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)
Which agents can provoke acute haemolysis in G6PD deficiency?
Anti-malarials: Primaquine
Antibiotics:
- Sulphonamides
- Ciprofloxacin
- Nitrofurantoin
Other drugs:
- Dapsone
- Vitamin k
Fava beans
Mothballs
What is involved in Embden-Meyerhof part of glycolysis?
NADPH
ATP
What is involved in Hexose monophosphate shunt (pentose phosphate) part of glycolysis?
NADPH
What is involved in Rapoport-Luebering shuttle part of glycolysis?
2,3-DPG
What is involved in nucleotide metabolism part of glycolysis?
Adenine salvage
Adenosine phosphate equilibrium
Removal of pyrimidine nucleotides
What is involved in glutathione biosynthesis part of glycolysis?
GSH
What is involved in cytochrome b5 reductase part of glycolysis?
Methemoglobin reduction
What is this?
Pyruvate kinase deficiency (post-splenectomy)
What is this?
Pyrimidine 5’-nucleotidase deficiency
What are the first line investigations for G6PD deficiency?
- Direct antiglobulin test
- Urinary haemosiderin/haemoglobin
- Osmotic fragility
- G6PD +/- PK activity
- Haemoglobin separation A and F%
- Heinz body stain
- Ham’s test/Flow cytometry of GPI-linked proteins
- Thick and thin blood film
What are the principles of management of G6PD deficiency?
- Folic acid supplementation
- Avoidance of precipitating factors e.g. oxidants in G6PD deficiency
- Red cell transfusion/exchange
- Immunisation against blood borne viruses e.g. hepatitis A and B
- Monitor for chronic complications
- Cholecystectomy for symptomatic gallstones
- Splenectomy if indicated
What are indications for splenectomy?
- PK deficiency and some other enzymopathies
- Hereditary spherocytosis
- Severe elliptocytosis/pyropoikilocytosis
- Thalassaemia syndromes
- Immune haemolytic anaemia
What are risks of splenectomy?
Risk of overwhelming sepsis:
- Capsulated bacteria e.g. Pneumococcus
- Penicillin prophylaxis and immunisation
What is the criteria for splenectomy?
Transfusion dependence
Growth delay
Physical limitation Hb
Hypersplenism
Age not < 3 years, before 10 years to maximise prepubertal growth.
