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The EPO gene variant, c.577del (VAR‐EPO), was discovered in the Chinese population in 2021. The mutated protein is naturally present in urine from individuals heterozygous for the variant. Electrophoresis methods currently applied in anti‐doping laboratories produce a pattern in samples from individuals carrying VAR‐EPO that cannot be unambiguously distinguished from individuals who received recombinant EPO doses. Consequently, the analysis of blood samples is obligatory to facilitate interpretation of suspicious findings from urine samples. However, this complicates the process and delays the reporting. Objective of this study was to develop EPO c.577del detection in urine and dried blood samples (DBS) in order to facilitate and accelerate EPO results management. Moreover, estimation of the success rate of sequencing regarding concentration of DNA in urine and DBS was evaluated. Conclusive results regarding Sanger sequencing were obtained for all samples with DNA concentrations above 0.024 ng/μL DNA in 80% of urines samples from volunteers. The potential success of DNA sequencing rate in athletes' urines was investigated. A total of 191 urine samples were considered. DNA concentration exceeding 0.024 ng/μL was detected in 85% of the samples. Interestingly, in‐competition samples had a significantly higher DNA concentration than out‐of‐competition male urine samples (0.330 vs. 0.084 ng/μL). Moreover, conclusive EPO sequences were obtained for 100% of DBS (cellulose and polymer matrices). In conclusion, method for detection of EPO gene variant was developed in urine and DBS. Characterization of DNA concentration was performed in order to evaluate the probability of success of sequencing EPO gene in anti‐doping field. [ABSTRACT FROM AUTHOR]

Introduction: The study demonstrated the feasibility of incorporating RNA biomarkers, specifically 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), to improve the hematological module of the Athlete Biological Passport (ABP) in routine antidoping context. Objective: The aim was to investigate the implementation of reticulocyte (RET) related biomarkers, specifically ALAS2 and CA1, using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on dried blood spots (DBS) from elite athletes. Hemoglobin changes over time in DBS samples was measured as well. Combining hemoglobin and messenger RNA (mRNA) analyses allowed to monitor alterations of the established marker, "DBS OFF-score". Methodology: Ten athletes were selected for sampling by the Swiss national antidoping organization, Swiss Sports Integrity (SSI). Samples were collected, transported and analyzed for ABP following the World Anti-Doping Agency (WADA) procedures and spotted onto Protein Saver DBS cards. Results: Most athletes exhibited stable biomarker levels, except for one individual involved in ski mountaineering, who demonstrated a sustained increase in ALAS2 compared to the individual baseline. This elevation could be due to blood withdrawal or other factors, such as doping with substances outside the targeted test menu. Conclusion: In this study, RNA-biomarkers were successfully analyzed in routine blood samples, and the project demonstrated promising results for the implementation of ALAS2 and CA1 in routine analysis to complement the ABP. [ABSTRACT FROM AUTHOR]

In humans and many animals, a trade-off between a sufficiently high concentration of erythrocytes (hematocrit) to bind oxygen and sufficiently low blood viscosity to allow rapid blood flow has been achieved during evolution. The optimal value lies between the extreme cases of pure blood plasma, which cannot practically transport any oxygen, and 100% hematocrit, which would imply very slow blood flow or none at all. As oxygen delivery to tissues is the main task of the cardiovascular system, it is reasonable to expect that maximum oxygen delivery has been achieved during evolution. Optimal hematocrit theory, based on this optimality principle, has been successful in predicting hematocrit values of about 0.3–0.5, which are indeed observed in the systemic circulation of humans and many animal species. Similarly, the theory can explain why a hematocrit higher than normal, ranging from 0.5 to 0.7, can promote better exertional performance. Here, we present a review of theoretical approaches to the calculation of the optimal hematocrit value under different conditions and discuss them in a broad physiological context. Several physiological and medical implications are outlined, for example, in view of blood doping, temperature adaptation, dehydration, and life at high altitudes. [ABSTRACT FROM AUTHOR]

Blood doping remains a significant problem that threatens the integrity of sport. The current indirect method for detecting blood doping involves the longitudinal measurement of an athlete's haematological variables and identification of suspicious results that are indicative of doping (i.e., the athlete biological passport). While this has played a significant role in the protection of clean sport, improvements are needed. The development of a transcriptomic test, that can be used to detect the use of blood doping has been discussed and researched for decades and yet, an anti-doping test that can be adopted by the World Anti-Doping Agency (WADA) is yet to be established. With recent advancements in our understanding, as well as in methods of sample collection, the possibility of a transcriptomic test that can be used by WADA, is imminent. There are, however, several practical considerations that must first be made, that will be highlighted in this perspective article. [ABSTRACT FROM AUTHOR]

IntroductionThe study demonstrated the feasibility of incorporating RNA biomarkers, specifically 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), to improve the hematological module of the Athlete Biological Passport (ABP) in routine antidoping context.ObjectiveThe aim was to investigate the implementation of reticulocyte (RET) related biomarkers, specifically ALAS2 and CA1, using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on dried blood spots (DBS) from elite athletes. Hemoglobin changes over time in DBS samples was measured as well. Combining hemoglobin and messenger RNA (mRNA) analyses allowed to monitor alterations of the established marker, “DBS OFF-score”.MethodologyTen athletes were selected for sampling by the Swiss national antidoping organization, Swiss Sports Integrity (SSI). Samples were collected, transported and analyzed for ABP following the World Anti-Doping Agency (WADA) procedures and spotted onto Protein Saver DBS cards.ResultsMost athletes exhibited stable biomarker levels, except for one individual involved in ski mountaineering, who demonstrated a sustained increase in ALAS2 compared to the individual baseline. This elevation could be due to blood withdrawal or other factors, such as doping with substances outside the targeted test menu.ConclusionIn this study, RNA-biomarkers were successfully analyzed in routine blood samples, and the project demonstrated promising results for the implementation of ALAS2 and CA1 in routine analysis to complement the ABP.

