Haemolysis Flashcards
What is haemolysis?
Premature red cell destruction
What is the difference between compensated and decompensated haemolysis?
Compensated = Hb maintained by increased red cell production
Decompensated = rate of red cell destruction exceeding bone marrow capacity for production (haemolytic anaemia)
What are the consequences of haemolysis used to identify in on investigation?
Erythroid hyperplasia (increased bone marrow production of red cells) --> reticulocytosis Excess red cell breakdown products
What does reticulocytosis look like on a blood film?
Polychromasia (different colours) –> due to ribosomal RNA in reticulocytes (NOT nucleated)
How is haemolysis classified and how can you tell the difference?
Intravascular vs extravascular
–> different breakdown products
Where are the red cells destroyed in extravascular haemolysis?
Liver and spleen –> hyperplasia (hepatosplenomegaly)
Which breakdown products are seen in extravascular haemolysis?
Normal products in excess:
- unconjugated bilirubinaemia (jaundice, gall stones)
- urobilinogenuria
Which breakdown products are seen in intravascular haemolysis?
Haemoglobinaemia (free Hb in circulation)
Methaemalbuminaemia
Haemoglobinuria (pink urine, turns black on standing)
Haemosiderinuria
–> abnormal products, may be life threatening
What are the causes of intravascular haemolysis?
ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (Blackwater fever)
PNH or PCH (very rare)
How is autoimmune haemolysis classified?
Warm or cold autoantibody
- warm = IgG
- cold = IgM
What are the causes of warm autoimmune haemolysis?
Idiopathic (most common) SLE CLL Drugs e.g. penicillins Infection
What are the causes of cold autoimmune haemolysis and how is it triggered?
Idiopathic
Infection (EBV, mycoplasma)
Lymphoproliferative disorders
Triggered by: cold weather, cold drinks, unwarmed IV fluids etc
How is autoimmune haemolysis diagnosed?
Direct Coombs’ test
How does the Direct Coombs’ test work?
Patient RBCs + mouse anti-human IgG –> agglutination
–> identifies antibody bound to OWN red cells
Give two examples of allogenic haemoylsis?
Haemolytic transfusion reaction (immune response - antibodies produced)
Haemolytic disease of the newborn (passive transfer of antibody)
Give some examples of haemolysis caused by abnormal cell membranes
Genetic:
- Hereditary spherocytosis
Acquired:
- Zieve’s syndrome
- Vitamin E deficiency
- Paroxysmal nocturnal haemoglobinuria (PNH)
- (all very rare)
What is Zeive’s syndrome?
Haemolysis, alcohol liver disease + hyperlipidaemia
What is Paroxysmal nocturnal haemoglobinuria (PNH)?
Triad of:
- haemolytic anaemia
- pancytopenia
- large vein thrombosis
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant
What is the pathophysiology of hereditary spherocytosis?
Sphere shaped red cells:
- reduced membrane deformability
- increased transit time in spleen
- oxidative environment in spleen causes extravascular red cell destruction
Which genetic conditions cause haemolysis due to abnormal red cell metabolism? How are they inherited?
G6PD deficiency –> X linked
Pyruvate kinase deficiency –> autosomal recessive
What causes the haemolysis in G6PD deficiency?
Failure to cope with oxidative stress Haemolysis triggered by: - infection - drugs (primaquine, chloroquine, sulphonamides) - fava beans --> FAVISM
Which conditions cause haemolysis due to abnormal Hb?
Sickle cell disease
Thalassaemia
What is Microangiopathic Haemolytic Anaemia (MAHA)?
Traumatic intravascular destruction of RBCs, often with endothelial injury, clotting activation + platelet aggregation
Give some examples of MAHA?
Thrombotic thrombocytopenia purpura (TTP)
Haemolytic uraemic syndrome (HUS)
Disseminated intravascular coagulation (DIC)
HELLP syndrome
Autoimmune: vasculitis, SLE, scleroderma renal crisis
Mechanical heart valves
Malignant hypertension
Severe burns (red cells sheared as they pass through damaged capillaries)
What are the clinical features of haemolysis?
Pallor, fatigue, SOB
Pre-hepatic jaundice
Splenomegaly
RUQ pain if there are pigment gallstones
How is warm AI haemolysis treated?
Steroids first line
Other immunosuppressants e.g. rituximab, cyclophosphamide, azathioprine
Plasmapheresis
Splenectomy if refractory
How is cold AI haemolysis treated?
Avoid cold, use warmed IV fluids/transfusion if needed
Usually mild so not requiring immunosuppression
What is the treatment for hereditary spherocytosis?
Transfusions
Folic acid (required for RBC production)
Splenectomy
What is the treatment for TTP?
Plasma exchange
- 90% mortality if untreated
