1.06 Haemoglobinopathies

Question 1

HbA

Answer 1

2 alpha

2 beta

Question 2

HbA2

Answer 2

2 alpha

2 delta

Question 3

HbF

Answer 3

2 alpha

2 gamma

Question 4

What is the distribution of Hb in adults?

Answer 4

HbA- 97%
HbA2- 2.5%
HbF 0.5%

Question 5

alpha genes

• number
• chromsome

Answer 5

4 per cell - 2 per chromosome

on chromosome 16

Question 6

beta genes

• number
• chromosome

Answer 6

2 per cell - 1 per chromosome

on chromosome 11

Question 7

thalassaemias

Answer 7

decreased rate of globin chain production

unbalanced accumulation of globin chains –> ineffective erythropoiesis and haemolysis

Question 8

structural hb variants

Answer 8

normal production of structurally abnormal globin chains

-HbS

Question 9

alpha thalassaemia

Answer 9

alpha chains affected

Question 10

beta thalassaemia

Answer 10

beta chains affected

Question 11

reduced synthesis of alpha globin

Answer 11

a^+

Question 12

absent synthesis of alpha globin

Answer 12

a^o

Question 13

which mutation is most common in the cause of alpha thalassaemia?

Answer 13

deletional mutation

Question 14

point mutation alpha thalassaemia

Answer 14

rare
more profound alpha chain reduction
non-deletional a-thalassaemia

Question 15

which hb are affected in alpha thalassaemia?

Answer 15

HbA
HbA2
HbF

Question 16

what are the 4 classifications of alpha thalassaemias?

Answer 16

• a/aa= silent a-thal trait
• a/-a or –/aa = a-thal trait
• -/-a = HbH disease
• -/– = Barts hydrops fetalis = no functional a-genes

Question 17

alpha thal trait
–/aa

clinical and lab findings?

Answer 17

clinically asymptomatic
microcytic hypochromic red cells, mild anaemia
normal ferritin
raised red cell count
HbH bodis - red ell inclusions can be seen sometimes = golf ball appearance

Question 18

HbH disease

lab findings?

Answer 18

severe

a-chain production is

Question 19

HbH clinical findings?

Answer 19

asymptomatic to transfusion dependent
splenomegaly- extramedullary haematopoiesis
jaundice- haemolysis, ineffective erythropoiesis
growth retardation
gallstones
iron overload

Question 20

Inheritance of HbH?

Answer 20

autosomal recessive

Question 21

Mx of HbH?

Answer 21

mild- tranfusion at intercurrent illness
severe- transfusion dependent
splenectomy- vaccinate and prophylaxis for encapsulated bacteria
folic acid supplements

Question 22

HbBarts

Answer 22

4 gamma globulins

Question 23

clinical features of barts hydrops fetalis syndrome

Answer 23

pallor 
oedema
cardiac failure
growth retardation 
severe hepatosplenomegaly
skeletal and cardiovascular abnormalities

most die in utero, some de shortly after birth

Question 24

preventing barts hydrops fetalis

Answer 24

antenatal screening high risk parents

• family origin questionnaire
• fbc
• further testing if either flagged up

counsel couples at risk
prenatal diagnosis with selective termination

Question 25

dx of alpha thalassaemia

Answer 25

red cell indices + ethnicity rule out iron deficiency blood film- target cells, anisopoikilocytosis liquid chromatography or electrophoresis to quantify Hb, identify abnormal Hb, and exclude beta-thal trait

Question 26

what alpha-thal mutation is found in all populations?

Answer 26

-a^3.7 (a+ mutation)

Question 27

what alpha thal mutation is more common in SE asia?

Answer 27

--^SEA (a0 mutation)

Question 28

Which Hb type is affected in beta-thalassaemia?

Answer 28

HbA

Question 29

what is the usual mutation and inheritance pattern of beta thal?

