Changes in immature reticulocytes aid the indirect detection of microdose recombinant erythropoietin use in males and females
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Changes in immature reticulocytes aid the indirect detection of microdose recombinant erythropoietin use in males and females. / Breenfeldt Andersen, Andreas; Bejder, Jacob; Bonne, Thomas Christian; Graae, Jonathan; Seier, Søren; Nordsborg, Nikolai Baastrup.
I: Medicine and Science in Sports and Exercise, Bind 55, Nr. 9, 2023, s. 1695-1705.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Changes in immature reticulocytes aid the indirect detection of microdose recombinant erythropoietin use in males and females
AU - Breenfeldt Andersen, Andreas
AU - Bejder, Jacob
AU - Bonne, Thomas Christian
AU - Graae, Jonathan
AU - Seier, Søren
AU - Nordsborg, Nikolai Baastrup
N1 - Copyright © 2023 by the American College of Sports Medicine.
PY - 2023
Y1 - 2023
N2 - Purpose: We investigated whether immature reticulocyte fraction (IRF) and the immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive and specific biomarkers for microdose recombinant human erythropoietin (rHuEPO) and whether the inclusion of reticulocyte percentage (RET%) and the algorithm "abnormal blood profile score (ABPS)" increased the athlete biological passport (ABP) sensitivity compared to hemoglobin concentration ([Hb]) and the OFF-hr score ([Hb]-60 × √RET%).Methods: Forty-eight (♀ = 24, ♂ = 24) participants completed a 2-wk baseline period followed by a 4-wk intervention period with three weekly intravenous injections of 9 IU × kg bw-1 epoetin β (♀ = 12, ♂ = 12) or saline (0.9% NaCl, ♀ = 12, ♂ = 12) and a 10-d follow-up. Blood samples were collected weekly during baseline and intervention as well as 3, 5, and 10 d after treatment.Results: The rHuEPO treatment increased [Hb] (time×treatment, P < 0.001), RET% (time×treatment, P < 0.001), IRF (time×treatment, P < 0.001) and IR/RBC (time×treatment, P < 0.001). IRF and IR/RBC were up to ~58% (P < 0.001) and ~ 141% (P < 0.001) higher compared to placebo, and calculated thresholds provided a peak sensitivity across timepoints of 58% and 54% with ~98% specificity, respectively. To achieve >99% specificity for IRF and IR/RBC, sensitivity was reduced to 46% and 50%, respectively. Across all timepoints, the addition of RET% and ABPS to the ABP increased sensitivity from 29% to 46%. Identification of true-positive outliers obtained via the ABP and IRF and IR/RBC increased sensitivity across all timepoints to 79%.Conclusions: In summary, IRF, IR/RBC, RET% and ABPS are sensitive and specific biomarkers for microdose rHuEPO in both males and females and complement the ABP.
AB - Purpose: We investigated whether immature reticulocyte fraction (IRF) and the immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive and specific biomarkers for microdose recombinant human erythropoietin (rHuEPO) and whether the inclusion of reticulocyte percentage (RET%) and the algorithm "abnormal blood profile score (ABPS)" increased the athlete biological passport (ABP) sensitivity compared to hemoglobin concentration ([Hb]) and the OFF-hr score ([Hb]-60 × √RET%).Methods: Forty-eight (♀ = 24, ♂ = 24) participants completed a 2-wk baseline period followed by a 4-wk intervention period with three weekly intravenous injections of 9 IU × kg bw-1 epoetin β (♀ = 12, ♂ = 12) or saline (0.9% NaCl, ♀ = 12, ♂ = 12) and a 10-d follow-up. Blood samples were collected weekly during baseline and intervention as well as 3, 5, and 10 d after treatment.Results: The rHuEPO treatment increased [Hb] (time×treatment, P < 0.001), RET% (time×treatment, P < 0.001), IRF (time×treatment, P < 0.001) and IR/RBC (time×treatment, P < 0.001). IRF and IR/RBC were up to ~58% (P < 0.001) and ~ 141% (P < 0.001) higher compared to placebo, and calculated thresholds provided a peak sensitivity across timepoints of 58% and 54% with ~98% specificity, respectively. To achieve >99% specificity for IRF and IR/RBC, sensitivity was reduced to 46% and 50%, respectively. Across all timepoints, the addition of RET% and ABPS to the ABP increased sensitivity from 29% to 46%. Identification of true-positive outliers obtained via the ABP and IRF and IR/RBC increased sensitivity across all timepoints to 79%.Conclusions: In summary, IRF, IR/RBC, RET% and ABPS are sensitive and specific biomarkers for microdose rHuEPO in both males and females and complement the ABP.
KW - Faculty of Science
KW - Anti-doping
KW - Blood manipulation
KW - Erythropoietin
KW - Microdosing
U2 - 10.1249/MSS.0000000000003197
DO - 10.1249/MSS.0000000000003197
M3 - Journal article
C2 - 37095637
VL - 55
SP - 1695
EP - 1705
JO - Medicine and Science in Sports and Exercise
JF - Medicine and Science in Sports and Exercise
SN - 0195-9131
IS - 9
ER -
ID: 344907834