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Haematology Year 3 > Haemaglobinopathies > Flashcards

Haemaglobinopathies Flashcards

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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
where is HbH disease most prevalent
South east Asia, Middle East and the mediterranean
26
treatment of severe HbH disease
splenectomy +/- transfusion
27
what is the most severe form of alpha thalassaemia
Hb Bart's hydrops fetalis
28
what happens in Hb Bart's hydrops fetalis syndrome
no alpha genes inherited from either parent (--/--) | minimal or no alpha chain production -- HbA can't be made
29
what form of Hb is the majority at birth in Hb Barts hypos fetalis syndrome
Hb Barts (y4) HbH(B4)
30
symptoms of Hb Barts Hydrops Fetalis
``` severe anaemia cardiac failure, oedema growth retardation severe hepatosplenomegaly skeletal and cardiovascular abnormalities most foetuses die in utero ```
31
what is beta thalassaemia
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
what causes beta thalassaemia
usually a point mutation
33
what are the 3 forms of beta thalassaemia
beta thalassaemia trait beta thalassaemia intermedia beta thalassaemia major
34
what are the features of beta thalassaemia trait
asymptomatic No/mild anaemia low MCV/MCH raised HbA2
35
features of beta thalassaemia intermedia
moderate severity requiring occasional transaction
36
features of beta thalassaemia major
severe, lifelong transfusion dependency
37
presentation of beta thalassaemia major
``` presents aged 6-24 months pallor, failure to thrive extra medullary haematopoiesis causing: - hepatosplenomegaly - skeletal changes - organ damage ```
38
lab features of beta thalassaemia major
severe anaemia reticulocytosis very low MCV/MCH film: microcytosis, hypochromia, anisopoikilocytosis and target cells
39
complication of extramedullarly haematopoiesis
cord compression
40
management of beta thalassaemia major
regular transfusion programme - to main Hb 95-105 g/l - suppress ineffective erythropoiesis - inhibit over-absorption of iron
41
main side effect of treatment of beta thalassaemia major
Iron overload from transfusion- main cause of mortality
42
consequences of iron overload
endocrine dysfunction: impaired growth/pubertal development, diabetes, osteoporosis cardiac disease: arrhythmia/cardiomyopathy Liver disease: cirrhosis, hepatocellular cancer
43
management of iron overload
desferrioxamine - iron chelating drug
44
how does desferrioxamine work
chelators bind to iron, complexes form and are excreted in urine/stool
45
pathophysiology behind iron overload
chronic anaemia drives increased iron absorption
46
what does iron overload make you more susceptible to
bacterial infections
47
what makes it hard to cross match blood in thalassaemia patients
formation of alloantibodies- formed against an antigen that is not present in their own blood
48
how is the diagnosis of thalassaemia made
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
pathophysiology of sickle cell disorders
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
what is the mutation in sickle cell disorders
codon 6 of the beta globin gene
51
what amino acid is changed in sickle cell disorders
glutamine to valine
52
what are the two forms of sickle cell disorders
sickle trait- HbAS | sickle cell anaemia - HbSS
53
features of sickle trait
one normal beta gene, one abnormal beta gene | asymptomatic
54
symptoms of sickle cell trait
few clinical features as HbS level is too low to polymerise | may sickle in severe hypoxia i.e. high altitude, under anaesthesia
55
features of sickle cell anaemia
two abnormal beta genes autosomal recessive HbS > 80% no HbA
56
what is a sickle crisis
episodes of tissue infarction due to vascular occlusion
57
symptoms of sickle cell crisis
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
what is sickle cell disease
heterozygosity for HbS and another beta chain mutation | e.g. sickle + beta thalassaemia
59
precipitants of a sickle cell crisis
``` hypoxia dehydration- makes HbS more likely to polymerise Infection Cold exposure stress/fatigue ```
60
treatment of sickle cell crisis
``` opiate analgesia hydration rest oxygen antibiotics if infection ``` in severe crisis (e.g. chest/neurological symptoms)- red cell exchange transfusion
61
how do you do a transfusion in a severe sickle crisis
venesection - transfuse and repeat
62
longterm effects of sickle cell anaemia
``` impaired growth risk of end organ damage: - pulmonary hypertension - renal disease - avascular necrosis - leg ulcers - stroke ```
63
long term treatment of sickle cell anaemia
splenectomy folic acid supplementation hydroxycarbamide
64
what would a patient need if they had a splenectomy
prophylactic penicillin | vaccination against pneumococcus, meningococcus, haemophilus
65
why do sickle cell anaemia patients need folic acid supplementation
increased RBC turnover causes increased demand
66
how does hydroxycarbamide work
reduces severity of disease by inducing HbF production
67
what does HPLC stand for and what does it do
high performance liquid chromatography: quantities haemoglobin present
68
what is raised HbA2 on HPLC diagnostic of
beta thalassaemia trait

Haematology Year 3 (21 decks)

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