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Flashcards in Haemolytic Anaemia Deck (51)
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1

What is haemolytic anaemia? 

Anaemia due to shortened RBC survival 

 

 

MAIN BROAD FEATURES 

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

 

 

2

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) 

3

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) 

4

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 

5

How does the body compesate for haemolysis? 

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

6

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) 

7

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)  

8

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 

9

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) 

10

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 

11

What does a blood film look like in haemolytic anaemia? 

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

12

How can haemolytic anaemia be classified? 

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

13

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) 

14

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 

15

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 

16

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 

17

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

  • Hereditary spherocytosis 
  • Hereditary elliptocytosis 

18

What is hereditary spherocytosis? 

Defects in vertical interaction between lipid bilayer and cytoskeleton 

  • Spectrin
  • Band 3
  • Protein 4.2
  • Ankyrin

19

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 

20

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

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

21

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 

22

How do we manage hereditary spherocytosis? 

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

23

What is hereditary elliptocytosis? 

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

  • Protein 4.1
  • Glycophorin C
  • Spectrin (HPP)

24

What is the role of the hexose monophosphate shunt? 

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

25

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 

26

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 

27

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

28

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 

29

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

Reticulocytes have high enzyme levels 

30

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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