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Year 2 MCD Haematology > Haemoglobin and Thalassaemia > Flashcards

Haemoglobin and Thalassaemia Flashcards

1
Q

Explain the Function of Haemoglobin

A

To transport Oxygen from lungs to tissues, Co2 from tissues to lungs

Determines shape of erythrocytes

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2
Q

Explain the overalls structure of Haemoglobin

A

2 parts:

  1. Haem molecule with centrally bound iron
  2. Globin chains (4 per Hb molecule, mostly 2 each (2a2ß, 2a2x etc.)

Usually form spheres

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3
Q

Where is Haem synthesised?

What is required for this?

A

Haem is synthesised in the Mitochondrium

It requires Iron (ususally Fe2+) and protoprophyrin that together form feroprotoprophyrin

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4
Q

Explain the genetic origin of the globin chain

A

Various combinations of two chains possible to give rise to different form of Haemoglobin but overall

Two clusters

  1. Beta-cluster (in chormosome 11) –> loci for ß, gamma, delta, epsilon chains
  2. Alpha cluster (on chromosome 16) –> loci for alpha and zeta chains
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5
Q

Explain the different presence of Haemoglobin chains in different stages of life

A
  1. Up to 7 Weeks–> Zeta chains present , zeta Hb
  2. Pre-birth (up to 6 month after birth) –> HbF consisting of 2a2gamma
  3. In adulthood (and from 6month after birth on)
    • mainly HbA--> 2a2ß but also
    • HbF<0.8%
    • HbA2 (2a2delta) <3%
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6
Q

Why do symptoms of ß-thalassaemia and sickle cell disease normally occur after 3-6 month of life?

A

Because that is the time when ß-globin chains are fist produced (where defects are implemented)

Before HbF is more present (no ß chains)

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7
Q

What does complete alpha thalassaemia normally result in (all 4 loci)?

A

It normally results in fetal death

–> used from 7 Weeks of fetal development onwards–> fatal if not working at all

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8
Q

What is the secondary and tertiary structure of haemoglobin?

A

Secondary: Mainly Helical (75%)

Tertiary: sperical shape wiht haem pockets

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9
Q

Explain the ODC

A
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10
Q

What is P50 in the Oxygen Dissociation curve?

What is it used for?

A

P 50= (partial pressure of O2 at which Hb is half saturated with O2) 26.6mmHg

–> used to compare the different binding affinities of Hb chains

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11
Q

What is thalassaemia?

A

Defects in globin chain synthesis

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12
Q

What different types of Haemoglobinopathies are there?

A

Structural variants of haemoglobin

or

Defects in globin chain synthesis (thalassaemia)

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13
Q

How can you classify thalassaemia?

A
  1. Globin type affected
    • alpha thalassaemia
    • beta thalassaemia
  2. Clinical severity
    • minor “trait”–> usually asymptomatic carrier
    • intermedia –> non-transfusion dependant
    • major –> diffusion dependant
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14
Q

How many genes encode for the ß-globin chain?

How does this effect thalassaemia?

A

There are 2 genes coding for thalassaemia

  • if one is affected: carrier, traid thalassaemia
  • if both are affected: symptomatic thalassaemia
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15
Q

How does the Intermedia thalassaemia differ from the major thalassaemia?

A

There are many many mutations in the ß globin chain genes with different severities

In Major: two defect genes with severe mutation are inherided

In intermdia: two defect genes with either less severe mutation or one with severe, one with less severe mutation are inherited

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16
Q

What is thalassaemia?

How is it inherited

A

Single gene defect in the ß globin chains causing a reduced or absent production of ß-globin

It is an autosomal recessive condition

17
Q

How would you diagnose someone you’d suspect to have thalassaemia?

A
  1. FBC
    • Microcytic Hypochromic
    • Increased RBCs relative to Hb
  2. Film
    • Target cells,
    • poikilocytosis
    • no anisocytosis
  3. Hb EPS / HPLC
    1. in a-thal: Normal HbA2 & HbF, +/- HbH (not enough for diagnosis)
    2. in b-thal: Raised HbA2 & raised HbF
  4. Globin Chain synthesis/ DNA studies
    1. Genetic analysis for β-thalassaemia mutations and XmnI polymorphism (in β-thalassaemias) –> just in some cases
    2. α-thalassaemia genotype (in all cases)
18
Q

What is the clinical presentation of someone with thalassaemia major?

A
  • Severe anaemia usually presenting after 4 months
  • Hepatosplenomegaly —> due to extra-medullar haematoppisis (also can be seen in enlarged mandible + forehead if not managed)
  • Blood film shows gross hypochromia, poikilocytosis and many NRBCs
  • Bone marrow - erythroid hyperplasia
19
Q

What are the signs and symptoms of someone having ß thalassaemia?

A
  • Chronic fatigue (anaemia)
  • Jaundice (increased haemolysis)
  • Delay in growth and puberty
  • Skeletal deformity
  • Splenomegaly
  • Iron overload
20
Q

What are the main complications in someone with thalassaemia?

A
  • Cholelithiasis and biliary sepsis –> Infections
  • Cardiac failure (main cause of death)
  • Endocrinopathies –> due to occlusion of endocrine glands
  • Liver failure
21
Q

How do you treat someone with Thalassaemia Major?

A

Main Ways

  1. Regular blood transfusions (every 2-4 weeks)
    • ideally with phenotyped red cells
  2. Iron chelation therapy (to prevent iron overload)
    • Start after 10-2 transfusions or when serum ferritin >1000 mcg/l
  • Splenectomy
  • Supportive medical care (e.g. vaccinations)
  • Hormone therapy (in endocrine problems)
  • Hydroxyurea to boost HbF
  • Bone marrow transplant (in severe cases, balance risk to profit)
22
Q

Explain the relationship between infections and thalassaemia

A

Patients are more prone to infections because

  1. •Yersinia

•Other Gram negative sepsis thrive in iron-rich environents

  1. Splenectomy –> reduces immune system
23
Q

How are the iron levels in a patient measured?

A

Serum ferritin

Liver biopsy (rarely done right now)

Cardiac or hepatic T2 MRI

24
Q

Which drugs might be used as iron chelation therapy?

What are their advantages and disadvantages?

A
25
Q

What is the HbH Disease?

A

It is a intermidia form of a thalasssemia with three alpha chians mutated

26
Q

How would be blood film of someone with ß-Thalassemia trait look like?

A
  • Microcytosis
  • hypochromia and
  • occasional cells showing basophillic stippling
27
Q

How would the blood film in someone wiht ß-Thalasemia major look like?

A

The peripheral blood film will show

  • extreme hypochromia
  • microcytosis and
  • poikilocytosis

Might show

  • Howell Jolly bodies and
  • nucleated RBC’s will be present as a result of splenectophy and a hyper plastic bone marrow.

+ Inclusion bodies

  1. , Alpha globin precipitates and pappenheimer bodies

Year 2 MCD Haematology (14 decks)

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