Haemoglobinopathy

Question 1

what is the structure of adult haemoglobulin

Answer 1

2 alpha globin chains
2 beta globin chains
4 Haem groups (1 per chain)

Question 2

what makes up Haem

Answer 2

porphyrin ring with iron in the middle

Question 3

what are the 2 main forms of haemoglobin

Answer 3

HbA - adult (2 alpha, 2 beta chains)

HbA2 (2 alpha, 2 delta chains)

HbF - fetal (2 alpha, 2 gamma)

Question 4

what are the percentages of the different types of Hb in the blood

Answer 4

97% HbA
2.5% HbA2
0-0.5% HbF

Question 5

where are alpha globing genes produced

Answer 5

chromosome 16

Question 6

where are beta globulin genes produced

Answer 6

chromosome 11

Question 7

when do adult haemoglobin levels reach max

Answer 7

6-12 months

therefore beta chain problems won’t manifest until then

Question 8

what are the haemoglobinopathies

Answer 8

hereditary conditions affecting globin chain synthesis

autosomal recessive disorders

Question 9

what are the two main groups of haemoglobinopathies

Answer 9

Thhalassaemias
-decreased rate of normal globin chain synthesis

Structural haemoglobin variants

• normal production of abnormal global chain
• eg. sickle cell anaemia

Question 10

what are the two main thalassaemia categories

Answer 10

alpha thalassaemia
-underproducing alpha chains

beta thalassaemia
-underproducing beta chains

Question 11

what are the consequences of thalassaemias

Answer 11

Inadequate Hb production leading to MICROCYTIC HYPOCHROMIC ANAEMIA (small red blood cells with no Jb in them)

Question 12

severe side effects of thalassaemias

Answer 12

unbalanced accumulation of globing chains which are toxic to the cells

haemolysis

ineffective erythropoiesis

Question 13

what infectious disease is linked to thalassaemias

Answer 13

malarias

-haemoglobinopaties protect against malaria

Question 14

what is alpha thalassaemia trait

Answer 14

one or two alpha chains are missing

in normal person there are 4

leads to mild microcytic hypochromic anaemia

does not need treated but need to distinguish from iron deficiency

Question 15

what is HbH disease

Answer 15

only 1 alpha chain left
red cells are even smaller
much more serious

inherited no working genes from one parent and none from the other

Question 16

what is Hb Parts hydros fetalis

Answer 16

no functional alpha genes

antenatal screening to avoid

gamma 4 chains and beta 4 chains form which aren’t functional

Question 17

what happens in HbH disease

Answer 17

not enough alpha chains

therefor the beta chains form tetramers (B4) called HbH - these are non-functional

common in Asia

Question 18

clinical features of Hb Parts hydros fetalis

Answer 18

profound anaemia 
cardiac failure 
growth retardation 
severe hepatosplenomegaly 
skeletal and cardiovascular abnormalities 
almost all die in utero

Question 19

what is beta thalassaemia

Answer 19

disorder of beta chain synthesis

reduced or absent beta chain production

only HbA affected not HbF so doesn’t present until a few months into life

Question 20

3 classifications of beta thalassaemia

Answer 20

B thalassaemia train
B thalassaemia intermedia
B thalassamia major

Question 21

what is b thalassaemia major

Answer 21

most severe 
presents at 6-24 months 
pallor, failure to thrive 
extra medullar haematopoiesis causing 
-hepatosplenomegaly 
-skeletal changes 
-organ damage

Question 22

treatment of b thalasassaemia major

Answer 22

regular transfusion program to maintain Hb at 95-105g/l

• suppresses ineffective erythropoiesis
• inhibit over-absorption of iron

bone marrow transplant could be an option before complications occur

Question 23

risks of blood transfusions in b thalassaemia major

Answer 23

iron overload - can cause mortality

damages endocrine glands, heart and liver

need to give iron chelating drugs

other complications:

• infection
• alloantibodies
• transfusion reactions
• increased sepsis risk

Question 24

what are sickling disorders

-making haemoglobin just abnormal Hb

Answer 24

altered form of haemoglobin

sickle cell anaemia = point mutation in codon 6 of the b globing gene

results in HbS production

Question 25

what does HbS do to RBCs

Answer 25

polymerised if exposed to low oxygen levels

distorts the red cell, damaging RBC membrane

Question 26

what is sickle cell trait

Answer 26

asymptomatic carrier - people are well

not enough HbS to cause disease (polymerise) but may sickle under severe hypoxia eg. high altitude or anaesthetic

Question 27

what happens in sickle cell anaemia

Answer 27

two abnormal B genes

HbS>80% with no HbA

episodes of tissue infarction due to vascular occlusion - sickle crisis giving extreme pain

chronic haemolysis

hyposplenism due to repeated splenic infarcts

Question 28

what is sickle cell crisis

Answer 28

severe pain due to vast-occlusion causing infarction of tissue

Question 29

what can trigger sickle crisis

Answer 29

hypoxia 
dehydration 
infection 
cold exposure 
stress/fatigue

Question 30

treatment of sickle crisis

Answer 30

opiate analgesia 
hydration 
rest
oxygen 
antibiotics if evidence of infection 
red cell exchange transfusion in severe crisis eg. (Lung, or brain)

Question 31

long term management of sickle cell disease

Answer 31

Hyposplenism - reduce risk of infection

• prophylactic penicillin
• vaccination

Folic acid supplementation

Hydroxycarbamide - induces HbF production

regular transfusion to prevent stroke

Question 32

how do you diagnose a haemoglobinopathy

Answer 32

FBC, Hb, red cell count
blood film
ferritin - rule out iron deficiency
ethnic origin

High performance liquid chromatography to quantify haemoglobins present

Question 33

what is a diagnostic trait of beta thalassamia trait

Answer 33

raised HbA2