Iron deficiency (ID) is a major contributor to global disease burden and the leading cause of anaemia. Early detection is important for proactive management, but conventional complete blood count (CBC) screening often fails to identify non-anaemic iron deficiency (NAID) as many individuals maintain haemoglobin and red cell indices within reference ranges. Analysing 153,565 subjects from the INTERVAL, COMPARE and STRIDES studies, we show that CBC screening has only 40.5 % sensitivity for ID detection, falling to 21.9 % for NAID, highlighting a detection gap. CBC analysers generate a wealth of data beyond Electronic Health Record CBC parameters. We demonstrate that artificial intelligence applied to single-cell flow cytometry data from the CBC analyser achieves 83.7 % sensitivity for ID and 79.3 % for NAID. Our findings show that AI can greatly improve detection of a high-prevalence, important condition without changing infrastructure or diagnostic pathways, providing a valuable tool for proactive anaemia management.
Competing Interest StatementM.B. has received honoraria for Speaking/Teaching at Pfizer, Terumo, and Vertex. He is also on the advisory boards of Agios, Pfizer, Forma Therapeutics, Octapharma, Global Blood Therapeutics, Novonordisk, Everycure, and Prime Global. P.N. is co-founder of Hologen, a healthcare AI company with a focus on late-stage interventional agent development. M.R. is co-founder of Octiocor, an company developing tools for intracoronary image analysis. N.S.G. has a consultancy agreement with Thermo Fisher Scientific to provide computational and scientific support for research and development. E.D.A. holds an NIHR Senior Investigator Award.
Funding StatementD.K, J.T., S.D., J.G., C.-B.S, S.S., N.S.G., M.R. have received support from the Trinity Challenge grant awarded to establish the BloodCounts! consortium, along with NIHR UCLH Biomedical Research Centre, the NIHR Cambridge Biomedical Research Centre, National Health Service Blood and Transplant (NHSBT) and the Medical Research Council. J.T., receives support from MRC GAP Fund (UKRI/814). N.S.G. has been supported by NHSBT grants 1701-GEN; 20-01-GEN; G120400. O.S. has been supported by NIHR grant G111294. D.V. is a member of the Health Protection Research Unit in Chemical and Radiation Threats and Hazards, a partnership between Public Health England and Imperial College London which is funded by the National Institute for Health Research (NIHR); D.V. is a member of the MRC Centre for Environment and Health funded by the grant number MR/L01341X/1. J.H.F.R. is part-supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation Centre of Research Excellence (RE/24/130011) and the Wellcome Trust. C.-B.S. acknowledges support from the EPSRC programme grant in "The Mathematics of Deep Learning" (EP/L015684), Cantab Capital Institute for the Mathematics of Information, the Philip Leverhulme Prize, the Royal Society Wolfson Fellowship, the EPSRC grants EP/S026045/1 and EP/T003553/1, EP/N014588/1, EP/T017961/1, the Wellcome Innovator Award RG98755 and the Alan Turing Institute P.N. is funded by Wellcome Trust and the UCLH NIHR Biomedical Research Centre. M.R. is additionally supported by the British Heart Foundation (TA/F/20/210001).
Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The INTERVAL, COMPARE, and STRIDES trials are compiled into the Blood Donors Studies BioResource (BDSB), which received ethical approval from the East of England - Cambridge Central Research Ethics Committee, Health Research Authority, NHS, United Kingdom (REC reference 20/EE/0115). The East of England - Cambridge Central Research Ethics Committee is part of the UK Health Departments' Research Ethics Service, operated by the Health Research Authority, which provides independent ethical review of health and social care research across England. Ethical approval was granted for the use of data from these studies for the current research.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
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