because of its (i) absorbance at ~450 nm (bilirubin), (ii) absorbance at ~550 nm (diazo-bilirubin) and (iii) it can cause yellowish discoloration of the eyes at normal circulating bilirubin levels.MethodsWe collected 66 samples from patients on a range of eltrombopag dosages up to 150 mg daily. Bilirubin was measured using multiple routine spectrophotometric analyzers, the Doumas reference method and high-performance liquid chromatography (HPLC). Plasma/serum eltrombopag concentrations were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spike-in and admixture experiments delineated the effects of eltrombopag and its metabolites.ResultsForty-nine of 52 samples from patients on ≥50 mg daily eltrombopag therapy showed significantly discrepant inter-analyzer total bilirubin results, a difference up to 64 μmol/L (3.7 mg/dL). In one sample, total bilirubin varied from 8 to 65 μmol/L (0.4–3.8 mg/dL) by different routine analyzers, with direct bilirubin ≤4 μmol/L (0.2 mg/dL). There was a positive correlation between total bilirubin difference and plasma eltrombopag concentration (r = 0.679), and spike-in experiments demonstrated that Beckman AU and Doumas reference methods were susceptible to positive interference. HPLC can quantify bilirubin after separating eltrombopag, and results suggest different analyzers are affected to varying degrees by eltrombopag and its metabolites.ConclusionsEltrombopag and its metabolites can cause positive interference to the spectrophotometric measurements of total bilirubin. Accurate measurements of total bilirubin may improve our understanding of the prevalence of hyperbilirubinemia in patients on eltrombopag therapy.

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