Skip to main content
SpringerLink
Log in

Erythropoietin use and abuse

When physiology and pharmacology collide

  • Chapter
Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 502))

Abstract

The major function of the erythrocyte is to transport oxygen from the lungs to the other tissues, a function ensured by the glycoprotein hormone erythropoietin which couples red cell production to long term tissue oxygen requirements. Tissue hypoxia is the only physiological mechanism for increasing erythropoietin production but there are a variety of mechanisms for its down regulation including hyperoxia, increased catabolism by an expanded erythroid progenitor cell pool, blood hyperviscosity independently of its oxygen content, renal disease and the cytokines produced in inflammatory, infectious and neoplastic disorders. Erythropoietin lack results in severe and often transfusion-dependent anemia but if bone marrow function is otherwise normal, recombinant human erythropoietin therapy can restore the red cell mass and alleviate the transfusion need. However, elevation of the red cell mass by recombinant human erythropoietin is associated with a reduction in plasma volume and in some patients, hypertension is induced. Elevation of the red cell mass is also associated with a reduction in cerebral blood flow. When used to gradually elevate the hematocrit to 36% in anemic patients, recombinant human erythropoietin therapy is usually uneventful. However, when the normal hematocrit level is exceeded, the risk for thrombotic events increases since blood viscosity varies exponentially with the hematocrit. Increasing the hematocrit by autologous blood transfusions can enhance athletic performance in fit individuals and recombinant human erythropoietin administration is an obvious surrogate for autologous blood transfusions. However, paradoxically, its effects are the opposite of those of endurance training, namely a change in red cell mass without an increase in the total blood volume. Thus, the use of recombinant human erythropoietin as a performance-enhancing agent is dangerous, particularly in the less fit athlete, and probably of little benefit in the highly conditioned one. Differences in the carbohydrate content of native and recombinant human erythropoietin are identifiable by isoelectric focusing, providing a direct means for detecting erythropoietin abuse using urine specimens; a panel of surrogate blood markers of enhanced erythropoiesis such as soluble transferrin receptors, serum erythropoietin, reticulocyte hematocrit and percent macrocytes provide an indirect means for this purpose. Timing of surveillance is, of course, critical due to biological limitations on the physical presence of the hormone. However, education about its dangers may prove to be the most valuable solution to abuse of recombinant human erythropoietin for competitive advantage.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abbrecht, PH and JK Littell. Plasma erythropoietin in men and mice during acclimatization to different altitudes. J ApplPhysiol 32: 54–58, 1972.

    PubMed  CAS  Google Scholar 

  2. Berglund, B and B Ekblom. Effect of recombinant human erythropoietin treatment on blood pressure and some haematological parameters in healthy men. J Intern.Med. 229: 125–130, 1991.

    Article  PubMed  CAS  Google Scholar 

  3. Berglund, B and P Hemmingson. Effect of reinfusion of autologous blood on exercise performance in cross-country skiers. IntJ Sports Med. 8: 231–233, 1987.

    Article  CAS  Google Scholar 

  4. Berglund, B, P Hemmingsson, and G Birgegard. Detection of Autologous Blood Transfusions in Cross-Country Skiers. Int. J. Sports Med 8: 66–70, 1987.

    Article  PubMed  CAS  Google Scholar 

  5. Besa, EC, D Gorshein, and FH Gardner. Androgens and human blood volume changes. Comparison in normal and various anemic states. Arch Intern.Med. 133: 418–425, 1974.

    Article  PubMed  CAS  Google Scholar 

  6. Birkeland, KI, M Donike, A Ljungqvist, M Fagerhol, J Jensen, P Hemmersbach, H Oftebro, and E Haug. Blood sampling in doping control. First experiences from regular testing in athletics. Int. J Sports Med 18: 8–12, 1997.

    Article  PubMed  CAS  Google Scholar 

  7. Breymann, C, C Bauer, A Major, R Zimmerman, G Kurt, A Huch, and R Huch. Optimal timing of repeated rh-erythropoietin administration improves its effectiveness in stimulating erythropoiesis in healthy volunteers. British Journal of Hematology 92: 295–301, 1995.

