Reticulocytes in sports medicine

Reticulocytes are the transitional cells from erythroblasts to mature erythrocytes. Reticulocytes are present in blood for a period of 1-4 days and can be recognized by staining with supravital dyes, such as new methylene blue, or fluorescent markers, which couple residual nucleic acid molecules, a hallmark of the immature forms of erythrocytes. Although reticulocytes could be counted through a microscope (there is a standard of International Committee for Standardisation in Haematology for manual counting), this method is reported to be time consuming, inaccurate and imprecise. The integration of the reticulocyte count in automated haematology systems allowed the widespread use of these parameters, although the lack of calibration material and different markers, technologies and software used in automated systems could engender discrepancies among data obtained from different analytical systems. The importance of reticulocytes in sports medicine derives from their sensitivity, the highest among haematology parameters, in identifying the bone marrow stimulation, especially when recombinant human erythropoietin is fraudulently used. Automated systems are also able to supply information on volume, density and the haemoglobin content of reticulocytes. Some of the related parameters are also used in algorithms for identifying abnormal stimulation of bone marrow as reticulocytes haematocrit. The pre-analytical variability of reticulocytes (transportation, storage, biological variability) should be taken into account in sports medicine also. Reticulocytes remain stable for almost 24 hours at 4 degrees C from blood drawing, they are affected by transportation, and biological variability is not high in general. It could be remarked, however, that the intra-individual variability is high when compared with other haematological parameters such as haemoglobin and haematocrit. The intervals of data reported in athletes are very similar to reference intervals characterizing the general population. The reticulocyte count shows some modifications after training and during the competition season. The variability induced by exercise cannot be overlooked since the so-called haematological passport, a personal athlete's document in which haemoglobin and other parameters are registered, may be introduced by sports federations. Exposure to naturally high altitude and 'living high-training low' programmes determined contentious results on reticulocytes. Simulated high altitude induced by intermittent hypobaric hypoxia does not modify reticulocytes, despite an increase in erythropoietin serum concentration. The variability among athletes competing in different sport disciplines is apparently limited. The knowledge of the behaviour of reticulocytes in training and competitions is crucial for defining their role in an antidoping control context. It is important for sport physicians and clinical pathologists to know the reticulocyte variability in the general population and in athletes, the pre-analytical warnings, the different methodologies for counting reticulocytes and the derived parameters automatically available, and, finally, the possible influence of training, competitions, type of sport and altitude.