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Haematology > Haemoglobinopathies (Thalassaemia & Sickle Cell) > Flashcards

Haemoglobinopathies (Thalassaemia & Sickle Cell) Flashcards

1
Q

Describe haemoglobin structure

A

Tetramer with 4 haem groups (one attached to each globin)

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2
Q

Name the 4 different chains in the major forms of haemoglobin (HbA, HbA2, HbF)

A

•HbA 2 alpha chains and 2 beta chains α2β2
•HbA2 2 alpha and 2 delta chains α2δ2
•HbF 2 alpha and 2 gamma chains α2γ2

•In adults HbA is the major form present (~97%)
•In foetus HbF is the major form present

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3
Q

Describe how the form of Hb changes in early life and explain the clinical relevance of this

A

Prenatal/ foetus - HbF
Birth to ~6 months - Mix of HbA & HbF
~6 months onwards - HbA

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4
Q

Define haemoglobinopathy & state the two main types

A

Hereditary (monogenic, autosomal recessive) conditions affecting globin chain synthesis

1) Thalassaemia - decreased globin chain synthesis (quantity)
2) Sickle cell - abnormal globin chain (quality)

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5
Q

Define thalassaemia, state the two main types and describe the consequences

A
  • Thalassaemia - Reduced globin chain synthesis resulting in impaired haemoglobin production
  • Alpha thalassaemia; α chains affected
  • Beta thalassaemia; β chains affected
  • Inadequate Hb production => microcytic hypochromic anaemia
  • If severe => ineffective erythropoiesis & haemolysis
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6
Q

Describe the difference between alpha thalassaemia trait vs disease (HbH disease) vs Hb Bart’s Hydrops Foetalis Syndrome

A

Alpha thalassaemia trait
- Missing one or two alpha genes
- Asymptomatic or mild anaemia with low MCV & MCH

Alpha thalassaemia disease (HbH disease)
- Missing three alpha genes (only have one)
- Anaemia with very low MCV & MCH
- Impaired erythropoiesis & Haemolysis (jaundice & splenomegaly)

Hb Bart’s Hydrops Foetalis Syndrome
- No alpha genes, HbF & HbA can’t be made
- Usually die in utero

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7
Q

How to rule iron deficiency out when diagnosing alpha/beta thalassaemia trait

A

Ferritin will be normal

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8
Q

Describe the difference between beta thalassaemia trait vs intermedia vs major

A

Beta thalassaemia trait (minor)
- Missing one or two beta genes
- Asymptomatic or mild anaemia, low MCV & MCH

Beta thalassaemia intermedia
- Missing three beta genes (only have one)
- Anaemia with very low MCV & MCH
- Impaired erythropoiesis & Haemolysis (jaundice & splenomegaly)

Bet thalassaemia major
- No beta genes, (only) HbA can’t be made
- lifelong transfusion dependency

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9
Q

What test is diagnostic for beta thalassaemmia trait

A

Raised HbA2

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10
Q

Why does beta thalassaemia major not present at birth

A

Only presents when HbF falls and HbA rises (~6 months)

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11
Q

Beta thalassaemia major initial and definitive management and explain how they each work.

A

Initial - Regular transfusion programme
- suppresses ineffective erythropoiesis
- allows normal growth and development
- must monitor for and then treat iron overload from transfusion

Definitive - Bone marrow transplant
- Not regularly done
- Must be carried out before complications

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12
Q

Iron overload consequences

A

Cardiac disease
- cardiomyopathy
- arrhythmias

Liver disease
- cirrhosis
- hepatocellular cancer

Endocrine
- impaired growth & puberty
- diabetes
- osteoporosis

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13
Q

Iron overload treatment

A

Iron chelating drugs e.g. desferrioxamine
(Bind to Fe and excrete)

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14
Q

Sickling disorders aetiology & pathophysiology

A
  • point mutation causes an abnormal beta chain
  • this creates a different Hb called HbS
  • HbS polymerises in the cytoplasm when exposed to oxygen
  • This changes the RBC shape and damages the membrane
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15
Q

Compare the two main types of sickling disorders (sickle cell disease)

A

Sickle cell trait (HbAS)
- one normal and one abnormal beta gene
- asymptomatic carrier (HbS levels too low to polymerise)
- may sickle in severe hypoxia (high altitude, anaesthesia)