    Article  Google Scholar 

  8. Breymann, C, R Rohling, A Krafft, A Huch, and R Huch. ‘Blood doping’ with recombinant erythropoietin (rhEPO) and assessment of functional iron deficiency in healthy volunteers. Br. J Haematol. 108: 883–884, 2000.

    Article  PubMed  CAS  Google Scholar 

  9. Brien, AJ. and TL Simon. The effects of red blood cell infusion on 10-km race time. JAMA 257: 2761–2765, 1987.

    Article  PubMed  CAS  Google Scholar 

  10. Brugnara, C, D Zelmanovic, M Sorette, SK Ballas, and O Platt. Reticulocyte hemoglobin: an integrated parameter for evaluation of erythropoietic activity. Am. J Clin.Pathol. 108: 133–142, 1997.

    PubMed  CAS  Google Scholar 

  11. Buick, FJ, N Gledhill, AB. Froese, L Spriet, and EC Meyers. Effect of induced erythrocythemia on aerobic work capacity. J ApplPhysiol 48: 636–642, 1980.

    PubMed  CAS  Google Scholar 

  12. Casoni, I, G Ricci, E Ballarin, C Borsetto, G Grazzi, C Guglielmini, F Manfredini, G Mazzoni, M Patracchini, V De Paoli, and et al. Hematological indices of erythropoietin administration in athletes. Int. J Sports Med 14: 307–311, 1993.

    Article  PubMed  CAS  Google Scholar 

  13. Cazzola, M. A global strategy for prevention and detection of blood doping with erythropoietin and related drugs. Haematologica 85: 561–563, 2000.

    PubMed  CAS  Google Scholar 

  14. Celsing, F, J Svedenhag, P Pihlstedt, and B Ekblom. Effects of anaemia and stepwise-induced polycythaemia on maximal aerobic power in individuals with high and low haemoglobin concentrations. Acta Physiol Scand. 129: 47–54, 1987.

    Article  PubMed  CAS  Google Scholar 

  15. Chandra, M, GK Clemons, and MI McVicar. Relation of serum erythropoietin levels to renal excretory function: evidence for lowered set point for erythropoietin production in chronic renal failure. J Pediatr. 113: 1015–1021, 1988.

    Article  PubMed  CAS  Google Scholar 

  16. Cook, JD. The effect of endurance training on iron metabolism. Semin.Hematol 31: 146–154, 1994.

    PubMed  CAS  Google Scholar 

  17. Daniel, MK., B Bennett, AA. Dawson, and JM Rawles. Haemoglobin concentration and linear cardiac output, peripheral resistance, and oxygen transport. Br.Med.J (Clin.Res.Ed) 292: 1396–1397, 1986.

    Article  Google Scholar 

  18. Demetri, GD, M Kris, J Wade, L Degos, and D Cella. Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group. J Clin.Oncol 16: 3412–3425, 1998.

    PubMed  CAS  Google Scholar 

  19. Egrie, JC, PM. Cotes, J Lane, RE Gaines Das, and RC Tarn. Development of radioimmunoassays for human erythropoietin using recombinant erythropoietin as tracer and immunogen. J Immunol.Methods 99: 235–241, 1987.

    Article  PubMed  CAS  Google Scholar 

  20. Eichner, ER. Better dead than second. J Lab Clin.Med. 120: 359–360, 1992.

    Google Scholar 

  21. Eichner, ER. Erythropoietin in Sydney: Olympic Fanfare vs. Unsetting Reality. Sports Medicine Digest 22: 105–106, 2000.

    Google Scholar 

  22. Ekblom, B, AN Goldbarg, and B Gullbring. Response to exercise after blood loss and reinfusion. J Appl.Physiol 33: 175–180, 1972.

