Questions for the Expert panel

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Questions for the Expert panel A. analytical and peri-analytical aspects (complete: instrument reports, storage temperature, QC, etc.) can the abnormal result be explained by the analytical or pre-analytical process? B. physiological variability can it be explained by the influence of environmental conditions or exercise before or at the time of sample collection? C. pathological events or conditions can it explained by a congenital disorder or an acute event (blood loss, surgery, etc.)? D. blood doping can the abnormal result be explained by one or more of the known blood manipulations? 2

How likely is the abnormal Athlete s profile assuming : ESA intake? recent suspension of ESA? blood withdrawal? blood reinfusion? EPO microdoses? EPO combined with transfusion? blood boosting for collection EPO stimulation after reinfusion. any of these masked by dilution? Avoid speculations and description of a rigid, detailed scenario in the first individual opinion and in the joint panel report. 3

Blood doping scenario Definition: a postulated sequence or development of events In ABP: hematologic constellation indicating a specific manipulation, on the basis of published experimental studies i.e, the OFF phase Patterns within a sequence Information from athlete s biographies and depositions, CAS awards, physiopathology of erythropoiesis New doping scenarios: low-doses, intermingled ESA-transfusion ESA doping for training, far from races The word «compatible» is not appropriate (better: likely, plausible )

Doping scenario at CAS CAS n. 1: A match with the Athlete s competition schedule is additional evidence to be taken into account if the abnormality occurs at a time when the Athlete in question could benefit from blood manipulation. A chronological coincidence reinforces the inferences to be drawn if attributing the abnormal values to blood manipulation. CAS n. 2: Explanations must be decided on the basis of the scientific evidence alone, and cannot be influenced by circumstantial evidence as to the motive or opportunity for the rider to have used a prohibited substance or method. 5

Pattern n. 1: the ON phase Within a sequence, one or more samples display high HB, high retics, normal OFFs Scenario: Ongoing ESA stimulation pre-competition (naif athlete, Helsinki 2012) out-of-season preparatory to blood collection (winter in cycling) increased training and recovery (Africans, not only) Altitude (uncertain: when HB is high, reticulocytes should be normalized) If stable, congenital erythrocytosis should be considered 6

Pattern 2: reactive ON, decreased HB Low or low-normal HB, high reticulocytes, low OFFs (erythropoietic stimulation) Scenario: blood withdrawal (for frozen or refrigerated storage) October, after 2013 Moscow WCh, winter sports in summer, cyclists after preparatory small tours early onset of ESA intake medical condition: blood loss, donation, hemolytic anemia, pregnancy

Pattern n. 3: OFF, the top player High HB, low retics, high OFFs Scenario: typical OFF phase consequent to: cessation of ESA courses before competition reinfusion of an important amount of blood in moderate form, 2-3 weeks after return from a long stay at high altitude

Pattern n. 4: «decapitated» OFF Normal-to-low HB, low retics, moderately high or normal OFFs Scenario: hemodilution (oral or intravenous), masking a typical OFF phase return from a stay at high altitude exceptionally, medical conditions should be considered (viruses?) HB-60 ret% X

Pattern n. 5: «amputated OFF» Variously increased HB, normal or slighlty increased reticulocytes, normal OFFs Scenario: ESA microdoses (after regular dose course) African pattern: ESA intake + altitude hypoxia (lower HB INC, at sea-level competition sites) first days after reinfusion of blood first weeks of a stay at high altitude exceptionally, medical conditions should be considered HB-60 ret% X

Pattern n. 6: normalization of an abnormal passport Scenario (deterrence effect): change of doping strategy cessation of doping Alternative explanations: change of training programs different hypoxic exposure change of discipline

Pattern n. 7: abnormalities in a previously normal passport Strong long-lasting baseline Sudden occurrence of typical doping anomalies Scenario depends on the type of anomalies Athletes can change doping tactic or decide for doping during their career to maintain top level (increasing age) to imitate known doping competitors

Pattern n. 8: paradoxical changes Increased HB during long, multistage races (instead of the expected hemodilution) Scenario: reinfusion of blood Alternative scenario: physiological adaptation (?) Mørkeberg JS, Belhage B, Damsgaard R. Changes in blood values in elite cyclist. Int J Sports Med. 2009 Feb;30(2):130-8. Gore CJ, Morkeberg J, Schmidt W, Garvican LA, Fellman N. Plasma volume shifts during multiday racing. Clin Chem Lab med 2012