Detection of autologous blood transfusions in athletes: a historical perspective.

Autologous blood transfusions (ABTs) has been used by athletes for approximately 4 decades to enhance their performance. Although the method was prohibited by the International Olympic Committee in the mid 1980s, no direct detection method has yet been developed and implemented by the World Anti-Doping Agency (WADA). Several indirect methods have been proposed with the majority relying on changes in erythropoiesis-sensitive blood markers. Compared with the first methods developed in 1987, the sensitivity of subsequent tests has not improved the detection of blood doping. Nevertheless, the use of sophisticated statistical algorithms has assured a higher level of specificity in subsequent detection models, which is a crucial aspect of antidoping testing particularly to avoid "false positives." Today, the testing markers with the best sensitivity/specificity ratio are the Hbmr model (an algorithm based on the total amount of circulating hemoglobin level [hemoglobin level mass] and percentage of reticulocytes, 4.51·ln(Hbmass)-√%ret) and the OFF-hr model (algorithm based on hemoglobin level concentration and percentage of reticulocytes, Hb(g/L)-60·√%ret). Only the OFF-hr model is currently approved by WADA. Recently, alternative indirect strategies for detecting blood doping have been proposed. One method is based upon a transfusion-induced immune-response resulting in specific changes in gene expression related to leukocytes such as T lymphocytes. Another method relies on detecting increased plasticizer metabolite levels in the urine caused by the leakage of plasticizers from the blood bags used during the blood storage. These methods need further development and validation across different types of transfusion regimes before they can be implemented. In addition, several research projects have been funded by WADA in recent years and are now under development including "Detection of Autologous Blood Transfusions Using Activated Red Blood Cells (the red blood cells eNOS system)" and "Detection of Autologous Blood Transfusion by Proteomic: Screening to find Unique Biomarkers, Detecting Blood Manipulation from Total Hemoglobin Mass using 15-nitric Oxide as a Tracer Gas, Storage Contamination as a Potential Diagnostic Test for Autologous Blood Transfusion and Test for Blood Transfusion (Autologous/Homologous) based on Changes of Erythrocyte Membrane Protome" (WADA, WADA Funded Research Projects. http://www.wada-ama.org/en/Science-Medicine/Research/Funded-Research-Projects/. 2010). Although strategies to detect autologous blood transfusion have improved, a highly sensitive test to detect small volumes of transfused autologous blood has not yet been implemented.