    PubMed  CAS  Google Scholar 

  23. Ekblom, B and L Hermansen. Cardiac output in athletes. J Appl.Physiol 25: 619–625, 1968.

    PubMed  CAS  Google Scholar 

  24. Emmanouel, DS., E Goldwasser, and AI Katz. Metabolism of pure human erythropoietin, in the rat. Am. J Physiol 247: F168-F176, 1984.

    PubMed  CAS  Google Scholar 

  25. Eschbach, JW, MH Abdulhadi, JK Browne, BG Delano, MR Downing, JC Egrie, RW Evans, EA Friedman, SE Graber, NR Haley, and et al. Recombinant human erythropoietin in anemic patients with end-stage renal disease. Results of a phase III multicenter clinical trial. Ann.Intern.Med 111: 992–1000, 1989.

    PubMed  CAS  Google Scholar 

  26. Faquin, WC, TJ Schneider, and MA Goldberg. Effect of inflammatory cytokines on hypoxia-induced erythropoietin production. Blood 79: 1987–1994, 1992.

    PubMed  CAS  Google Scholar 

  27. Gareau, R, M Audran, RD Baynes, CH Flowers, A Duvallet, L Senecal, and GR Brisson. Erythropoietin abuse in athletes. Nature 380: 113, 1996.

    Article  PubMed  CAS  Google Scholar 

  28. Gareau, R, GR Brisson, C Chenard, MG Gagnon, and M Audran. Total fibrin and fibrinogen degradation products in urine: a possible probe to detect illicit users of the physical-performance enhancer erythropoietin? Horm.Res. 44: 189–192, 1995.

    Article  PubMed  CAS  Google Scholar 

  29. Gareau, R, MG. Gagnon, C Ayotte, C Chenard, and GR Brisson. rHuEPO increases urinary excretion of fibrin degradation products in haemodialysed patients. Thromb.Haemost. 70: 373–374, 1993.

    PubMed  CAS  Google Scholar 

  30. Gibson, JG, A Seligman, WC Peacock, JC Aub, J Fine, and R Evans. The Distribution of Red Cells and Plasma in Large and Minute Vessels of the Normal Dog, Determined by Radioactive Isotopes of Iron and Iodine. J. Clin.Invest 25:848–857, 1946.

    Article  CAS  Google Scholar 

  31. Gimenez, LF., AJ Watson, and JL Spivak. Serum immunoreactive erythropoietin in patients with end stage renal disease. Prog.Clin.Biol Res. 352: 493–504, 1990.

    PubMed  CAS  Google Scholar 

  32. Gledhill, N, D Warburton, and V Jamnik. Haemoglobin, blood volume, cardiac function, and aerobic power. Can. J Appl.Physiol 24: 54–65, 1999.

    Article  PubMed  CAS  Google Scholar 

  33. Goldberg, MA, CC Gaut, and HF Bunn. Erythropoietin mRNA levels are governed by both the rate of gene transcription and posttranscriptional events. Blood 77: 271–277, 1991.

    PubMed  CAS  Google Scholar 

  34. Green, HJ, JR Sutton, G Coates, M Ali, and S Jones. Response of red cell and plasma volume to prolonged training in humans. J Appl.Physiol 70: 1810–1815, 1991.

    PubMed  CAS  Google Scholar 

  35. Gregory, CJ. Erythropoietin sensitivity as a differentiation marker in the hemopoietic system: studies of three erythropoietic colony responses in culture. J Cell Physiol 89: 289–301, 1976.

    Article  PubMed  CAS  Google Scholar 

  36. Haga, P, PM Cotes, JA Till, BD Minty and EA Shinebourne. Serum immunoreactive erythropoietin in children with cyanotic and acyanotic congenital heart disease. Blood 70: 822–826, 1987.

    PubMed  CAS  Google Scholar 

  37. Henry, DH, GN Beall, CA Benson, J Carey, LA Cone, LJ Eron, M Fiala, MA Fischl, SJ Gabin, MS Gottlieb, and et al. Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials. Ann. Intern. Med 117: 739–748, 1992.

