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Flashcards in Haemolytic Anaemia Deck (51)
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What is haemolytic anaemia? 

Anaemia due to shortened RBC survival 




  •  Reticulocytosis
  • Unconjugated hyperbilirubinaemia 
  • Raised LDH (lactate dehydrogenase) 




Describe the normal RBC lifecycle 

  • RBC production (in bone marrow) 
    • Kidneys will produce EPO which signals for RBC production 
    • Requires B12, folate, globin chains, protoporphyrins 
  • Circulating RBCs 
    • 120 days 
  • Senescent RBCs 
    • As they age they will accumulate changes on their RBC membrane, recognised by liver + spleen (removal of these cells) 


What are the metabolic pathways which occur in a mature RBC? 

  • Glycolytic pathway 
    • ATP produced in RBCs through anaerobic glycolysis 
  • Hexose-monosphosphate pathway 
    • Required to produce NADPH for reduced glutathione (GSH)  production (protects from oxidative damage) 
  • Rapoport Luebering shunt/ pathway 
    • Involved in producing 2,3 BPG (biphosphoglycerate) 


What metabolic pathway produces 2,3 BPG (biphosphoglycerate) and what is its role? 

  • Produced by the Rapoport Luebering shunt 
  • Binds to haemoglobin reducing its affinity for oxygen 


How does the body compesate for haemolysis? 

  • The bone marrow will compensate through increased RBC production 
  • Increased young cells in circulation 
    • + Reticulocytosis 
    • - Nucleated RBCs 


What is the difference between compensated haemolysis and incompletely compensated haemolysis? 

Compensated haemolysis = RBC production able to compensate for decreased RBC lifespain 

Incompletely compensated haemolysis = RBC production unable to keep up with decreased RBC life span (decreased Hb) 


What are the clinical findings of haemolytic anaemia? 

  • Jaundice 
    • Breakdown of RBC (unconjugated bilirubin) 
  • Pallor/fatigue 
  • Splenomegaly 
  • Dark urine 
  • Haemolytic crisis (increased anaemia and jaundice with infections and precipitants) 
  • Aplastic crisis (anaemia, reticulocytopenia, parvovirus infection)  


What is an Aplastic crisis? 

  • When the body does not make enough new red blood cells to replace the ones already in the blood. 
  • You get anaemia and reticulocytopenia 
  • Can occur in parvovirus infection where it can trigger acute cessation of RBC production 


What are chronic clinical findings of haemolytic anaemia? 

  • Gallstones (pigment) (NOT CHOLSTEROL) 
  • Splenomegaly 
  • Leg ulcers (due to nitric oxide scavenging from free Hb) 
  • Folate deficiency (increased use to make more RBC) 


What are the laboratory findings of haemolytic anaemia? 

  • Normal/ low Hb 
  • Increased reticulocyte count 
  • Increased unconjugated bilirubin 
  • Increased LDH (lactate dehydrogenase) 
    • → released from haemolysed RBCs 
  • Low serum haptoglobin 
    • → protein binding free Hb 
  • Increased urobilinogen 
  • Increased urinary haemosiderin 
  • Abnormal blood film 


What does a blood film look like in haemolytic anaemia? 

  • Reticulocytes 
  • Polychromasia (many immature RBCs) 
  • Nucleated RBCs 


How can haemolytic anaemia be classified? 

  • Inheritance 
    • Congenital 
    • Acquired 
  • Site of RBC destruction 
    • Intravascular 
    • Extravascular 
  • Origin of RBC damage 
    • Intrinsic 
    • Extrinsic 


Give examples of inherited congenital anaemia 

  • Congenital/ Inherited 
    • Membrane disorders (Spherocytosis, Elliptocytosis) 
    • Enzyme disorders (G6PD def, PK deficiency) 
    • Hb Disorders (Sickle Cell Anaemia, Thalassaemia) 
  • Acquired 
    • Immune (auto-immune haemolysis) 
    • Drugs 
    • Mechanical (leaking heart valves) 
    • Infections 
    • Burns 
    • Microangiopathic (high BP causes red cell fragmentation) 


How is a RBC broken down in extravascular haemolysis? 

