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Flashcards in haemoglobinopathies Deck (91):
1

what shape are RBC

biconcave

2

what shape are RBC

biconcave

3

do RBC have nuclei

no

4

what is the function of RBC

transport oxygen which is found to haemoglobin

5

what molecule controls RBC levels and where is this molecule synthesised

Erythropoetein (EPO)
Kidney.

6

are the globin chains covalently bonded in haemoglobin

No.

7

what is the composition of haemoglobin in terms of the alpha and beta chains

2 alpha chains
2 beta chains

8

what is the function of glob in

protect harm from oxidation
renders the molecule soluble.

9

what is the composition of feral haemoglobin in terms of the alpha and gamma chains

2 alpha and 2 gamma chains

10

which 2 chromosomes control the glob in chains

chromosome 16- alpha
chromosome 11- gamma, delta and beta.

11

where is haemoglobin produced
(3 places from inter to at birth)

in the yolk sac -in utero
liver or spleen -10-12 weeks development in utero
bone marrow- end of gestation

12

define haemoglobinopathies

changes in globin genes or their expression leads to disease.

13

2 main types of haemoglobinpathies

structural-sickle cell (base substitution)
Thalassaemia- change in globin gene expression leads to reduced rate of synthesis of NORMAL globin chains.

14

plasma volume expands by how much in pregnancy

50%

15

red cell mass expands by how much in pregnancy

25%

16

what is defined as anaemia in the 1st and 3rd trimester

17

what is defined as anaemia in the second trimester

18

what happens to the number of white blood cells in pregnancy

Leukocytosis- increase in WBC

19

what happens to the platelet count during pregnancy

thrombocytopenia
platelet count is low- below the normal level but this is a physiological process.

20

causes of thrombocyopenia in pregnancy

production failure- severe folate deficiency.
Consumptive- gestational, pre-eclampsia and HELLP syndrome, AFLP, DIC e.g. in abruption TTP/HUS.

21

what makes pregnancy a prothrombotic state

platelet activation
increase in procoagulant factors
reduction in natural anticoagulants.
reduction in fibrinolysis
rise in markers of thrombin generation
coagulation factors

22

how are haemoglobinopathies diagnosed/ detected.

Electrophoresis- for structural abnormalities.
Isoelectric focusing
High performance liquid chromatography.
Oxygen dissociation curve (p50, high affinity)
DNA analysis (genetic counseling, prenatal Dx)
Mass spectrometry
Kleihauer testing, Supravital staining, Sickle solubility

23

what is the substation which occurs in sickle cell anaemia

valine substituted for glutamine at postion 6 on B globin chain

24

why is the presentation of sickle cell only present 6 months after birth

foetal haemoglobin is present until 6 months after birth.

25

when do symptoms of sickle cell anaemia become evident

when extreme hypoxia/dehydration (eg very bad anaesthetia, flying unpressurised military aircraft)

26

acute complications of sickle cell disease.

Vaso-occlusicve crisis- hands and feet (dactylitis), chest syndrome, abdominal pain (mesenteric), bones (long bones, ribs, sin, brain, priapism-painful erection).
Septicaemia.
Aplastic crisis.
Sequestration crisis (spleen, liver).

27

chronic complications of sickle cell anaemia

Hyposplenism - due to infarction and atrophy of spleen, increased risk of infection.
Renal disease: medullary infarction with papillary necrosis. Tubular damage - can’t concentrate urine (bed-wetting at night). Glomerular – chronic renal failure/dialysis
Avascular necrosis (AVN) –femoral/humeral heads- need replacement, life long peniciclin.
Leg ulcers, osteomyelitis, gall stones, retinopathy, cardiac, respiratory

28

treatment for sickle cell anaemia.

Penicillin etc from 6 months

29

treatment for vaso-oclussion in sickle cell anaemia

analgesia (usually opiates), hydration (to maintain red cell water)

30

why is blood transfused in sickle cell anaemia.