    PubMed  CAS  Google Scholar 

  38. Jelkmann, W, H Pagel, M Wolff, and J Fandrey. Monokines inhibiting erythropoietin production in human hepatoma cultures and in isolated perfused rat kidneys. Life Sci. 50: 301–308, 1992.

    Article  PubMed  CAS  Google Scholar 

  39. Kaufman, JS, DJ Reda, CL Fye, DS Goldfarb, WG Henderson, JG Kleinman, and CA Vaamonde. Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients. N.Engl J Med 339: 578–583, 1998.

    Article  PubMed  CAS  Google Scholar 

  40. Kilbridge, TM, W Fried, and P Heller. The mechanism by which plethora suppresses erythropoiesis. Blood 33: 104–113, 1969.

    PubMed  CAS  Google Scholar 

  41. Kling, PJ, PR Dragsten, RA Roberts, B Dos Santos, DJ Brooks, BE Hedlung, and R Taetle. Iron deprivation increases erythropoietin production in vitro, in normal subjects and patients with malignancy. British Journal of Haematology 95: 241–248, 1996.

    Article  PubMed  CAS  Google Scholar 

  42. Koeffler, HP. and E Goldwasser. Erythropoietin radioimmunoassay in evaluating patients with polycythemia. Ann.Intern.Med 94: 44–47, 1981.

    PubMed  CAS  Google Scholar 

  43. Koury, M J and MC Bondurant. A survival model of erythropoietin action. Science 248: 378–381, 1990.

    Article  PubMed  CAS  Google Scholar 

  44. Koury, ST, MC Bondurant, MJ Koury, and GL Semenza. Localization of cells producing erythropoietin in murine liver by in situ hybridization. Blood 11: 2497–2503, 1991.

    Google Scholar 

  45. Koury, ST, MJ Koury, MC Bondurant, J Caro, and SE Graber. Quantitation of erythropoietin-producing cells in kidneys of mice by in situ hybridization: correlation with hematocrit, renal erythropoietin mRNA, and serum erythropoietin concentration. Blood 74: 645–651, 1989.

    PubMed  CAS  Google Scholar 

  46. Lasne, F and J de Ceaurriz. Recombinant erythropoietin in urine. Nature 405: 635, 2000.

    Article  PubMed  CAS  Google Scholar 

  47. Lim, VS, RL DeGowin, D Zavala, PT Kirchner, R Abels, P Perry, and J Fangman. Recombinant human erythropoietin treatment in pre-dialysis patients. A double-blind placebo-controlled trial. Ann.Intern.Med 110: 108–114, 1989.

    PubMed  CAS  Google Scholar 

  48. Longmore, GD. Erythropoietin receptor mutations and Olympic glory. Nat.Genet. 4: 108–110,1993.

    Article  PubMed  CAS  Google Scholar 

  49. Ludwig, H, E Fritz, C Leitgeb, M Pecherstorfer, H Samonigg, and J Schuster. Prediction of response to erythropoietin treatment in chronic anemia of cancer. Blood 84: 1056–1063, 1994.

    PubMed  CAS  Google Scholar 

  50. Macdougall, IC, DE Roberts, P Neubert, AD Dharmasena, GA Coles, and JD Williams. Pharmacokinetics of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Lancet 1: 425–427, 1989.

    Article  PubMed  CAS  Google Scholar 

  51. Magnani, M, D Corsi, M Bianchi, M Paiardini, L Galluzzi, A Parisi, and F Pigozzi. Monitoring erythropoietin abuse in athletes. Br. J Haematol. 106: 260–261, 1999.

    Article  PubMed  CAS  Google Scholar 

  52. Malczewska, J, W Blach, and R Stupnicki. The Effects of Physical Exercise on the Concentration of Ferritin and Transferrin Receptor in Plasma of Female Judoists. International Journal of Sports Medicine 21: 175–179, 2000.

    Article  PubMed  CAS  Google Scholar 

  53. Mayer, G, J Thum, EM Cada, HK Stummvoll, and H Graf. Working capacity is increased following recombinant human erythropoietin treatment. Kidney Int. 34: 525–528, 1988.

