Improved alignment of reticulocyte counts between Sysmex XT-2000i instruments.

Background: Reticulocytes are the most sensitive index available to authorities who seek to sanction athletes for blood doping based on deviations beyond individual reference ranges. Because such data comprise longitudinal results that are generated by different laboratories, the comparability of reticulocyte counts from different instruments is of crucial importance.

Aims: To enhance between-instrument comparability of reticulocyte counts reported by the Sysmex XT-2000i automated haematology analyser.

Evaluation of the MAIIA dipstick test to detect recombinant human erythropoietin in plasma.

Recently a novel technology, referred to as the 'EPO WGA MAIIA' test, has been developed by Swedish researchers to discriminate between endogenous and recombinant human erythropoietin. In contrast to existing electrophoretic methods that are used by antidoping laboratories, this dipstick-based technique is simple and fast. Moreover it can be applied to either blood or urine specimens.

Preanalytical mixing of whole-blood specimens in the context of the Athlete Passport.

Background: Full blood counts are now used as evidence that athletes have used banned blood doping. This has led to legal scrutiny of the efficacy of preanalytical procedures such as specimen homogenisation.

Aims: To characterise the impact of different mixing strategies on whole-blood homogeneity.

Current markers of the Athlete Blood Passport do not flag microdose EPO doping.

The Athlete Blood Passport is the most recent tool adopted by anti-doping authorities to detect athletes using performance-enhancing drugs such as recombinant human erythropoietin (rhEPO). This strategy relies on detecting abnormal variations in haematological variables caused by doping, against a background of biological and analytical variability. Ten subjects were given twice weekly intravenous injections of rhEPO for up to 12 weeks.

Current and upcoming erythropoiesis-stimulating agents, iron products, and other novel anemia medications.

Treatment for anemia has come a long way in the last 20 years since the first recombinant human erythropoietins were licensed for the management of anemia in chronic kidney disease. The first-generation epoetins were succeeded by the development and production of a longer-acting erythropoietin (EPO) analog, darbepoetin alpha, which allowed less frequent dosing, usually once weekly or once every 2 weeks. More recently, another EPO-related molecule has been manufactured called Continuous Erythropoietin Receptor Activator with an even longer half-life, and although for patent reasons this is not available in the United States, it is licensed and is already being used in Europe.

The effects of microdose recombinant human erythropoietin regimens in athletes.

This study appraised the veracity of claims that athletes can evade doping controls by injecting microdoses of recombinant human erythropoietin (rHuEPO), which rapidly disappear from the circulation. We confirmed that microdosing can reduce the window of detection to as little as 12-18 hours post-injection, suggesting that authorities must adopt appropriate counter measures.

A third generation approach to detect erythropoietin abuse in athletes.

Background And Objectives: Information derived from blood analyses can assist in the detection and/or deterrence of blood doping in sport. We investigated whether comparing an athlete's hematologic values against his or her own historical baseline rather than population-derived thresholds enhanced the ability to detect blood doping.

Design And Methods: We developed an approach whereby an athlete's true baseline value could be estimated with just one prior blood test.

Longitudinal variation of hemoglobin and reticulocytes in elite rowers.

Longitudinal monitoring of athlete's hematologic parameters holds considerable promise as a strategy to detect and thereby deter illicit blood doping. This study documents temporal changes of hemoglobin concentration (Hb) and reticulocyte counts in elite rowers. The 'within subject' variation in rowers was comparable to that of athletes from other sports.

Effect of pre-competition and altitude training on blood models used to detect erythropoietin abuse by athletes.

This study reports blood model scores used for detection of recombinant human erythropoietin (rHuEPO) abuse by athletes. Elite female rowers were monitored prior to their World Championships, including a period spent training at moderate altitude. In contrast to previous results, no substantial increase in model scores was found following altitude exposure.

Standardization of reticulocyte values in an antidoping context.

The lack of standardization of reticulocyte results hinders the ability of sports authorities to recognize the telltale fluctuations over time that are typical for athletes using illegal blood doping to improve their performance. Therefore, the aim of the present study was to devise a tenable approach for antidoping authorities to quantify, instrument bias. We evaluated reticulocyte data derived during a 42-week period from 210 hospital patient blood samples measured in duplicate simultaneously on up to 11 hematology analyzers located in a single laboratory.

Doping with artificial oxygen carriers: an update.

There is a long history of science seeking to develop artificial substitutes for body parts damaged by disease or trauma. While defective teeth and limbs are commonly replaced by imitations without major loss of functionality, the development of a substitute for red blood cells has proved elusive. There is a permanent shortage of donor blood in western societies.

