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    Estimation of Plasma Volume by Machine Learning to Improve the Interpretation of the Athlete Biological Passport

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        ABSTRACT

        The identification of confounding factors related to plasma volume (PV) fluctuations is crucial for appropriate qualitative interpretations of Athlete Biological Passport (ABP) profiles. As part of ongoing efforts to remove PV variance from the concentration‐based biomarkers such as hemoglobin concentration ([Hb]), a new machine learning model for blood volume (BV) estimation using a single complete blood count analysis was applied within the ABP framework. Forty existing ABP profiles from elite athletes and healthy control subjects were used. PV was estimated using a machine learning model trained on a previous dataset. First, a visual display of the estimated PV shift was added in overlay of individual profiles. Alternatively, individual [Hb] thresholds were adjusted in a new graphical profile to account for PV variations. Finally, a set of ABP profiles with PV estimations was presented to ABP experts to assess the model's relevance in interpreting hematological data. A moderate correlation was found between measured and estimated PV in both men ( r = 0.40, p < 0.0001) and women ( r = 0.39, p < 0.0001), supporting the validity of the estimation model. In addition, ABP experts favorably assessed the available PV information, particularly the visual representation of PV. This novel estimation model offers distinct advantages (e.g., same biomarkers currently analyzed from routine ABP analyses) and could therefore be of particular interest. Further application of this model in the presence of specific and transient confounding factors may allow to confirm these results.

        Abstract

        A new machine learning model for plasma volume (PV) estimation was applied within the ABP framework. PV estimation was applied through visual displays or corrected ABP thresholds. With a favorable assessment from ABP experts, these results support further application of this model in the presence of specific confounding factors.

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        Most cited references33

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        Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration.

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          Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness.

          This paper reviews the influence of several perturbations (physical exercise, heat stress, terrestrial altitude, microgravity, and trauma/sickness) on adaptations of blood volume (BV), erythrocyte volume (EV), and plasma volume (PV). Exercise training can induce BV expansion: PV expansion usually occurs immediately, but EV expansion takes weeks. EV and PV expansion contribute to aerobic power improvements associated with exercise training. Repeated heat exposure induces PV expansion but does not alter EV. PV expansion does not improve thermoregulation, but EV expansion improves thermoregulation during exercise in the heat. Dehydration decreases PV (and increases plasma tonicity) which elevates heat strain and reduces exercise performance. High altitude exposure causes rapid (hours) plasma loss. During initial weeks at altitude, EV is unaffected, but a gradual expansion occurs with extended acclimatization. BV adjustments contribute, but are not key, to altitude acclimatization. Microgravity decreases PV and EV which contribute to orthostatic intolerance and decreased exercise capacity in astronauts. PV decreases may result from lower set points for total body water and central venous pressure, while EV decreases may result from increased erythrocyte destruction. Trauma, renal disease, and chronic diseases cause anemia from hemorrhage and immune activation which suppresses erythropoiesis. The re-establishment of EV is associated with healing, improved life quality, and exercise capabilities for these injured/sick persons.
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            CORP: The assessment of total hemoglobin mass by carbon monoxide rebreathing.

            In this Cores of Reproducibility in Physiology (CORP) article, we present the theory and practical aspects of the carbon monoxide (CO) rebreathing method for the determination of total hemoglobin mass in humans. With CO rebreathing, a small quantity of CO is diluted in O2 and rebreathed for a specified time period, during which most of the CO is absorbed and bound to circulating hemoglobin. The dilution principle then allows calculation of the total number of circulating hemoglobin molecules based on the number of absorbed CO molecules and the resulting changes in the fraction of carboxyhemoglobin in blood. Total hemoglobin mass is derived by multiplication with the molar weight of hemoglobin. CO rebreathing has been used for >100 yr and has undergone steady improvement so that today excellent values in terms of accuracy and precision can be achieved if the methodological precautions are carefully followed.

              Author and article information

              Contributors
              [email protected]
              Journal
              Drug Test Anal
              Drug Test Anal
              10.1002/(ISSN)1942-7611
              DTA
              Drug Testing and Analysis
              John Wiley and Sons Inc. (Hoboken )
              1942-7603
              1942-7611
              09 August 2025
              November 2025
              : 17
              : 11 ( doiID: 10.1002/dta.v17.11 )
              : 2283-2290
              Affiliations
              [ 1 ] Research and Expertise in Antidoping Sciences, Institute of Sport Sciences University of Lausanne Lausanne Switzerland
              [ 2 ] US Anti‐Doping Agency Colorado Springs Colorado USA
              [ 3 ] Science and Research Anti Doping Denmark Brøndby Denmark
              [ 4 ] Aspetar Orthopedic and Sports Medicine Hospital Doha Qatar
              [ 5 ] Catholic University of the Sacred Heart Rome Italy
              Author notes
              [*] [* ] Correspondence:

              Raphael Faiss ( raphael.faiss@ 123456unil.ch )

              Author information
              https://orcid.org/0000-0002-9132-606X
              https://orcid.org/0000-0001-6029-9516
              Article
              DTA3938 5055889
              10.1002/dta.3938
              12580168
              40781891
              484457e2-02f7-468e-a393-d38aefa3e2f3
              © 2025 The Author(s). Drug Testing and Analysis published by John Wiley & Sons Ltd.

              This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

              History
              : 25 July 2025
              : 13 June 2025
              : 29 July 2025
              Page count
              Figures: 5, Tables: 0, Pages: 8, Words: 5400
              Categories
              Research Article
              Research Article
              Custom metadata
              2.0
              November 2025
              Converter:WILEY_ML3GV2_TO_JATSPMC version:6.6.4 mode:remove_FC converted:02.11.2025

              athlete biological passport,machine learning,plasma volume

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