    Article  PubMed  CAS  Google Scholar 

  54. McMahon, FG, R Vargas, M Ryan, AK Jain, RI Abels, B Perry, and IL Smith. Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers. Blood 76: 1718–1722, 1990.

    PubMed  CAS  Google Scholar 

  55. Means, RT and SB Krantz. Progress in understanding the pathogenesis of the anemia of chronic disease. Blood 80: 1639–1647, 1992.

    PubMed  Google Scholar 

  56. Milledge, JS and PM Cotes. Serum erythropoietin in humans at high altitude and its relation to plasma renin. J Appl.Physiol 59: 360–364, 1985.

    PubMed  CAS  Google Scholar 

  57. Miyake, T, CK Kung, and E Goldwasser. Purification of human erythropoietin. J Biol Chem 252: 5558–5564, 1977.

    PubMed  CAS  Google Scholar 

  58. Murray, JF, P Gold, and BL Johnson. The Circulatory Effects of Hematocrit Variations in Normovolemic and Hypervolemic Dogs. J.Clin.Invest 42: 1150–1159, 1963.

    Article  PubMed  CAS  Google Scholar 

  59. Neff, MS, KE Kim, M Persoff, G Onesti, and C Swartz. Hemodynamics of uremic anemia. Circulation 43: 876–883, 1971.

    Article  PubMed  CAS  Google Scholar 

  60. Oscai, LB., BT. Williams, and BA Hertig. Effect of exercise on blood volume. J ApplPhysiol 24: 622–624, 1968.

    PubMed  CAS  Google Scholar 

  61. Pace, N, EL Lazner, and WV Consologno. The increase in hypoxia tolerance of normal men accompanying the polycythemia induced by transfusion of erythrocytes. Am. J Physiol 152–163, 1947.

    Google Scholar 

  62. Parisotto, R, M Wu, MJ Ashenden, KR Emslie, CJ Gore, C Howe, R Kazlauskas, K Sharpe, GJ Trout, and M Xie. Detection of recombinant human erythropoietin abuse in athletes utilizing markers of altered erythropoiesis. Haematologica 86: 128–137, 2001.

    PubMed  CAS  Google Scholar 

  63. Remacha, AF, J. Ordonez, MJ Barcelo, F Garcia-Die, B Arza, and A Estruch. Evaluation of erythropoietin in endurance runners. Haematologica 79: 350–352, 1994.

    PubMed  CAS  Google Scholar 

  64. Roberts, BE and AH Smith. Use of radioactive phosphorus in haematology. Blood Reviews 11: 146–153, 1997.

    Article  PubMed  CAS  Google Scholar 

  65. Rocker, L, KA Kirsch, and H Stoboy. Plasma volume, albumin and globulin concentrations and their intravascular masses. A comparative study in endurance athletes and sedentary subjects. Eur. J Appl. Physiol Occup.Physiol 36: 57–64, 1976.

    Article  PubMed  CAS  Google Scholar 

  66. Rutherford, CJ, TJ Schneider, H Dempsey, DH Kirn, C Brugnara, and MA Goldberg. Efficacy of different dosing regimens for recombinant human erythropoietin in a simulated perisurgical setting: the importance of iron availability in optimizing response. Am J Med 96: 139–145, 1994.

    Article  PubMed  CAS  Google Scholar 

  67. Samtleben, W, CA Baldamus, J Bommer, P Grutzmacher, B Nonnast-Daniel, P Scigalla, and HJ Gurland. Indications and contraindications for recombinant human erythropoietin treatment. Results in hemodialysis patients. Contrib. Nephrol. 76: 193–200, 1989.

    PubMed  CAS  Google Scholar 

  68. Sanchez, C, C Merino, and M Figallo. Simultaneous measurement of plasma volume and cell mass in polycythemia of high altitude. J ApplPhysiol 28: 775–778, 1970.

