The evolving science of detection of 'blood doping'

British Journal of Pharmacology

Volumn 165, Issue 5, 2012, Pages 1306-1315

  Lundby, Carsten ^a   Robach, Paul ^b   Saltin, Bengt ^c  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b Ecole Nationale de Ski et d'Alpinisme (ENSM)   (France)

^c Rigshospitalet   (Denmark)

Author keywords

blood passport; Epo; exercise; haematocrit; haemoglobin mass; Hb; Htc; performance; red blood cell; rhEpo; transfusion

Indexed keywords

ERYTHROPOIETIN; HYPOXIA INDUCIBLE FACTOR; RECOMBINANT ERYTHROPOIETIN;

ANALYTIC METHOD; BLOOD TRANSFUSION; CARBOHYDRATE ANALYSIS; CELL FUNCTION; CLINICAL PRACTICE; DOPING; ERYTHROPOIESIS; FLUID INTAKE; HEART OUTPUT; HEMATOCRIT; HEMODILUTION; HUMAN; IRON BALANCE; LIMIT OF DETECTION; MEDICAL RESEARCH; METABOLIC STRESS; OXYGEN CONSUMPTION; PRIORITY JOURNAL; PROTEIN SYNTHESIS; REVIEW; SPORT;

ANIMALS; ATHLETES; BIOLOGICAL MARKERS; DOPING IN SPORTS; ERYTHROPOIETIN; HUMANS; INTERNATIONAL AGENCIES; SPORTS;

EID: 84857096656     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01822.x     Document Type: Review

References (66)

1. Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND, Cairns TD, et al,. (2010). Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica 95: 505-508.
2. Ashenden M, Gough C, Garnham A, Gore C, Sharpe K, (2011). Current markers of the Athlete Blood Passport do not flag microdose EPO doping. Eur J Appl Physiol 111: 2307-2314.
3. Banfi G, (2011). Limits and pitfalls of Athlete's Biological Passport. Clin Chem Lab Med 49: 1417-1421.
4. Bernhardt WM, Wiesener MS, Scigalla P, Chou J, Schmieder RE, Günzler V, et al,. (2010). Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. J Am Soc Nephrol 21: 2151-2156.
5. Bonetti DL, Hopkins WG, (2009). Sea-level exercise performance following adaptation to hypoxia: a meta-analysis. Sports Med 39: 107-127.
6. Bornø A, Aachmann-Andersen N, Munch-Andersen T, Hulston C, Lundby C, (2010). Screening for recombinant human erythropoietin using [Hb], reticulocytes, the OFF(hr score), OFF(z score) and Hb(z score): status of the Blood Passport. Eur J Appl Physiol 109: 537-543.
7. 2 content? Am J Physiol Regul Integr Comp Physiol 284: R304-R316.
8. Calbet JAL, Lundby C, Koskolou M, Boushel R, (2006). Importance of hemoglobin concentration to exercise: acute manipulations. Respir Physiol Neurobiol 151: 132-140.
9. Callaway E, (2011). Sports doping: racing just to keep up. Nature 475: 283-285.
10. Cazzola M, (2000). A global strategy for prevention and detection of blood doping with erythropoietin and related drugs. Haematologica 85: 561-563.
11. Christensen B, Sackmann-Sala L, Cruz-Topete D, Jørgensen JOL, Jessen N, Lundby C, et al,. (2011). Novel serum biomarkers for erythropoietin use in humans: a proteomic approach. J Appl Physiol 110: 149-156.
12. Eastwood A, Sharpe K, Bourdon PC, Woolford SM, Saunders PU, Robertson EY, et al,. (2011). Within subject variation in hemoglobin mass in elite athletes. Med Sci Sports Exerc. Sep 24. [Epub ahead of print].
13. Ekblom B, Goldbarg AN, Gullbring B, (1972). Response to exercise after blood loss and reinfusion. J Appl Physiol 33: 175-180.
14. Ekblom B, Wilson G, Astrand PO, (1976). Central circulation during exercise after venesection and reinfusion of red blood cells. J Appl Physiol 40: 379-383.
15. Elliott S, (2008). Erythropoiesis-stimulating agents and other methods to enhance oxygen transport. Br J Pharmacol 154: 529-541.
16. Fania C, Vasso M, Torretta E, Robach P, Cairo G, Lundby C, et al,. (2011). Setup for human sera MALDI profiling: the case of rhEPO treatment. Electrophoresis 32: 1715-1727.
17. Franco Fraguas L, Carlsson J, Lönnberg M, (2008). Lectin affinity chromatography as a tool to differentiate endogenous and recombinant erythropoietins. J Chromatogr A 1212: 82-88.
18. Fulwood R, Johnson CL, Bryner JD, Gunther EW, McGrath CR, (1982). Hematological and Nutritional Biochemistry References Data for Persons 6 Months-74 Years of Age: United States, 1976-1982. National Center for Health Statistics: Bethesta.
19. Harrison MH, (1985). Effects on thermal stress and exercise on blood volume in humans. Physiol Rev 65: 149-209.
20. Jacobs RA, Rasmussen P, Siebenmann C, Díaz V, Gassmann M, Pesta D, et al,. (2011). Determinants of time trial performance and maximal incremental exercise in highly trained endurance athletes. J Appl Physiol 111: 1422-1430.
21. Jelkmann W, Lundby C, (2011). Blood doping and its detection. Blood 118: 2395-2404.
22. Johansson PI, Ullum H, Jensen K, Secher NH, (2009). A retrospective cohort study of blood hemoglobin levels in blood donors and competitive rowers. Scand J Med Sci Sports 19: 92-95.
23. Kohler M, Ayotte C, Desharnais P, Flenker U, Lüdke S, Thevis M, et al,. (2008). Discrimination of recombinant and endogenous urinary erythropoietin by calculating relative mobility values from SDS gels. Int J Sports Med 29: 1-6.
24. Kroot JJ, Kemna EH, Bansal SS, Busbridge M, Campostrini N, Girelli D, et al,. (2009). Results of the first international round robin for the quantification of urinary and plasma hepcidin assays: need for standardization. Haematologica 94: 1748-1752.
25. Lasne F, Martin L, Crepin N, de Ceaurriz J, (2002). Detection of isoelectric profiles of erythropoietin in urine: differentiation of natural and administered recombinant hormones. Anal Biochem 311: 119-126.
26. Lasocki S, Millot S, Andrieu V, Letteron P, Pilard N, Muzeau F, et al,. (2008). Phlebotomies or erythropoietin injections allow mobilization of iron stores in a mouse model mimicking intensive care anemia. Crit Care Med 36: 2388-2394.
27. Levine BD, Stray-Gundersen J, (1997). 'Living high-training low': effect of moderate-altitude acclimatization with low-altitude training on performance. J Appl Physiol 83: 102-112.
28. Lönnberg M, Andrén M, BirgegÃrd G, Drevin M, Garle M, Carlsson J, (2012). Rapid detection of erythropoiesis-stimulating agents in urine and serum. Anal Biochem 420: 101-114.
29. Lundby C, Olsen NV, (2011). Effects of recombinant human erythropoietin in normal humans. J Physiol 589: 1265-1271.
30. Lundby C, Robach P, (2010). Assessment of total haemoglobin mass: can it detect erythropoietin-induced blood manipulations? Eur J Appl Physiol 108: 197-200.
31. Lundby C, Sander M, van Hall G, Saltin B, Calbet JAL, (2006). Maximal exercise and muscle oxygen extraction in acclimatizing lowlanders and high altitude natives. J Physiol 573: 535-547.
32. Lundby C, Thomsen JJ, Boushel R, Koskolou M, Warberg J, Calbet JAL, et al,. (2007). Erythropoietin treatment elevates haemoglobin concentration by increasing red cell volume and depressing plasma volume. J Physiol 578: 309-314.
33. Lundby C, Achman-Andersen NJ, Thomsen JJ, Norgaard AM, Robach P, (2008a). Testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing. J Appl Physiol 105: 417-419.
