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Haematology SB > Haemaglobinopathies > Flashcards

Haemaglobinopathies Flashcards

1
Q

what is the structure of haemoglobin

A

Tetramer made up of 2 alpha globin like chains and 2 beta globin like chains

One haem group attached to each globin chain = 4 haem groups

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2
Q

what are the major forms of haemoglobin

A

HbA (two alpha chains and two beta chains, α2β2 )

HbA2 (two alpha and two delta, α2δ2)

HbF (two alpha and two gamma, α2γ2)

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3
Q

what type of haemoglobin is most common

A

HbA

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4
Q

what chromosome is the alpha like genes on

A

chromosome 16

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5
Q

how many alpha genes are present per chromosome

A

2

i.e. 4 per cell

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6
Q

what chromosome is the beta like genes on

A

chromosome 11

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7
Q

how many beta genes are present per chromosome

A

1

i.e. 2 per cell

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8
Q

expression of globin genes stays the same throughout life - true or false

A

false

- changes during embryonic life and childhood

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9
Q

what are haemoglobinopathies

A

Hereditary conditions affecting globin chain synthesis

behave as autosomal recessive disorders

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10
Q

what are the 2 main groups of haemoglobinopathies

A

1 - Thalassaemias; decreased rate of globin chain synthesis

2 - Structural haemoglobin variants; normal production of structurally abnormal globin chain

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11
Q

what is thalassaemias

A

Hereditary disorders of globin chain synthesis resulting in impaired haemoglobin production

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12
Q

what are the 2 forms of thalassaemia

A

Alpha thalassaemia; α chains affected

Beta thalassaemia; β chains affected

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13
Q

what type of anaemia is seen in thalassaemia

A

microcytic hypochromic

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14
Q

what goes wrong in thalassaemia

A

Inadequate Hb production → microcytic hypochromic anaemia

Unbalanced accumulation of globin chains → ineffective erythropoiesis and haemolysis

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15
Q

what happens in alpha thalassaemia to cause Sx

A

Mutations affecting α globin chain synthesis

Reduced or absent synthesis of α chains

Results from deletion of one (-α) or both (- -) alpha genes from ch 16

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16
Q

why does alpha thalassaemia tend to present more severely

A

alpha chains present in all adult forms of Hb therefore HbA, HbA2 and HbF all affected

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17
Q

what are the types of alpha thalassaemia

A

Unaffected individuals have 4 normal α genes (αα/αα)

Alpha thalassaemia trait; one or two genes missing (-α/αα), (–/αα) or (-α/-α)

HbH disease; only one alpha gene left (–/-α )

Hb Barts hydrops fetalis; no functional α genes (–/–)

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18
Q

what are features of Alpha thalassaemia trait

A

Usually (–/αα) or (-α/-α)

Asymptomatic, no Rx needed

Microcytic, hypochromic red cells with mild anaemia

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19
Q

what can alpha thalassaemia trait be mistaken for and how can you tell it apart

A

iron deficiency anaemia

in trait = ferritin normal, RBC raised

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20
Q

what is HbH disease

A

Severe form of α thalassaemia

Only one α gene per cell (–/-α )

α chain production < 30% of normal

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21
Q

what blood results are seen in HbH disease

A

anaemia with very low MCV and MCH

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22
Q

why is it called HbH disease

A

Excess β chains form tetramers (β4) called HbH which cannot carry oxygen

Red cell inclusions (HbH bodies) can be seen with special stains

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23
Q

what are Sx of HbH disease

A

From mild anaemia to transfusion dependant

Splenomegaly due to extramedullary haematopoiesis

Jaundice due to

  • Haemolysis
  • Ineffective erythropoiesis
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24
Q

what is the Tx of HbH disease

A

Severe cases splenectomy+/-transfusion

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25
Q

where is HbH disease prevalent

A

S.E. Asia, Middle East and the Mediterranean

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26
Q

what is the most severe form of alpha thalassaemia

A

Hb Bart’s hydrops fetalis syndrome

27
Q

what happens in Hb Bart’s hydrops fetalis syndrome

A

No α genes inherited from either parent (–/–)

Minimal or no α chain production →HbA can’t be made

28
Q

what is the majority Hb at birth

A

Hb Barts (γ4) and HbH (β4)