    PubMed  CAS  Google Scholar 

  69. Sasaki, H, B Bothner, A Dell, and M Fukuda. Carbohydrate structure of erythropoietin expressed in Chinese hamster ovary cells by a human erythropoietin cDNA. J Biol Chem 262: 12059–12076, 1987.

    PubMed  CAS  Google Scholar 

  70. Sawada, K., SB Krantz, CH Dai, ST Koury, ST Horn, AD Glick, and CI Civin. Purification of human blood burst-forming units-erythroid and demonstration of the evolution of erythropoietin receptors. J Cell Physiol 142: 219–230, 1990.

    Article  PubMed  CAS  Google Scholar 

  71. Sawka, MN, RC Dennis, RR Gonzalez, AJ Young, SR Muza, JW Martin, CB Wenger, RP Francesconi, KB Pandolf, and CR Valeri. Influence of polycythemia on blood volume and thermoregulation during exercise-heat stress. J ApplPhysiol 62: 912–918, 1987.

    Article  PubMed  CAS  Google Scholar 

  72. Sawka, MN, AJ Young, SR Muza, RR Gonzalez, and KB Pandolf. Erythrocyte reinfusion and maximal aerobic power. An examination of modifying factors. JAMA 257: 1496–1499, 1987.

    Article  PubMed  CAS  Google Scholar 

  73. Sawyer, ST, SB Krantz, and E Goldwasser. Binding and receptor-mediated endocytosis of erythropoietin in Friend virus-infected erythroid cells. J Biol Chem 262: 5554–5562, 1987.

    PubMed  CAS  Google Scholar 

  74. Schmidt, W, B Biermann, P Winchenbach, S Lison, and D Boning. How valid is the determination of hematocrit values to detect blood manipulations? Int. J Sports Med 21: 133–138,2000.

    Article  PubMed  CAS  Google Scholar 

  75. Schmidt, W, N Maassen, F Trost, and D Boning. Training induced effects on blood volume, erythrocyte turnover and haemoglobin oxygen binding properties. Eur J Appl Physiol Occup.Physiol 57: 490–498, 1988.

    Article  PubMed  CAS  Google Scholar 

  76. Schumacher, YO, D Grathwohl, JM Barturen, M Wollenweber, L Heinrich, A Schmid, G Huber, and J Keul. Haemoglobin, haematocrit and red blood cell indices in elite cyclists. Are the control values for blood testing valid? Int J Sports Med 21: 380–385, 2000.

    Article  PubMed  CAS  Google Scholar 

  77. Schwandt, HJ, B Heyduck, HC Gunga, and L Rocker. Influence of prolonged physical exercise on the erythropoietin concentration in blood. Eur J ApplPhysiol Occup.Physiol 63: 463–466, 1991.

    Article  CAS  Google Scholar 

  78. Selby, GB and ER Eichner. Hematocrit and performance: the effect of endurance training on blood volume. Semin.Hematol. 31: 122–127, 1994.

    PubMed  CAS  Google Scholar 

  79. Silva, M, D Grillot, A Benito, C Richard, G Nunez, and JL Fernandez-Luna. Erythropoietin can promote erythroid progenitor survival by repressing apoptosis through Bcl-XL and Bcl-2. Blood 88: 1576–1582, 1996.

    PubMed  CAS  Google Scholar 

  80. Singh, A, KU Eckardt, A Zimmermann, KH Gotz, M Hamann, PJ Ratcliffe, A Kurtz, and WH Reinhart. Increased plasma viscosity as a reason for inappropriate erythropoietin formation. J. Clin .In vest 91: 251–256, 1993.

    Article  CAS  Google Scholar 

  81. Smith, JR and SA Landaw. Smokers’ polycythemia. N.Engl. J Med. 298: 972–973, 1978.

    Article  Google Scholar 

  82. Souillard, A, M Audran, F Bressolle, R Gareau, A Duvallet, and JL Chanal. Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in athletes. Blood sampling and doping control. Br.J Clin.Pharmacol. 42: 355–364, 1996.

