Biology Reference
In-Depth Information
A disadvantage of the hematocrit test is that it draws attention to the bene-
fits of an increased hematocrit, thus tempting athletes with a natural baseline
<50% to find a way to increase it. Indeed, it is common lore that some athletes
check their hematocrits using portable centrifuges and self-administer saline
infusions and phlebotomy if the values are too high. They are also reported to
take anticoagulants to prevent thromboembolic events.
Hypochromic macrocytes
Casoni et al. [55] studied red cell indices after administering rHuEPO every
other day at an average dose of 15 U/kg/day for up to 45 days. The parameters
that changed the most were mean corpuscular volume (MCV) and mean cor-
puscular hemoglobin (MCH). The authors defined red cells with MCV>128
fL and MCH <28 pg as hypochromic macrocytes and proposed a cut-off of
0.6% to distinguish rHuEPO users from healthy controls. No further work on
this particular index has been published.
Serum transferrin receptor (TfR) and Ferritin
Serum levels of serum transferrin receptor (TfR) and ferritin are regulated by
cellular iron status, and cellular iron uptake is facilitated by TfR-mediated
endocytosis. As a result of externalization of TfR during the endocytic cycle,
a soluble form of TfR can be detected in serum. Thus, the major determinants
of serum TfR concentration are cellular iron demands and red blood cell pro-
liferation rate. Since rHuEPO expands the red cell mass, it was logical to deter-
mine if serum TfR and ferritin could serve as indirect markers of rHuEPO
administration.
Several studies have shown that amounts of serum TfR increase, amounts of
ferritin decrease, and that the ratio of serum TfR/ferritin increases when
rHuEPO is administered [41, 56, 57]. Furthermore, these changes are
detectable in most subjects for up to one week after discontinuing rHuEPO
[41]. The change in serum TfR/ferritin ratio was less dramatic in subjects treat-
ed with supplemental iron [41] than in subjects who did not receive iron [56].
Thus, the absence of supplemental iron may exaggerate the sTfR/ferritin ratio.
Most users of rHuEPO are likely to take supplemental iron. The specificity of
the changes in serum TfR, ferritin, and sTfR/ferritin has not been evaluated in
a large group of healthy normal controls of different ethnicities, subjects with
disease, or under various conditions of iron supplementation, altitude, or train-
ing. Nevertheless, these markers are relatively simple to measure and they may
be useful as indirect markers of the use of erythropoietic proteins, either alone
or in combination with other markers.
Multiple markers of erythropoietic activity: the Australian studies
In the year before the Sydney Olympic Games of 2000, Australian scientists
did an extensive series of studies designed to find a combination of blood
markers that would indicate which athletes were using rHuEPO [39, 58]. The
approach was to administer rHuEPO for three weeks, collect blood for analy-