Detection of hemoglobin-based oxygen carriers in human serum for doping analysis: confirmation by size-exclusion HPLC.

Background: Hemoglobin-based oxygen carriers (HBOCs) are being developed as potential substitutes for the oxygen-carrying functions of erythrocytes, but athletes may obtain and experiment with HBOCs as an illicit means of enhancing oxygen transport. An electrophoretic technique has been developed to screen for the presence of HBOCs in blood samples (Lasne et al. Clin Chem 2004;50:410-5).

Detection of hemoglobin-based oxygen carriers in human serum for doping analysis: screening by electrophoresis.

Background: Hemoglobin-based oxygen carriers (HBOCs) have recently been included in the International Olympic Committee and World Anti-Doping Agency lists of substances and methods prohibited in sports. To enforce this rule and deter abuse of HBOCs in elite sports, it is necessary to develop HBOC-specific screening and confirmation tests that are the usual steps in antidoping control analysis.

Methods: We developed a screening method based on electrophoresis of serum samples cleared of haptoglobin (Hp).

Proof of homologous blood transfusion through quantification of blood group antigens.

Background And Objectives: Athletes may illegally enhance endurance performance by transfusing homologous red blood cells (RBCs) and thereby increasing the oxygen carrying capacity of their blood. Detecting this dangerous practice is difficult by currently used methods. The aim of this work was to develop tests capable of detecting a mixed red cell population by flow cytometry, utilizing the likelihood of differences in minor blood group antigens.

Effect of altitude on second-generation blood tests to detect erythropoietin abuse by athletes.

Background And Objectives: ON- and OFF-model scores derived from blood parameters sensitive to erythropoiesis have been shown to be a useful tool to identify athletes who are currently injecting erythropoietin to enhance performance or those who have recently stopped doing so. We investigated changes in blood parameters and model scores during and after exposure to terrestrial and simulated altitudes.

Design And Methods: We retrospectively evaluated changes in hematologic data collected from 19 elite cyclists who lived and trained 2690 m above sea level for 26-31 days, from six elite Kenyan runners who lived 2100 m above sea level but descended to compete at sea level competitions, and from 39 well-trained subjects who resided at sea level but slept at a simulated altitude of 2650-3000 m for 20-23 days of either consecutive or intermittent nightly exposure.

The effect of common hematologic abnormalities on the ability of blood models to detect erythropoietin abuse by athletes.

Background And Objectives: Algorithms that combine scores from multiple blood parameters are demonstrably effective in highlighting recombinant human erythropoietin (rHuEPO) administration, and have been used to deter rHuEPO use by athletes. These models are sensitive to atypical levels of blood parameters encountered during altered states of red cell production. Because hematologic abnormalities can also result in unusual blood profiles, the aim of this study was to document the incidence and magnitude of such abnormalities in an elite athlete population.

Second-generation blood tests to detect erythropoietin abuse by athletes.

Background And Objectives: We previously developed blood tests that were introduced at the Sydney 2000 Olympic Games to identify athletes injecting recombinant human erythropoietin (rHuEPO). The aim of this study was to re-analyse our existing database to develop models with heightened sensitivity, using wherever possible blood parameters measurable with appropriate standards of analytical performance.

Design And Methods: The principal database for this study was derived from a double-blind trial in which 57 recreational athletes were administered either rHuEPO or placebo.

Development of reference ranges in elite athletes for markers of altered erythropoiesis.

Background And Objectives: Our previous research developed two statistical models that are useful indicators of current (ON-model) or recently discontinued (OFF-model) recombinant human erythropoietin (rHuEPO) use by athletes. The component variables of the ON-model are hematocrit (Hct), reticulocyte hematocrit (RetHct), serum erythropoietin (EPO), percent macrocytes (%Macro), and soluble transferrin receptor (sTfr), whilst the OFF-model uses only the first three variables. Genetics and training modalities of elite athletes may conceivably produce unusual values for blood parameters related to erythropoiesis.

Effects of prolonged low doses of recombinant human erythropoietin during submaximal and maximal exercise.

The aim of this study was to characterise the effect of prolonged low doses of recombinant erythropoietin (r-HuEPO) on the responses to submaximal and maximal exercise. Volunteer recreational athletes ( n=21) were divided into three groups: r-HuEPO+intravenous iron (EPO+IV, n=7), r-HuEPO+oral iron (EPO+OR, n=9) and placebo ( n=5). During the 12 week study, r-HuEPO or saline injections were given three times a week for the first 8 weeks and for the final 4 weeks the subjects were monitored but no injections were administered.