haemolytic anaemias Flashcards
Define hemolytic anaemia.
Anemia caused by shortened red cell survival
- List some examples of extra-vascular haemolysis.
Autoimmune h aemolytic an aemia
Hereditary spherocytosis
- List some examples of intra-vascular haemolysis.
Malaria G6PD deficiencv Pyruvate kinase deficiency Mismatched blood transfusion MAHA Paroxysmal nocturnal haemoglobinuria
- What is the most common cause of intravascular haemolysis worldwide?
Malaria
- What is paroxysmal nocturnal haemoglobinuria caused by?
An acquired defect in the GPI anchor which is one of two mechanisms by
which cells attach proteins to their surface
- List some consequences of hemolytic anaemia.
Anaemia Erythroid hyperplasia Increased folate demand Susceptibility to parvovirus B19 infection Propensity to gallstones Increased risk of iron overload Increased risk of osteoporosis
- Why is parvovirus B19 infection dangerous in patients with haemolytic anaemia?
It infects erythroid cells in the bone marrow and arrests their maturation
If this happens in someone with shortened red cell survival, it can cause a
dramatic drop in Hb (aplastic crisis)
NOTE: this can be identified by observing a low reticulocyte count
- Why do people with hemolytic anemia have an increased risk of developing gallstones?
Increased generation of bilirubin
- Co-inheritance of which condition with HA could further increase the risk of gallstones?
Gilbert’s syndrome
- Describe the genetic cause of Gilbert’s syndrome.
Caused by the UGT TA7/TA7 genotype
This means that in stead of the usual 6 TA repeats, there is an extra dinucleotide on each allele which is associated with reduced transcription of UGT 1A1 and, consequently, reduced production of enzyme in the liver and less efficient bilirubin conjugation
- Why is there an increased risk of iron overload with haemolytic anaemia?
Increased intestinal iron absorption (also due to transfusions)
- List some clinical features of haemolytic anaemia.
Pallor Jaundice Splenomegaly Family history Pigmenturia
- List some laboratory features of haemolytic anaemia.
Anaemia Increased reticulocytes Polychromasia Increased LDH Increased bilirubin Reduced/absent haptoglobins Haemoglobinuria Haemosiderinuria
- What is polychromasia?
Red cells take up both eosinophilic and basophilic dye giving them a bluish appearance – this is due to the presence of reticulocytes
- What is increased LDH a marker of?
LDH is an enzyme found in high concentrations within red cells
Increased LDH suggests intravascular haemolysis
- What are haptoglobins? What is the significance of reduced haptoglobins?
Haptoglobins are proteins in the bloodstream that bind to and remove free haemoglobin from the bloodstream
Low haptoglobins suggests that there is a lot of free haemoglobin in the bloodstream
- Which stains are used for haemosiderinaemia?
Perl’s stain
Prussian blue stain
- What does the presence of haemoglobinuria and haemosiderinaemia imply?
Intravascular haemolysis
- The red cell lipid membrane rests on a cytoskeleton. What is this cytoskeleton made up of?
Spectrin
- List some proteins that link the lipid bilayer to the cytoskeleton.
Band 3
Ankyrin-1
GPI
- What is the difference between vertical interaction and horizontal interaction with regards to the red cell membrane?
Vertical – between proteins that link the lipid bilayer to the cytoskeleton (band 3, protein 4.2, ANKYRIN, beta SPECTRIN)
Horizontal – mainly involving alpha and beta spectrin (also protein 4.1)
- Describe the inheritance of hereditary spherocytosis.
75% family history (autosomal dominant)
25% de novo mutations
NOTE: this is the most common defect of the red cell cytoskeleton
- What is the hall mark of red cells in hereditary spherocytosis?
Osmotic fragility – red cells show increases sensitivity to lysis in hypotonic saline
- What is another test for hereditary spherocytosis?
Reduced binding to eosin 5-maleimide (dye)
This is shown by flow cytometry
- Describe the appearance of the blood film in hereditary spherocytosis.
The cells lack a central area of pallor because they have lost the biconcave shape
The cells are small and more densely stained
There may be polychromatic cells (due to the presence of a young red cell population)
- What is hereditary eliptocytosis?
