Hematological adaptations and detection of recombinant human erythropoietin combined with chronic hypoxia
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Hematological adaptations and detection of recombinant human erythropoietin combined with chronic hypoxia. / Bejder, Jacob; Andersen, Andreas Breenfeldt; Bonne, Thomas Christian; Linkis, Jesper; Olsen, Niels Vidiendal; Huertas, Jesús Rodríguez; Nordsborg, Nikolai Baastrup.
I: Drug Testing and Analysis, Bind 13, Nr. 2, 2021, s. 360-368.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Hematological adaptations and detection of recombinant human erythropoietin combined with chronic hypoxia
AU - Bejder, Jacob
AU - Andersen, Andreas Breenfeldt
AU - Bonne, Thomas Christian
AU - Linkis, Jesper
AU - Olsen, Niels Vidiendal
AU - Huertas, Jesús Rodríguez
AU - Nordsborg, Nikolai Baastrup
N1 - This article is protected by copyright. All rights reserved.
PY - 2021
Y1 - 2021
N2 - This study evaluated whether recombinant human erythropoietin (rhEpo) treatment combined with chronic hypoxia provided an additive erythropoietic response and whether the Athlete Biological Passport (ABP) sensitivity improved with hypoxia. Two interventions were completed, each containing four weeks baseline, four weeks exposure at sea-level or 2,320m of altitude and four weeks follow-up. Participants were randomly assigned to 20 IU·kg bw-1 rhEpo or placebo injections every second day for three weeks during the exposure period at sea-level (rhEpo n=25, placebo n=9) or at altitude (rhEpo n=12, placebo n=27). Venous blood was analyzed weekly. Combining rhEpo and hypoxia induced larger changes compared with rhEpo or hypoxia alone for [Hb] (p < 0.001, p > 0.05, respectively), reticulocyte percentage (p < 0.001) and OFF-hr score (p < 0.01, p < 0.001, respectively). The most pronounced effect was observed for reticulocyte percentage with up to ~35% (p < 0.001) and ~45% (p < 0.001) higher levels compared with rhEpo or hypoxia only, respectively. The ABP sensitivity for the combined treatment was 54 and 35 percentage points higher for [Hb] (p < 0.05) and reticulocyte percentage (p < 0.05), respectively, but similar for OFF-hr score, compared with rhEpo at sea-level. Across any time point, [Hb] and OFF-hr score combined identified 14 unique true-positive participants (56%) at sea-level and 12 unique true-positive participants (100%) at altitude. However, a concurrent reduction in specificity existed at altitude. In conclusion, rhEpo treatment combined with hypoxic exposure provided an additive erythropoietic response compared to rhEpo or hypoxic exposure alone. Correspondingly, ABP was more sensitive to rhEpo at altitude than at sea-level, but a compromised specificity existed with hypoxic exposure.
AB - This study evaluated whether recombinant human erythropoietin (rhEpo) treatment combined with chronic hypoxia provided an additive erythropoietic response and whether the Athlete Biological Passport (ABP) sensitivity improved with hypoxia. Two interventions were completed, each containing four weeks baseline, four weeks exposure at sea-level or 2,320m of altitude and four weeks follow-up. Participants were randomly assigned to 20 IU·kg bw-1 rhEpo or placebo injections every second day for three weeks during the exposure period at sea-level (rhEpo n=25, placebo n=9) or at altitude (rhEpo n=12, placebo n=27). Venous blood was analyzed weekly. Combining rhEpo and hypoxia induced larger changes compared with rhEpo or hypoxia alone for [Hb] (p < 0.001, p > 0.05, respectively), reticulocyte percentage (p < 0.001) and OFF-hr score (p < 0.01, p < 0.001, respectively). The most pronounced effect was observed for reticulocyte percentage with up to ~35% (p < 0.001) and ~45% (p < 0.001) higher levels compared with rhEpo or hypoxia only, respectively. The ABP sensitivity for the combined treatment was 54 and 35 percentage points higher for [Hb] (p < 0.05) and reticulocyte percentage (p < 0.05), respectively, but similar for OFF-hr score, compared with rhEpo at sea-level. Across any time point, [Hb] and OFF-hr score combined identified 14 unique true-positive participants (56%) at sea-level and 12 unique true-positive participants (100%) at altitude. However, a concurrent reduction in specificity existed at altitude. In conclusion, rhEpo treatment combined with hypoxic exposure provided an additive erythropoietic response compared to rhEpo or hypoxic exposure alone. Correspondingly, ABP was more sensitive to rhEpo at altitude than at sea-level, but a compromised specificity existed with hypoxic exposure.
KW - Faculty of Science
KW - Altitude
KW - Athlete biological passport
KW - Blood manipulation
U2 - 10.1002/dta.2931
DO - 10.1002/dta.2931
M3 - Journal article
C2 - 32955164
VL - 13
SP - 360
EP - 368
JO - Drug Testing and Analysis
JF - Drug Testing and Analysis
SN - 1942-7603
IS - 2
ER -
ID: 249061665