How Valid is the Determination of Hematocrit Values to Detect Blood Manipulations?

The aim of this paper is a critical reflection of the practice in competitive cycling to use the hematocrit value (Hct) as an indirect control measure for doping with erythropoietin. To demonstrate the individual physiological variation of Hct values, five different studies were performed: 1. Eight subjects were observed (i) during 23 h after a 1 h lasting bout of cycle exercise at 60 % of maximum performance and (ii) during 24 h under control conditions. 2. Seven subjects were exposed to a 20 min period of -7 ° head down tilt (HDT), which was followed by 15 min in sitting position. 3. From four subjects blood samples were taken in a sitting position up to 60 min after they had ingested 1 liter isotonic saline solution. 4. Ten subjects performed a vita maxima test on a cycle ergometer, starting at 100 W and increasing the workload by 17 W every minute. 5. Four elite cyclists participated in a 10 days competition (1700 km).

Results: 1. During the 24 h observation period Hct decreased during the night from 45.3 ± 3.1 % to 42.9 ± 1.5 % and returned to the initial values in the morning. This diurnal variation was even more pronounced after submaximal exercise (−4.1 %). 2. Due to fluid shifts from the interstitial into the intravasal compartment, HDT was accompanied by a 3.1 ± 0.5 % lower Hct. 3. Drinking of the isotonic saline solution also reduced the hematocrit by 3.3 ± 0.5 % after one hour. 4. Maximum cycle exercise increased the Hct from 46.8 ± 2.4 % to 51.3 ± 1.9 % which was due to a 15 % decrease in plasma volume. 5. Repeated bouts of cycle-exercise reduced the Hct from 46.4 ± 1.5 % to 41.3 ± 1.6 %.

Conclusions: All experiments demonstrate that the Hct is not a constant value but can be considerably changed by physiological measures. Clinical studies show that brain oxygen supply decreases with increasing Hct-values, which are also associated with a higher risk of stroke accidents. We therefore recommend to use a Hct-limit solely under strongly controlled standardized conditions to protect professional cyclists from hazardous manoeuvre until more appropriate methods to detect EPO-doping are developed.

Key words:

EPO - doping - plasma volume - exercise - diurnal changes - head down tilt - saline

