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Systems: Haematology + Immunology > RBC: Congenital Anaemias > Flashcards

RBC: Congenital Anaemias Flashcards

1
Q

What is anaemia?

A

Reduction in red cells or their haemoglobin content?

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2
Q

What is the aetiology of anaemia?

A
  • Blood loss
  • Increased destruction
  • Lack of production
  • Defective production
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3
Q

What substances are essential for red cell production in marrow?

A
  • Iron
  • B12
  • Folic acid
  • Erythropoietin
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4
Q

Where does red cell breakdown occur?

A

Reticuloendothelial system by macrophages in the spleen, liver, lymph nodes, lungs etc.

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5
Q

What are the products of red cell breakdown?

A

Globin
-Amino acids reutilised

Haem

  • Iron reutilised
  • Haem converted to bilirubin (bound to albumin in the plasma, unconjugated)
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6
Q

What are the components of the erythrocyte?

A
  • Membrane
  • Enzymes
  • Haemoglobin
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7
Q

What types of genetic defects can cause congenital anaemias?

A

Genetic defects described

  • In red cell membrane
  • In metabolic pathways (Enzymes)
  • In haemoglobin
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8
Q

What do most genetic defects of RBC/haemoglobin result in?

A

Reduced RBC survival by haemolysis

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9
Q

How do carried states of congenital anaemias present?

A

Often silent: asymptomatic

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10
Q

What maintains the shape of RBC?

A

Skeletal proteins

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11
Q

What do defects in skeletal proteins leads to?

A

Increased cell destruction

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12
Q

How is hereditary spherocytosis inherited?

A

Most common form is autosomal dominant

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13
Q

What is the hereditary spherocytosis?

A

Defects in 5 different structural proteins described

  • Ankyrin
  • Alpha Spectrin
  • Beta Spectrin
  • Band 3
  • Protein 4.2
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14
Q

What is the pathogenesis of hereditary spherocytosis?

A
  • Red cells are spherical

- They are removed from the circulation by the RE system (extravascular)

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15
Q

How does hereditary spherocytosis present?

A
  • Anaemia
  • Jaundice (neonatal)
  • Splenomegaly
  • Pigment gallstones
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16
Q

How is hereditary spherocytosis treated?

A
  • Folic acid (increased requirements)
  • Transfusion
  • Splenectomy
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17
Q

Give examples of rare membrane disorders.

A
  • Hereditary Elliptocytosis
  • Hereditary Pyropoikilocytosis
  • South East Asian Ovalocytosis
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18
Q

What are 2 importance enzyme pathways in RBCs?

A

Glycolysis
-Provides energy

Pentose phosphate shunt
-Protects from oxidative stress

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19
Q

What is the most common red cell metabolism disorder?

A

Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency

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20
Q

What does Glucose 6 Phosphate Dehydrogenase (G6PD) do?

A

Protects red cell proteins (Haemoglobin) from oxidative damage

  • Produces NADPH - Vital for reduction of glutathione
  • Reduced glutathione scavenges and detoxifies reactive oxygen species
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21
Q

Why are there high rates of G6PD deficiency in malarial areas?

A

Confers protection against malaria

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22
Q

What is the inheritance of G6PD deficiency?

A

X linked

  • Affects males
  • Female carriers
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23
Q

What types of RBC do you get in G6PD deficiency?

A
  • Blister cells

- Bite cells

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24
Q

What is the clinical presentation of G6PD defiecency?

A

-Variable
-Neonatal Jaundice
Drug, broad bean or infection precipitated jaundice and anaemia (intravascular haemolysis, haemoglobinuria)
-Splenomegaly
-Pigment Gallstones

25
Q

What can trigger haemolysis in G6PD deficiency?

A
  • Infection/acute illness
  • Broad beans
  • Certain drugs
26
Q

Name an enzyme deficiency apart from G6PD deficiency.

A

Pyruvate kinase deficiency

27
Q

What is the pathogenesis of pyruvate kinase deficiency?

A
  • Reduction in ATP
  • Increase in 2-3DPG
  • Cells become rigid
28
Q

How does pyruvate kinase deficiency present?

A
  • Variable severity
  • Anaemia
  • Jaundice
  • Gallstones
29
Q

What is the structure of haemoglobin?

A

4 globin chains

  • 2 alpha
  • 2 beta

4 haem groups containing iron

30
Q

What is the function of haemoglobin?

A

Gas exchange

  • O2 to tissues
  • CO2 to lungs
31
Q

What causes a compensatory shift in the oxygen dissociation curve?

A
  • Acidosis
  • Increase DPG
  • Increased temperature
  • Increased CO2
32
Q

How does HbF affinity for oxygen compare to HbA?

A

It has a higher affinity for oxygen

33
Q

What is the normal composition of adult haemoglobin?

A

Haem molecule and

  • 2 alpha chains= 4 alpha genes (Chr16)
  • 2 beta chains= 2 beta genes (Chr11)
34
Q

What is the composition of haemoglobin in a normal adult?