Top up: splenic sequestration, aplastic crisis, pre-operative, acute chest crisis (usually when Hb

31

what is the function of Hydroxycarbamide

Increases Hb F

32

how do you cure sickle cell anaemia

Bone Marrow Transplant from normal donor

33

how can sickle cell be prevented

genetic counselling/prenatal diagnosis, avoiding precipitants

34

how many forms of thalasemia are there

4
α, β, δβ and γδβ

35

what is Hb harts

consists of four gamma chains. It is moderately insoluble, and therefore accumulates in the red blood cells

36

why is little oxygen delivered to tissues when you have Hb harts

It has an extremely high affinity for oxygen,

37

HbA thalassemia is more severe than B

foetal haemoglobin requires alpha but not b chains.

38

do RBC have nuclei

no

39

what is the function of RBC

transport oxygen which is found to haemoglobin

40

what molecule controls RBC levels and where is this molecule synthesised

Erythropoetein (EPO)
Kidney.

41

are the globin chains covalently bonded in haemoglobin

No.

42

what is the composition of haemoglobin in terms of the alpha and beta chains

2 alpha chains
2 beta chains

43

what is the function of glob in

protect harm from oxidation
renders the molecule soluble.

44

what is the composition of feral haemoglobin in terms of the alpha and gamma chains

2 alpha and 2 gamma chains

45

which 2 chromosomes control the glob in chains

chromosome 16- alpha
chromosome 11- gamma, delta and beta.

46

where is haemoglobin produced
(3 places from inter to at birth)

in the yolk sac -in utero
liver or spleen -10-12 weeks development in utero
bone marrow- end of gestation

47

define haemoglobinopathies

changes in globin genes or their expression leads to disease.

48

2 main types of haemoglobinpathies

structural-sickle cell (base substitution)
Thalassaemia- change in globin gene expression leads to reduced rate of synthesis of NORMAL globin chains.

49

plasma volume expands by how much in pregnancy

50%

50

red cell mass expands by how much in pregnancy

25%

51

what is defined as anaemia in the 1st and 3rd trimester

52

what is defined as anaemia in the second trimester

53

Endocrine complications of iron chelation.

Growth and development, screening for glucose intolerance, hypothyroidism and hypoparathyroidism.

54

liver complications of iron chelation

LFT, ferritin, Hep Serology, MRI. Hepatologist if established disease

55

causes of thrombocyopenia in pregnancy

production failure- severe folate deficiency.
Consumptive- gestational, pre-eclampsia and HELLP syndrome, AFLP, DIC e.g. in abruption TTP/HUS.

56

what makes pregnancy a prothrombotic state

platelet activation
increase in procoagulant factors
reduction in natural anticoagulants.
reduction in fibrinolysis
rise in markers of thrombin generation
coagulation factors

57

how are haemoglobinopathies diagnosed/ detected.

Electrophoresis- for structural abnormalities.
Isoelectric focusing
High performance liquid chromatography.
Oxygen dissociation curve (p50, high affinity)
DNA analysis (genetic counseling, prenatal Dx)
Mass spectrometry
Kleihauer testing, Supravital staining, Sickle solubility

58

what is the substation which occurs in sickle cell anaemia

valine substituted for glutamine at postion 6 on B globin chain

59

why is the presentation of sickle cell only present 6 months after birth

foetal haemoglobin is present until 6 months after birth.

60

when do symptoms of sickle cell anaemia become evident

when extreme hypoxia/dehydration (eg very bad anaesthetia, flying unpressurised military aircraft)

61

acute complications of sickle cell disease.

Vaso-occlusicve crisis- hands and feet (dactylitis), chest syndrome, abdominal pain (mesenteric), bones (long bones, ribs, sin, brain, priapism-painful erection).
Septicaemia.
Aplastic crisis.
Sequestration crisis (spleen, liver).