Abstract Background Autologous blood transfusion is one of the illicit strategies, banned by the World Anti-Doping Agency, to increase the levels of hemoglobin, with a consequent improvement in the delivery of oxygen to tissues. At present, this practice is detectable exclusively by the individual, longitudinal monitoring of hematological biomarkers, as in the hematological module of the Athlete Biological Passport; but this indirect approach may suffer from different confounding factors. We are presenting a multi-parametric, analytical strategy to detect autologous blood transfusions by targeting the modification of the red blood cells during storage. We focused on the assessment of “storage lesions”, targeting (i) membrane proteins: Glycophorin-A and Band 3 complex, (ii) biomarkers of oxidative stress: Peroxiredoxin-2, (iii) biomarkers of senescence: CD47 and Phosphatidylserine, (iv) erythrocytes microparticles. Results All of the above markers were monitored, by immunological and flow cytofluorimetric methods, on samples of stored whole blood collected at different time intervals, and on fresh blood samples, collected for official doping control tests, mixed “ex vivo” to simulate an autotransfusion. Although anonymized before the delivery to the laboratory, it was possible to mix samples belonging to the same subject based on the “athlete biological passport” code. Our results showed that the irreversible alteration of RBCs morphology, the loss of membrane integrity, the occurrence of hemolysis phenomena, and, more in general, the “aging” of the erythrocytes during storage are closely related to: (i) the reduced concentration, on the erythrocyte membrane, of Band 3 protein (decrease of 19% and of 39% after 20 and 40 days of storage respectively) and of glycophorin A (− 47% and − 63% respectively); (ii) the externalization of phosphatidyl serine (with a five-fold increase after 20 days and a further 2× increase after 40 days); (iii) the reduced concentration of CD47; and (iv) increased levels of erythrocyte microparticles. Conclusions The most promising method to detect the presence of transfused blood in whole blood samples can be based on a multi-parametric strategy, considering jointly both protein expression on RBCs membranes and micro-vesiculation phenomena.

This study investigated the impact of low‐volume blood withdrawal on the hematological biomarkers currently considered for anti‐doping purposes. After baseline measurement (D − 7), a 140 mL blood withdrawal was completed (D + 0) on 12 healthy volunteers, followed by weekly monitoring for 21 days (D + 7 – 21). Each visit consisted of a full blood count (Sysmex XN‐1000) and duplicate blood volume measurements by CO‐rebreathing. A significant decrease in total hemoglobin mass (Hbmass) (−2.3%, p = 0.007) and red blood cell volume (RBCV) (−2.8%, p = 0.028) was reported at D + 7. Despite no atypical passport finding (ATPF) when considering the athlete biological passport adaptive longitudinal model, hemoglobin concentration ([Hb]) increased significantly at D + 21 (+3.8%, p = 0.031). Besides, ferritin (FERR) was significantly downregulated at all points following blood withdrawal, with the largest decrease occurring at D + 7 (−26.6%, p < 0.001). Regardless of the presumable effect of blood reinfusion on ABP biomarkers, these results illustrate the challenge of monitoring hematological variables for the detection of low‐volume blood withdrawal. Finally, this study outlines the sensitivity of FERR to altered erythropoiesis to support the implementation of iron markers as complementary variables for the longitudinal monitoring of blood doping, despite the potential influence of confounding factors (e.g., iron supplementations). [ABSTRACT FROM AUTHOR]

Blood doping is prohibited for athletes but has been a well‐described practice within endurance sports throughout the years. With improved direct and indirect detection methods, the practice has allegedly moved towards micro‐dosing, that is, reducing the blood doping regime amplitude. This narrative review evaluates whether blood doping, specifically recombinant human erythropoietin (rhEpo) treatment and blood transfusions are performance‐enhancing, the responsible mechanism as well as detection possibilities with a special emphasis on micro‐dosing. In general, studies evaluating micro‐doses of blood doping are limited. However, in randomized, double‐blinded, placebo‐controlled trials, three studies find that infusing as little as 130 ml red blood cells or injecting 9 IU × kg bw−1 rhEpo three times per week for 4 weeks improve endurance performance ~4%–6%. The responsible mechanism for a performance‐enhancing effect following rhEpo or blood transfusions appear to be increased O2‐carrying capacity, which is accompanied by an increased muscular O2 extraction and likely increased blood flow to the working muscles, enabling the ability to sustain a higher exercise intensity for a given period. Blood doping in micro‐doses challenges indirect detection by the Athlete Biological Passport, albeit it can identify ~20%–60% of the individuals depending on the sample timing. However, novel biomarkers are emerging, and some may provide additive value for detection of micro blood doping such as the immature reticulocytes or the iron regulatory hormones hepcidin and erythroferrone. Future studies should attempt to validate these biomarkers for implementation in real‐world anti‐doping efforts and continue the biomarker discovery. [ABSTRACT FROM AUTHOR]

The prevalence of autologous blood transfusions (ABTs) presents a formidable challenge in maintaining fair competition in sports, as it significantly enhances hemoglobin mass and oxygen capacity. In recognizing ABT as a prohibited form of doping, the World Anti-Doping Agency (WADA) mandates stringent detection methodologies. While current methods effectively identify homologous erythrocyte transfusions, a critical gap persists in detecting autologous transfusions. The gold standard practice of longitudinally monitoring hematological markers exhibits promise but is encumbered by limitations. Despite its potential, instances of blood doping often go undetected due to the absence of definitive verification processes. Moreover, some cases remain unpenalized due to conservative athlete-sanctioning approaches. This gap underscores the imperative need for a more reliable and comprehensive detection method capable of unequivocally differentiating autologous transfusions, addressing the challenges faced in accurately identifying such prohibited practices. The development of an advanced detection methodology is crucial to uphold the integrity of anti-doping measures, effectively identifying and penalizing instances of autologous blood transfusion. This, in turn, safeguards the fairness and equality essential to competitive sports. Our review tackles this critical gap by harnessing the potential of microRNAs in ABT doping detection. We aim to summarize alterations in the total microRNA profiles of erythrocyte concentrates during storage and explore the viability of observing these changes post-transfusion. This innovative approach opens avenues for anti-doping technologies and commercialization, positioning it as a cornerstone in the ongoing fight against doping in sports and beyond. The significance of developing a robust detection method cannot be overstated, as it ensures the credibility of anti-doping efforts and promotes a level playing field for all athletes. [ABSTRACT FROM AUTHOR]

The detection of blood doping represents a current major issue in sports and an ongoing challenge for antidoping research. Initially focusing on direct detection methods to identify a banned substance or its metabolites, the antidoping effort has been progressively complemented by indirect approaches. The longitudinal and individual monitoring of specific biomarkers aims to identify nonphysiological variations that may be related to doping practices. From this perspective, the identification of markers sensitive to erythropoiesis alteration is key in the screening of blood doping. The current Athlete Biological Passport implemented since 2009 is composed of 14 variables (including two primary markers, i.e., hemoglobin concentration and OFF score) for the hematological module to be used for indirect detection of blood doping. Nevertheless, research has continually proposed and investigated new markers sensitive to an alteration of the erythropoietic cascade and specific to blood doping. If multiple early markers have been identified (at the transcriptomic level) or developed directly in a diagnostics' kit (at a proteomic level), other target variables at the end of the erythropoietic process (linked with the red blood cell functions) may strengthen the hematological module in the future. Therefore, this review aims to provide a global systematic overview of the biomarkers considered to date in the indirect investigation of blood doping. [ABSTRACT FROM AUTHOR]