34. Lundby C, Robach P, Boushel R, Thomsen JJ, Rasmussen P, Koskolou M, et al,. (2008b). Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport? J Appl Physiol 105: 581-587.
35. Malcovati L, Pascutto C, Cazzola M, (2003). Hematologic passport for athletes competing in endurance sports: a feasibility study. Haematologica 88: 570-581.
36. 2max with no history of training is primarily due to high blood volume. Med Sci Sports Exerc 34: 966-971.
37. Mørkeberg J, Sharpe K, Belhage B, Damsgaard R, Schmidt W, Prommer N, et al,. (2011). Detecting autologous blood transfusions: a comparison of three passport approaches and four blood markers. Scand J Med Sci Sports 21: 235-243.
38. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, et al,. (2002). The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110: 1037-1044.
39. Nordenberg D, Yip R, Binkin NJ, (1990). The effect of cigarette smoking on hemoglobin levels and anemia screening. JAMA 264: 1556-1559.
40. Pace N, Consolazio WV, Lozner FL, (1945). The effect of transfusions of red blood cells on the hypoxia tolerence of normal men. Science 102: 589-591.
41. Parisotto R, Gore C, Emslie K, Ashenden M, Brugnara C, Howe C, et al,. (2000a). A novel method utilising markers of altered erythropoiesis for the detection of recombinant human erythropoietin abuse in athletes. Haematologica 85: 564-572.
42. Parisotto R, Gore CJ, Hahn AG, Ashenden MJ, Olds TS, Martin DT, et al,. (2000b). Reticulocyte parameters as potential discriminators of recombinant human erythropoietin abuse in elite athletes. Int J Sports Med 21: 471-479.
43. Parisotto R, Wu M, Ashenden MJ, Emslie KR, Gore CJ, Howe C, et al,. (2001). Detection of recombinant human erythropoietin abuse in athletes utilizing markers of altered erythropoiesis. Haematologica 86: 128-137.
44. Perry GS, Byers T, Yip R, Margen S, (1992). Iron nutrition does not account for the hemoglobin differences between Blacks and Whites. J Nutr 122: 1417-1424.
45. Piperno A, Galimberti S, Mariani R, Pelucchi S, Ravasi G, Lombardi C, et al,. (2011). Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project. Blood 117: 2953-2959.
46. Pirofsky B, (1953). The determination of blood viscosity in man by a method based on Poiseuille's law. J Clin Invest 32: 292-298.
47. Pottgiesser T, Schumacher YO, Funke H, Rennert K, Baumstark MW, Neunuebel K, et al,. (2009). Gene expression in the detection of autologous blood transfusion in sports-a pilot study. Vox Sang 96: 333-336.
48. Pottgiesser T, Sottas P-E, Echteler T, Robinson N, Umhau M, Schumacher YO, (2011). Detection of autologous blood doping with adaptively evaluated biomarkers of doping: a longitudinal blinded study. Transfusion 51: 1707-1715.
49. Pugh LGCE, (1969). Blood volume changes in outdoor exercise of 8-10 hour duration. J Physiol 200: 345-351.
50. Rasmussen P, Foged EM, Krogh-Madsen R, Nielsen J, Nielsen TR, Olsen NV, et al,. (2010). Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men. J Appl Physiol 109: 476-483.
51. Reichel C, (2011). Recent developments in doping testing for erythropoietin. Anal Bioanal Chem 401: 463-481.
52. 2max depends on the severity of arterial hypoxemia. PLoS ONE 3: e2996.
53. Robach P, Recalcati S, Girelli D, Gelfi C, Aachmann-Andersen NJ, Thomsen JJ, et al,. (2009). Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin. Blood 113: 6707-6715.
54. Sawka MN, Convertino VA, Eichner EA, Schnieder SM, Young AJ, (2000). Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness. Med Sci Sports Exerc 32: 332-348.
55. Schuler B, Thomsen JJ, Gassmann M, Lundby C, (2007). Timing the arrival at 2340 m altitude for aerobic performance. Scand J Med Sci Sports 17: 588-594.
56. Schumacher YO, Wenning M, Robinson N, Sottas PE, Ruecker G, Pottgiesser T, (2010). Diurnal and exercise-related variability of haemoglobin and reticulocytes in athletes. Int J Sports Med 31: 225-230.
57. Siebenmann C, Robach P, Jacobs RA, Rasmussen P, Nordsborg NB, Díaz V, et al,. (2011). 'Live high-train low' using normobaric hypoxia: a double-blinded, placebo-controlled study. J Appl Physiol 112: 106-117.
58. Solymos E, Guddat S, Geyer H, Flenker U, Thomas A, Segura J, et al,. (2010). Rapid determination of urinary di(2-ethylhexyl) phthalate metabolites based on liquid chromatography/tandem mass spectrometry as a marker for blood transfusion in sports drug testing. Anal Bioanal Chem 401: 517-528.
59. Sottas P-E, Robinson N, Rabin O, Saugy M, (2011). The Athlete Biological Passport. Clin Chem 57: 969-976.
60. Spedding M, Spedding C, (2008). Drugs in sport: a scientist-athlete's perspective: from ambition to neurochemistry. Br J Pharmacol 154: 496-501.
61. Thirup P, (2003). Haematocrit: within-subject and seasonal variation. Sports Med 33: 231-243.
62. Thomsen J, Rentsch R, Robach P, Calbet J, Boushel R, Rasmussen P, et al,. (2007). Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity. Eur J Appl Physiol 101: 481-486.
63. Waddington I, Smith A, (2008). An Introduction to Drugs in Sport: Addicted to Winning. Routledge Chapman & Hall: Abingdon, Oxon.
64. Weil JV, Jamieson G, Brown DW, Grover RF, (1968). The red cell mass-arterial oxygen relationship in normal man: application to patients with chronic obstructive airway disease. J Clin Invest 47: 1627-1639.
65. Wide L, Bengtsson C, (1990). Molecular charge heterogeneity of human serum erythropoietin. Br J Haematol 76: 121-127.
66. Wide L, Bengtsson C, Berglund B, Ekblom B, (1995). Detection in blood and urine of recombinant erythropoietin administered to healthy men. Med Sci Sports Exerc 27: 1569-1576.