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Haematology Year 3 > Haemaglobinopathies > Flashcards

Haemaglobinopathies Flashcards

1
Q

what is the structure of haemoglobin

A

tetramer made up of 2 alpha globin chains and 2 beta globin chains
there is one haem group attached to each globin chain = 4 haem groups in total

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2
Q

what are the major forms of haemoglobin

A

HbA (2 alpha, 2 beta chains)
HbA2 (2 alpha, 2 delta chains)
HbF (2 alpha and 2 gamma)

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3
Q

what form of haemoglobin is the most common

A

HbA

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4
Q

What chromosomes are alpha like genes on

A

chromosome 16

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5
Q

how many alpha genes are there per chromosome

A

2

i.e. 4 per cell

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6
Q

what chromosome are beta like genes on

A

chromosome 11

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7
Q

how many beta genes are there per chromosome

A

1

i.e. 2 per cell

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8
Q

does the expression of globin genes stay the same throughout life?

A

NO

changes during embryonic life + childhood

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9
Q

what are haemoglobinopathies

A

hereditary conditions affecting globin chain synthesis

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10
Q

how are haemoglobinopathies inherited

A

autosomal recessive

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11
Q

what are the two main groups of haemoglobinopathies

A
  1. Thalassaemias: decreased rate of globin chain synthesis

2. Structural haemoglobin variants: normal production of a structurally abnormal chain

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12
Q

what is thalassaemia

A

reduced globin chain synthesis resulting in impaired haemoglobin production

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13
Q

2 forms of thalassaemia

A

alpha thalassaemia – alpha chains affected

beta thalassaemia – beta chains affected

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14
Q

what type of anaemia is seen in thalassaemia

A

microcytic hypochromatic

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15
Q

what does wrong in thalassaemia

A

inadequate Hb production – microcytic hypo chromatic anaemia

Unbalanced accumulation of globin chains – ineffective erythropoiesis and haemolysis

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16
Q

what happens in alpha thalassaemia

A

mutations affecting alpha globin chain synthesis – reduced or absent synthesis of alpha chains
Results from a deletion of one or both alpha genes from chromosome 16

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17
Q

why does alpha thalassaemia present more severely

A

alpha chains are present in all forms of Hb

therefore HbA, HbA2 and HbF are all affected

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18
Q

what are the genotypes of alpha thalassaemia

A

Unaffected individuals have 4 normal alpha genes (aa/aa)

Alpha thalassaemia trait: one or 2 missing (-a/aa), (–/aa) or
(-a/-a)

HbH disease: only one alpha gene left (–/-a)

Hb Barts Hydrops fetalis: no functional genes (–/–)

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19
Q

features of alpha thalassaemia trait

A

usually (–/aa) or (-a/-a)

Asymptomatic
Microcytic hypochromatic red cells with mild anaemia

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20
Q

what can alpha thalassaemia trait be mistaken for and how can you tell the difference

A

iron deficiency anaemia (low ferritin)

in trait ferritin is normal, RBC count is high

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21
Q

what is HbH disease

A

severe form of alpha thalassaemia
only one alpha gene per cell |(–/-a)
chain production <30% of normal

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22
Q

blood results seen in HbH disease

A

anaemia with very low MCV and MCH (mean corpuscular haemoglobin)

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23
Q

why is it called HbH disease

A

excess beta chains form tetramers called HbH which cannot carry oxygen

red cell inclusions of HbH can be seen with special stains

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24
Q

symptoms of HbH disease

A

from mild anaemia to transfusion dependant
splenomegaly due to extramedullarly haematopoiesis
jaundice due to haemolysis and ineffective erythropoiesis

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25
Q

where is HbH disease most prevalent

A

South east Asia, Middle East and the mediterranean

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26
Q

treatment of severe HbH disease

A

splenectomy +/- transfusion

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27
Q

what is the most severe form of alpha thalassaemia

A

Hb Bart’s hydrops fetalis

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28
Q

what happens in Hb Bart’s hydrops fetalis syndrome

A

no alpha genes inherited from either parent (–/–)

minimal or no alpha chain production – HbA can’t be made

29
Q

what form of Hb is the majority at birth in Hb Barts hypos fetalis syndrome

A

Hb Barts (y4) HbH(B4)

30
Q

symptoms of Hb Barts Hydrops Fetalis

A 
severe anaemia 
cardiac failure, oedema
growth retardation 
severe hepatosplenomegaly 
skeletal and cardiovascular abnormalities
most foetuses die in utero
31
Q

what is beta thalassaemia

A

disorder of beta chain synthesis
reduced or absent beta chain production
only affects beta chains and so HbA (2 alpha, 2 beta) is the only form of Hb affected