Background: Autologous blood transfusion is one of the illicit strategies, banned by the World Anti-Doping Agency, to increase the levels of hemoglobin, with a consequent improvement in the delivery of oxygen to tissues. At present, this practice is detectable exclusively by the individual, longitudinal monitoring of hematological biomarkers, as in the hematological module of the Athlete Biological Passport; but this indirect approach may suffer from different confounding factors. We are presenting a multi-parametric, analytical strategy to detect autologous blood transfusions by targeting the modification of the red blood cells during storage. We focused on the assessment of "storage lesions", targeting (i) membrane proteins: Glycophorin-A and Band 3 complex, (ii) biomarkers of oxidative stress: Peroxiredoxin-2, (iii) biomarkers of senescence: CD47 and Phosphatidylserine, (iv) erythrocytes microparticles. Results: All of the above markers were monitored, by immunological and flow cytofluorimetric methods, on samples of stored whole blood collected at different time intervals, and on fresh blood samples, collected for official doping control tests, mixed "ex vivo" to simulate an autotransfusion. Although anonymized before the delivery to the laboratory, it was possible to mix samples belonging to the same subject based on the "athlete biological passport" code. Our results showed that the irreversible alteration of RBCs morphology, the loss of membrane integrity, the occurrence of hemolysis phenomena, and, more in general, the "aging" of the erythrocytes during storage are closely related to: (i) the reduced concentration, on the erythrocyte membrane, of Band 3 protein (decrease of 19% and of 39% after 20 and 40 days of storage respectively) and of glycophorin A (− 47% and − 63% respectively); (ii) the externalization of phosphatidyl serine (with a five-fold increase after 20 days and a further 2× increase after 40 days); (iii) the reduced concentration of CD47; and (iv) increased levels of erythrocyte microparticles. Conclusions: The most promising method to detect the presence of transfused blood in whole blood samples can be based on a multi-parametric strategy, considering jointly both protein expression on RBCs membranes and micro-vesiculation phenomena. Key Points: Potential biomarkers of "blood storage" were specifically considered in this study to detect autologous blood transfusions in sport doping. The irreversible alteration of RBCs morphology, the loss of membrane integrity, the occurrence of hemolysis phenomena, and, more in general, the "aging" of the erythrocytes during storage are closely related to: (i) the reduction, on the erythrocyte membrane, of Band 3 protein and of glycophorin A; (ii) the externalization of phosphatidyl serine; (iii) the reduced concentration of CD47; and (iv) the increased levels of erythrocyte microparticles. Freshly collected samples showed differences from stored or mixed ones in terms of both protein expression on the RBCs membranes and micro-vesiculation phenomena. [ABSTRACT FROM AUTHOR]

The purpose of this research was to evaluate the performances of female middle- and long-distance runners before and after the implementation of a new antidoping strategy (the Athlete Biological Passport [ABP]) in a country accused of systematic doping. A retrospective analysis of the results of Russian National Championships from 2008 to 2017 was performed. The 8 best female performances for the 800-m, 1500-m, 3000-m steeplechase, 5000-m, and 10,000-m events from the semifinals and finals were analyzed. The yearly number of athletes fulfilling standard qualifications for international competitions was also evaluated. Overall, numbers of athletes banned for doping in 2008–2017 were calculated. As a result, 4 events (800, 1500, 5000 [all P <.001], and 10,000 m [P <.01]) out of 5 showed statistically significant deterioration in the performances when comparing before and after the introduction of the ABP. The 3000-m steeplechase was the only event that did not show statistically significant change. The highest relative decrease in the number of runners who met standard qualification for international competition was for the 5000-m event (46%), followed by 1500-m (42%), 800-m (38%), 10,000-m (17%), and 3000-m steeplechase (1%). In conclusion, implementation of the ABP was followed by a significant reduction in the performance of female runners in a country accused of systematic doping. It can be reasonably speculated that more stringent antidoping testing, more specifically the introduction of the ABP, is a key reason for this reduction. [ABSTRACT FROM AUTHOR]

The athlete's desire to achieve victory is why some of them decide to use doping. Blood doping, the common type of doping in endurance sports, increases hemoglobin, oxygen tissue delivery, and improves maximal aerobic capacity. The usual illegal ways for hemoglobin elevation are abuse of substances (recombinant human erythropoietin, hypoxia inducible factors) and/or methods (autologous blood transfusions) in concordance with exact protocols to avoid adverse finding either with approved direct methods or with indirect methods. Since direct methods are not sensitive enough to autologous blood transfusion, novel molecular substances, or to detect variants of recombinant human erythropoietin in different application protocols, indirect anti-doping methods marking the changes in the human body related to doping abuse, are being developed. The successful example of indirect method is the Athlete biological passport, with its hematological module consisting of twelve parameters and two scores that enable longitudinal monitoring of each athlete. Personal reference values at each sampling time are calculated in concordance with the Bayes network. Changes in blood parameters related to doping are marked as adverse analytical finding with 99% certainty, but new application regimens and various athletes' explanations for adverse analytical finding represent a novel challenge. Possibility of doping detection with Athlete biological passport has triggered athletes and their teams to use various explanations for the adverse analytical findings, which is why numerous studies are being conducted to explain influence of various conditions on the hematological biomarkers. Simultaneously, authorities are developing novel direct (e.g., additional substances, metabolites) and indirect (e.g., immature reticulocyte fraction, transcriptomics, etc.) methods to detect anti-doping rules violation. The substances/methods used by athletes to improve maximal aerobic capacity are being developed more rapidly than anti-doping authorities can implement adequate direct detection methods, which is why constant novel studies are needed. [ABSTRACT FROM AUTHOR]

Iron supplementation is not considered as a doping method; however, it can affect the levels of several biomarkers of the hematologic module of the athlete biological passport (ABP), such as the reticulocyte percentage (%RET) and hemoglobin (HGB) level. Thus, iron injection could be a confounding factor in antidoping analyses. Previous studies have suggested that the HGB level and the expression levels of reticulocyte‐related‐mRNAs, such as 5′‐aminolevulinate synthase 2 (ALAS2) and carbonic anhydrase 1 (CA1), could be promising biomarkers for the ABP and detectable in dried blood spots (DBSs). Therefore, in this study, we examined the impact of iron injection on the levels of these potential biomarkers in DBSs. Reticulocyte‐related‐mRNAs analyses were performed by RT‐qPCR. Ferritin level in DBS was measured with enzyme‐linked immunosorbent assay (ELISA) method. Notably, there were no significant effects of iron supplementation on the levels of ALAS2 and CA1 mRNAs but by contrast, the %RET and immature reticulocyte fraction (IRF) measured in whole blood increased significantly following iron injection. As expected, iron supplementation increased the ferritin level significantly in both serum and DBS samples. In conclusion, these findings reinforce the specificity of reticulocyte‐related mRNAs in DBSs as biomarkers of blood doping to target in antidoping analyses. [ABSTRACT FROM AUTHOR]

