A novel method utilising markers of altered erythropoiesis for the detection of recombinant human erythropoietin abuse in athletes

• Published in: Haematologica (Roma) Vol. 85; no. 6; pp. 564 - 572
• Main Authors: Parisotto, R, Gore, CJ, Emslie, KR, Ashenden, MJ, Brugnara, C, Howe, C, Martin, DT, Trout, GJ, Hahn, AG
• Format: Journal Article
• Language: English
• Published: Pavia Haematologica 01-06-2000
• Subjects: Adult; Analysis of Variance; Biological and medical sciences; Biomarkers - blood; Blood Gas Analysis; Diagnosis, Computer-Assisted - methods; Doping in Sports - prevention & control; Double-Blind Method; Erythrocytes - cytology; Erythropoietin - administration & dosage; Erythropoietin - blood; False Positive Reactions; Female; Ferritins - blood; Hematocrit; Hematology; Hemoglobins - metabolism; Humans; Investigative techniques, diagnostic techniques (general aspects); Iron - administration & dosage; Male; Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Receptors, Transferrin - blood; Recombinant Proteins - blood; Reticulocytes - cytology; Sport (general aspects); Substance-Related Disorders - diagnosis; Traumas. Diseases due to physical agents; Erythropoiesis; Human; Transferrin; Biochemical analysis; Erythropoietin; Doping; Biological marker; Medical screening; Athlete; Dose activity relation; Athletics; Iron ion; Hematocrite; Reticulocyte; Comparative study
• ISSN: 0390-6078; 1592-8721

Department of Physiology, Australian Institute of Sport, P.O. Box 176, Belconnen ACT 2616, Australia. [e-mail].
BACKGROUND AND OBJECTIVE: The use of recombinant human erythropoietin (r-HuEPO) to enhance athletic performance is prohibited. Existing tests cannot readily differentiate between exogenous and endogenous EPO. Therefore the aim of our study was to investigate possible indirect detection of r-HuEPO use via blood markers of altered erythropoiesis. DESIGN AND METHODS: Twenty-seven recreational athletes were assigned to three groups prior to a 25 day drug administration phase, with the following protocols: EPO+IM group (n = 10), 50 Ukg(-1) r-HuEPO at a frequency of 3wk(-1), 100 mg intramuscular (IM) iron 1wk(-1) and a sham iron tablet daily; EPO+OR group (n = 8), 50 U.kg(-1) r-HuEPO 3wk(-1), sham iron injection 1wk(-1) and 105 mg of oral elemental iron daily; placebo group (n = 9), sham r-HuEPO injections 3wk(-1), sham iron injections 1wk(-1) and sham iron tablets daily. Each group was monitored during and for 4 weeks after drug administration. RESULTS: Models incorporating combinations of the variables reticulocyte hematocrit (RetHct), serum EPO, soluble transferrin receptor, hematocrit (Hct) and % macrocytes were analyzed by logistic regression. One model (ON-model) repeatedly identified 94-100% of r-HuEPO group members during the final 2 wk of the r-HuEPO administration phase. One false positive was recorded from a possible 189. Another model (OFF-model) incorporating RetHct, EPO and Hct was applied during the wash-out phase and, during the period of 12-21 days after the last r-HuEPO injection, it repeatedly identified 67-72% of recent users with no false positives. INTERPRETATION AND CONCLUSIONS: Multiple indirect hematologic and biochemical markers used simultaneously are potentially effective for identifying current or recent users of r-HuEPO.