Haemolytic Anaemia Flashcards
What is the lifespan of a normal red blood cell?
120 days
What are different categories of haemolysis?
- Intravascular: Within circulation
- Extravascular: Removal/destruction by reticuloendothelial (RE) system.
Inherited or acquired
What are causes of extravascular haemolytic anaemia?
Autoimmune
Alloimmune
Hereditary spherocytosis
What are causes of intravascular haemolytic anaemia?
- Malaria
- G6PD deficiency
- Mismatched blood transfusion (ABO)
- Cold antibody haemolytic syndromes
- Drugs
- Microangiopathic haemolytic anaemia
- Haemolytic uraemic syndrome
- Thrombotic thrombocytopenic purpura
- Paroxysmal nocturnal haemoglobinuria
What are causes of hereditary haemolytic anaemia?
Disorders of:
Membrane
- Cytoskeletal proteins
- Cation permeability
Red cell metabolism
Haemoglobin:
- Thalassaemia
- Sickle cell syndromes
- Unstable Hb variants
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant
What are consequences of haemolytic anaemia?
Anaemia(+/-)
Erythroid hyperplasia with increased rate of red cell production and circulating reticulocytes
Increased folate demand
Susceptibility to effect of parvovirus B19
Propensity to gallstones(cholelithiasis)
Increased risk of:
- Iron overload
- Osteoporosis
What is this?
Parvovirus B19 infection
What is this?
Hepatic siderosis (Perl’s stain)
What does coinheritence of Gilbert syndrome with chronic haemolytic anaemia lead to increased risk for?
Cholelithiasis
What are clinical features of haemolytic anaemia?
Pallor
Jaundice
Splenomegaly
Pigmenturia
Family history
What are laboratory findings of haemolytic anaemia?
Anaemia
Increased reticulocytes
Polychromasia
Hyperbilirubinaemia
Increased LDH
Reduced/absent haptoglobins
Haemoglobinuria
Haemosiderinuria
What are defects in red cell membrane disorders in hereditary spherocytosis?
Vertical interaction:
- Band 3
- Protein 4.2
- Ankyrin
- Beta-Spectrin
What are defects in red cell membrane in hereditary elliptocytosis?
Horizontal interaction:
- Alpha-Spectrin
- Beta-Spectrin
- Protein 4.1
What is hereditary spherocytosis?
Genetic defect of red cell cytoskeleton.
- Family history in 75% - typically autosomal dominant
- 25% recessive or de novo mutation
In vitro red cells show increased sensitivity to lysis in hypotonic saline (osmotic fragilty test).
Reduced binding of dye eosin-5-maleimide.
What is this?
Hereditary spherocytosis (HS)
What is this?
Hereditary elliptocytosis
What is this?
Hereditary pyropoikilocytosis
What is the epidemiology and pattern of inheritence of Glucose-6-phosphate dehydrogenase deficiency?
Affects up to 400 million worldwide.
Prevalent in areas of malarial endemicity - selection.
X-linked - clinical effects seen predominantly in hemizygous males and homozygous females.
What is the pathophysiology of G6PD deficiency?
Enzyme catalyses first step in pentose phosphate (hexose monophosphate) pathway - generates NADPH required to maintain intracellular glutathione (GSH).
What are the clinical effects of G6PD deficiency?
Neonatal jaundice
Acute haemolysis (triggered by oxidants/infection)
Chronic haemolytic anaemia (rare)
What triggers symptoms of G6PD deficiency?
Steady state is asymptomatic, however, drugs, infections or fava beans can lead to acute haemolysis.
What is this?
G6PD deficiency
What is this?
Heinz bodies (Methylviolet)
