Anaemia in the elderly and the evaluation of anaemia

Definition and magnitude. Anaemia is defined by WHO as haemoglobin below 13 g/dL in men and below 12 g/dL in women. Prevalence rises steeply with age — about 10% over 65 years and over 20–25% beyond 85 years, and higher still in nursing homes and hospital inpatients. Anaemia is never a normal consequence of ageing and must always be investigated.

Why it matters. Even mild anaemia in older people is independently associated with fatigue and reduced quality of life, falls, frailty and sarcopenia, cognitive decline, prolonged hospital stay, poorer surgical outcomes and increased mortality. It also decompensates existing coronary artery disease, heart failure and cerebrovascular disease.

The classical "rule of thirds" (NHANES). Approximately one third is due to nutritional deficiency (iron, B , 12 folate); one third to anaemia of chronic disease and chronic kidney disease; and one third is "unexplained anaemia of ageing" — attributed to blunted erythropoietin response, low-grade inflammation, reduced marrow reserve, testosterone decline and occult clonal haematopoiesis or early myelodysplasia.

Morphological approach by MCV. Microcytic (MCV <80 fL) — iron deficiency, thalassaemia trait, sideroblastic anaemia, some anaemia of chronic disease. Normocytic (80–100 fL) — anaemia of chronic disease, CKD, acute blood loss, haemolysis, marrow infiltration, endocrine disease. Macrocytic (>100 fL) — B and folate deficiency, 12 alcohol, hypothyroidism, liver disease, myelodysplasia, drugs (methotrexate, hydroxyurea, zidovudine).

First-line evaluation. History (bleeding, diet, alcohol, drugs including NSAIDs and aspirin, weight loss, comorbidity) and examination for lymphadenopathy, organomegaly and per-rectal examination. Tests: complete blood count with indices and RDW, peripheral smear, reticulocyte count, ferritin with transferrin saturation, B and folate, renal function, LFT, thyroid function, CRP/ESR. The reticulocyte count is the 12 key branch point — high suggests haemolysis or blood loss, low suggests production failure.

Second-line evaluation and treatment principles. Bidirectional endoscopy in every older adult with unexplained iron deficiency; serum protein electrophoresis with free light chains and urine Bence-Jones protein if there is a raised ESR, renal impairment, bone pain or rouleaux; haemolytic screen (LDH, bilirubin, haptoglobin, direct antiglobulin test) if reticulocytes are high; and bone marrow aspiration and biopsy if there is pancytopenia, blasts, dysplasia or a persistently unexplained anaemia. Treat the cause rather than transfusing — replace iron, B or folate; use erythropoiesis-stimulating agents only in CKD or MDS with a target 12 Hb of 10–11.5 g/dL (never normalise); and reserve transfusion for symptomatic anaemia at Hb <7 g/dL (<8 g/dL with cardiovascular disease).

WHO revised haemoglobin thresholds (2024) — a technical review reaffirmed the diagnostic cut-offs but recommended adjustment for smoking and altitude, and emphasised that ferritin below 30 µg/L (rather than 15) should be used to identify iron deficiency in the presence of inflammation. In parallel, "unexplained anaemia of ageing" is increasingly attributed to clonal haematopoiesis of indeterminate potential (CHIP) and early clonal cytopenia, which reframes it as a pre-malignant rather than purely physiological state and justifies bone marrow evaluation in persistent unexplained anaemia.