Anaemia: pattern-based investigation

Also known as Anemia · Low haemoglobin · Microcytic anaemia · Macrocytosis

GP-fellowship guide to anaemia investigation: WHO haemoglobin thresholds and their modern re-derivation, MCV-based pattern classification, iron studies and inflammation confounding, thalassaemia trait versus iron deficiency (Mentzer index and confirmatory HPLC), macrocytosis workup including B12 and alcohol, the haemolysis screen, hepcidin-mediated anaemia of chronic disease, restrictive transfusion thresholds from TRICS III and TRIGGER, and referral triggers.

high14 referencesUpdated 22 Aug 20266 min readVerification in progress

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Key points

Anaemia is defined by haemoglobin thresholds, and those thresholds have just been re-derived: the fifth centile is 119.7 g/L in non-pregnant women and 134.9 g/L in men aged 18–65 — close to the classic WHO numbers but now evidence-based across eight international datasets.^[1]
Classify first by MCV (microcytic / normocytic / macrocytic), then narrow with ferritin, B12/folate and reticulocytes; the reticulocyte count separates failure of production from loss or destruction.^[8]
Iron studies are pattern recognition: low ferritin confirms deficiency, but inflammation raises ferritin — a normal ferritin does not exclude iron deficiency when CRP is elevated.^[9]
Transfuse restrictively: TRICS III showed a 7.5 g/dL threshold was non-inferior to 9.5 g/dL in cardiac surgery with far fewer units transfused.^[3]

Overview

Anaemia is one of the most common abnormal results a GP encounters, and its investigation is pattern recognition built on three questions: how low is the haemoglobin, what is the MCV, and what do the reticulocytes say. The WHO thresholds that anchor global definitions were statistical estimates set over fifty years ago; a 2024 re-derivation from international datasets has confirmed they remain broadly correct while giving them an evidentiary basis.^[1]

The modern thresholds matter clinically: the pooled fifth-centile haemoglobin for non-pregnant women aged 18–65 was 119.7 g/L and for men 134.9 g/L, with pregnancy lowering the threshold to about 110 g/L in the first trimester and 105.9 g/L in the second. Thresholds diverge between sexes only from adolescence onwards.^[1]

References14Show

[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. The Lancet. Haematology, 2024.PMID 38432242
[2]Mazer CD, Whitlock RP, Fergusson DA et al. Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery. The New England journal of medicine, 2017.PMID 29130845
[3]Jairath V, Kahan BC, Gray A et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet (London, England), 2015.PMID 25956718
[4]von Siebenthal HK, Gessler S, Vallelian F et al. Alternate day versus consecutive day oral iron supplementation in iron-depleted women: a randomized double-blind placebo-controlled study. EClinicalMedicine, 2023.PMID 38021373
[5]Kamath S, Parveen RS, Hegde S et al. Daily versus alternate day oral iron therapy in iron deficiency anemia: a systematic review. Naunyn-Schmiedeberg's archives of pharmacology, 2024.PMID 37979057
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[9]Jensen MCH, Holm C, Jørgensen KJ et al. Treatment for women with postpartum iron deficiency anaemia. The Cochrane database of systematic reviews, 2024.PMID 39670550
[10]Sultana N, Bajwa FA, Sikandar MZ et al. Effect of iron therapy on fatigue symptoms in non-anaemic iron deficient women of reproductive age- A Randomized Controlled Trial. JPMA. The Journal of the Pakistan Medical Association, 2026.PMID 41736325
[11]Bamrah D, Nautiyal R, Kala M et al. Screening for β-Thalassemia Trait in Pregnant Women With Microcytic Hypochromic Anemia and Its Impact on Pregnancy Outcomes. Cureus, 2026.PMID 42245877
[12]Shao J, Zhang Y, Lin W et al. Restrictive versus liberal red blood cell transfusion strategies for cardiac surgery: a systematic review and meta-analysis of randomized controlled trials. Journal of cardiothoracic surgery, 2026.PMID 42021257
[13]Bamrah D, Nautiyal R, Kala M et al. Screening for β-Thalassemia Trait in Pregnant Women With Microcytic Hypochromic Anemia and Its Impact on Pregnancy Outcomes. Cureus, 2026.PMID 42245877
[14]Shao J, Zhang Y, Lin W et al. Restrictive versus liberal red blood cell transfusion strategies for cardiac surgery: a systematic review and meta-analysis of randomized controlled trials. Journal of cardiothoracic surgery, 2026.PMID 42021257