Anaemia

Definitions: men — Hb < 130g/L, haematocrit < 0.42, RBC < 4.5×10¹²/L. Women — Hb < 120g/L, haematocrit < 0.37, RBC < 4×10¹²/L. Pregnancy and school-aged children — Hb < 110g/L. Symptoms: general fatigue, weakness, dyspnoea on exertion, pallor, plus features specific to the underlying cause.

Causes, by mechanism

Blood loss — acute (childbirth, GI bleeding, injury, surgery) or chronic (bladder tumours, GI cancer/polyps, heavy menstrual bleeding, renal tumours, peptic ulcer).

Deficient erythropoiesis, by MCV:

• Microcytic: iron deficiency, iron-transport deficiency (IRIDA), iron utilisation defects (inherited sideroblastic anaemia).
• Normochromic-normocytic: anaemia of chronic inflammation/infection/cancer (see Anaemia of Chronic Disease), kidney disease, endocrine failure (thyroid, pituitary), malnutrition, myelodysplasia, myelophthisis, pure red cell aplasia.
• Macrocytic: alcohol use disorder, copper deficiency, folate deficiency, liver disease, malabsorption, myelodysplasia, vitamin B12 deficiency (see B12 Deficiency/Pernicious Anaemia).

Excessive haemolysis (see Haemolytic Anaemia for full detail) — extrinsic causes (hypersplenism, immune, infective, mechanical, drugs/ toxins) or intrinsic RBC defects (membrane disorders, metabolic/enzyme deficiencies, haemoglobinopathies including sickle cell disease and the thalassaemias).

Investigations

• FBC/MCV: microcytic (iron deficiency, thalassaemia, anaemia of chronic disease); macrocytic (B12/folate deficiency, chemotherapy agents such as hydroxyurea and antifolates, alcohol-related membrane changes).
• Peripheral smear: target cells, schistocytes, poikilocytosis, anisocytosis.
• Bone marrow aspirate/biopsy — not usually indicated unless: unexplained anaemia, more than one cell lineage abnormality (e.g. concurrent anaemia + thrombocytopenia/ leukopenia), or a suspected primary bone marrow disorder (leukaemia, myeloma, aplastic anaemia, MDS, metastatic carcinoma, myelofibrosis).
• Other: bilirubin and LDH (elevated in haemolysis, normal in simple blood loss); B12, folate, iron studies.

Characteristics of common anaemias (summary)

Type	Morphology	Special features
Acute blood loss	Normochromic-normocytic, polychromatophilia	If severe: nucleated RBCs, leukocytosis, thrombocytosis
Chronic blood loss / iron deficiency	Microcytic, anisocytosis, poikilocytosis, reticulocytopenia	Low serum iron/ferritin, increased total iron-binding capacity; possible achlorhydria, smooth tongue, spoon nails
Anaemia of infection/cancer/chronic inflammation	Normochromic-normocytic early, may become microcytic	Decreased serum iron and TIBC; normal/high ferritin
Folate deficiency	Same as B12 deficiency (below)	Serum folate < 11nmol/L; nutritional/malabsorptive (sprue, pregnancy, alcoholism)
B12 deficiency (incl. pernicious anaemia)	Oval macrocytes, anisocytosis, hypersegmented neutrophils, megaloblastic marrow	Serum B12 < 130pmol/L; reticulocytopenia; GI/CNS involvement common; intrinsic factor antibodies in pernicious anaemia
Hereditary spherocytosis / haemolysis	Spheroidal microcytes, reticulocytosis, marrow erythroid hyperplasia	Increased indirect bilirubin and LDH, increased RBC fragility, shortened RBC survival
Marrow failure	Normochromic-normocytic (may be macrocytic), reticulocytopenia, hypoplastic marrow	Idiopathic (>50%) or secondary to toxic drug/chemical exposure
Marrow replacement (myelophthisis)	Anisocytosis, poikilocytosis, nucleated RBCs, early granulocyte precursors	Marrow infiltration (granulomas, tumour, fibrosis, lipid histiocytosis); possible hepatosplenomegaly
Sideroblastic	Usually hypochromic, dimorphic (normocytes + macrocytes)	Ringed sideroblasts, plentiful stainable marrow iron; some inherited forms respond to vitamin B6
Thalassaemia	Microcytic, target cells, basophilic stippling, anisocytosis/poikilocytosis	Elevated Hb A2 (beta-thalassaemia minor) or Hb F (major); Mediterranean ancestry common
Sickle cell disease	Sickled cells on smear, reticulocytosis	Hb S on electrophoresis; vaso-occlusive crises, bone changes on X-ray
Paroxysmal nocturnal haemoglobinuria	Reticulocytosis	Dark morning urine, haemosiderinuria, thrombosis risk

For iron-deficiency anaemia, IV ferric carboxymaltose (FCM) allows a large iron dose in a single infusion (vs older iron polymaltose regimens needing longer/multiple infusions), with a small but important risk of hypophosphataemia with repeated dosing.