Haemolytic anaemia Flashcards
What is the normal red cell life span?
120 days
- What is haemolysis?
- What are the two types?
- Haemolysis is defined as shortended red cell survival. May be predominantly:
- Intravascular - within circulation
- Extravascular - remova;/destructio by reticuloendothelial system
- Inherited for acquired
What are the 3 main causes of extravascular haemolytic anemia?
- Autoimmune
- Alloimmune
- Hereditary spherocytosis
What are some of the causes of intravascular haemolytic anaemia?
- Malaria
- G6PD deficiency
- Mismatched blood transfusion
- Cold antibody haemolytic syndromes
- Drugs
- Microangiopathic haemolytic anaemia (MAHA) e.g. HUS
- Thrombotic thrombocytopenic purpura
- Paroxysmal nocturnal haemoglobinuria
What form of inheritance is hereditary spherocytosis?
Autosomal dominant
What are the consequences of having haemolytic anaemia?
- Anaemia
- Erythroid hyperplasia with increased rate of red cell production and circulating reticulocytes
- Increased folate demand
- Susceptibility to effect of Parvovirus B19 (slap cheek)
- Propensity to gallstones
- Increased risk of iron overload and osteoporosis
What other syndrome when coinherited further increase risk of gallstones in chronic haemolytic anaemia?
Gilbert syndrome
UGT 1A1 TA7/TA7 genotype
What are the clinical features of chronic haemolytic anemia?
- Pallor
- Jaundice
- Splenomegaly
- Pigmenturia
- Family history
What are the possible laboratory findings in people with chronic haemolytic anemia?
- Anaemia
- Increased reticulocytes
- Polychromasia
- Hyperbilirubinaemia
- Increased LDH
- Reduced/absent haptoglobins
- Haemoglobinuria
- Haemosiderinuria - brown urine and a side effect of chronic intravascular haemolytic anemia
What are the two main red cell membrane disorders that can cause haemolytic anemia?
- Hereditary spherocytosis
- Hereditary elliptocytosis
What are the red cell membrane disorders in hereditary spherocytosis?
- Vertical interaction
- Band 3, protein 4.2, Ankyrin and/or Beta spectrin
What are the red cell membrane defects in hereditary elliptocytosis?
- Horizontal interaction
- Alpha spectrin
- Beta spectrin
- Protein 4.1
- What is hereditary spherocytosis?
- What is the mode of inheritance?
- Genetic defect of red cell cytoskeleton
- Autosomal dominant - 75% of cases
Red cells have an increased risk of lysis - osmotic fragility test
Reduced binding of dye eosin-5-maleimide
What does this image show?
Hereditary spherocytosis
What does this image show?
Hereditary elliptocytosis
What does this image show?
Hereditary pyropoikilocytosis
irregularly shaped cells - an autsomal recessive disorder
- What is G6PD-deficiency (inc. full name)?
- How do people develop it?
- What are the clinical effects?
- Glucose-6-phosphate dehydrogenase deficiency. G6PD is an enzyme that catalyzes the first step in the pentose phosphate pathway, that leads to the generation of NADPH which is required to maintain intracellular glutathione (GSH)
- X linked inheritance, seen in hemizygous males and homozygous females
- Clinical effects include
- Neonatal jaundice
- Acute hemolysis (triggered by oxidants/infection)
- Chronic hemolytic anemia (rare)
What can cause acute hemolysis in people with G6PD deficiency?
Usually asymptomatic
However, drugs, infections or fava beans can cause acute hemolysis in people with G6PD deficiency
What does this image show?
G6PD deficiency blood film
What does this blood film show? (features)
Heinz bodies, stained with methylviolet
Sign of intravascular hemolysis and of G6PD deficiency
Name some common agents that provoke G6PD deficiency
- Anti-malarials
- Antibiotics - sulphonamides, ciprofloxacin
- Vitamin K
- Fava beans
- Moth balls
There are more!
What does this image show?
Pyruvate kinase deficiency (post-splenectomy)
What does this image show?
Pyrimidine 5’-nucleotidase deficiency
What are the first line investigations if G6PD deficiency is suspected?
- Direct antiglobulin test (DAT) or Coombs test - hemolytic anemia
- Urinary haemosiderin/haemoglobin
- Osmotic fragility
- G6PD +/- PK activity
- Haemoglobin seperation 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 for 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. Hep A and B
- Monitor for chronic complications
- Cholecystectomy for symptomatic gallstones
- Splenectomy if indicated
What are the indications for a splenectomy?
Substantial benefit in:
- PK deficiency and some other enzymeopathies
- Hereditary spherocytosis
- Severe elliptocytosis/pyropoikilocytosis
- Thalassaemia syndromes
- Immune haemolytic anemia
What is one of the main risks for people who have a splenectomy?
- Risk of overwhelming sepsis by capsulated bacteria e.g. Pneumococcus
- Penicillin prophylaxis and immunisation
What are the indications for a splenectomy?
- Criteria?
- Age?
- Criteria
- Transfusion dependence
- Growth delay
- Physical limitation Hb < 8g/dl
- Hypersplenism
- Not before teh age of 3 years but before 10 years to maximise pubertal growth