Extravascular haemolysis 

  1. Macrophage of reticuloendothelial system will break down RBC 
  2. RBC will be broken down into (globin, iron and protoporphyrin) 
  3. Globin is broken down to amino acids, iron binds to transferrin and transported to liver, protoporphyrin broken down to bilirubin and released to blood (unconjugated) where it is further broken down in liver and excreted in the urine 


How is a RBC broken down in intravascular haemolysis? 

  • RBC will not be systematically broken down but Hb will be released as free Hb into blood + urine 


Describe the normal RBC membrane structure 

  • Lipid bilayer is anchored to the cytoskeleton by a number of different proteins 
  • Mutations in proteins affecting the anchoring of lipid bilayer to cytoskeleton will affect membrane stabillity 


What are the two inherited membrane disorders which cause haemolytic anaemia? 

  • Hereditary spherocytosis 
  • Hereditary elliptocytosis 


What is hereditary spherocytosis? 

Defects in vertical interaction between lipid bilayer and cytoskeleton 

  • Spectrin
  • Band 3
  • Protein 4.2
  • Ankyrin


What is the effect of hereditary spherocytosis? 

In what form is this inherited? 


  • Decreased membrane deformabillity (deformation required to fit through capillaries)
  • Inherited in autosomal dominant fashion 


What does the blood film look like on an individual with hereditary spherocytosis? 

  • Rounder more spherical RBCs 
  • Absence of ring of central pallor 


What are the clinical features of hereditary spherocytosis? 

  • Asymptomatic to severe haemolysis 
  • Neonatal jaundice 
  • Jaundice, splenomegaly, pigment gallstones 
  • Reduced eosin 5-maleimide (EMA 
    • usually binds band 3 membrane protein 
  • Posotive family history 
  • Negative direct antibody test 


How do we manage hereditary spherocytosis? 

  • Monitor 
  • Folic acid (avoids limitations of RBC production) 
  • Transfusion (common following parvovirus) 
  • Splenectomy 


What is hereditary elliptocytosis? 

Defects in proteins involved in HORIZONTAL interactions between lipid bilayer and cytoskeleton 

  • Protein 4.1
  • Glycophorin C
  • Spectrin (HPP)


What is the role of the hexose monophosphate shunt? 

Protects RBCS from oxidative stress by maintaining GSH in the reduced form via NADPH 


What can be the effect of oxidative stress on RBCs? 

  • Oxidant radicals oxidise Hb
  • This will denature and aggregate and cause formation of Heinz bodies (common in G6PD)
    • Heinz bodies (inclusions within RBCs composed of denatured Hb) 
  • Oxidised membrane protein = reduced RBC deformabillity 


Describe the inheritance pattern of glucose-6-phosphate dehdyrogenase deficiency (G6PD)

  • Hereditary X-linked disorder 
    • Females can display symptoms due to X-inactivation 
  • Affects the hexose monophosphate shunt 


What are some oxidative precipitants? 

(These can be avoided in G6PD deficiency to prevent symptoms) 

  • Infections (obviously harder to avoid)
  • Fava/ broad beans
  • Many drugs
    • Dapsone
    • Nitrofurantoin
    • Ciprofloxacin
    • Primaquine


What are features of G6PD deficiency? 

  • Oxidative haemolysis 
  • Film 
    • Bite cells 
    • Blister and ghost cells 
    • Heinz bodies 
  • Reduced G6PD activity on enzyme assay 
    • May be falsely normal if reticulocytosis 


Why would G6PD activity on an enzyme assay be falsely normal if there is reticulocytosis? 

Reticulocytes have high enzyme levels 


What is the inheritance pattern of pyruvate kinase deficiency? 


  • Autosomal recessive causing chronic haemolytic anaemia 
    • Mild to transfusion dependant 
    • Improves with splenectomy 

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