Haemoglobinopathy

Question 1

HbA2 is made up of what chains?

Answer 1

2 alpha 2 delta

Question 2

main form of Hb

Answer 2

HbA (2 alpha 2 beta)

Question 3

alpha like genes are found on what chromosome?

Answer 3

16

Question 4

beta like genes are found on what chromosome?

Answer 4

11

Question 5

when are adult levels of Hb reached after birth?

Answer 5

6-12 months

Question 6

how does fetal Hb become adult Hb?

Answer 6

gamma chains switched off, beta chains switched on and replace it

Question 7

what are haemoglobinopathies?

Answer 7

hereditary conditions affecting the globin chain

Question 8

what happens in thalassaemia?

Answer 8

make a globin chain but not ENOUGH of it because of decreased rate of globin chain synthesis

Question 9

what happens in structural Hb variants?

Answer 9

make a structurally abnormal globin chain

Question 10

name the 2 main types of h-opathy

Answer 10

thalassaemia

structural Hb variants

Question 11

2 types of thalassaemia

Answer 11

alpha and beta (depending on which chains are affected)

Question 12

what anaemia is caused from thalassaemia and why?

Answer 12

microcytic hypochromic anaemia because of inadequate Hb production from lack of or ineffective globin

Question 13

why do you get haemolysis and ineffective erythropoesis in thalassaemia?

Answer 13

unbalanced accumulation of globin chains is toxic

Question 14

thalassaemia is mono/polygenic

Answer 14

mono

Question 15

normally have _ alpha genes per cell, _ from each parent

Answer 15

4

2

Question 16

normally have _ beta genes per cell, _

from each parent

Answer 16

2

1

Question 17

what types of Hb are affected in alpha thalassaemia?

Answer 17

all of them as they all contain alpha chains

Question 18

what happens when you lose all your alpha genes?

Answer 18

hydrops fetalis

Question 19

what is HbH disease?

Answer 19

only 1 functional alpha chain out of 4

Question 20

how many genes are lost to give you alpha thalassaemia trait?

Answer 20

one or two

Question 21

symptoms of alpha thalassaemia trait

Answer 21

asymptomatic

Question 22

describe a film of alpha thal trait

Answer 22

microcytic, hypochromic red cells

mild anaemia

Question 23

how can you differentiate alpha thal trait from ID anaemia?

Answer 23

ferritin is normal in ATT

Question 24

describe a blood film of HbH disease

Answer 24

anaemia
VERY low MCV
MCH

Question 25

what is HbH

Answer 25

tetramers formed by excess B chains in the presence of alpha thalassaemia

Question 26

clinical presentation of HbH

Answer 26

SE asian patient moderate-severe anaemia splenomegaly jaundice from haemolysis/ineffective erythopoesis

Question 27

why do patients with thalassaemias get splenomegaly sometimes?

Answer 27

undergo extramedullary haematopoesis as bone marrow cant make RBCs

Question 28

clinical features of hydrops fetalis

Answer 28

``` severe anaemia cardiac failure growth retardation severe hepatosplenomegaly skeletal problems death in utero ```

Question 29

blood film of hydrops fetalis?

Answer 29

nucleated RBCs in peripheral blood

Question 30

genetic cause of beta thal?

Answer 30

point mutation

Question 31

what Hb type is affected in beta thal?

Answer 31

HbA

Question 32

name the 3 types of beta thal

Answer 32

b thal trait b thal intermedia b thal major

Question 33

symptoms of b thal trait

Answer 33

asymptomatic no/mild anaemia low MCV/MCH

Question 34

what Hb type is raised in b thal trait

Answer 34

raised HbA2

Question 35

which type(s) of b thal is/are transfusion dependent

Answer 35

b thal major

Question 36

when does b thal major present? why?

Answer 36

6-24 months | HbF falls and HbB should take over

Question 37

clinical presentation of b thal major

Answer 37

``` pallor failure to thrive hepatosplenomegaly skeletal changes organ damage (from extramedullary haematopoesis) ```

Question 38

what Hb types are most prominent in b thal major?

Answer 38

HbF mainly | minimal HbA

Question 39

complication of extramedullary haematopoesis

Answer 39

cord compression

Question 40

Tx b thal major

Answer 40

transfusion- Hb 95-105g/l | BM transplant

Question 41

main complication of transfusion in b thal major

Answer 41

iron overload

Question 42

consequences of iron overload in thalassaemia?

Answer 42

endocrine- impaired growth/diabetes/osteo cardiac disease - arrhythmias/myopathy liver - cirrhosis/hepatocellular cancer

Question 43

Tx iron overload

Answer 43

iron chelating drug eg desferrioxamine | keep iron to 250mg per unit of red cells in transfusions

Question 44

what do iron chelating drugs do?

Answer 44

bind to iron to create a complex that allows it to be excreted

Question 45

genetic cause of sickle cell? what substance is affected?

Answer 45

point mutation in the B globin gene | produces substance called "beta S"

Question 46

what is the Hb structure in sickle cell?

Answer 46

HbS (A2 BS2)

Question 47

describe the B genes in sickle trait

Answer 47

1 normal B gene | 1 abnormal Bs gene

Question 48

sickle trait is asymptomatic T or F

Answer 48

T

Question 49

what Hb type is mainly in sickle trait?

Answer 49

HbA | do get HbS

Question 50

B genes present in sickle cell anaemia?

Answer 50

2 Bs genes

Question 51

inheritance of SCA

Answer 51

AR

Question 52

what types of Hb are present in SCA

Answer 52

HbS in most | NO HbA!!

Question 53

what is sickle crisis?

Answer 53

episodes of tissue infarction due to vascular occlusion by wedged sickle cells

Question 54

symptoms of sickle crisis

Answer 54

depend on site and severity | pain

Question 55

locations of sickle crisis?

Answer 55

digits, BM, lung, spleen, CNS

Question 56

why is there haemolysis in SCA?

Answer 56

RBCs have much shorter life span as they have a sickle shape

Question 57

precipitants of sickle crisis

Answer 57

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

Question 58

Tx sickle crisis

Answer 58

``` opiate analgesia hydration rest O2 antibiotics if infection venesect-transfuse if severe ```

Question 59

why do SCA patients get hyposplenism

Answer 59

common site of infarction in sickle crisis

Question 60

long term effects of SCA

Answer 60

impaired growth | end organ damage eg pulm HT, renal disease, stroke

Question 61

long term Tx of SCA

Answer 61

prophylactic ABs for hyposplenism folic acid supplements to inc RBC turnover hydroxycarbamide regular transfusion

Question 62

Ix haemoglobinopathy

Answer 62

FBC Hb red cell indices liquid chromatography orgel electrophoresis to check what Hbs are present

Question 63

raised HbA2 is diagnostic of....

Answer 63

beta thal trait