Describe what is meant by haemolytic anaemia and how the body compensates for this condition.
- Anaemia caused by shortened RBC survival - i.e. 30-80 days.
- Normal lifespan is 120 days.
- Occurs when incompletely compensated haemolysis - rate of RBC production unable to keep up with reduced RBC lifespan.
- Increased haemolysis - reticulocytosis and nucleated RBCs in blood film.
What are the 2 main metabolic pathways used in erythrocytes?
- Glycolytic pathway
- Hexose-monophosphate shunt
Describe the main clinical findings in haemolytic anaemia.
- Dark urine
Haemolytic crises - increased anaemia and jaundice with infections/precipitants.
Aplastic crises - anaemia, reticulocytopenia with parvovirus infection.
Describe the main findings in chronic haemolysis.
- Gallstones - pigment
- Leg ulcers
- Folate deficiency - increased use in RBC production
What are the main findings on a blood film in haemolytic anaemia?
- Nucleated RBCs
- Immature RBCs in blood increase MCV
- Polychromasia in reticulocytes - bluish colour
Describe the main inherited conditions that cause haemolytic anaemia.
- Hereditary spherocytosis
- Hereditary elliptocytosis
- G6PD deficiency
- Pyruvate kinase deficiency
- Sickle cell anaemia (SCA)
Name 5 acquired causes of haemolytic anaemia.
- Infections - e.g. malaria
- Paroxysmal nocturnal hemoglobinuria
Describe the cellular membrane defects seen in hereditary spherocytosis and elliptocytosis.
- Hereditary spherocytosis - defects in vertical membrane interaction: spectrin, band 3, protein 4.2, ankyrin.
- Hereditary elliptocytosis - defects in horizontal membrane interaction: protein 4.1, glycophorin C.
Outline the clinical features and signs/symptoms of hereditary spherocytosis.
- 75% cases - autosomal dominant
- Defects in vertical interactions between lipid bilayer and membrane skeleton
- Decreased membrane deformability
- Bone marrow makes biconcave RBC, but as membrane is lost RBCs become spherical
- Neonatal jaundice
- Jaundice, splenomegaly, pigment gallstones
How is hereditary spherocytosis managed?
- Folic acid supplementation
What are Howell-Jolly bodies and when are they seen in a blood film?
- Remnants of nucleus - small purple spots seen inside RBCs
- Normally removed by the spleen
- Seen in splenectomised and hyposplenic patients
- Coeliac disease
What is hereditary pyropoikilocytosis (HPP)?
- Membrane disorder similar to severe hereditary elliptocytosis
- Severe haemolysis and anaemia
- Presents with spherocytes and elliptocytes
- Associated with defect in spectrin membrane protein
Outline the epidemiology, pathophysiology and clinical features of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Hereditary, X-linked disorder.
- Common in African, Asian, Mediterranean and Middle Eastern populations.
- Type A in Africans less severe, type B in Mediterraneans more severe.
- HMP shunt generates reduced glutathione, protecting the cell from oxidative stress.
- G6PD - lack of protection from oxidation.
- Oxidation of Hb to form Heinz bodies, oxidised membrane proteins - reduced deformability.
- Acute episodes induced by oxidative precipitants.
- Chronic haemolysis may develop.
Outline the pathophysiology and clinical features of pyruvate kinase deficiency.
- Autosomal recessive.
- Pyruvate kinase required to generate ATP and essential for membrane cation pumps.
- PK deficiency - defect in membrane deformability.
- Chronic anaemia - mild to transfusion dependency.
- Improves with splenectomy.
Outline the clinical features of beta thalassaemia.
- Imbalanced α and β globin chain production.
- Excess unpaired globin chains are unstable - precipitate and damage RBC and precursors.
- Ineffective erythropoiesis and haemolytic anaemia.
- β thalassaemia - reduced or absent production of β globin - depending on hetero/homozygous for faulty β0 allele.
- β thalassaemia major - 2 β0 alleles.
- β thalassaemia trait - 1 β0 allele.
Outline the epidemiology, pathophysiology and clinical features of sickle cell disease.
- Autosomal recessive.
- 1 faulty allele - sickle cell trait.
- Sickle cell trait protective against malaria - common in Sub-Saharan Africa, Middle East, India.
- 2 faulty alleles - sickle cell disease (SCD).
- Point mutation in beta globin gene - glutamic acid > valine at position 6.
- Insoluble Hb tetramer - polymerisation and crystallisation > sickle-shaped cells.
- Blockage of blood flow in spleen and brain - commonest cause of stroke in childhood.
Describe the 3 main features characteristic of haemolysis.