Red cell disorders

• Inherited membranopathies =

  Cytoskeleton protein loss

  • hereditary spherocytosis - small round RBC
  • hereditary elliptocytosis - cigar-shape

  Membrane transport dysfunction

  • hereditary ovalocytosis - egg
  • hereditary stomatocytosis - mouth
• Hereditary spherocytosis =

  Mutation of ANK1 gene for ankyrin on chromosome 8

  Most common - AD mutations

  Mild form anaemia with reticulocytosis + compensated haemolysis

  Presentation = splenomegaly + gall stones

  Tx = splenectomy - need vaccine pre and post
• Hereditary ovalocytosis =

  Mutation of SLC4A1 gene for ion exchanger protein - band 3 on chromosome 17

  Protection against malaria

  Pseudo-hyperkalemia - leakage of K+ from RBC
• Hereditary elliptocytosis =

  Mutation of SPTA1 gene for spectrin on chromosome 1

  Protection against malaria
• Hereditary stomatocytosis =

  Mutation of PIEZO1 gene for proteins of ion channel on chromosome 16

  AD mutation

  Feature - pseudohyperkalemia

  Very rare
• Haemoglobinopathies =

  A) quality

  B) quantity

  C) HbS HbC

  D) sickling + haemolysis

  E) reduced production

  F) sickle cell

  G) thalassemia alpha and beta

  
• Beta thalassemia =

  two genes on chromosome 11 - produces beta subunit of haemoglobin
• Alpha thalassemia =

  four genes on chromosome 16 - produces alpha subunit of haemoglobin
• G6PD deficiency =

  • most common metabolic disorders of RBCs
  • protection from malaria
  • X-chromosome linked hereditary transmission
  • Acute haemolytic episodes during oxidative stress - fava beans
  • Primaquine can cause haemolytic crisis - needs testing
  • Glutathione is deficient - limited protection against reactive oxygen species
• Iron chelation treatment =

  1. spontaneous iron overload - due to low hepcidin in anaemia. Enhanced absorption of iron in bowels
  2. iron overload from regular transfusions

  Most dangerous in heart failure. Needs regular monitoring in organs

  Ferriscan - MRI looking for Fe deposits in heart or liver
• Symptoms of thalassaemia =

  Jaundice

  Fatigue

  Facial bone deformities

  severe anaemia
• Diagnosis of thalassemia =

  FBC

  genetic testing
• Alpha - thalassaemia =

  Inheritance = autosomal recessive

  4 genes - 2 defective = trait

  3 defective = haemoglobin H disease

  Microcytic anaemia

  Haemolysis

  Splenomegaly

  4 defective = incompatible with life

  Tx =

  blood transfusions + stem cell transplant
• Beta - thalassemia =

  Inheritance = autosomal recessive

  1 defective = trait - asymptomatic

  2 defective = major

  Severe symptomatic anaemia at 3-9 months

  Facial bone deformities
• Complications of B-thalassemia =

  Cardiomyopathy

  Acute sepsis

  Liver cirrhosis

  Endocrine dysfunction

  Diabetes
• Thalassaemia shows a microcytic anaemia