Haematology: Haemolytic Anaemias Flashcards
what is haemolysis?
- Decreased red cell survival
- Either intravascular: within the circulation
- Or extravascular: removal/ destruction by reticuloendothelial system.
List the causes of extravascular haemolysis
- Autoimmune haemolytic anaemia
- Alloimmune haemolytic anaemia
- Hereditary spherocytosis (Autosomal dominant)
- Other membrane disorders
List the causes of intravascular haemolysis
- Malaria (Plasmodium flaciparum)
- G6PD deficiency
- ABO incompatibility
- Cold antibody haemolytic syndromes
- Drugs (eg dapsone)
- Microangiopathic haemolytic anaemia
- Thrombotic thrombocytopenic purpura (TTP)
- Paroxysmal nocturnal haemoglobinuria
- Haemoglobin disorders (eg β Thalassaemia)
Describe the consequences of haemolysis
- Anaemia can occur
- Erythroid hyperplasia (Increased red cell production)
- Increased folate demand as a result
- Increased susceptibility to effects of parvovirus B19
- Gallstones (Due to ↑ generation of bilirubin, due to ↑ haem metabolism).
- ↑ risk of iron overload
- ↑ risk of osteoporosis.
Outline the clinical features of haemolytic anaemia
- Pallor (Due to anaemia)
- Jaundice (Due to more billirubin)
- Splenomegaly (Increased red cell breakdown)
- Pigmenturia (Excess billirubin excretion)
- Family history (Is common)
Describe the laboratory features of haemolytic anaemia
- Anaemia (Hb <115g/L)
- Raised reticulocytes
- Polychromasia on blood film
- Haemoglobinuria
- Haemosiderinaemia
- Intravascular: Raised LDH, reduced haptoglobins
Give 2 red cell membrane disorders
- Hereditary spherocytosis (Vertical interactions)
- Hereditary elliptocytosis (Horizontal interactions)
Which cause of haemolytic anaemia is diagnosed with a dibinding test (Testing mean cell fluoresence)?
-Hereditary spherocytosis
What are the lab features of hereditary spherocytosis?
- Anaemia
- Raised reticulocytes
- Polychromasia on blood film
- Haemoglobinuria
- Haemosiderinaemia
- Intravascular: Raised LDH, reduced haptoglobins
- Blood film: spherocytes, loss of central pallor, polychromasia
- Eosin-5-maleimide (reduced?)
- Reduced mean cell fluorescence (Dibinding test)
What cause of haemolytic anaemia affects horizontal interactions of the red cell membrane (eg α spectrin)?
-Hereditary elliptocytosis
Give 3 red cell metabolism disorders
- G6PD deficiency
- Pyruvate kinase deficiency
- Pyrimidine 5’-nucleotidase deficiency (Basophillic stippling)
Outline the pathogenesis of G6PD deficiency
- G6PD catalyses the first step in the pentose phosphate pathway
- G6PD generates NADPH, which protects the red cell from oxidant stress.
- Reduced G6PD leads to decreased NADPH, causing red cells to be susceptible to lysis by triggers of oxidative stress.
Describe the clinical features of G6PD deficiency
- Mainly asymptomatic in steady-state
- Neonatal jaundice
-Acute episodes of haemolysis (upon exposure to triggers)
-Chronic haemolytic anaemia (rare)
What triggers haemolysis in G6PD deficiency
- Fava beans
- Moth Balls
- Antimalarials: eg primaquine
- Antibiotics: eg sulphonamides
What are the first line investigations to perform in patients with haemolytic anaemia?
- Direct antiglobulin test: detects IG on red cells (Excludes autoimmune causes)
- Urinary haemosiderin (detects intravascular haemolysis) -Haemoglobin
- Osmotic fragility test (detects membrane disorders)
- Dibinding test (detects hereditary spherocytosis -
- Enzyme activity (Such as G6PD or PK).
- HPLC (detects haemoglobinopathies)
- Supravital stain with methyl violet (Detects Heinz bodies [denatured Hb]).
