Haemaglobinopathies and sickle cell

Question 1

what is the problem in haemoglobinopathies

Answer 1

problems with globin chains

Question 2

HbA2 has 2 alpha chains and 2 ____ chains

Answer 2

delta

Question 3

HbA has 2 alpha chains and 2 _______ chains

Answer 3

beta

Question 4

alpha like genes are on chromosome ___

Answer 4

16

Question 5

beta like genes are on chromosome ___

Answer 5

11

Question 6

adult levels of Hb reached by what age?

Answer 6

6-9 months

Question 7

when does beta chain production kind of start

Answer 7

few months after birth

Question 8

what are haemoglobinopathies

Answer 8

hereditary conditions affecting globin chain synthesis

Question 9

two main groups of

Answer 9

• thalassaemias
• structural haemoglobin variants

Question 10

thalassaemias

Answer 10

mutation resulted in you not producing enough of the globin chains

Question 11

structural haemoglobin variants

Answer 11

normal production of abnormal globin chain

Question 12

alpha thalassaemia

Answer 12

not making enough alpha globin chains

Question 13

beta thalassaemia

Answer 13

not making enough beta globin chains

Question 14

consequences of thalassaemias

Answer 14

inadequate Hb production —> microcytic hypochromic anaemia

If severe:
- Unbalanced accumulation of globin chains which are toxic to the cell
- Ineffective erythropoiesis
- Haemolysis

Question 15

what does alpha thalassaemia result from?

Answer 15

results from deletion of one or both alpha genes from chromosome 16

Question 16

alpha thalassaemia trait

Answer 16

missing one or two alpha genes

Microcytic, hypochromic red cells with mild anaemia

asymptomatic

don’t need treatment
carrier state

Question 17

HbH disease

Answer 17

a form of alpha thalassaemia.
only one working alpha gene per cell - moderate to severe anaemia

Question 18

Hb Barts hydrops fetalis

Answer 18

no functional α genes (–/–) incompatible with life

Question 19

HbH disease signs symptoms

Answer 19

jaundice, splenomegaly

Question 20

what is the most severe form of alpha thalassaemia

Answer 20

Hb Barts Hydrops Foetalis Syndrome

Question 21

How can alpha thalassaemia trait be distinguished from iron deficiency?

Answer 21

ferritin will be normal in alpha thalassaemia trait

Question 22

beta thalassaemia is usually caused by ______ mutations within the beta gene

Answer 22

point

Question 23

alpha thalassaemia is usually to do with ________ of alpha genes

Answer 23

deletion

Question 24

classification of beta thalassaemia

Answer 24

beta thalassaemia trait

beta thalassaemia intermedia

beta thalassaemia major

Question 25

beta thalassaemia trait diagnosis

Answer 25

increased HbA2

Question 26

beta thalassaemia trait

Answer 26

asymptomatic

Question 27

do beta thalassaemia intermedia patients need transfusion?

Answer 27

require occasional blood transfusion

Question 28

beta thalassaemia major when does it present

Answer 28

6-24 months (as HbF falls)

Question 29

beta thalassaemia major symptoms

Answer 29

pallor, failure to thrive

Question 30

beta thalassaemia major - extramedullary haematopoiesis complications:

Answer 30

- hepatosplenomegaly - skeletal changes - organ damage

Question 31

beta thalassaemia major haemoglobin analysis

Answer 31

- mainly HbF - no HbA (or possibly a little bit)

Question 32

management of beta thalassaemia major

Answer 32

Regular transfusion programme to maintain Hb at 95-105g/l Bone marrow transplant may be an option if carried out before complications develop

Question 33

blood transfusions for management of beta thalassaemia major - what is the main cause of mortality

Answer 33

iron overload from transfusion

Question 34

consequences of iron overload - endocrine dysfunction

Answer 34

Impaired growth and pubertal development Diabetes Osteoporosis

Question 35

consequences of iron overload - cardiac disease

Answer 35

Cardiomyopathy Arrhythmias

Question 36

consequences of iron overload - liver disease

Answer 36

Cirrhosis Hepatocellular cancer

Question 37

management of iron overload

Answer 37

iron chelating drugs (e.g. desferrioxamine)

Question 38

transfusion related complications

Answer 38

Viral infection - HIV, Hepatitis B and C Alloantibodies – hard to crossmatch Transfusion reactions

Question 39

what cause sickle cell

Answer 39

point mutation in codon of the beta globin gene (so altered beta chain 'beta S')

Question 40

HbAS

Answer 40

sickle cell trait asymptomatic carrier state mainly HbA, HbS <50%

Question 41

HbSS

Answer 41

sickle cell anaemia HbS >80%, no HbA

Question 42

sickle cell anaemia genes

Answer 42

two abnormal beta genes

Question 43

what is sickle crisis

Answer 43

episodes of tissue infarction due to vascular occlusion symptoms depend on site and severity pain may be extremely severe

Question 44

sickle crisis consequences

Answer 44

tissue ischaemia and pain

Question 45

precipitants of sickle crisis

Answer 45

- hypoxia - dehydration - infection - cold exposure - stress/fatigue

Question 46

sickle crisis treatment

Answer 46

medical emergency - opiate analgesia - hydration (IV fluids) - rest - oxygen - antibiotics if evidence of infection if life-threatening (if sickling is happening in lungs or brain) - red cell exchange transfusion

Question 47

when would red cell exchange transfusion be used in the treatment of sickle crisis

Answer 47

severe crisis eg (lung) chest crisis or (brain)stroke to rapidly reduce proportion of HbS in blood

Question 48

longterm management of sickle

Answer 48

Hyposplenism - reduce risk of infection: - prophylactic penicillin - vaccination; pneumococcus, meningococcus, haemophilus Folic acid supplementation (↑ RBC turnover so ↑demand) Hydroxycarbamide can reduce severity of disease by inducing HbF production Regular transfusion to prevent stroke in selected cases

Question 49

haemoglobinopathy diagnosis - simple first things

Answer 49

- FBC; Hb, red cell indices - Blood film - Ethnic origin

Question 50

haemoglobinopathy diagnosis - high performance liquid chromatography or electrophoresis what are these tests for

Answer 50

to quantify haemoglobins present Identifies abnormal haemoglobins eg HbS Raised HbA2 diagnostic of beta thal trait

Question 51

screening for haemoglobinopathies

Answer 51

antenatal to identify carrier parents now standard family origin questionnaire and FBC further testing if from high risk area or abnormal RBC indices newborn screening programme also in place

Question 52

thalassaemia trait is believed to confer some protection against _________ __________

Answer 52

falciparum malaria