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Undifferentiated presentations - anaemia

Red flags

Anaemia + PR bleeding/melaena/weight loss - GI malignancy until excluded
Severe symptomatic anaemia (angina, dyspnoea, haemodynamic compromise) - needs urgent transfusion
Anaemia + jaundice + reticulocytosis - haemolysis, needs urgent workup (esp. if rapidly progressive)
Pancytopenia - marrow failure/infiltration, needs urgent haematology review
New iron-deficiency anaemia in a man or postmenopausal woman - GI malignancy until proven otherwise

By mechanism (MCV-directed)

Microcytic: iron deficiency (commonest cause overall - GI blood loss until proven otherwise in adults), thalassaemia trait, anaemia of chronic disease (can also be normocytic)
Normocytic: anaemia of chronic disease/inflammation, chronic kidney disease (reduced erythropoietin), acute blood loss, marrow infiltration/failure, haemolysis (if not yet macrocytic from reticulocytosis)
Macrocytic: B12/folate deficiency, hypothyroidism, alcohol excess, liver disease, myelodysplasia, reticulocytosis (haemolysis, acute blood loss recovery), drug-induced (methotrexate, hydroxyurea)

By additional mechanism

Haemolytic: autoimmune (warm/cold), hereditary spherocytosis, G6PD deficiency, microangiopathic (TTP/HUS, DIC, mechanical valve)
Marrow failure: aplastic anaemia, myelodysplasia, marrow infiltration (leukaemia, myeloma, metastases)

Symptoms of anaemia (fatigue, dyspnoea, palpitations) and their tempo (acute vs chronic - chronic anaemia often surprisingly well-tolerated)
GI symptoms - PR bleeding, melaena, dyspepsia; menstrual history in women
Diet (vegan/vegetarian - B12/iron), alcohol use, family history (thalassaemia, hereditary spherocytosis)
Medication (NSAIDs, anticoagulants), jaundice/dark urine (haemolysis)

Pallor (conjunctival, palmar crease), jaundice, glossitis/angular stomatitis (iron/B12 deficiency)
Lymphadenopathy, hepatosplenomegaly (marrow infiltration, haemolysis)
Signs of chronic liver disease, koilonychia (chronic iron deficiency)

FBE with MCV, blood film, reticulocyte count
Iron studies (ferritin - acute phase reactant, can be falsely normal/high with concurrent inflammation), B12/folate, TFT
Haemolysis screen if indicated: LDH, haptoglobin, direct Coombs test, bilirubin
Faecal occult blood/colonoscopy + gastroscopy for unexplained iron deficiency in adults (bidirectional endoscopy)
Bone marrow biopsy if unexplained pancytopenia/suspected infiltration

Treat the underlying cause, not just the anaemia
Iron deficiency - oral iron first-line; IV iron if intolerant/malabsorption/ongoing losses exceeding oral replacement capacity; investigate the source (endoscopy) in every adult with unexplained iron deficiency
B12/folate deficiency - replace (parenteral B12 if severe/neurological involvement or malabsorption); replace B12 before folate if both are low (folate alone can precipitate/worsen subacute combined degeneration)
Anaemia of chronic disease - treat underlying condition, erythropoiesis-stimulating agents in select CKD/oncology settings
Transfuse for symptomatic/severe anaemia per restrictive threshold (generally Hb <70-80 g/L, higher in active cardiac ischaemia)
Autoimmune haemolytic anaemia - corticosteroids first-line

Iron-deficiency anaemia in an adult male or postmenopausal woman is a GI cancer until excluded, not "probably diet"
Replacing folate without checking/replacing B12 first can precipitate neurological deterioration
Ferritin is an acute phase reactant - a "normal" ferritin does not exclude iron deficiency in the presence of inflammation
Chronic anaemia can be remarkably well-tolerated, masking a serious underlying cause until an incidental blood test

"MCV tells me which direction to investigate before I order a single extra test."
"Any new iron deficiency in an adult gets a bowel and stomach look, not just an iron tablet."

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