Blood transfusion is performed by cheating athletes to rapidly increase oxygen delivery to exercise muscles and enhance their performance. This method is banned by the World Anti‐doping Agency (WADA). Heterologous or allogenic blood transfusion happens when blood from a different person is transfused. The method used to detect this type of doping is based on flow cytometry, by identifying variations in blood group minor antigens present on the red blood cells' surface. Transfusion practices have regained interest since the introduction of human recombinant erythropoietin detection method. It has been reported that the number of occurrences of two athletes sharing an identical phenotype in the same sport was five times higher than the theoretical populational probability. The present work describes the prevalence of 10 erythrocytes surface antigens in a population of 261 athletes from all five continents. The matching phenotype per sport is also described. [ABSTRACT FROM AUTHOR]

The prevalence of autologous blood transfusions (ABTs) presents a formidable challenge in maintaining fair competition in sports, as it significantly enhances hemoglobin mass and oxygen capacity. In recognizing ABT as a prohibited form of doping, the World Anti-Doping Agency (WADA) mandates stringent detection methodologies. While current methods effectively identify homologous erythrocyte transfusions, a critical gap persists in detecting autologous transfusions. The gold standard practice of longitudinally monitoring hematological markers exhibits promise but is encumbered by limitations. Despite its potential, instances of blood doping often go undetected due to the absence of definitive verification processes. Moreover, some cases remain unpenalized due to conservative athlete-sanctioning approaches. This gap underscores the imperative need for a more reliable and comprehensive detection method capable of unequivocally differentiating autologous transfusions, addressing the challenges faced in accurately identifying such prohibited practices. The development of an advanced detection methodology is crucial to uphold the integrity of anti-doping measures, effectively identifying and penalizing instances of autologous blood transfusion. This, in turn, safeguards the fairness and equality essential to competitive sports. Our review tackles this critical gap by harnessing the potential of microRNAs in ABT doping detection. We aim to summarize alterations in the total microRNA profiles of erythrocyte concentrates during storage and explore the viability of observing these changes post-transfusion. This innovative approach opens avenues for anti-doping technologies and commercialization, positioning it as a cornerstone in the ongoing fight against doping in sports and beyond. The significance of developing a robust detection method cannot be overstated, as it ensures the credibility of anti-doping efforts and promotes a level playing field for all athletes.

Purpose: We investigated the effects of recombinant human erythropoietin (rHuEPO) administration on exercise endurance, maximal aerobic performance, and total hemoglobin mass (tHb). We hypothesized that frequent, small intravenous injections of epoetin β would increase time trial performance, peak oxygen uptake (V̇O2peak), and tHb in both males and females. Methods: We included 48 healthy, recreational to trained males (n = 24, mean ± SD V̇O2peak = 55 ± 5 mL O2·kg−1⋅min−1) and females (n = 24; V̇O2peak of 46 ± 4 mL O2·kg−1⋅min−1) in a counterbalanced, double-blind, randomized, placebo-controlled study design stratified by sex. Time trial performance, V̇O2peak, and tHb were determined before and after intravenous injections of either rHuEPO (9 IU·kg bw−1 epoetin β) or saline (0.9% NaCl) three times weekly for 4 wk. Results: A time–treatment effect (P < 0.05) existed for time trial performance. Within the rHuEPO group, mean power output increased by 4.1% ± 4.2% (P < 0.001). Likewise, a time–treatment effect (P < 0.001) existed for V̇O2peak, where the rHuEPO group improved V̇O2peak and peak aerobic power by 4.2% ± 6.1% (P < 0.001) and 2.9% ± 4.0% (P < 0.01), respectively. A time–treatment effect (P < 0.001) existed for tHb, where the rHuEPO group increased tHb by 6.7% ± 3.4% (P < 0.001). A main effect of "sex" alone was also evident (P < 0.001), but no sex-specific interactions were found. No changes were observed in the placebo group for mean power output, V̇O2peak, peak aerobic power, or tHb. Conclusions: Microdoses with intravenous rHuEPO provide a sufficient erythropoietic stimuli to augment tHb and enhance aerobic-dominated performance in both trained males and females. [ABSTRACT FROM AUTHOR]

The purpose of this pilot study was to investigate the effects of the transfusion of one erythrocyte concentrate on the number of circulating red blood cell extracellular vesicles (RBC‐EVs) and their clearance time. Six, healthy volunteers donated their blood and were transfused with their RBC concentrate after 35–36 days of storage. One K2EDTA and one serum sample were collected before donation, at four timepoints after donation and at another six timepoints after transfusion. RBC‐EVs were analyzed on a Cytek Aurora flow cytometer. A highly significant increase (p < 0.001) of RBC‐EVs from an average of 60.1 ± 19.8 (103/μL) at baseline to 179.3 ± 84.7 (103/μL) in the first 1–3 h after transfusion could be observed. Individual differences in the response to transfusion became apparent with one volunteer showing no increase and another an increased concentration at one timepoint after donation due to an influenza infection. We concluded that in an individualized passport approach, increased RBC‐EVs might be considered as additional evidence when interpreting suspicious Athletes Biological Passport (ABPs) but for this additional research related to sample collection and transport processes as well as method development and harmonization would be necessary. [ABSTRACT FROM AUTHOR]

The hematological module of the Athlete Biological Passport (ABP) aims to reveal blood doping indirectly by looking at selected biomarkers of doping over time. For Anti-Doping Organizations (ADOs), the ABP is a vital tool in the fight against doping in sports through improved target testing and analysis, investigations, deterrence, and as indirect evidence for use of prohibited methods or substances. The physiological characteristics of sport disciplines is an important risk factor in the overall risk assessment and when implementing the hematological module. Sharing of experiences with implementing the hematological ABP between ADOs is key to further strengthen and extend its use. In this study, we present 10 years of experience with the hematological ABP program from the perspectives of a National ADO with special attention to sport disciplines' physiological characteristics as a potential risk factor for blood doping. Not surprisingly, most samples were collected in sport disciplines where the aerobic capacity is vital for performance. The study highlights strengths in Anti-Doping Norway's testing program but also areas that could be improved. For example, it was shown that samples were collected both in and out of season in a subset of the data material that included three popular sports in Norway (Cross-Country Skiing, Nordic Combined, and Biathlon), however, from the total data material it was clear that athletes were more likely to be tested out of competition and on certain days of the week and times of the day. The use of doping control officers with a flexible time schedule and testing outside an athlete's 60 min time-slot could help with a more even distribution during the week and day, and thus reduce the predictability of testing. In addition to promoting a discussion on testing strategies, the study can be used as a starting point for other ADOs on how to examine their own testing program.