Sickle cell anaemia (HbSS)
- two abnormal beta genes
- episodes of tissue infarction due to vascular occlusion (sickle crisis)
- chronic haemolysis
- hyposplenism due to repeated splenic infarcts

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16
Q

What is sickle crisis and what can precipitate it

A

Vaso-occlusion due to sickle cells
Leading to tissue ischaemia & pain
Preciptants include hypoxia, dehydration, infection, cold, stress

17
Q

Sickle crisis management

A
  • High flow oxygen
  • IV analgesia & fluids

If severe e.g. (acute chest/stroke) - RBC exchange transfusion
If infection - antibiotics

18
Q

What long term management measures are used to reduce the risk of death in patients with sickle cell anaemia.

A
  • Prophylactic penicillin and vaccinations (to reduce risk of infection with hyposplenism)
  • Folic acid supplements (to cope with increased RBC turnover)
  • Hydroxycarbamide can reduce severity of disease by inducing HbF production
  • Regular transfusion to prevent stroke in selected cases
19
Q

Summarise investigation for haemoglobinopathies

A

First line tests
- FBC, Hb, RBC indices
- blood film
- ethnic origin

Diagnostic tests
- High performance liquid chromatography or electrophoresis to quantify haemoglobin types present

20
Q

What are the complications of beta thalassaemia major

A
  • failure to thrive

Extramedullary haematopoiesis causing…
- Hepatomegaly & splenomegaly
- Skeletal changes
- Organ damage

Medulla overgrowth
- Front bossing
- Maxillary overgrowth

21
Q

Summarise the diagnostic investigations for each type of alpha & beta thalassaemia

A

Alpha (diagnostic) - genetic testing

Beta trait (diagnostic) - raised HbA2 levels on HPLC or electrophoresis
Beta major (diagnostic) - HbF elevation on HPLC or electrophoresis

22
Q

How would alpha thalassaemia differ from beta thalassaemia trait & beta thalassaemia major on a high-performance liquid chromatography/ electrophoresis? Why?

A

Alpha thalassaemia - Can be normal
Beta thalassaemia trait - Raised HbA2
Beta thalassaemia major - Raised HbF & mildly raised HbA2

Alpha globin is in all Hb (HbF, HbA, HbA2)
Beta globin is only in HbA
HbF levels increase as severity of beta thalassaemia increases

23
Q

If a patient came in and you suspected thalassaemia, what investigation would you order?

A
  • FBC & RBC indices (microcytic, hypochromic anaemia)
  • Blood film (target cells with bull’s-eye appearance)
  • Ferritin levels (to exclude iron deficiency)
  • Genetic testing (in alpha thalassaemia)
  • HPLC or electrophoresis (in beta thalassaemia)
24
Q

Summarise Alpha & beta thalassaemia management

A
  • ‘Minor’ disease - may not require treatment
  • ‘Severe’ disease - lifelong blood transfusions

Other treatments
- Splenectomy in HbH disease (controversial)
- Bone marrow transplant (if before complications, can be curative)

25
Q

What drug can be used in severe sickle crisis to stimulate HbF production and what risks does it have?

A

Hydroxycarbamide

  • It stimulates HbF production
  • It also interferes with blood cell DNA production
    • bone marrow suppression & pancytopenia
  • It also reduces fertility
26
Q

Sickle cell patients have an increased risk of pulmonary hypertension. True or False?

A

True

27
Q

First line & diagnostic investigations for sickle cell disease (trait/ anaemia).

A

First line - FBC, Hb, RBC indices, blood film
Diagnostic - HPLC or electrophoresis (show abnormal HbS)

28
Q

What is the cause, symptoms/signs and management of acute chest syndrome in sickle cell disease

A

Aetiology
- infection,
- fat embolism from necrotic bone marrow,
- pulmonary infarction due to sequestration of sickle cells

Symptoms/Signs
- SOB,
- Chest pain,
- Pyrexia,
- Hypoxia
- New X-ray consolidation

Management
- Similar to sickle cell crisis
+/- antibiotics if infection
+/- blood transfusion
+/- hydroxycarbamine

29
Q

How many alpha and how many beta genes are there

A

Alpha - 4
Beta - 2

Haematology (32 decks)

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