The hybrid algorithm (Hbmr) to fight against blood doping in sports

Plasma volume expanders (PVEs) have a ‘‘diluting effect’’ and the potential to mask erythropoietin (EPO) administration in sports. Thus, PVEs are considered prohibited substances (Guddat et al., 2005, 2008). In 2001, six Finnish skiers tested positive for hydroxy-ethyl starch, a banned PVE, during the world championships in Finland. This is considered one of the biggest doping scandals in the sports (Seiler, 2001). Athletes, often through their medical consultants, have rapidly learned that PVEs can be used combined with recombinant erythropoietin (rHuEPO) to adjust different hematological parameters to physiological levels (Gutierrez Gallego & Segura, 2004). Recently, we have published that treatment with desmopressin (DDAVP) combined with water has a very effective hemodiluting effect, decreasing the hematological values measured by the anti-doping authorities to detect blood doping. After treatment with DDAVP, we found a significant decrease in hematocrit and hemoglobin. However, reticulocytes values were not altered. The OFF-Hr Score value (Hb (in g/L) [60 p ret%]) changed significantly after the hemodilution induced by DDAVP (100.8 0.7 before hemodilution and 90.9 5.9 after hemodilution) (Sanchis-Gomar et al., 2010), being favorable for the athlete. With the OFF-Hr Score value, the antidoping authorities can detect approximately twothirds of the athletes that have suspended the rHuEPO treatment 2 or 3 weeks before competition (Parisotto et al., 2000). We have demonstrated, in an animal model, that the OFF-Hr Score can also be modified with hypoxia treatments due to a faster recovery in the reticulocyte count after rHuEPO administration (Sanchis-Gomar et al., 2009). The OFF-Hr Score values rely on elevated hemoglobin at the same time as depressed reticulocytes, which occurs when athletes cease injecting rHuEPO or after blood transfusions. However, when these doping methods are combined with hemodilution strategies and/or hypoxia treatments, the OFF-Hr score effectiveness is diminished. This may change the final outcome of this indirect marker (Borno et al., 2010). Recently, it has been postulated that the determination of the hemoglobin mass (Hbmass) can be an alternative method to allow the long-term identification of a supraphysiologically elevated Hb levels induced by autologous blood transfusions (Pottgiesser et al., 2009) and that Hbmass remains stable over time (Garvican et al., 2010). However, it does not appear to be so suitable for detecting low doses of rHuEPO treatment (Lundby & Robach, 2010). In an excellent paper published recently by Mørkeberg et al.(2009), the authors have evaluated four indirect markers of blood doping: hemoglobin concentration ([Hb]), OFF-Hr Score, Hbmass and a hybrid algorithm (Hbmr) to investigate the sensitivity of the different hematological markers to detect autologous transfusions. The novel Hbmr marker proposed by Mørkeberg and colleagues offers the advantage to combine Hbmass with %ret. Both parameters, as mentioned above, are very stable, which makes their modification difficult with natural (after high-intensity exercise) or artificial (with the use of PVEs or DDAVP) hemodilution modifications. The %ret represents the ratio between the concentration of mature erythrocytes and immature erythrocytes in a sample, and therefore any plasma volume changes (either natural or manipulated) can be neglected (Mørkeberg et al., 2009). However, we should take into account that Mørkeberg and colleagues performed their study under controlled and ideal conditions, where the initial pre-reinfusion values and the time-point of reinfusion were known. Although in this study only 44% of the samples in the postinfusion period were exceeding the limit of Hbmr after reinfusion of three bags of blood, and no subjects reinfused with one bag of blood exceeded this limit, Hbmr and OFF-Hr showed superior but equal sensitivities from 1 to 4 weeks after transfusion compared with [Hb] and Hbmass, with Hbmass being the only tenable prospect to detect acute transfusions. From an anti-doping point of view, the stability of the variable under exercise conditions strengthens the potential of Hbmr as an indirect method to detect blood manipulations and rHuEPO administration in sports. A handicap of the Hbmass determination is that no standardization or quality control method is available for its Scand J Med Sci Sports 2010: 20: 789–790 & 2010 John Wiley & Sons A/S