Simple Summary: Autologous blood doping (ABD) refers to the artificial increase in circulating red blood cell (RBC) mass by sampling, storage, and transfusion of one's own blood. It is assumed that some athletes apply this prohibited technique to improve oxygen transport capacity and thus exercise performance. The primary aim of this study was to test whether RBC rheological and associated parameters significantly change due to ABD with the consideration of whether this type of measurement might be suitable for detecting ABD. Further, it was assessed whether those changes are translated into indices of endurance performance. Eight males underwent an ABD protocol combined with several blood parameter measurements and two exercise tests (pre and post transfusion). Results of this investigation suggest a change in the distribution of age-related RBC sub-populations and altered deformability of total RBC as well as of the respective sub-populations. Further, the identified changes in RBC also appear to improve sports performance. In conclusion, these data demonstrate significant changes in hematological and hemorheological parameters, which could be of interest in the context of new methods for ABD detection. However, additional research is needed with larger and more diverse study groups to widen the knowledge gained by this study. Autologous blood doping (ABD) refers to the transfusion of one's own blood after it has been stored. Although its application is prohibited in sports, it is assumed that ABD is applied by a variety of athletes because of its benefits on exercise performance and the fact that it is not detectable so far. Therefore, this study aims at identifying changes in hematological and hemorheological parameters during the whole course of ABD procedure and to relate those changes to exercise performance. Eight healthy men conducted a 31-week ABD protocol including two blood donations and the transfusion of their own stored RBC volume corresponding to 7.7% of total blood volume. Longitudinal blood and rheological parameter measurements and analyses of RBC membrane proteins and electrolyte levels were performed. Thereby, responses of RBC sub-populations—young to old RBC—were detected. Finally, exercise tests were carried out before and after transfusion. Results indicate a higher percentage of young RBC, altered RBC deformability and electrolyte concentration due to ABD. In contrast, RBC membrane proteins remained unaffected. Running economy improved after blood transfusion. Thus, close analysis of RBC variables related to ABD detection seems feasible but should be verified in further more-detailed studies. [ABSTRACT FROM AUTHOR]

The hematological module of the Athlete Biological Passport (ABP) is used for indirect detection of blood manipulations; however, the use of this method to detect doping, such as with microdoses of recombinant human erythropoietin (rhEPO), is problematic. For this reason, the sensitivity of ABP must be enhanced by implementing novel biomarkers. Here, we show that 5'‐aminolevulinate synthase 2 (ALAS2) mRNAs are useful transcriptomic biomarkers to improve the indirect detection of rhEPO microdosing. Moreover, the sensitivity was sufficient to distinguish rhEPO administration from exposure to hypoxic conditions. Levels of mRNAs encoding carbonate anhydrase 1 (CA1) and solute carrier family 4 member 1 (SLC4A1) RNA, as well as the linear (L) and linear + circular (LC) forms of ALAS2 mRNA, were monitored for 16 days after rhEPO microdosing and during exposure to hypoxic conditions. ALAS2 mRNAs increased by 300% compared with the baseline values after rhEPO microdosing. Moreover, ALAS2 mRNAs were not significantly increased under hypoxic conditions. By contrast, CA1 mRNA was increased after both rhEPO microdosing and hypoxia, whereas SLC4A1 mRNA did not significantly increase under either condition. Furthermore, the analyses described here were performed using dried blood spots (DBSs), which provide advantages in terms of the sample collection, transport, and storage logistics. This study demonstrates that ALAS2 mRNA levels are sensitive and specific transcriptomic biomarkers for the detection of rhEPO microdosing using the hematological module of the ABP, and this method is compatible with the use of DBSs for anti‐doping analyses. [ABSTRACT FROM AUTHOR]

Introduction: The athlete biological passport monitors blood variables over time to uncover blood doping. With the phasing in of a new series of blood analyzers, the Sysmex XN series, it was necessary to examine the comparability of results with the previously employed XT/XE series. A previous comparison between XN and XT/XE series suggested a small but significant bias between the two instruments in the measurements of RET%. Here, we examined the comparability of RET% on the XN and XT/XE platform using data collected over the first year since the transition. Methods: The comparability of results obtained from XN and XT/XE instruments was assessed using three datasets: (i) 767 blood samples measured on both instrument series in 22 WADA‐accredited laboratories, (ii) 27 323 samples measured on either instrument across 31 laboratories, and (iii) 119 clinical samples and 110 anti‐doping samples measured on both instruments in a single laboratory. Results: Analysis of the three datasets confirms the previous observation of a bias toward higher RET% values for samples measured on Sysmex XN instruments compared with the XT/XE series. Using data across a larger number of XN instruments and a larger athlete population, the current work suggests that the bias is proportional and slightly higher than previously observed across most of the range RET% values. Conclusion: A model is proposed for the comparison of data across XN and XT/XE technologies whereby the instrument bias increases proportionally with RET% measured on Sysmex XN Series, but where the rate of increase is negatively related to IRF%. [ABSTRACT FROM AUTHOR]

Autologous blood doping (ABD) refers to the transfusion of one’s own blood after it has been stored. Although its application is prohibited in sports, it is assumed that ABD is applied by a variety of athletes because of its benefits on exercise performance and the fact that it is not detectable so far. Therefore, this study aims at identifying changes in hematological and hemorheological parameters during the whole course of ABD procedure and to relate those changes to exercise performance. Eight healthy men conducted a 31-week ABD protocol including two blood donations and the transfusion of their own stored RBC volume corresponding to 7.7% of total blood volume. Longitudinal blood and rheological parameter measurements and analyses of RBC membrane proteins and electrolyte levels were performed. Thereby, responses of RBC sub-populations—young to old RBC—were detected. Finally, exercise tests were carried out before and after transfusion. Results indicate a higher percentage of young RBC, altered RBC deformability and electrolyte concentration due to ABD. In contrast, RBC membrane proteins remained unaffected. Running economy improved after blood transfusion. Thus, close analysis of RBC variables related to ABD detection seems feasible but should be verified in further more-detailed studies.

