Haematologica 2002; 87:(07)ELT31

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Addendum to strategies to deter blood doping in sports
Giuseppe d'Onofrio, Gina Zini
Institute of Hematology, Catholic University, Rome. E-mail:
donofrio.lab@rm.unicatt.it


Transfusion of autologous blood for doping became obsolete after the advent of rHuEpo. The development of rHuEpo administration associated with aggressive phlebotomy before elective surgery, however, could provide unfair athletes with an additional powerful tool for blood doping. In the March 2002 issue of Haematologica Dr Ashenden published a brilliant and exhaustive review on blood doping,1 describing the different illegitimate practices that athletes use to increase oxygen transport by their blood. He also drew up a critical review of direct and indirect methods for blood doping detection and underscored the effectiveness of monitoring athletes' blood profile over time to point out unexpected deviation (Hematologic Passport). Dr Ashenden reported that collection of autologous blood for doping purposes, according to storage time of blood, would produce negative effects during the training period. Decreased hemoglobin following phlebotomy, in fact, would reduce aerobic capacity before a major competition. Hematologists and sports scientists involved in blood doping, however, should take into consideration that the combination of two illegal methods of blood doping, i.e. rHuEpo use and autologous blood infusion, can increase their respective efficacy and reduce chances of detection. It is not unlikely, in fact, that clever athletes experiment with a surrogate of the well-established pre-surgical practice of rHuEpo-enhanced autologous transfusion (EEAT). A number of studies have shown that administration of rhu-Epo to patients undergoing aggressive phlebotomy for autologous transfusion determines a dose-dependent increase in the volume of predeposited blood before elective surgery.2 rHuEpo administration permits the collection of up to three-to-five units of blood in 30-35 days with minimal changes in blood hemoglobin. Intravenous iron supplementation is necessary to avoid true and/or functional iron deficiency.3,4 Such erythropoietic stimulation for preoperative autologous donation has been described as one of the major indication to the use of rHuEpo in transfusion medicine.5
Autologous blood infusion was in fact one of the first effective illegal tools for increasing red cell mass in athletes.6 It was outclassed by the diffusion of rHuEpo. The efficacy and safety of EEAT, however, and the receptivness of a number of athletes to new invasive medical techniques to improving performance could rescue autologous transfusion from oblivion, once technical and logistic difficulties are overcome.1 A moderate version of EEAT could easily permit to healthy young subiects to collect and store two or three units of their own blood to be transfused to themselves immediately before important competitions.7 Such a practice would not decrease the hemoglobin level, nor deteriorate training capabilities. Administration of rHuEpo could be stopped several days before competion, thus avoiding positive in-competition urine testing. Full exploitation of EEAT would require illicit skilled medical support.
It is important that we can anticipate new ways of doping, differently from what happened in the past, to devise, develop and refine in advance adequate tests. Detection of EEAT could be difficult with the present indirect methods, if not specifically researched. Infused autologous blood cannot be reliably recognized with available methods.
8 Hemoglobin and hematocrit would remain most of the time within or just below normal limits, owing to the opposite effect of phlebotomies and rhuEpo-induced erythropoietic stimulation. It is possible that reticulocyte count, as well as reticulocytes indices such as immature fraction, mean volume and mean hemoglobin content or CD71 measurement, are more sensitive and informative about EEAT for random out-competition testing,9 owing to its more intense effect on the production and release of new young red cells.
Finally, Dr Ashenden mentioned in his paper the "Science and Industry Against Blood Doping" (SIAB) project, as a multinational collaboration between scientists and industry. He wrote that the aim of his paper was to inform the scientific community of the issues faced by such group. Unfortunately he did not provide readers with any information concerning the composition of the group and the participants in this project, including the delicate issue of supporting industries. Reference to any public meeting or published material was also lacking. As a very slight and constructive criticism, we would like to suggest that interested readers, researchers and any people involved in the fight against blood dooping should be fully informed about similar enterprises which, otherwise, would appear as a duty of an esoteric group, closed to participation and cohoperation.

References

  1. Ashenden M. A strategy to deter blood doping in sport. Haematologica 2002; 87:225-234.
  2. Goodnough LT, Monk TG, Andriole GL. Erythropoietin therapy. N Engl J Med 1997; 336:933-8.
  3. Brugnara C, Chambers LA, Malynn E, Goldberg MA, Kruskall MS. Red blood cell regeneration induced by subcutaneous recombinant erythropoietin: iron-deficient erythropoiesis in iron-replete subjects. Blood 1993; 81:956-64.
  4. Mercuriali F, Zanella A, Barosi G, Inghilleri G, Biffi E, Vinci A, Colotti MT. Use of erythropoietin to increase the volume of autologous blood donated by orthopedic patients. Transfusion 1993; 33:55-60.
  5. Cazzola M, Mercuriali F, Brugnara C. Use of recombinant human erythropoietin outside the setting of uremia. Blood 1997; 89:4248-67.
  6. Brien AJ, Simon TL. The effects of red blood cell infusion on 10-km race time. JAMA 1987; 257:2761-5.
  7. Kasper SM, Gerlich W, Buzello W. Preoperative red cell production in patients undergoing weekly autologous blood donation. Transfusion 1997; 37: 1058-1062.
  8. Ekblom BT. Blood boosting and sport. Baillieres Best Pract Res Clin Endocrinol Metab 2000; 14:89-98.
  9. d'Onofrio G, Zini G, Brugnara C. Clinical application of automated reticulocyte indices. Hematology 1998; 3:165-76.