29
Q

what are Sx of Hb Bart’s hydrops fetalis syndrome

A

Severe anaemia

Cardiac failure, oedema

Growth retardation

Severe hepatosplenomegaly

Skeletal and cardiovascular abnormalities

Most die in utero

30
Q

what is beta thalassaemia

A

Disorder of beta chain synthesis

Reduced, or absent beta chain production

Only β chains and hence only HbA (α2β2) affected

31
Q

what causes beta thalassaemia

A

usually a point mutation

32
Q

what are the 3 forms of beta thalassaemia

A

beta thalassaemia trait
beta thalassaemia intermedia
beta thalassaemia major

33
Q

what are the features of beta thalassaemia trait

A

asymptomatic
no/mild anaemia
low MCV/MCH

34
Q

what are the features of beta thalassaemia intermedia

A

moderate severity requiring occasional transfusion

35
Q

what are the features of beta thalassaemia major

A

severe, lifelong transfusion dependency

36
Q

what are lab features of beta thalassaemia major

A

severe anaemia
Reticulocytosis
very low MCV/MCH

Film; microcytosis, hypochromia, anisopoikilocytosis and target cells

37
Q

what is seen on HPLC in beta thalassaemia major

A

mainly HbF present

small amounts of HbA

38
Q

what are features of beta thelassaemia major

A

Presents aged 6-24 months

Failure to thrive
Pallor

Extramedullary haematopoiesis causing:

  • Hepatosplenomegaly
  • Skeletal changes
  • Organ damage
39
Q

what are complications of extra medullary haematopoiesis

A

can cause spinal cord compression

40
Q

what is Mx of beta thal major

A

Regular transfusion programme to maintain Hb at 95-105g/l

  • suppress ineffective erythropoiesis
  • inhibit over-absorption of iron

Allows for relatively normal growth and development

41
Q

what can tx cause in beta thal major

A

iron overload > can lead to mortality

42
Q

what are consequences of iron overload

A

Endocrine dysfunction

  • Impaired growth and pubertal development
  • Diabetes
  • Osteoporosis

Cardiac disease

  • Cardiomyopathy
  • Arrhythmias

Liver disease

  • Cirrhosis
  • Hepatocellular cancer
43
Q

what is the Mx of iron overload

A

Desferrioxamine - iron chelating drug

44
Q

how does desferrioxamine work

A

Chelators bind to iron, complexes formed are excreted in urine or stool

45
Q

what does iron overload make you susceptible too

A

bacterial infection

46
Q

how is diagnosis of thalassaemia made

A

exclude iron deficiency first

Blood film; hypochromia, target cells, anisopoikilocytosis

HPLC: Raised HbA2 diagnostic of beta thal trait. Will be normal in alpha thal trait so DNA testing needed to confirm

47
Q

what is the pathophysiology of sickle cell disease

A

Point mutation in codon 6 of the β globin gene that substitutes glutamine to valine

Alters the structure of the resulting Hb→ HbS

HbS polymerises if exposed to low oxygen levels for a prolonged period

This distorts the red cell, damaging the RBC membrane

48
Q

what are the two from of sickle cell disease

A 
sickle trait (HbAS) 
sickle cell anaemia (HbSS)
49
Q

what are features of sickle trait

A

One normal, one abnormal β gene (β/βs)

Asymptomatic carrier state

50
Q

what are Sx of sickle trait

A

Few clinical features as HbS level too low to polymerise

May sickle in severe hypoxia eg high altitude, under anaesthesia

51
Q

what are lab results of sickle trait

A

Blood film normal

Mainly HbA, HbS <50%

52
Q

what are features of sickle cell anaemia

A

Two abnormal β genes (βs/βs) autosomal recessive

HbS > 80%, no HbA

53
Q

what is sickle crisis

A

Episodes of tissue infarction due to vascular occlusion

54
Q

what are symptoms of sickle cell anaemia

A

Symptoms depend on site and severity

  • Digits (dactylitis), bone marrow, lung, spleen, CNS
  • Pain may be extremely severe

Hyposplenism (due to repeated splenic infarcts)
Chronic haemolysis

55
Q

what is uncommon in sickle cell anaemia

A

iron overload

56
Q

what are precipitants of sickle crisis

A

Hypoxia ‏(can be caused by chest infection)

Dehydration (makes HbS more likely to polymerise)

Infection

Cold exposure

Stress/fatigue

57
Q

what is the Tx of a sickle crisis

A 
Opiate analgesia 
Hydration 
Rest
Oxygen 
Antibiotics if evidence of infection

Red cell exchange transfusion in severe crises eg chest crisis or neurological symptoms
(venesect&raquo_space; transfuse)

58
Q

what are long term effects of sickle cell anaemia

A

Impaired growth

Risk of sepsis

Risk of organ damage

  • pulmonary hypertension
  • renal disease
  • avascular necrosis
  • leg ulcers
  • stroke
59
Q

what is long term treatment of sickle cell anaemia

A

splenectomy

folic acid supplementation

hydroxycarbamide

60
Q

what would a patient need if they had a splenectomy

A

prophylactic penicillin

vaccination; pneumococcus, meningococcus, haemophilus

61
Q

why does a patient with sickle cell need folic acid supplementation

A

↑ RBC turnover so ↑demand

62
Q

how does hydroxycarbamide work

A

reduces severity of disease by inducing HbF production

63
Q

what is sickle cell disease

A

heterozygosity for HbS and another β chain mutation

e.g. HbS/β thalassaemia; mild if β+, severe if β0

Haematology SB (19 decks)

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