Supplemental digital content is available in the text. Purpose: Autologous blood transfusion is performance enhancing and prohibited in sport but remains difficult to detect. This study explored the hypothesis that an untargeted urine metabolomics analysis can reveal one or more novel metabolites with high sensitivity and specificity for detection of autologous blood transfusion. Methods: In a randomized, double-blinded, placebo-controlled, crossover design, exercise-trained men (n = 12) donated 900 mL blood or were sham phlebotomized. After 4 wk, red blood cells or saline were reinfused. Urine samples were collected before phlebotomy and 2 h and 1, 2, 3, 5, and 10 d after reinfusion and analyzed by ultraperformance liquid chromatography–quadrupole time-of-flight mass spectrometry. Models of unique metabolites reflecting autologous blood transfusion were attained by partial least-squares discriminant analysis. Results: The strongest model was obtained 2 h after reinfusion with a misclassification error of 6.3% and 98.8% specificity. However, combining only a few of the strongest metabolites selected by this model provided a sensitivity of 100% at days 1 and 2 and 66% at day 3 with 100% specificity. Metabolite identification revealed the presence of secondary di-2-ethylhexyl phtalate metabolites and putatively identified the presence of (iso)caproic acid glucuronide as the strongest candidate biomarker. Conclusions: Untargeted urine metabolomics revealed several plasticizers as the strongest metabolic pattern for detection of autologous blood transfusion for up to 3 d. Importantly, no other metabolites in urine seem of value for antidoping purposes. [ABSTRACT FROM AUTHOR]

We provide a new wrinkle to the Argument from Unfair Advantage, a rather popular one in the ethics of doping in sports discussions. But we add a new argument that we believe places the moral burden on those who favor doping in sports. We also defend our position against some important concerns that might be raised against it. In the end, we argue that for the time being, doping in sports ought to be banned until it can be demonstrated that our concerns can be satisfied. [ABSTRACT FROM AUTHOR]

BACKGROUND: Autologous blood doping (ABD) is applied to improve performance capacity. ABD includes blood donation, red blood cell (RBC) storage at –80°C and re-infusion prior to or during competition. ABD is not directly detectable with current detection techniques. OBJECTIVE: Since cryopreservation is known to affect RBC physiology in vitro, the aim of the study was to examine whether these alterations are detectable in vivo. METHODS: Blood from six healthy male donors was transferred into conventional blood bags, cryopreserved, stored for 18 weeks at –80°C and re-infused with a RBC volume corresponding to ∼4% of total blood volume into respective donor. RBC physiology parameters were measured before blood donation/re-infusion, and 0/1/2/6/24/48/72 h and 1 w post re-infusion. RESULTS: RBC parameters and age markers were unaffected during intervention. RBC deformability increased from pre-blood-sampling to pre-re-infusion while deformability and viscosity values remained unaltered post re-infusion. RBC nitric oxide associated analytes, metabolic parameters and electrolyte concentrations remained unaffected. CONCLUSIONS: The data of this pilot study indicate that the increase in RBC deformability might be related to neoformation of RBC after blood donation. The lack of changes in tested parameters might be related to the low re-infused RBC volume which might explain differences to in vitro results. [ABSTRACT FROM AUTHOR]

Fluctuations in plasma volume (PV) present potential confounders within the concentration‐based markers of the haematological athlete biological passport (ABP). Here, a multi‐parametric approach involving a simple blood test is applied to the current ABP adaptive model in an attempt to remove the influence of PV expansion, induced by a cycling stage race. Blood samples were obtained from 29 professional cyclists (14 male, 15 female) before, during and after 4–5 consecutive days of racing. Whole blood was analysed in accordance with the World Anti‐Doping Agency ABP guidelines for haemoglobin ([Hb]) concentration and platelets. Serum and plasma were analysed for transferrin, albumin, calcium, creatinine, total protein and low‐density lipoprotein. PV variation (Z‐scores) was estimated using a multi‐parametric model (consisting of the biomarkers mentioned earlier) and compared against calculated variations in PV (measured via CO‐rebreathing). Significant reductions in [Hb] and the OFF‐score were observed in female cyclists after 3 and 4 days of racing, with accompanying increases in PV, which returned to baseline values 4 days post competition. Similarly, a significant increase in PV was observed in male cyclists after 3 and 5 days of racing. When individual estimations of PV variance were applied to the adaptive model, the upper and lower reference predictions for [Hb] and the OFF‐score were refined such that all outliers consistent with racing‐induced PV changes were removed. The PV model appears capable of reducing the influence of PV on concentration‐dependent markers during competition. This is an important step towards the inclusion of the PV correction in the ABP haematological module. [ABSTRACT FROM AUTHOR]

Athlete Biological Passport (ABP) is an indirect approach, implemented by WADA, aimed at detecting blood manipulation based on abnormal changes in haematological markers. Cases report the use of hyperhydration as masking method during anti-doping urine sample collection which could potentially mask suspicious fluctuations on ABP profiles. This study investigated the hyperhydration effect on haemoglobin concentration, reticulocyte percentage and OFF-hr score (an algorithm based on haemoglobin concentration and reticulocyte percentage), with and without recombinant human erythropoietin (rHuEPO) administration. A five-week clinical study performed; Baseline and rHuEPO Phase. Water and a sports drink were used as hyperhydration agents. To examine the hyperhydration effect on the normal ABP profile per volunteer, hyperhydration was implemented at 0, 24 and 48 hours during the baseline. During the rHuEPO phase, volunteers received Epoetin beta (3000 IU) with hyperhydration to be implemented at 0, 24 and 48 hours after drug administration. Blood and urine samples were collected and analysed according to WADA guidelines. No significant effect on ABP markers was observed due to hyperhydration at any time during the study. Pre- and post-hyperhydration data were not statistically different compared to individual baseline data. In conclusion, hyperhydration does not affect the ABP haematological markers under the examined conditions. [ABSTRACT FROM AUTHOR]

In order to inform the Athlete Biological Passport (ABP), this study determined whether the elevation in hemoglobin (Hb) following intracellular or extracellular dehydration would trigger an atypical passport finding (ATPF). Seven male and three female volunteers (age: 23 ± 4 y; height: 170 ± 8 cm; body mass: 78 ± 12 kg) were carefully euhydrated (EUH) to determine baseline Hb levels. Volunteers then completed both an exercise‐induced sweating dehydration (SW) protocol and a diuretic‐induced dehydration (DI) protocol. Dehydration was assessed via body mass changes and Hb was measured via a bench‐top automated hematology analyzer. Using the ABP module, the expected baseline range for each individual was determined using EUH trials, and the impact of each dehydration protocol was then assessed in comparison with these thresholds. Volunteers lost on average 3.1% and 3.7% body mass in the SW and DI trials, respectively. While only one subject exceeded the upper threshold following DI dehydration, six additional subjects demonstrated highly unusual ABP profiles; this was not the case for SW. Sweating is not a feasible explanation for elevated Hb during ABP testing; however, recent illness such as secretory diarrhea, which is mimicked by diuretic administration, may be capable of producing elevated Hb in athletes' biological passports. [ABSTRACT FROM AUTHOR]