The carrier state for eliptocytosis
- Outline the blood film and FBC features of eliptocytosis.
The red cells are elliptical but there is no polychromasia and the blood count is likely to be normal because there is little haemolysis
- What is the homozygous form of eliptocytosis called?
Hereditary pyropoikilocytosis
- Describe the appearance of the blood film in eliptocytosis.
Fragmentation of red cells and a lot of variation in the shape of red cells (poikilocytosis)
It can cause severe haemolytic anaemia
- Describe the inheritance pattern of G6PD deficiency.
X-linked recessive
- Outline the importance of G6PD in the red cell.
G6PD catalyses the first step in the pentose phosphate pathway
This reaction generates NADPH which is required to maintain intracellular glutathione
Glutathione protects red cells against oxidative stress
A lack of G6PD, means that red cells are at increased risk of oxidative damage
- List the possible clinical effects of G6PD deficiency.
Neonatal jaundice
Acute haemolysis
Chronic haemolytic anaemia (rare)
- List some triggers for haemolysis in G6PD deficiency.
Drugs (antimalarials, antibiotics, dapsone, vitamin K)
Infections
Fava beans
Naphthalene mothballs
- Describe the appearance of the blood film in G6PD deficiency during acute haemolysis.
Contracted cells
Nucleated red cells
Bite cells
Hemighosts (Hb retracted to one side of the cell)
- What is a Heinz body? What is it suggestive of?
Denatured haemoglobin
Suggestive of oxidative haemolysis
- Which stain is used to look for Heinz bodies?
Methylviolet
- List some other key metabolic pathways in red cells.
Embden-Meyerhof Hexose monophosphate shunt Rapoport-Luebering shuttle Nucleotide metabolism Glutathione biosynthesis Cytochrome b5 reductase
- What is the role of pyruvate kinase in red cells?
Part of the glycolytic pathway
- What is a characteristic blood film feature of pyruvate kinase deficiency?
Echinocytes – red cells with a lot of short projections
NOTE: as the cells decrease in size due to dehydration, the cells will resemble spherocytes. The number of echinocytes usually increases post-splenectomy
- Describe how pyrimidine 5-nucleotidase deficiency leads to haemolytic anaemia.
Defect in nucleotide metabolism
Pyrimidine nucleotides are toxic to the cell but the cell must recycle purines
This means that red cells have a mechanism for selectively eliminating pyrimidines – this is dependent on pyrimidine 5-nucleotidase
Deficiency of pyrimidine 5-nucleotidase leads to an accumulation of toxic pyrimidines
- What is a characteristic blood film feature of pyrimidine 5-nucleotidase deficiency?
Basophilic stippling
NOTE: this is also seen in lead poisoning because lead inhibits pyrimidine 5-nucleotidase
- What are Ham’s test and flow cytometry for GPI-linked proteins used for?
Paroxysmal nocturnal haemoglobinuria
NOTE: Ham’s test looks at the sensitivity of red cells to lysis by acidified serum
- What investigations are used for malaria?
Thick and thin blood film
duces a Heinz body haemolytic anaemia
- Outline the principles of management of haemolytic anaemia.
Folic acid supplementation
Avoidance of triggers in G6PD deficiency
Blood transfusions/exchange
Immunisations against blood-borne viruses
Monitor for chronic complications (e.g. gallstones)
Splenectomy if needed
- List some indications for splenectomy related to haemolytic anaemia.
Pyruvate kinase deficiency Hereditary spherocytosis Severe eliptocytosis/pyropoikilocytosis Thalassemia syndromes Autoimmune haemolytic anaemia
- What is the main risk of splenectomy?
Overwhelming sepsis due to susceptibility to capsulated bacteria (e.g. pneumococcus)
NOTE: risk can be reduced by using penicillin prophylaxis and immunisations
- List some specific criteria for splenectomy.
Transfusion dependence Growth delay Physical limitation Hypersplenism (where it causes pooling and physical symptoms) Age > 3 years and < 10 years
- What is Haemoglobin Hammersmith?
Severe unstable haemoglobin variant that produces a Heinz body haemolytic anaemia