A
  • Hb A (aa,BB) =97%
  • Hb A2 (aa,δδ) = 2%
  • Hb F (aaγγ) =1%
35
Q

What are haemoglobinopathies?

A

Inherited abnormalities of haemoglobin synthesis

36
Q

How can haemoglobinopathies occur?

A

Reduced or absent globin chain production
-Thalassaemia (alpha α, Beta β, delta δ, gamma γ)

Mutations leading to structurally abnormal globin chain
-HbS (Sickle cell ), HbC, HbD, HbE, HbO Arab……

37
Q

What is the inheritance of haemoflobinopathies?

A

Autosomal recessive inheritance

  • 1 in 4 chance of having affected child
  • 1 in 2 chance of being a carrier or “trait”
38
Q

What is the composition of Sickle cell haemoglobin (HbS)?

A

Haem molecule and:

  • 2 α chains
  • 2 β (sickle) chains
39
Q

What happens in Sicklce cell anaemia?

A
  • Normally RBCs take up and give up oxygen without chnageing shape
  • In Sickle cell anaemia, the cells become sickled in shape when they give up oxygen. This is irreversible
40
Q

What are the consequences of HbS polymerisation?

A
  • Red cell injury, cation loss and dehydration
  • Haemolysis
  • Endothelial activation
  • Promotion of inflammation
  • Coagulation activation
  • Dysregulation of vasomotor tone by vasodilator mediators (NO)
  • All leading to vaso-occlusion
41
Q

What are the clinical presentations of sickle cell disease?

A
  • Painful vaso-occlusive crisis (bone)
  • Chest crisis
  • Stroke
  • Increased infection risk due to hyposplenism
  • Chronic haemolytic anaemia (gallstones, aplastic crisis)
  • Sequestration crises *spleen, liver)
42
Q

What is the life expeactancy of sickle cell disease?

A

Median age of death

  • Males 42
  • Females 48

Childhood and perinatal mortality contribute to this reduction

43
Q

What is the treatment for a painful crisis in sickle cell disease?

A
  • Opiates ASAP for severe pain
  • Hydration
  • Oxygen
  • Consider antibiotic
  • Transfusion not routine
44
Q

How does a sickle cell chest crisis present?

A
  • Chest Pain
  • Fever
  • Worsening hypoxia
  • Infiltrates on CXRay
45
Q

How should a chest crisis in sickle cell disease be managed?

A
  • Respiratory Support
  • Antibiotics
  • IV Fluids
  • Analgaesia
  • Transfusion – top up or exchange, target HbS <30%
46
Q

What prophylactic treatment should those sickle cell disease receive?

A

Life long prophylaxis

  • Vaccination
  • Penicillin (and malarial) prophylaxis
  • Folic acid
47
Q

How should acute events be managed in sickle cell disease?

A
  • Hydration
  • Oxygenation
  • Prompt treatment of infection
  • Analgaesia (opiates or NSAIDs)
48
Q

What treatment is there for sickle cell disease?

A
  • Prophylaxis
  • Acute event management
  • Blood transfusion (beware of iron overloading)
  • Disease modifying drugs: hydroxycarbamide
  • Bone marrow transplantation reserved as a last resort
  • Gene therapy in the future?
49
Q

What is thalassaemia caused by?

A

Reduced or absent globin chains caused by mutations or deletion in alpha or beat genes

50
Q

What does chain imbalance cause?

A

Chronic haemolysis and anaemia

51
Q

What are the different types of thalassemia?

A
  • Homozygous alpha zero thalassaemia
  • Beta thalassaemia major
  • Non-transfusion dependent thalassaemia
  • Thalassemia minor
52
Q

What happens in homozygous alpha zero thalassaemia?

A
  • No alpha chains

- Hydrops Fetalis –incompatible with life

53
Q

What happens in beta thalassaemia major?

A
  • No beta chains

- Transfusion dependent anaemia

54
Q

What happens in thalassaemia minor?

A
  • ‘Trait’ or carrier state

- Hypochromic microcytic red cell indices

55
Q

How does beta thalassaemia major present?

A
  • Present at 3-6 months of age
  • Expansion of ineffective bone marrow
  • Bony deformities
  • Splenomegaly
  • Growth retardation
56
Q

What is the prognosis of beta thalassaemia major?

A

Life expectancy untreated or with irregular transfusions <10 years

57
Q

What is the treatment for beta thalassaemia major?

A

Chronic transfusion support - 4-6 weekly

  • Normal growth and development
  • BUT - Iron overload risk
  • Death in 2nd or 3rd decades due to heart/liver/endocrine failure if iron loading untreated

Iron chelation therapy

  • SC desferriozamin infusions or oral tablets
  • Good adherence= life expectancy >40 years

Bone marrow transplant
-Curative

58
Q

How do sideroblastic anaemias occur?

A

Defects in mitochondrial steps of haem synthesis

  • ALA synthase mutations
  • Hereditary (X-Linked)
  • Aquired - Myelodysplasia
59
Q

How do porphyrias occur?

A

Defects in cytoplasmic steps of haem synthesis

Systems: Haematology + Immunology (19 decks)

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