Known blood doping patterns

(ESAs , blood withdrawal and reinfusion)

effects on

HGB, RET% and OFF-score values

ABP Symposium Rome November 5-7, 2018 ROME

Michel AUDRAN

0

1

2

3

4

5

0 5 10 15 20 25 30 35 40 45 50Days

RET%

13

14

15

16

17

18

0 5 10 15 20 25 30 35 40 45 50Days

HGB g/dl

0

20

40

60

80

100

120

140

0 5 10 15 20 25 30 35 40 45 50

Days

OFF-score

Audran M et al. Med Sci Sports Exerc. 1999.

« ON-phase » « OFF-Phase »

rHuEPO NESP

Rentsch RL, et a J Appl Physiol 2006l

« ON-phase »: High Ret% + High HGB« OFF-phase »: Low RET% + High HGB = High OFFS

Effects of ESAs administrations

Date HB g/dl

Ret%

OFFS

1 08/05 15.8 0.93 100.12 19/05 15.6 1.36 86.03 28/05 16.1 1.82 80.14 01/06 17.6 0.64 128.05 11/06 17.3 0.41 134.6

GORE et al. Haematologica 2003

Date HB g/dl

Ret%

OFFS

1 08/05 15.8 0.93 100.12 19/05 15.6 1.36 86.03 28/05 16.1 1.82 80.14 01/06 17.6 0.64 128.05 11/06 17.3 0.41 134.6

J Physiol (2007)C. Lundby and al.

8 healthy subjects receiving 5000 IU recombinant rhuEpo for 15 weeks at a dose frequency aimed to increase and maintain haematocrit at approximately 50%.

5

RET♯Hb

MCHC MCV

Week 1 Week 2 Weeks 3/4 iron IVVit B12

rHuEPO 300UI/kg1/08 2/08 3/08 4/08

iron IVVit B12

WORD Championship

hypoxic tent

19/08 20/08 24/08

Date HGB g/dl

HCT RET%

OFFS

24/08 15.7 44.8 0.66 108.2620/08 16.7 48.4 0.51 124.1514/07 14.1 39.2 1.08 78.6004/06 14.8 41.3 1.59 72.34

test ESA negative

P3 P10 P17 P23 P30D0 D2 D4 D7 D9 D11

250 UI/Kg

D0 D2 D4 D7 D9 D11 P3 P10 P17 P23 P30

a single 100 mg dose

of intravenous iron

Clark B. et al. Drug Test Anal. 2017

HGB: ≈ 14.3 ≈ 16.3

RET% : ≈0.75 ≈ 2.6 ≈ 0.4

OFFS ≈ 91 ≈ 68 ≈128

00.5

11.5

22.5

33.5

44.5

0 5 10 15 20 25 30 35 40 45

Ret%

020406080

100120140

0 5 10 15 20 25 30 35 40 45

OFF-score

12

14

16

18

20

0 40

Hb g/dl

Days Hb g/dl RET% OFFS

J0 14.0 1,19 74,6 265 UI (SC)J2 15.1 1,6 75,1 265 UI (SC)J4 14.5 2,92 42,5 265 UI (SC)J7 15.3 4,29 28,7 265 UI (SC)J9 16.3 4,43 36,7 265 UI (SC)

J11 16.5 4,31 39J14 18.6 3,43 61,4J17 16.4 1,13 100,2 10 UI (IV)J18 16.6 1,06 104,2J19 6,7 UI (IV)J21 17.0 0,59 123,9J23 15.7 0,48 115,4J24 10 UI (IV)J25 17.1 0,51 128,1J28 6,7 UI (IV)J30 16.7 0,51 124,1 6,7 UI (IV)J31 17 0,57 124,7J32 5 UI (IV)J36 16.2 0,38 125J37 6,7 UI (IV)J44 16.2 0,45 121,7

Ashenden M et al.Haematologica. 2006

Subject receving: high rHuEPO doses to increase Hb around 16-17 g/dllow rHuEPO doses to maintain Hb at high level

250 UI/Kg

D0 D2 D4 D7 D9 D11 D15 D17 D19 D22 D24 D26 D29 D31 D33 P3 P10 P17 P23 P30

6-15 UI/Kg

HGB: ≈15.0 ≈17.2 ≈16.5

Ret %: ≈0.8 ≈ 3.4 ≈ 0.35

Off-score: ≈ 90 ≈ 65 ≈ 140

Clark et al. Drug Test Anal. 2017a single 100 mg dose

of intravenous iron

13

14

15

16

17

-10 -5 0 5 10 15 20 25

Days

Hb g/dl

0

0.5

1

1.5

2

-10 -5 0 5 10 15 20 25

Days

Ret%

60

70

80

90

100

110

-10 -5 0 5 10 15 20 25

Days

Off-score

8 subjects, ≈10 UI/Kg, 3/week for 2weeks

Low EPO doses

0

0.5

1

1.5

2

0 2 4 6 8 10 12 14 16 18 20 22

Ret%

11.512

12.513

13.514

14.515

15.5

0 2 4 6 8 10 12 14 16 18 20 22

Hb g/dl

40

50

60

70

80

90

100

0 2 4 6 8 10 12 14 16 18 20 22

Off score

weeks

weeks

weeks

Malm CB et al. Plos One 2016

W0 W1 W2 W3 W4 W5 W6 W7 W8 W9 W10W11W12W13W14W15W16W17W18W19W20W21D

450 ml

D 450 ml

BT: 2 unitsRBCs

W16 W 17 W18

Hb g/dl 13.9 ±0.8 14.8 ±0.3 14.5 ±0.5RET% 1.0 ±0.3 1.0 ±0.3 0.8 ±0.4

OFF-sc 79 88 91.3

100 mg Iron/d

Group transfusion N=11, group placebo N=8

Sallet et al Int J Hematol 2008

reinfusion 250 ml RBCs + 200ml plasma

D-1 D0 D+2 D+5 D+12Hb

g/dl15.0 ±0.7 16.1 ±0.9 15.8 ±1.1 15.5 ±0.9

Ret% 1.07 ±0.23 0.89 ±0.22 0.77 ±0.2 0.79 ±0.16OFFS 87.7 ±11 104.5 ±11.9 105.6 ±12.9 101.9 ±9.3

blood transfusion 1 unit