    Article  PubMed  CAS  Google Scholar 

  83. Spivak, JL. Serum immunoreactive erythropoietin in health and disease. Int. J Cell Cloning 8 Suppl 1: 211–224, 1990.

    Article  PubMed  Google Scholar 

  84. Spivak, JL. The clinical physiology of erythropoietin. Semin.Hematol. 30: 2–11, 1993.

    PubMed  CAS  Google Scholar 

  85. Spivak, JL, DK Ferris, J Fisher, SJ Noga, M Isaacs, E Connor, and WD Hankins. Cell cycle-specific behavior of erythropoietin. Exp.Hematol. 24: 141–150, 1996.

    PubMed  CAS  Google Scholar 

  86. Spivak, JL. and BB Hogans. The in vivo metabolism of recombinant human erythropoietin in the rat. Blood 73: 90–99, 1989.

    PubMed  CAS  Google Scholar 

  87. Spivak, JL, T Pham, M Isaacs, and WD Hankins. Erythropoietin is both a mitogen and a survival factor. Blood 77: 1228–1233, 1991.

    PubMed  CAS  Google Scholar 

  88. Stead, EA and RF Ebert. Relationship of the Plasma Volume and the Cell Plasma Ratio to the total Red cell Volume. Am J Physiol 132: 411–417, 1941.

    Google Scholar 

  89. Szewczuk, J, M Mazerska, J Malyszko, M Kalinowski, and M Mysliwiec. Increase in fibrinolytic activity after erythropoietin therapy. Thromb.Haemost. 67: 284, 1992.

    PubMed  CAS  Google Scholar 

  90. Thomson, JM, JA Stone, AD Ginsburg, and P Hamilton. O2 transport during exercise following blood reinfusion. J Appl. Physiol 53: 1213–1219, 1982.

    PubMed  CAS  Google Scholar 

  91. Vaziri, ND. Mechanism of erythropoietin-induced hypertension. Am. J Kidney Dis. 33: 821–828, 1999.

    Article  PubMed  CAS  Google Scholar 

  92. Vergouwen, PC, T Collee, and JJ Marx. Haematocrit in elite athletes. Int. J Sports Med 20: 538–541, 1999.

    Article  PubMed  CAS  Google Scholar 

  93. Walle, AJ, GY Wong, GK Clemons, JF Garcia, and W Niedermayer. Erythropoietin- hematocrit feedback circuit in the anemia of end-stage renal disease. Kidney Int. 31: 1205–1209, 1987.

    Article  PubMed  CAS  Google Scholar 

  94. Weber, JP, PC Walsh, CA Peters, and JL Spivak. Effect of reversible androgen deprivation on hemoglobin and serum immunoreactive erythropoietin in men. Am.J Hematol 36: 190–194, 1991.

    Article  PubMed  CAS  Google Scholar 

  95. Weiss, G, T Houston, S Kastner, K Johrer, K Grunewald, and JH Brock. Regulation of cellular iron metabolism by erythropoietin: activation of iron-regulatory protein and upregulation of transferrin receptor expression in erythroid cells. Blood 89: 680–687, 1997.

    PubMed  CAS  Google Scholar 

  96. Wide, L and C Bengtsson. Molecular charge heterogeneity of human serum erythropoietin. Br. J Haematol. 76: 121–127, 1990.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Jerry L. Spivak

Authors
  1. Jerry L. Spivak
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. New Mexico Resonance, Montezuma, New Mexico, USA

    Robert C. Roach

  2. University of California, San Diego, La Jolla, California, USA

    Peter D. Wagner

  3. International Society for Mountain Medicine, Ridgeway, Colorado, USA

    Peter H. Hackett

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media New York

About this chapter

Cite this chapter

Spivak, J.L. (2001). Erythropoietin use and abuse. In: Roach, R.C., Wagner, P.D., Hackett, P.H. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 502. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3401-0_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-3401-0_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3374-4

  • Online ISBN: 978-1-4757-3401-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation