approach to anaemia

Classify by MCV: microcytic (<80 fL), normocytic (80–100 fL), macrocytic (>100 fL). Then layer on reticulocyte count — high (appropriate marrow response → blood loss or haemolysis) vs low (production failure). Iron studies and a blood film answer most questions.

do not miss

active haemorrhage — tachycardia, hypotension, dropping Hb over hours → resuscitate, crossmatch, find the source
severe haemolysis — LDH ↑, haptoglobin ↓, unconjugated bilirubin ↑, schistocytes on film → think TMA (TTP/HUS), AIHA, or mechanical valve; TTP needs plasma exchange within hours
new pancytopaenia → marrow failure (leukaemia, aplastic anaemia, myelodysplasia) — urgent blood film and haematology referral

classification by MCV

microcytic (<80 fL)

cause	key distinguishing features
iron deficiency	ferritin <30 µg/L (or <100 in inflammation); transferrin saturation <20%; most common cause worldwide
anaemia of chronic disease	ferritin normal or ↑; transferrin saturation <20%; TIBC normal or ↓ (vs ↑ in iron deficiency)
thalassaemia trait	lifelong microcytosis out of proportion to anaemia; RBC count often ↑; Mentzer index <13 (MCV/RBC); Hb electrophoresis
sideroblastic	ring sideroblasts on marrow aspirate; consider if iron studies suggest overload

ferritin in inflammation

Ferritin is an acute-phase reactant. In the context of infection, malignancy, or autoimmune disease, a ferritin <100 µg/L still suggests iron deficiency. Above 100, a transferrin saturation <20% and a soluble transferrin receptor (if available) can help distinguish.

normocytic (80–100 fL)

Split by reticulocyte count:

High reticulocytes → haemolysis or acute blood loss
Low reticulocytes → marrow failure: anaemia of chronic disease (most common), renal anaemia (↓ EPO), marrow infiltration (multiple myeloma, metastatic disease), aplastic anaemia, myelodysplasia, pure red cell aplasia

macrocytic (>100 fL)

megaloblastic	non-megaloblastic
B12 deficiency, folate deficiency	alcohol, liver disease, hypothyroidism, myelodysplasia, drugs (methotrexate, hydroxyurea, azathioprine), reticulocytosis

Hypersegmented neutrophils (≥5 lobes) on blood film → megaloblastic until proven otherwise.

workup

first-pass panel for all anaemias

CBC with differential and reticulocyte count
Iron studies: ferritin, serum iron, TIBC (or transferrin), transferrin saturation
Blood film — free diagnostic information; request it
B12, folate (add if macrocytic or if cause unclear)
LDH, haptoglobin, unconjugated bilirubin (haemolysis screen if reticulocytes ↑)

haemolysis workup (when suspected)

test	expected in haemolysis
LDH	↑
haptoglobin	↓ (often undetectable)
unconjugated bilirubin	↑
blood film	schistocytes (TMA), spherocytes (AIHA, hereditary spherocytosis)
DAT (Coombs)	positive in AIHA; negative in TMA, mechanical, PNH
reticulocytes	↑ (unless concurrent marrow suppression)

DAT positive → warm AIHA (IgG) vs cold agglutinin disease (complement). DAT negative haemolysis → consider TMA, PNH (flow cytometry), enzyme defects (G6PD), mechanical (prosthetic valve).

transfusion thresholds

Hb <70 g/L → transfuse (general threshold for haemodynamically stable patients)
Hb <80 g/L → transfuse in ACS, symptomatic cardiac disease
Each unit of pRBCs raises Hb by ~10 g/L
Transfuse one unit at a time and reassess — single-unit strategy unless actively bleeding

do not transfuse to correct a number

Transfusion carries risks (volume overload, alloimmunisation, febrile reactions, TRALI, TACO). Treat the underlying cause. In chronic anaemia, the patient is often asymptomatic at Hb levels that would incapacitate someone with acute blood loss.

traps

Ferritin normal ≠ iron-replete — in inflammation, ferritin can be “normal” (30–100 µg/L) despite true iron deficiency. Check transferrin saturation.
B12 deficiency with normal B12 level — serum B12 has poor sensitivity in the low-normal range. If clinical suspicion is high, check methylmalonic acid (↑ in B12 deficiency, not folate deficiency).
Reticulocyte count must be corrected — a “normal” absolute reticulocyte count in severe anaemia is actually inadequate. Use the reticulocyte production index (RPI): reticulocyte % × (patient Hct / 0.45) / maturation factor.
Missing the blood film — automated indices miss schistocytes, spherocytes, blasts, and rouleaux. A manual film changes the diagnosis in a meaningful minority of cases.
“Anaemia of chronic disease” as a wastebasket — always exclude coexisting iron deficiency before settling on this diagnosis. They commonly coexist.

anaemia