References

• 1 Anthony A J. Der Einfluß kurzdauernder Sauerstoffatmung auf Hämoglobingehalt und Erythrozytenzahl des menschlichen Blutes. II.  Z Exp Med. 1939;  104 417-422
• 2 Anthony A J, Biedenkopf H. Der Einfluß kurzdauernder Sauerstoffatmung auf Hämoglobingehalt und Erythrozytenzahl des menschlichen Blutes I.  Z Exp Med. 1938;  103 451-457
• 3 Celsing F, Svedenhag J, Pihlstedt P, Ekblom B. Effects of anaemia and stepwise induced polycythaemia on maximal aerobic power in individuals with high and low haemoglobin concentrations.  Acta Physiol Scand. 1987;  129 47-54
• 4 Böning D, Schweigart U, Kunze M. Diurnal variations of protein and electrolyte concentrations and of acid-base status in plasma and red cells of normal man.  Eur J Appl Physiol. 1974;  32 239-250
• 5 Dill D B, Costill D L. Calculation of percentage changes in volumes of blood, plasma and red cells in rehydration.  J Appl Physiol. 1974;  37 247-248
• 6 Eichner E R. Sports anemia, iron supplementation, and blood doping.  Med Sci Sports Exerc. 1992;  24 315-318
• 7 Ekblom B, Berglund B. Effects of erythropoietin administration on maximal aerobic power.  Scand J Med Sci Sports. 1991;  1 88-93
• 8 Finsleyson D C, Dagher F J, Vandam L D. Diurnal variations in blood volume of man.  J Surg Res. 1964;  416 286-288
• 9 Fogh-Andersen N, Eidemak I, Lokkegaard H, Levin-Nielsen S. Changes in blood and plasma volume during treatment with recombinant human erythropoietin.  Scand J Clin Lab Invest. 1993;  214 61-65
• 10 Fricke G. Über das Verhalten des Zellfaktors bei Arbeit.  Cardiologia. 1965;  47 25-44
• 11 Gaethgens P, Kreutz F, Albrecht K H. Optimal hematocrit for canine skeletal muscle during rhythmic isotonic exercise.  Eur J Appl Physiol. 1979;  41 27-39
• 12 Gallaugher P, Thorarensen H, Farrell A P. Hematocrit in oxygen transport and swimming in rainbow trout (Oncorhynchus mykiss). .  Respir Physiol. 1995;  102 279-292
• 13 Gareau R, Audran M, Baynes R D, Duvallet A, Senecal L, Brisson G R. Erythropoietin abuse in athletes.  Nature. 1996;  380 113
• 14 Guyton A C. Venous return. Handbook of Physiology. Circulation. Washington, DC. Sect 2. Vol. II.   Am Phys Soc. 1963;  32 1099-1127
• 15 Halter H. Schlamm in den Adern. Der Spiegel 1991 24
• 16 Harrison M J. The hematocrit and cerebrovascular accidents.  Presse Med. 1983;  12 3095-3097
• 17 Hoffkes H G, Ehrly A M. Hematocrit dependent changes of muscle tissue oxygen supply in the lower limb muscle of patients with intermittent claudication.  Vasa. 1992;  21 350-354
• 18 Kusunoki M, Kimura K, Nakamura M, Isaka Y, Yoneda S, Abe H. Effects of hematocrit variations on cerebral blood flow and oxygen transport in ischemic cerebrovascular disease.  J Cereb Blood Flow Metab. 1981;  1 413-417
• 19 Lee S H, Heros R C, Mullan J C, Korosue K. Optimum degree of hemodilution for brain protection in a canine model of focal cerebral ischemia.  J Neurosurg. 1994;  80 469-475
• 20 Lundvall J, Bjerkhoel P, Quittenbaum S, Lindgren P. Rapid plasma volume decline upon quiet standing reflects large filtration capacity in dependent limbs.  Acta Physiol Scand. 1996;  158 161-167
• 21 Maw G J, Mackenzie I L, Taylor N A. Redistribution of body fluids during postural manipulations.  Acta Physiol Scand. 1995;  155 157-163
• 22 Pavy-Le-Traon A, Allevard A M, Fortrat J O, Gauquelin G, Guell A, Bes A, Gharib C. Cardiovascular and hormonal changes induced by a simulation of a lunar mission.  Aviat Space Environ Med. 1997;  68 829-837
• 23 Schaffartzik W, Barton E D, Poole D C, Tsukimoto K, Hogan M C, Bebout D D, Wagner P D. Effect of reduced hemoglobin concentration on leg oxygen uptake during maximal exercise in human.  J Appl Physiol. 1993;  75 491-498
• 24 Schmidt W, Bohnsack M, Maassen N, Winchenbach P, Biermann B, Zapf J. Physiological variations of hemoglobin concentration and hemoglobin mass in athletes. Abstracts 26th FIMS World Congress of Sports Medicine. 30.5. - 3.6.1998. Orlando; 1998: 42
• 25 Schmidt W, Brabant G, Kröger C, Hilgendorf A, Strauch S. Atrial natriuretic peptide during and after maximal and submaximal exercise under normoxic and hypoxic conditions.  Eur J Appl Physiol. 1990;  61 398-407
• 26 Schmidt W, Bub A, Meyer M, Weiß T, Schneider G, Maassen N, Forssmann W G. Is urodilatin the missing link in exercise-dependent renal sodium retention?.  J Appl Physiol. 1998;  84 123-128
• 27 Schmidt W, Weiglein K, Himmelsbach-Wegner B, Böning D. Gesamtkörperhämoglobinmenge, Zinkprotoporphyrin und Transferrinrezeptor - Neue Marker in der Eisendiagnostik bei Ausdauersportlerinnen?. In: Jeschke D, Lorenz R (eds) Sportartspezifische Leistungsdiagnostik - Energetische Aspekte. Köln; Sport und Buch - Strauß 1998: 353-361
• 28 Tu Y K, Kuo M F, Liu H M. Cerebral oxygen transport and metabolism during graded isovolemic hemodilution in experimental global ischemia.  J Neurol Sci. 1997;  150 115-122
• 29 Wade J P. Transport of oxygen to the brain in patients with elevated hematocrit values before and after venesection.  Brain. 1983;  106 513-523