62

chronic complications of sickle cell anaemia

Hyposplenism - due to infarction and atrophy of spleen, increased risk of infection.
Renal disease: medullary infarction with papillary necrosis. Tubular damage - can’t concentrate urine (bed-wetting at night). Glomerular – chronic renal failure/dialysis
Avascular necrosis (AVN) –femoral/humeral heads- need replacement, life long peniciclin.
Leg ulcers, osteomyelitis, gall stones, retinopathy, cardiac, respiratory

63

treatment for sickle cell anaemia.

Penicillin etc from 6 months

64

treatment for vaso-oclussion in sickle cell anaemia

analgesia (usually opiates), hydration (to maintain red cell water)

65

why is blood transfused in sickle cell anaemia.

Top up: splenic sequestration, aplastic crisis, pre-operative, acute chest crisis (usually when Hb

66

what is the function of Hydroxycarbamide

Increases Hb F

67

how do you cure sickle cell anaemia

Bone Marrow Transplant from normal donor

68

how can sickle cell be prevented

genetic counselling/prenatal diagnosis, avoiding precipitants

69

how many forms of thalasemia are there

4
α, β, δβ and γδβ

70

what is Hb harts

consists of four gamma chains. It is moderately insoluble, and therefore accumulates in the red blood cells

71

why is little oxygen delivered to tissues when you have Hb harts

It has an extremely high affinity for oxygen,

72

HbA thalassemia is more severe than B

foetal haemoglobin requires alpha but not b chains.

73

blood film b thalassaemia

abnormal with lots of nucleated red cells.

74

clinical features of thalassaemia

severe anaemia
death from infection
Short stature and distorted limb growth due to premature closure of epiphyses in long bonesEnlarged liver and spleen “extramedullary haemopoiesis”

75

thalassemia facies include

o Maxillary hypertrophy
o Abnormal dentition
o Frontal bossing due to expanded bone marrow

76

pathology of B thalassemia

Increased marrow activity- skeletal deformities and stunted growth, increased iron absorption and organ damage (exacerbated by blood transfusion, Protein malnutrition.

Enlarged and overactive spleen- pooling of RBC and increased trans fusion requirement.

77

classic X ray seen due to bone marrow expansion in thalassemia.

• X-ray showing classical “hair on end” skull due to widening of diploic cavities by marrow expansion

78

trearment for B thlassemia.

• Tranfusion- to maintain mean hb 12 g/dl (pre-transfusion Hb 9.5-10)
• Suppresses marrow red cell production and prevents skeletal deformity and liver/spleen enlargement

79

how often are transfusions for the first year of B thalassemia

3-4 weeks

80

complications of transfusions in thalassemia include

iron overload
each unit of red cells contains 200-250mg Iron and the body has
no excretory mechanism for iron, therefore iron has to be removed

81

complications of iron overload due to transfusion

gonads/hypothalamus – failure of puberty, growth failure
pancreas – diabetes
heart – dilated cardiomyopathy and heart failure
liver – cirrhosis.

82

major complications of blood transfusion

Transmission of infection
Allo-immunisation- immune response to foreign antigens after exposure to genetically different cells or tissues

83

Causes of death in thalassaemia

Most common is heart failure
Infection
Arrhythmias

84

solution to prevent iron overload from transfusion

chelation therapy

85

iron chelators include

Desferrioxamine
Deferiprone and Deferasirox

86

what is the target ferrite level to aim for with iron chelators and why is the peel still higher than normal

1000-1500µg/L
If tried to reduce iron levels further would result in toxicity from iron chelators.

87

Monitoring chelation

Ferritin (acute phase), liver biopsy, MRI (T2*)

88

prevention of haemoglobinopathies

genetic counselling
anatenatal screening
neonatal screening
gene therapy

89

Endocrine complications of blood transfusion.

Growth and development, screening for glucose intolerance, hypothyroidism and hypoparathyroidism.

90

liver complications of blood transfusion

LFT, ferritin, Hep Serology, MRI. Hepatologist if established disease

91

why does transfusion increase risk of infections

decreased CD4/8 ratio and defective neutrophil chemotaxis, increased virulence with excess iron (yersinia and DFO), line infections, transfusion transmitted infection.
Or
directly from donor blood