Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency - Individual Prediction and Prevention of Risks of Immunosuppressive Therapies in Transplantation Access content directly
Journal Articles British Journal of Clinical Pharmacology Year : 2022

Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency

Jérome Guitton
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Antonin Schmitt

Abstract

AIMS: Determining dihydropyrimidine dehydrogenase (DPD) activity by measuring patient’s uracil (U) plasma concentration is mandatory before fluoropyrimidines (FP) administration in France. In this study, we aimed to refine the pre-analytical recommendations for determining U and dihydrouracil (UH(2) ) concentrations, since they are essential in reliable DPD deficiency testing. METHODS: U and UH(2) concentrations were collected from 14 hospital laboratories. Stability in whole blood and plasma after centrifugation, the type of anticoagulant and long-term plasma storage were evaluated. The variation induced by time and temperature was calculated and compared to an acceptability range of ± 20%. Inter-occasion variability (IOV) of U and UH(2) was assessed in 573 patients double sampled for DPD-deficiency testing. RESULTS: Storage of blood samples before centrifugation at room temperature (RT) should not exceed 1 h, whereas cold (+4°C) storage maintains U stable after 5 hours. For patients correctly double sampled, IOV of U reached 22.4% for U (SD = 17.9%, range = [0-99%]). Notably, 17% of them were assigned with a different phenotype (normal or DPD deficient) based on the analysis of their two samples. For those having at least one non-compliant sample, this percentage increased up to 33.8%. The moment of blood collection did not affect the DPD phenotyping result. CONCLUSION: Caution should be taken when interpreting U concentrations if the time before centrifugation exceeds 1 h at RT, since it rises significantly afterwards. Not respecting the pre-analytical conditions for DPD phenotyping increases the risk of DPD status misclassification.
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licence : CC BY NC ND - Attribution - NonCommercial - NoDerivatives

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hal-03789849 , version 1 (20-06-2023)

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Attribution - NonCommercial - NoDerivatives

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Maud Maillard, Manon Launay, Bernard Royer, Jérome Guitton, Elodie Gautier-Veyret, et al.. Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency. British Journal of Clinical Pharmacology, 2022, Global Pharmacovigilance, 89 (5), pp.762-772. ⟨10.1111/bcp.15536⟩. ⟨hal-03789849⟩
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