Haemolytic Anaemia

Question 1

Definition

Answer 1

Premature erythrocyte breakdown causing shortened erythrocyte life span (< 120 days) with anaemia

Question 2

Aetiology (hereditary)

Answer 2

o Membrane Defects
• Hereditary spherocytosis
• Elliptocytosis

o Metabolic Defects
• G6PD deficiency
• Pyruvate kinase deficiency

o Haemoglobinopathies
• Sickle cell disease
• Thalassemia

Question 3

Aetiology (acquired)

Answer 3

o Autoimmune
• Antibodies attach to erythrocytes causing intravascular and extravascular
haemolysis

o Isoimmune
• Transfusion reaction
• Haemolytic disease of the newborn

o Drugs
• Penicillin
• Quinine
• NOTE: this is caused by the formation of a drug-antibody-erythrocyte complex

o Trauma
• Microangiopathic haemolytic anaemia (caused by RBC fragmentation in abnormal microcirculation)
▪ E.g. haemolytic uraemic syndrome, DIC, malignant hypertension

o Infection
• Malaria
• Sepsis

o Paroxysmal nocturnal haemoglobinuria

Question 4

Epidemiology

Answer 4

• COMMON
• Genetic causes are prevalent if African, Mediterranean and Middle Eastern populations
• Hereditary spherocytosis is the most common inherited haemolytic anaemia in northern Europe

Question 5

Presenting symptoms

Answer 5

• Jaundice
• Haematuria
• Anaemia

Question 6

Signs on physical examination

Answer 6

• Pallor
• Jaundice
• Hepatosplenomegaly

Question 7

Investigations (bloods)

Answer 7

o FBC:
• Low Hb
• High reticulocytes
• High MCV
• High unconjugated bilirubin
• Low haptoglobin (a protein that binds to free Hb released by red blood cells)

o U&Es

o Folate

Question 8

Investigations (blood film)

Answer 8

o Leucoerythroblastic picture
o Macrocytosis
o Nucleated erythrocytes or reticulocytes
o Polychromasia

o May identify specific abnormal cells such as:
• Spherocytes
• Elliptocytes
• Sickle cells
• Schistocytes
• Malarial parasites

Question 9

Investigations (urine)

Answer 9

o High urobilinogen
o Haemoglobinuria
o Haemosiderinuria

Question 10

Investigations (other)

Answer 10

• Direct antiglobulin test/Coombs’ Test
o Tests for autoimmune haemolytic anaemia
o Identifies erythrocytes coated with antibodies

• Osmotic fragility test or Spectrin mutation analysis
o Identifies membrane abnormalities

• Ham’s Test
o Lysis of erythrocytes in acidified serum in paroxysmal nocturnal haemoglobinuria

• Hb Electrophoresis or Enzyme Assays
o To exclude other causes

• Bone Marrow Biopsy (rarely performed)