The view that exertion of effort determines praiseworthiness for an achievement is implicit in 'no pain, no praise'-style objections to biomedical enhancement. On such views, if enhancements were to reduce the need for effort, agents would be less praiseworthy. Motivational enhancement would appear to be the most problematic in this respect, given that increased motivation reduces the need for agents to rally themselves and to exert effort in activity. We use the prospect of motivational enhancement to re-examine the grounds of praiseworthiness for achievements. We consider the place of effort amongst the grounds for praise, whether effort exhausts these grounds, and how they can be better specified. We argue that praiseworthiness depends on (i) the voluntariness and strength of the agent's committed pursuit of a valuable end (E), (ii) the costliness of the committed pursuit of E, and (iii) the value of E. Effort is just one cost amongst many, and costs of activities can be traded-off. Motivational enhancement reduces the praise due to an agent only when it reduces the net cost to the agent (without strengthening the voluntary commitment). We emphasize the importance of a diachronic perspective on active agency for praiseworthiness, to include training, prior planning, and deliberate strategies to overcome weakness of will, even where this reduces the need for effort. [ABSTRACT FROM AUTHOR]

Erythroferrone (ERFE) is a glycoprotein hormone secreted by erythroblasts in response to erythropoietin stimulation. ERFE suppresses the hepatic synthesis of the master iron‐regulatory hormone, hepcidin. The impact of erythropoiesis stimulation on ERFE secretion in humans is poorly understood. This paucity of information is due in part to the lack of available means for ERFE quantification in serum samples. The present study tested a new sensitive sandwich immunoassay for human ERFE. This assay was used to demonstrate that injection of various erythropoiesis stimulating agents (ESAs) increased the blood ERFE levels in healthy volunteers. After exogenous stimulation of erythropoiesis, ERFE increased up to 8‐fold with a detection window of 13 days. The impact of one unit of blood withdrawal on erythropoiesis stimulation of ERFE was also tested. ERFE significantly increased after blood withdrawal in subjects injected with both iron and saline solution, suggesting that iron supplementation did not mask the ERFE increase after blood withdrawal. The effects of exercise‐induced muscle damage on ERFE was assessed by comparing ERFE levels with creatine kinase levels in samples from subjects with heavy exercise loads, and determined that this was not a confounder. The ERFE assay is a sensitive means to investigate the connection between iron metabolism and erythropoiesis in humans, and to detect ESA abuse in the antidoping field. [ABSTRACT FROM AUTHOR]

The notion that pregnancy and abortion are forms of doping has persisted for 20 years. Popular and scientific literature on pregnancy/abortion doping was critically analyzed to compare pregnancy/abortion doping with definitions of doping and blood doping and to compare pregnancy/abortion doping themes to current scientific knowledge. Main themes included oxygenation advantage and hormonal advantage. During pregnancy, maximal oxygen uptake may improve but not exercise performance. Human chorionic gonadotropin, the only pregnancy hormone on National Collegiate Athletic Association and United States Anti-Doping Agency banned substances lists, increases during pregnancy but there is no evidence that hCG enhances athletic performance in women. Recommendations include revising USADA and NNCAA policies into congruence with World Anti-Doping Agency policies which ban hCG for men only. During the past seven years of advocating for college student-athlete athletic department pregnancy and parenting policies, popular nonscientific literature (websites, blogs, and personal anecdotes) and scientific literature have been examined to detect barriers to student-athlete health and policy change. One barrier is a persistent belief in popular literature that athletes can use pregnancy and/or abortion to enhance competitive performance; i.e., as a form of prohibited blood doping. The scientific and nonscientific resources on pregnancy and abortion doping have considerably diverged over the past 20 years. The purposes of this paper were to examine the biophysical themes in popular and scientific definitions of doping, blood doping, and pregnancy/abortion doping, compare pregnancy/abortion doping to current scientific knowledge, and make recommendations to the stakeholders: student-athletes, coaches, athletic trainers, team physicians, athletic and university administrators, university faculty, the United States Anti-Doping Agency (USADA) and the National Collegiate Athletic Association (NCAA). [ABSTRACT FROM AUTHOR]

There is growing evidence that various RNA molecules can serve as biomarkers for clinical diagnoses. Over the last decade, the high specificities and sensitivities of RNA biomarkers have led to proposals that they could be used to detect prohibited substances and practices in sports. mRNAs and circulating miRNAs have the potential to improve the detection of doping and expand the performance of the Athlete Biological Passport. This review provides a summary of the use of RNA biomarkers to detect human and equine doping practices, including a discussion of the use of dried blood spots as a stable matrix that supports and improves the general process of RNA biomarker detection. The advantages of RNA biomarkers over protein biomarkers are also discussed.

The prevalence of autologous blood transfusions (ABTs) presents a formidable challenge in maintaining fair competition in sports, as it significantly enhances hemoglobin mass and oxygen capacity. In recognizing ABT as a prohibited form of doping, the World Anti-Doping Agency (WADA) mandates stringent detection methodologies. While current methods effectively identify homologous erythrocyte transfusions, a critical gap persists in detecting autologous transfusions. The gold standard practice of longitudinally monitoring hematological markers exhibits promise but is encumbered by limitations. Despite its potential, instances of blood doping often go undetected due to the absence of definitive verification processes. Moreover, some cases remain unpenalized due to conservative athlete-sanctioning approaches. This gap underscores the imperative need for a more reliable and comprehensive detection method capable of unequivocally differentiating autologous transfusions, addressing the challenges faced in accurately identifying such prohibited practices. The development of an advanced detection methodology is crucial to uphold the integrity of anti-doping measures, effectively identifying and penalizing instances of autologous blood transfusion. This, in turn, safeguards the fairness and equality essential to competitive sports. Our review tackles this critical gap by harnessing the potential of microRNAs in ABT doping detection. We aim to summarize alterations in the total microRNA profiles of erythrocyte concentrates during storage and explore the viability of observing these changes post-transfusion. This innovative approach opens avenues for anti-doping technologies and commercialization, positioning it as a cornerstone in the ongoing fight against doping in sports and beyond. The significance of developing a robust detection method cannot be overstated, as it ensures the credibility of anti-doping efforts and promotes a level playing field for all athletes.

