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Blood manipulations are the major threat for all endurance disciplines. Increases in tHb-mass due to the abuse of erythropoietic agents (ESA’s) and blood transfusions improve endurance performance disproportionate to that which can be achieved by physiological means. An augmentation in tHb-mass by 1 gram increases VO2max by 3-4 ml/min (Schmidt and Prommer 2010).

By now, approx. 150 ESA’s including Epoietins of the first and second generation, Epoietin biosimilars, genetic Epoietin stimulation, Epoietin mimetics, and HIF 1-alpha stimulation are available (Jelkmann 2009) which offer a wide arsenal of substances for abuse in sports. Although many of the pharmaceutical products as well as homologous blood transfusions are detectable and new detection methods are in the pipeline non-traceable performance enhancing drugs will always be available.

A promising idea, therefore, is to monitor the biological effects of blood manipulations as implemented with the biological passport which has been introduced by UCI and FIS and is supported by WADA since December 2009. In this passport the individual change of several haematological parameters (i.e. Ed pillsss, reticulocytes, OFF-score, etc.) is compared with the variation of these parameters in matched athletic reference groups. The probability of abnormal values hinting to blood manipulation can be judged by applying the z-score (Sharpe et al. 2006), which indicates the degree of normality or abnormality of the individual changes or by using a Bayesian approach (Sottas et al. 2010), which also considers confounding factors.

Since the increase of tHb-mass is the key aim of all kinds of blood manipulation, i.e. use of ESA’s and of blood transfusions, the inclusion of this parameter into the blood pass has to be considered. Recent research shows that tHb-mass is only affected by few well defined confounding factors as altitude, illness/injury, and age until adulthood, but it is very stable in elite athletes in the absence of these factors (Prommer et al. 2008). Long periods of training and even several days or weeks lasting stage races (Schumacher et al. 2008, Garvican et al. 2010) do not influence tHb-mass.

According to Pottgiesser et al. (2009) reinfusion of one unit of blood yields increased tHb-mass values of up to 56 days. From these results the authors conclude that detection should be possible with the optimized CO-rebreathing method provided that the baseline value is known and not influenced by one of the above mentioned confounding factors. Also Lundby and co-workers (2010) described tHb-mass monitoring as a method to detect the effects of a 5-week rhEPO treatment (50 U/kg). However, low dose rhEPO application with an only small augmentation in tHb-mass seems not detectable. Again Pottgiesser et al. (2007) pointed out that the optimized CO-rebreathing method is able to detect manipulation induced by blood withdrawal and reinfusion of 108g (2 units). The detection if 1 unit (59g), however, seems to be problematic. Moerkeberg and his colleagues (2009) showed that blood transfusions can be detected via changes in tHb-mass with a sensitivity of up to 70% (probability of error 1:1.000) within the first days. Applying the OFF-score and Hbmr score (ratio between tHb-mass and reticulocytes) a detection is possible with a sensitivity of ~30-40% for up to three weeks after re-transfusion. For all these reasons the inclusion of tHb-mass into the biological blood pass is being considered by WADA.