Global harmonisation of haemoglobin thresholds for anaemia diagnosis

April 2024 Clinical trials Vanessa Vernimmen

Establishing an accurate case definition for anaemia is essential for effective clinical diagnosis and treatment. However, there is limited consensus on the definitions of anaemia among varied expert groups and public health bodies. This lack of agreement leads to inconsistent clinical interpretations and definitions.1

Anaemia is usually diagnosed when the haemoglobin concentration falls below a defined threshold for age and sex. However, the current WHO definitions of anaemia rely on statistical thresholds (fifth centiles) established over 50 years ago and there is limited consensus on the definitions of anaemia among different expert groups and public health bodies. In this study, the authors aimed to provide updated evidence supporting global, statistically-based haemoglobin thresholds for anaemia, with the goal of informing WHO guidelines and clinical practices.1


In this analysis, international data sources from populations in the USA, England, Australia, China, the Netherlands, Canada, Ecuador, and Bangladesh, with sufficient clinical and laboratory information collected from 1998-2020, were gathered to obtain a healthy reference sample. Individuals with clinical/biochemical evidence of a condition that could reduce haemoglobin concentrations were excluded. This study estimated haemoglobin thresholds for children aged 6-23 months, 24-59 months, 5-11 years, and 12-17 years, and adults aged 18-65 years for individual datasets and pooled across data sources. Findings from three large-scale genetic studies were collated to summarise genetic variants affecting haemoglobin concentrations in different ancestral populations.


This study identified eight data sources comprising eighteen individual datasets that were eligible for inclusion in the analysis. In pooled analyses, the haemoglobin fifth centile was 104.4 g/L (90% CI 103.5–105.3) in 924 children aged 6–23 months, 110.2 g/L (109.5–110.9) in 1,874 children aged 24–59 months, and 114.4 g/L (113.6–115.2) in 1,839 children aged 5–11 years. Values diverged by sex in adolescents and adults. In pooled analyses, the fifth centile was 122.2 g/L (90%CI: 121.3–123.1) in 1,741 female adolescents aged 12–17 years and 128.2 g/L (126.4–130.0) in 1,103 male adolescents aged 12–17 years. In pooled analyses of adults aged 18–65 years, the fifth centile was 119.7 g/L (90%CI: 119.1–120.3) in 3,640 non-pregnant females and 134.9 g/L (134.2–135.6) in 2,377 males. Fifth centiles in pregnancy were 110.3 g/L (90%CI: 109.5-111.0) in the first trimester (n=772) and 105.9 g/L (104.0–107.7) in the second trimester (n=111), with insufficient data for analysis in the third trimester. There were insufficient data for adults >65 years. Ancestry-specific high prevalence of non-clinically relevant genetic variants that influence haemoglobin concentrations were not identified.


These findings facilitate the global alignment of clinical and public health haemoglobin thresholds for diagnosing anaemia. The study reveals that haemoglobin thresholds are generally consistent between sexes until adolescence, after which males exhibit higher thresholds compared to females. Importantly, the study did not identify any evidence supporting the need for different thresholds based on ancestral backgrounds.1


1. Braat S, Fielding KL, Han J, et al. Haemoglobin thresholds to define anaemia from age 6 months to 65 years: estimates from international data sources. Lancet Haematol. 2024;11(4):e253-64.