Introduction: The percentage of circulating reticulocytes (RET%) is a useful marker of blood doping in the context of the Athlete Biological Passport (ABP). The viability of the ABP depends on the comparability of sample data obtained across multiple laboratories for a given athlete. With the recent introduction of a different technology for the measurement of reticulocytes, the goal of this study was to compare currently employed Sysmex XT/XE analyzers to the recently introduced Sysmex XN analyzer. Methods: RET% differences were searched in two independent data sets, the first consisting of 95 369 RET% values coming from 29 laboratories located in five continents as part of routine testing for the ABP, the second from a targeted study involving 510 samples analyzed on both a Sysmex XT and XN analyzers by two different laboratories. Results: A relatively small but significant bias of 0.27 ([0.22‐0.35] 95% CI) for the first data set and 0.19% ([0.16‐0.22] 95% CI) for the second data set was observed with Sysmex XN analyzers returning higher values than Sysmex XT/XE analyzers. This bias appears constant over most of the range of RET% measured in elite athletes. Conclusion: When RET% values are obtained for the same athlete with different technologies (XT/XE vs XN), an adjustment of RET% emanating from the XT/XE instruments through a decrease of 0.22% within the ABP calculated ranges appears to be sufficient to integrate the results from the two technologies. [ABSTRACT FROM AUTHOR]

Purpose The hydration status of an athlete at the time of a doping control sample collection is an important factor to consider when reviewing athlete biological passports (ABPs). Dehydration results in a reduction of the circulating plasma volume (PV), which may lead to artificially high values of some blood parameters. This study aimed to identify whether serum albumin could serve as a single marker of fluid shifts, which are not currently accounted for in the hematological passport. An additional marker could be used to assist experts when interpreting irregularities in the ABP. Methods: Twelve subjects underwent multiple controlled exercise trials designed to induce varying levels of PV shifts. Pre‐exercise blood samples were collected to establish baseline values for individual passports. During exercise interventions, blood samples were collected before the start of exercise and at 10 minute, 1 hour, 2 hours, and 24 hours following exercise. Results: Significant increases in hematological parameters – hemoglobin [Hb], hematocrit (HCT), albumin (ALB), and calculated OFF‐score – were identified at varying time points following fluid shift‐inducing exercise. Changes in ALB correlated strongly with changes in [Hb] (r = 0.753) and with estimated PV shifts (r = −0.764). In analyzing ABPs, the resulting increases in Hb did not trigger any atypical findings at 99% specificity. Perspective: Monitoring changes in ALB longitudinally may assist experts when reviewing PV shifts in the biological passport. [ABSTRACT FROM AUTHOR]

The benefit of training at altitude to enhance exercise performance remains equivocal although the most widely accepted approach is one where the athletes live and perform lower-intensity running at approximately 2300 m with high-intensity training at approximately 1250 m. The idea is that this method maintains maximal augmentations in total hemoglobin mass while reducing the performance impairment of high-intensity sessions performed at moderate altitude and thus preventing any detraining that can occur when athletes live and train at moderate altitude. This training regimen, however, is not universally accepted and some argue that the performance enhancement is due to placebo and training camp effects. Altitude training may affect an athlete's hematological parameters in ways similar to those observed following blood doping. Current methods of detection appear insufficient to differentiate between altitude training and blood doping making the interpretation of an athlete's biological passport difficult. Further research is required to determine the optimal method for altitude training and to enhance current detection methods to be able to differentiate better blood doping and altitude exposure. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the incidence and risk factors of intraventricular hemorrhage (IVH) as well as the role of cord blood erythropoietin (EPO) level in predicting the possibility of IVH in premature neonates.Materials and methods: This prospective study included 140 preterm neonates born at hospitals affiliated to Shiraz University of Medical Sciences from May 2014 to April 2015. Complete blood count and cord blood EPO level was measured after birth. Brain ultrasonography was performed at 3 and 7-10 days after birth in these newborns.Results: Brain ultrasonography showed IVH in 8.57% (12/140) until the third day and 20% (28/140) at 7-10 days of life in premature neonates. Early gestational age, low birth weight, low Apgar score, and failure to give prenatal steroid were significant risk factors for developing IVH. The mean level of cord blood EPO was 20.95 ± 21.09 mIU/mL in premature newborns without IVH and 15.82 ± 17.11 mIU/mL with IVH. There was no correlation between the cord blood EPO and IVH in premature newborns.Conclusion: Antenatal steroids therapy should be encouraged among women at risk of premature delivery. Our results showed that the cord blood EPO was not correlated with IVH in preterm neonates and further research is required to assess this relationship. [ABSTRACT FROM AUTHOR]

Professional athletes are expected to continuously improve their performance, and some might also use illegal methods—e.g., autologous blood doping (ABD)—to achieve improvements. This article applies a systematic literature review to investigate differences in the ABD methods and the related performance and blood parameters owing to different storage conditions—cryopreservation (CP) and cold storage (CS)—and different storage durations. The literature research resulted in 34 original articles. The majority of currently published studies employed CS during ABD. This contrasts to the applied storage technique in professional sports, which was mainly reported to be CP. The second outcome of the literature research revealed large differences in the storage durations applied, which were in the range of one day to 17 weeks between blood sampling and re-infusion, which might affect recovery of the red blood cell mass and thus performance outcome related to ABD. Data revealed that performance parameters were positively affected by ABD when a minimal storage duration of four weeks was adhered. This article identified a need for further research that reflect common ABD practice and its real effects on performance parameters, but also on related blood parameters in order to develop valid and reliable ABD detection methods.

The Abnormal Blood Profile Score (ABPS) is used to identify blood doping in sport. It combines seven hematological markers, including hemoglobin level, reticulocytes percent, and haematocrit level, using two different machine learning algorithms in order to create a single score that has a better ability to identify doping than each parameter taken alone. The resulting score allows the detection of several types of doping using a single score and is part of the current Athlete Biological Passport program managed by World Anti-Doping Agency (WADA). We describe ≪ ABPS ≫, an R package that allows the calculation of this score. This is the first software implementation calculating this score that is released publicly. The package also contains functions to calculate the OFF-score (another score used for detection of doping), as well as several test datasets. The package is useful for laboratories conducting anti-doping analyses and for researchers working on anti-doping research projects. In particular, it has been successfully used in projects estimating the prevalence of blood doping.

The efficient use of testing resources is a key issue in the fight against doping. The longitudinal tracking of sporting performances to identify unusual improvements possibly caused by doping, so-called “athlete's performance passport” (APP) is a new concept to improve targeted anti-doping testing. In fact, unusual performances by an athlete would trigger a more thorough testing program. In the present case report, performance data is modeled using the critical power concept for a group of athletes based on their past performances. By these means, an athlete with unusual deviations from his predicted performances was identified. Subsequent target testing using blood testing and the athlete biological passport resulted in an anti-doping rule violation procedure and suspension of the athlete. This case demonstrates the feasibility of the APP approach where athlete's performance is monitored and might serve as an example for the practical implementation of the method.