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Molecular Basis Of Disease/ Microbiology And Immunology > Haemolytic Anaemia > Flashcards

Haemolytic Anaemia Flashcards

1
Q

What is haemolytic anaemia?

A

Anaemia due to shortened RBC survival

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2
Q

How long do RBCs circle for?

A

Approx 120 days

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3
Q

Where are senescent RBCs removed?

A

Reticular endothelial system of the liver and spleen

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4
Q

How long do haemolytic anaemia RBCs survive for?

A

30-80 days

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5
Q

What does the shortened red cell survival mean for the blood?

A

Increased RBC production and increased young cells in circulation -> reticulocytosis

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6
Q

What is incomplete compensated haemolysis?

A

When RBC production is unable to keep up with decreased RBC lifespan -> decreased haemoglobin

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7
Q

What are the symptoms of haemolytic anaemia?

A 
Jaundice
Pallor
Fatigue
Splenomegaly
Gallstones
Leg ulcers
Folate deficiency line folate use in RBC production
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8
Q

What would a peripheral blood film show in haemolytic anaemia?

A

Polychromatophilia
Nucleated RBC
Thrombocytosis
Neutrophilia with left shift

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9
Q

What happens to the bone marrow in haemolytic anaemias?

A

Erythroid hyperplasia

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10
Q

What does haemolytic anaemia cause in the bone marrow?

A

Increase in unconjugated bilirubin, lactate dehydrogenase, urobilinogen and urinary haemosiderin

Decrease serum haploglobin protein that binds free haemoglobin

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11
Q

What does erythroid hyperplasia cause?

A

Normoblastic reactions
Reversal of myeloid: erythroid ratio
Variable reticulocytosis

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12
Q

What are the general classifications of haemolytic anaemia?

A

Inheritance
Site of RBC destruction
Origin of RBC damage

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13
Q

What are the inheritance classifications of haemolytic anaemia?

A

Hereditary

Acquired

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14
Q

What are the site of RBC destruction classifications of haemolytic anaemia?

A

Intravascular

Extravascular

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15
Q

What are the origin of RBC damage classifications of haemolytic anaemia?

A

Intrinsic

Extrinsic

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16
Q

What is an example of hereditary haemolytic anaemia?

A

Hereditary spherocytosis

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17
Q

What is an example of acquired haemolytic anaemia?

A

Immune haemolytic anaemia

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18
Q

What is an example of intravascular haemolytic anaemia?

A

Haemolytic transfusion reaction

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19
Q

What is an example of extravascular haemolytic anaemia?

A

Autoimmune haemolysis

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20
Q

What is an example of intrinsic haemolytic anaemia?

A

G6PD deficiency

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21
Q

What is an example of extrinsic haemolytic anaemia?

A

Delayed haemolytic transfusion reaction

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22
Q

What are examples of membrane defect intrinsic haemolytic anaemia?

A

Hereditary spherocytosis, elliptocytosis or pyroporkilocytosis

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23
Q

What are examples of enzyme defect intrinsic haemolytic anaemia?

A

G6PD, PK

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24
Q

What are examples of haemoglobin defect intrinsic haemolytic anaemia?

A

Sickle cell

Thalassaemias

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25
Q

What are examples of immune mediated extrinsic haemolytic anaemia?

A

Autoimmune (warm, cold, drug induced)

Alloimmune (HDN, haemolytic transfusion reaction)

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26
Q

What are examples of non-immune extrinsic haemolytic anaemia?

A

Red cell fragmentation syndromes
Drugs
Infections
Hypersplenism

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27
Q

What normally happens when RBCs breakdown?

A

Macrophages break them down and they go to the liver to be excreted from the kidney

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28
Q

What happens in haemolytic anaemia for RBC breakdown?

A

RBCs lyse in veins, which leads to haemoglobinurea

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29
Q

Which integral proteins are normally found in a cell membrane?

A

Glycophorin A and C

Bard 3

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30
Q

What are the cytoskeletal proteins found in the RBC membrane?

A

Ankyrin
Alpha and beta spectrin
Protein 4.2 and 4.1
Actin

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31
Q

What type of disease is hereditary spherocytosis?

A

Autosomal dominant

32
Q

What is hereditary spherocytosis caused by?

A

Defects in spectrin, ankyrin and protein 4.2

33
Q

How is hereditary spherocytosis managed?

A

Monitoring
Folic acid
Transfusion
Splenectomy

34
Q

What do hereditary spherocytotic cells look like?

A

Deeply stained with no central pallor

35
Q

What causes hereditary elliptocytosis?

A

Defects in alpha or beta spectrin
Or
Loss of interaction between ankyrin and spectrin or 4.1

36
Q

What do hereditary elliptocytotic cells look like?

A

Elongated RBCs with no pointy ends

37
Q

What are the clinical features of hereditary spherocytosis?

