Haemolytic Anaemia

Question 1

Define haemolytic anaemia

Answer 1

Anaemia due to the premature destruction of RBC in the blood (<120 days)

Question 2

What are the causes/risk factors of haemolytic anaemia?

Answer 2

Hereditary
• Membrane defects
- Hereditary spherocytosis
- Hereditary elliptocytosis
• Metabolic defects
- G6PD deficiency
• Haemoglobinopathies
- Sickle cell anaemia
- Thalassaemia

Accquired
• Autoimmune
- Warm antibodies (IgG) – SLE, lymphomas, CLL
- Cold antibodies (IgM) – Mycoplasma, EBV, lymphomas
- Paroxysmal cold haemoglobinuria
• Alloimmune
- Transfusion reaction
- Haemolytic disease of the newborn
• Drugs
- Penicillin
- Quinine
• Mechanical
- Artificial heart valves
- Microangiopathic haemolytic anaemia – HUS, DIC
• Infection
- Malaria
- Sepsis
• Liver disease
• Hypersplenism
• Paroxysmal nocturnal haemoglobinuria

Question 3

What are the symptoms of haemolytic anaemia?

Answer 3

General anaemia
• Tiredness
• Lethargy
• Dyspnoea
• Malaise
• Pallor

Haemolytic
• Haematuria
• Jaundice

Question 4

What are the signs of haemolytic anaemia?

Answer 4

General
• Pallor
• Tachycardia

Haemolytic
• Jaundice
• Hepatosplenomegaly

Question 5

What investigations are carried out for haemolytic anaemia?

Answer 5

• FBC - low Hb; High MCHC due to reticulocytosis and/or spherocytosis.
• Reticulocyte Count - increased as a physiological bone marrow response to haemolysis.
• Peripheral Smear - reticulocytosis: A physiological bone marrow response to haemolysis.
- Polychromasia - similar finding as reticulocytosis.
- Sickle Cells
- Schistocytes: MAHA

• Spherocytes : Hereditary Spherocytosis
• Elliptocytes: Hereditary Elliptocytosis
• Degmacytes: Bite Cells or Blister Cells result from the removal of denatured haemoglobin from RBCs by splenic macrophages.
• Howel-Jolly Body: DNA clusters in the RBC due to hyposplenism and severe haemolysis.
• Heinz Bodies: Denatured Hb in the RBCs –seen in G6PD Deficiency under a methyl violet stain.
• Acanthocytes: Spur Cells are spiked RBC membranes e.g. in Liver disease.
  • Unconjugated BR - increased haem catabolism.
  • Serum LDH - high in intravascular haemolysis.
  • Haptoglobin - low since haptoglobin binds free Hb, with low plasma values suggestive of increased free Hb.
  • Urinalysis - haemoglobinuria is present in intravascular haemolysis. Positive for blood; no RBCs.
  • Coomb’s Test -
  Identifies erythrocytes coated with antibodies (agglutinins) using antihuman globulin. Warm agglutinin and cold agglutinin. Positive suggests immune aetiology; negative suggests non-immune aetiology
  • Osmotic Fragility Test for Hereditary Spherocytosis (Spectrin mutation test).
  • Ham’s Test - lysis of erythrocytes is acidified serum in paroxysmal nocturnal haemoglobinuria. More recently – red cells are analysed, using monoclonal antibodies to the GPI-anchored proteins (CD55 and CD59) and flow cytometry.
  • Hb Electrophoresis
  HbS present in sickle cell disease; elevated levels of HbA2 and HbF in beta thalassaemia
  • Donath-Landsteiner Antibody - Indicated if associated with exposure to cold. The presence of complement on the red cells but negative direct antiglobulin test is also suggestive of a cold autoimmune haemolytic anaemia.
  • G6PDD - testing for glucose-6-phosphate dehydrogenase deficiency includes a fluorescent spot test followed by definitive assay of glucose-6-phosphate dehydrogenase activity by spectrophotometry.
  LFTs:

Elecated in Liver disease; Alcoholic cirrhosis in particular is associated with RBC membrane changes and haemolysis.