Session 5- Haemoglobinpathies and Haemolytic anaemias

Question 1

Haemoglobinopathies

Answer 1

inherited disorders where expression of one or more of the globin chains of haemoglobin are abnormal

autosmal recessive diseass

Question 2

abnormal haemoglobin variants

Answer 2

result from mutations in the genes fr alpha or beta chains that alter the stability and/or function of haemogobin

Question 3

thalassaemia

Answer 3

result from reduced or absent expression of normal alpha or beta globin chains. This leads to a reduced level of haemoglobin rather than the presence of an abmoraml haemoglobin

Question 4

what Hb variant is present in sickle cell

Answer 4

HbS- uncharged valine instead of a charged glutamic acid at position 6 of beta-globin making haemoglobin S more prone to polymerise at low oxygen tension.

Leads to the formation of long twisted haemoglobin polymers that can result in the deformation the red blood cell membrane

Question 5

consequences of sickle cell formation

Answer 5

vaso-occlusive episodes due to the occlusion of small capillaries from sickle cells getting trapped. Recuurent acute pain and syndromes such as stroke or acute chest syndrome as well as chronic kidney disease and joint damage from avascular necrosis

anaemia- due to sickle cells undergoing haemolysis resulting in a shortened erythrocyte lifespan

jaundice and gallstones due to increased bilirubin from chronic haemolysis

splenic atropy- splenic infarction with an associated susceptibility to infection by encapsulated bacteria such as strep pneumoniae and strep meningitidis

Question 6

cure for sickle cell disease

Answer 6

haematopoietic stem cell transportation is the only cure but rarely performed due to difficulty in finding a donor with a sufficient genetic match.

Question 7

treatment for sickle cell

Answer 7

concentrated on reducing symptoms with regular medical care to prevent complications

Question 8

what causes beta thalassaemia

Answer 8

m mutation in one or both of the β globin
genes leading to a reduction in the amount or total absence of the β
globin polypeptide chain.

Question 9

what causes microcytosis in beta thalassaemia

Answer 9

In heterozygous individuals where only one
of the two β globin genes are mutated the rate of β globin
production is reduced

Question 10

why doesnt thalassaemia usually result in anaemia

Answer 10

Despite this
reduction in red blood cell size, the total level of haemoglobin in
blood tends to remain normal because the bone marrow responds by
producing more red blood cells. Anaemia only really occurs in such
patients in times of increased demand such as pregnancy or
persistent infections

Question 11

beta-thalassaemia major

Answer 11

Synthesis of the β globin polypeptide chain is totally absent in such individuals and they are dependent on blood transfusions from the
first few months of life onwards in order to survive since the
synthesis of haemoglobin A cannot replace Haemoglobin F due to the lack of beta globin

Question 12

alpha thalassaemia

Answer 12

m deletion or loss of function of one or
more of the four α globin genes

mutation of the HBA gene on chromosome 16

Question 13

haemoglobin H disease

Answer 13

Lack of function in 3 of the 4
α globin genes

severe microcytosis, anaemia, haemolysis
and splenomegaly.

Question 14

haemolytic anaemia

Answer 14

Haemolytic anaemia results from the abnormal breakdown

(haemolysis) of red blood cells in blood vessels (intravascular
haemolysis) or the spleen (extravascular haemolysis).

Question 15

acquired damage to red cells - causes of haemolytic anaemia

Answer 15

mechanical damage 
antibody damage 
oxidant damage
heat damage-burns
enzymatic damage- snake venom

Question 16

inherited causes of haemolytic anaemia

Answer 16

glycolysis defect

pentose-p pathway- G6DPH deficiency leads to oxidative damage

membrane protein

haemoglobin defect

Question 17

symptoms of haemolytic anaemia

Answer 17

shortness of breath and fatigue,
however chronic increased haemolysis also leads accumulation of
bilirubin leading to jaundice and associated risk of complications such
as gallstones.

Question 18

micoangiopathic haemolytic anaemia

Answer 18

Microangiopathic haemolytic anaemias
(MAHA) are a group of acquired haemolytic
anaemias where red cells are damaged by
physical trauma

Question 19

what causes microangiopathic anaemia

Answer 19

Often the trauma results
from red cells getting snagged as they try to
pass through small vessels laden with fibrin strands in situations
where there is an increased activation of the coagulation cascade.

Question 20

disseminated intravascular coagulation

Answer 20

• a condition where bleeding and clotting occur at the same
  time in the patient e.g. in malignancy, obstetric complications,
  trauma, and sepsis

-blood clots form throughout the body

Question 21

thrombotic thrombocytopenic purpura

Answer 21

a

syndrome where small thrombi form within the microvasculature.

Question 22

aortic valve stenosis

Answer 22

Red blood
cells can also be damaged by the shear stress produced by a
defective heart valve

Question 23

schistocytes

Answer 23

red cell fragments resulting fro mechanical damage

a good indicator that some form of pathology is presnet

Question 24

causes of immune haemolytic anaemia

Answer 24

Immune haemolytic anaemias can result from infections,
lymphoproliferative disorders such as leukaemia or lymphoma and
reactions to drugs such as cephalosporins (class of antibiotic)

Question 25

warm immune haemolytic anaemia

Answer 25

IgG antibodies recognise epitopes on the red cell membrane. This leads to macrophages in the spleen recognising these antibody-coated red cells and either
disposing of the whole cell by phagocytosis or “nibbling” a bit off. In the latter case, since some membrane is lost, the red cell tends to “round up” forming a spherocyte often leads to splenomegaly

Question 26

cold immune haemolytic anaemia

Answer 26

autoantibodies recognise red cell epitopes and there is also complement fixed to the patient red cells. The IgM antibodies tend to bind to the red cells in more dital parts of the body such as fingertips especially in cold weather

Question 27

hereditary spherocytosis mode of inhertance and cause

Answer 27

s an inherited autosomal dominant disease
resulting in abnormalities in erythrocyte membrane proteins which
impede the ability of the cell to change shape.

mutations in the genes coding for spectrin, ankyrin, band 3 and protein 4.2 which are all invilved in facilating vertical interactions

Question 28

what does hereditary spherocytosis lead to

Answer 28

poor deformability of spherocytes means that they become trapped and damaged as they pass through the spleen (extravascular haemolysis) resulting in a reduction in the lifespan of erythrocytes and haemolytic anaemia.

Question 29

complications in hereditary spherocytosis

Answer 29

jaundice
splenomegaly
gall stones
anaemia

Question 30

EMA

Answer 30

(Eosin-5-Maleimide) binding test

a flourescent dye that binds to band 3 protien in the red cell membrane

analysis by flow cytometry measures the flourescent intensity of labelled intact red cells

Question 31

infectious mononucleosis

Answer 31

viral infection common in children

in young adults the disease often results in fever, sore throat, and enlarged lymph nodes

liver or spleen becomes enlarged

Question 32

what causes mono

Answer 32

epstein-barr virus

Question 33

how is mono spread

Answer 33

saliva, drinking glasses or toothbrushes

Question 34

how to test for mono

Answer 34

paul bunnell test