A

Neonatal jaundice
Splenomegaly
Pigment gallstones

38
Q

What tests for hereditary spherocytosis?

A

Flow cytometry showing reduced eosin-5-maleimide binding

39
Q

What happens if there is asymptomatic hereditary spherocytosis?

A

Severe haemolysis

40
Q

What is the role of the HMP shunt in the pentose phosphate pathway?

A

Generates NADPH and reduced gluthathione

Protects the cell from oxidative stress

41
Q

What genetic type of disease is a glucose-6-phosphate dehydrogenase deficiency?

42
Q

What is the cell morphology in G6P dehydrogenase deficiency?

A

Bite cells
Blister cells and ghost cells
Heinz bodies

43
Q

What are the effects of a G6P dehydrogenase deficiency?

A

Oxidative stress

-> oxidation of Hb by oxidant radicals and oxidised membrane proteins

44
Q

What does Hb oxidation by oxidant radicals result in?

A

Denatured Hb aggregates and forms heinz bodies that bind to the membrane

45
Q

What do oxidised membrane proteins do?

A

Reduced RBC deformability

46
Q

What are patients with G6P dehydrogenase deficiency advised to do (and why)?

A

Avoid oxidative drugs because they can cause oxidative stress

47
Q

What do defects in pyruvate kinase affect?

A

RBC shape and deformability and the intracellular cation core

48
Q

What are the general issues in thalassaemias?

A

Defect in the rate of synthesis of alpha or beta globin chain

49
Q

Why is it an issue if there’s a defect in the alpha or beta globin chain production?

A

Excess unpaired globin chains are unstable -> heterogenous genetic disorders -> ineffective erythropoeisis

50
Q

What are the types of thalassaemia?

A 
Hydrop foetalis
Beta thalassemia major
Beta Thalassaemia intermedia
Beta Thalassaemia minor
Alpha thalassaemias
Alpha Thalassaemia minor
51
Q

What are the clinical features of beta thalassaemia major?

A 
Severe anaemia
Progressive hepatosplenomegaly
Facial bone abnormalities
Mild jaundice
Intermittent infections
52
Q

What are the peripheral blood cell symptoms of beta thalassaemia major?

A 
Microcytic hypochromic cells 
Anisopoikilocytosis
Target cells
Nucleated RBCs
Teardrop cells
53
Q

What are the peripheral blood count symptoms of beta thalassaemia major?

A

Decreased MCV, MCH, MCHC

54
Q

What is thalassaemia intermedia?

A

Disorder with a clinical manifestation between thalassaemia major and minor

55
Q

What are the signs of beta thalassaemia intermedia?

A

Transfusion independent
Diverse clinical phenotype
Varying symptoms
Increased bilirubin level

56
Q

How do you diagnose thalassaemia intermedia?

A

Largely clinically

57
Q

What are the symptoms of thalassaemia minor?

A

Asymptomatic

58
Q

What is thalassaemia minor often confused with?

A

Iron deficiency

59
Q

How do you diagnose thalassaemia minor?

A

Finding that HbA2 is increased in beta thalassaemia

60
Q

What causes Hb barts hydrops syndromes?

A

Deletion of all four globin genes

61
Q

How long do patients with Hb barts hydrops syndrome live for?

A

They don’t

62
Q

What causes HbH disease?

A

3/4 alpha globin chains deleted

63
Q

Where is HbH common?

64
Q

What are the clinical features of HbH disease?

A

Hepatosplenomegaly

65
Q

What do you use to diagnose HbH disease?

A

Electrophoresis

66
Q

What are the two types of alpha thalassaemias?

A

HbH disease and Hb barts hydrops syndrome

67
Q

What are the features of blood cells in HbH disease?

A

Hypochromic microcytic
Poikilocytosis
Polychromasia
Target cells

68
Q

What are the features of alpha thalassaemia minor?

A

Normal or mild HA

MCV and MCH low

69
Q

What does ‘sickle cell disease’ refer to?

A

All diseases as a result of inherited HbS

70
Q

What is HbS caused by?

A

Single nucleotide substitution

71
Q

What are the clinical symptoms of sickle cell disease?

A

Painful crises
Aplastic crisis
Frequent Infections

72
Q

Why do sickle cell patients have frequent infections?

A

Hyposplenism

73
Q

What are the clinical symptoms of acute sickling in sickle cell anaemia?

A

Chest syndrome
Splenic sequestration
Stroke

74
Q

What are the clinical symptoms of chronic sickling in sickle cell anaemia?

A

Renal failure

Avascular bone necrosis

75
Q

What are the sickle cell signs in the lab?

A 
Anaemia (Hb 60-90) 
Reticulocytosis
Increased NRBC
Raised bilirubin
Low creatine
76
Q

How do you confirm a sickle cell diagnosis?

A

Solubility test:

  • Expose blood to a reducing agent
  • HbS precipitated

Molecular Basis Of Disease/ Microbiology And Immunology (57 decks)

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