Haemoglobinopathy

Question 1

structure of haemoglobin

Answer 1

tetramer made of 2 alpha and 2 beta chains

Question 2

how many haem groups are attached to each globin chain

Answer 2

one

Question 3

use of globin chains on heme

Answer 3

keep it soluble and protect it from oxidation

Question 4

in adults which form of haemoglobin is major present form

Answer 4

HbA

Question 5

major forms of haemoglobin

Answer 5

HbA 2 alpha chains and 2 beta chains α2β2

HbA2 2 alpha and 2 delta chains α2δ2

HbF 2 alpha and 2 gamma chains

Question 6

what are haemoglobinopathies

Answer 6

term for any hereditary conditins affecting global chain synthesis

autosomal recessive

Question 7

two groups of haemoglobinopathies

Answer 7

Thalassaemias; decreased rate of globin chain synthesis

Structural haemoglobin variants; mutations in globin genes leading to altered structures of haemoglobin molecule

Question 8

consequences of thalassemias

Answer 8

Inadequate Hb production → microcytic hypochromic anaemia
If severe:
Unbalanced accumulation of globin chains which are toxic to the cell
Ineffective erythropoiesis
Haemolysis

Question 9

alpha thalassaemia

Answer 9

mutations affecting alpha globin chain synthesis

results from deletion

normal people have four alpha genes

Question 10

alpha thalassaemia trait

Answer 10

one or two alpha genes missing

asymptomatic carrier state, microcytic hypochromic red cells but ferritin normal

Question 11

HbH disease

Answer 11

only one alpha gene left

moderate to severe anemia

very low MCV and MCH

jaundice, splenomegaly

common in se asia

Question 12

hb barts hydrops fetalis

Answer 12

no functional alpha genes

incompatible with life

Profound anaemia
Cardiac failure
Growth retardation
Severe hepatosplenomegaly
Skeletal and cardiovascular abnormalities
Almost all die in utero

Question 13

beta thalassaemia and common cause

Answer 13

disorder of beta chain synthesis and caused by point mutations

Question 14

b thalassaemia major

Answer 14

Presents aged 6-24 months (as HbF falls)

Pallor, failure to thrive

Extramedullary haematopoiesis causing;
Hepatosplenomegaly
Skeletal changes
Organ damage

lifelong transfusion dependancy

Question 15

consequences of iron overload

Answer 15

Endocrine dysfunction
Impaired growth and pubertal development
Diabetes
Osteoporosis
Cardiac disease
Cardiomyopathy
Arrhythmias
Liver disease
Cirrhosis
Hepatocellular cancer

Question 16

cause of sickle cell

Answer 16

point mutation i codon 6 of the b globin gene that substitute glutamine to valine producing bs

mutation alters the structure of the resulting hb > hbs

Question 17

what happens to hbs if exposed to o2 for long period of time

Answer 17

distorts the red cell damaging the rbc membrane

Question 18

sickle cell trait

Answer 18

one normal one abnormal b gene

HbAS

Question 19

how many abnormal genees in sickle cell anemia

Answer 19

two

Question 20

examples of other sickling disorders

Answer 20

HbS/β thalassaemia
HbSC disease; milder, but increased risk of thrombosis

Question 21

what is sickle vaso occlusion

Answer 21

a sickle crisis

blockage or restriction of blood flow in blood vessels cused by sickle shaped red blood ells

Question 22

precipitants of sickle crisis

Answer 22

Hypoxia ‏
Dehydration
Infection
Cold exposure
Stress/fatigue

Question 23

treatment of sickle crisis

Answer 23

Opiate analgesia
Hydration
Rest
Oxygen
Antibiotics if evidence of infection
Red cell exchange transfusion in severe crisis eg (lung) chest crisis or (brain)stroke to rapidly reduce proportion of HbS in blood

Question 24

long term management of sickle cell disease

Answer 24

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 25

haemoglobinopathy investigations

Answer 25

• Bloods - FBC, Hb, red cell indices, blood film
• High performance liquid chromatography (HPLC) or electophoresis to quantify haemoglobins present