Iron deficiency anaemia — red cell indices and investigation

Definition. Anaemia (WHO: Hb <13 g/dL in men, <12 g/dL in women) resulting from depleted body iron stores. It is the commonest anaemia worldwide and the commonest nutritional anaemia in Indian elderly. In an older adult, iron deficiency means blood loss until proved otherwise.

Causes in the elderly. Chronic gastrointestinal blood loss — peptic ulcer, NSAID/aspirin use, colonic carcinoma, angiodysplasia, oesophagitis and hookworm infestation (important in India); malabsorption — coeliac disease, atrophic gastritis, post-gastrectomy and long-term PPI use; poor dietary intake; and genitourinary blood loss.

Red cell indices. Low MCV (<80 fL) and low MCH (<27 pg) giving a microcytic hypochromic picture, with a raised RDW (>15%) — the earliest index to change. This distinguishes it from thalassaemia trait, which has a normal RDW, a disproportionately low MCV and a high red cell count (Mentzer index MCV/RBC >13 favours iron deficiency). Reticulocyte haemoglobin content (CHr/Ret-He) is an early marker. The film shows microcytes, hypochromia, pencil cells, target cells and mild thrombocytosis.

Confirmatory biochemistry. Serum ferritin is the single best test — below 30 ng/mL is diagnostic, but because ferritin is an acute-phase reactant a higher cut-off of 45–100 ng/mL is used in the elderly with inflammation. Also: low serum iron, raised TIBC, transferrin saturation <16%, raised soluble transferrin receptor and low hepcidin. Bone marrow iron staining is needed only when the diagnosis remains unclear.

Distinction from anaemia of chronic disease. Anaemia of chronic disease shows a normal or high ferritin, low TIBC, normal soluble transferrin receptor and raised CRP. Combined states are common in the elderly — use the sTfR/log-ferritin index to separate them.

Investigation of the source. Bidirectional endoscopy (upper GI endoscopy plus colonoscopy) is mandatory in every older adult with unexplained iron deficiency anaemia, with duodenal biopsy and coeliac serology. Also check urine for blood and stool for occult blood and ova. If both are negative and anaemia persists or recurs, proceed to capsule endoscopy or CT enterography for small bowel angiodysplasia or tumour.

Modern iron replacement. Hepcidin studies have shown that oral iron given on alternate days as a single morning dose achieves better fractional absorption with fewer side-effects than conventional twice or thrice daily dosing. New-generation intravenous preparations — ferric carboxymaltose and ferric derisomaltose — allow total-dose correction in a single sitting and are preferred in malabsorption, intolerance, CKD, heart failure and ongoing blood loss; watch for hypophosphataemia with ferric carboxymaltose. Cross-reference: Anaemia of chronic disease, with which iron deficiency frequently coexists, is covered in Question 24.