32
Q

what causes beta thalassaemia

A

usually a point mutation

33
Q

what are the 3 forms of beta thalassaemia

A

beta thalassaemia trait
beta thalassaemia intermedia
beta thalassaemia major

34
Q

what are the features of beta thalassaemia trait

A

asymptomatic
No/mild anaemia
low MCV/MCH
raised HbA2

35
Q

features of beta thalassaemia intermedia

A

moderate severity requiring occasional transaction

36
Q

features of beta thalassaemia major

A

severe, lifelong transfusion dependency

37
Q

presentation of beta thalassaemia major

A 
presents aged 6-24 months 
pallor, failure to thrive 
extra medullary haematopoiesis causing:
- hepatosplenomegaly 
- skeletal changes
- organ damage
38
Q

lab features of beta thalassaemia major

A

severe anaemia
reticulocytosis
very low MCV/MCH

film: microcytosis, hypochromia, anisopoikilocytosis and target cells

39
Q

complication of extramedullarly haematopoiesis

A

cord compression

40
Q

management of beta thalassaemia major

A

regular transfusion programme

  • to main Hb 95-105 g/l
  • suppress ineffective erythropoiesis
  • inhibit over-absorption of iron
41
Q

main side effect of treatment of beta thalassaemia major

A

Iron overload from transfusion- main cause of mortality

42
Q

consequences of iron overload

A

endocrine dysfunction: impaired growth/pubertal development, diabetes, osteoporosis

cardiac disease: arrhythmia/cardiomyopathy

Liver disease: cirrhosis, hepatocellular cancer

43
Q

management of iron overload

A

desferrioxamine - iron chelating drug

44
Q

how does desferrioxamine work

A

chelators bind to iron, complexes form and are excreted in urine/stool

45
Q

pathophysiology behind iron overload

A

chronic anaemia drives increased iron absorption

46
Q

what does iron overload make you more susceptible to

A

bacterial infections

47
Q

what makes it hard to cross match blood in thalassaemia patients

A

formation of alloantibodies- formed against an antigen that is not present in their own blood

48
Q

how is the diagnosis of thalassaemia made

A

Exclude iron deficiency

Blood film: hypochromia, target cells, anisopoikilocytosis

HPLC: raised HbA2 diagnostic of a beta thalassaemia trait (as there is no beta chains present in this form of Hb)
Genetic testing needed to see which form of alpha thalassaemia trait it is

49
Q

pathophysiology of sickle cell disorders

A

point mutation in codon 6 of the beta globin gene that substitutes glutamine to valine

This alters the structure of the resulting Hb – HbS

HbS polymerises if exposed to low oxygen levels for a long period of time

This distorts the red cell, damaging the red cell membrane

50
Q

what is the mutation in sickle cell disorders

A

codon 6 of the beta globin gene

51
Q

what amino acid is changed in sickle cell disorders

A

glutamine to valine

52
Q

what are the two forms of sickle cell disorders

A

sickle trait- HbAS

sickle cell anaemia - HbSS

53
Q

features of sickle trait

A

one normal beta gene, one abnormal beta gene

asymptomatic

54
Q

symptoms of sickle cell trait

A

few clinical features as HbS level is too low to polymerise

may sickle in severe hypoxia i.e. high altitude, under anaesthesia

55
Q

features of sickle cell anaemia

A

two abnormal beta genes
autosomal recessive
HbS > 80% no HbA

56
Q

what is a sickle crisis

A

episodes of tissue infarction due to vascular occlusion

57
Q

symptoms of sickle cell crisis

A

Symptoms depend on site and severity:
Digits, bone marrow, lung, spleen, CNS often affected
pain may be extremely severe
Chronic haemolysis
Hyposplenism due to repeated splenic infarcts

58
Q

what is sickle cell disease

A

heterozygosity for HbS and another beta chain mutation

e.g. sickle + beta thalassaemia

59
Q

precipitants of a sickle cell crisis

A 
hypoxia
dehydration- makes HbS more likely to polymerise 
Infection
Cold exposure
stress/fatigue
60
Q

treatment of sickle cell crisis

A 
opiate analgesia 
hydration 
rest
oxygen 
antibiotics if infection

in severe crisis (e.g. chest/neurological symptoms)- red cell exchange transfusion

61
Q

how do you do a transfusion in a severe sickle crisis

A

venesection - transfuse and repeat

62
Q

longterm effects of sickle cell anaemia

A 
impaired growth 
risk of end organ damage:
- pulmonary hypertension 
- renal disease
- avascular necrosis 
- leg ulcers 
- stroke
63
Q

long term treatment of sickle cell anaemia

A

splenectomy
folic acid supplementation
hydroxycarbamide

64
Q

what would a patient need if they had a splenectomy

A

prophylactic penicillin

vaccination against pneumococcus, meningococcus, haemophilus

65
Q

why do sickle cell anaemia patients need folic acid supplementation

A

increased RBC turnover causes increased demand

66
Q

how does hydroxycarbamide work

A

reduces severity of disease by inducing HbF production

67
Q

what does HPLC stand for and what does it do

A

high performance liquid chromatography: quantities haemoglobin present

68
Q

what is raised HbA2 on HPLC diagnostic of

A

beta thalassaemia trait

Haematology Year 3 (21 decks)

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