Answer 29

``` point mutation (opposite of alpha thal) autosomal recessive inheritance (like alpha thal) ```

Question 30

beta thal trait | -general description

Answer 30

B+/B or Bo/B asymptomatic low MCV/MCH raised HbA2 is diagnostic (2 alpha 2 delta)

Question 31

beta thal intermedia | -general description

Answer 31

B+/B+ or Bo/B+ moderate severity occasional transfusion

Question 32

beta thal major | -general description

Answer 32

severe, lifelong transfusion dependency

Question 33

Anaemia found in beta-thal major?

Answer 33

mod-severe anaemia 30-90g/L very low MCV/MCH reticulocytosis film: anisopoikilocytosis, target cells HPLC(liquid chroma) - HbF mainly - small amounts HbA - HbA2 often elevated

Question 34

clinical features of beta-thal major

Answer 34

``` presenting 6-24 months with failure to thrive pallow extrapedullar paematopoiesis- hepatospenomegaly skeletal change organ damage ```

Question 35

management of b-thal major

Answer 35

regular transfusion to maintain 95-105g/L - suppress erythropoiesis, inhibit overabsorption of iron - avoid iron overload (desferro) - consider bone marrow transplant before complications

Question 36

Transfusion related complications

Answer 36

viral- HIV, HepB, HepC alloantibodies = hard to cross match transfusion reactions Other: bacterial sepsis

Question 37

consequences of iron overload

Answer 37

endo: impaired growth and pubertal development, DM, osteoporosis cardiac: myopathy, arrhythmias liver: cirrhosis, hepatocellular cancer

Question 38

how much iron per unit of RBC?

Answer 38

250mg

Question 39

iron chelating drug

Answer 39

desferrioxamine | binds iron and complexes excreted in urine or stool

Question 40

sickle cell anaemia inheritance and mutation pattern?

Answer 40

autosomal recessive | point mutation in codon 6 of beta-globin gene (glutamine to valine)

Question 41

what is the problem with HbS?

Answer 41

polymerises at low oxygen levels distortion of red cell damages RBC membrane

Question 42

HbAS What is this disease? What is the impact?

Answer 42

sickle cell trait only 1 abnormal beta gene asymptomatic carrier state may sickle in severe hypoxia- high altitude, or under anaesthesia

Question 43

What are the lab findings of HbAS?

Answer 43

blood film- normal or mild decrease in MCV?MCH | mainly HbA, HbS

Question 44

HbSS what is this disease? what is the impact?

Answer 44

this is sickle cell anaemia- no abnormal b-genes HbS >80%, no HbA, variable HbF tisue infarction- digits, bone marrow, spleen, CNS, lung, renal, leg ulcers, pain +++ chronic haemolysis sequestration of sickle cells in liver and spleen

Question 45

What are the 5 ppts of sickle crisis?

Answer 45

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

Question 46

How do you treat a painful crisis of sickle cell anaemia?

Answer 46

opiates hydration rest oxygen antibiotics if s/s infection red cell exchange transufusion in extreme crisis- chest crisis or neurological symptoms

Question 47

LT effects of sickle cell anaemia?

Answer 47

poor growth infections- hypospleenism due to infarcts organ damage- pulmonary hypertension, renal disease, avascular necrosis of bines, CVA, impotence psychosocial problems

Question 48

long term treatment of sick cell anaemia

Answer 48

``` education/lifestyle avoid PPTs reduce infection risk -penicillin prophylaxis -vaccination- pneumococcus, meningococcus, haemophilus -folic acid supplmentation ``` -hydroxycarbamide, hydroxyurea can reduce severity of this disease by inducing HbF production

Question 49

mild or severe: | HbS/B thalassaemia

Answer 49

mild if B+ (reduced) | severe if Bo (absent)

Question 50

mild or severe: | HbSC

Answer 50

milder but increased risk of thrombosis

Question 51

mild or severe: | HbS/Dpunjab

Answer 51

severe

Question 52

mild or severe: | HbS/Oarab

Answer 52

severe