genetic conditions

Question 1

what does hydroycarbamide/ hydroxyurea do for sickle cell disease

Answer 1

increases the levels of HbF

Question 2

what is haemoglobin normally made of

Answer 2

2 alpha globin chains (4 genes) and 2 beta globin chains (2 genes)

Question 3

what are the consequences of thalassaemia

Answer 3

get haemolytic anaemia, get splenomegaly due to increased cell removal and EMH), get iron overload due to transfusions and get bone expansion

Question 4

universal features of thalassaemia

Answer 4

microcytic anaemia, splenomegaly, jaundice, pallor

Question 5

what are the three types of alpha thalassaemia

Answer 5

1) alpha thalassaemia trait
2) Haemoglobin H disease - 3 of the genes affected
3) Hydrops fatalis - all 4 of the alpha genes are defective, no alpha globin produced, not compatible with life

Question 6

what are the types of beta thalassamia

Answer 6

1) beta thalassaemia minor –> mild anaemia, just need monitoring
2) beta thalassaemia intermedia –> two defective genes or one defective and one deletion, get a more significant anaemia
3) beta thalassaemia major –> severe anaemia and failure to thrive. May have features like frontal bossing, enlarged maxilla and protruding teeth

Question 7

MX for thalassaemia

Answer 7

• tranfusions
• folic acid
• screening in pregnancy
• splenectomy
• bone marrow transplant can be curative

Question 8

what is the most common inherited thrombophilia

Answer 8

factor V leiden mutation

Question 9

what is factor V Leiden mutation

Answer 9

activated protein C resistance (and protein C normally has a role in anticoagulation)

Question 10

what is the consequence of factor V Leiden mutation

Answer 10

greater risk of VTE

Question 11

what is the pathophysiology of an acute chest crisis in SCD

Answer 11

vasoocclusion of the pulmonary microvasculature which then causes infarction

Question 12

symptoms of an acute chest crisis

Answer 12

sudden onset hypoxia, chest pain and see bilateral pulmonary infiltrates on Xray

Question 13

Mx of an acute chest crisis

Answer 13

pain relief, o2, abx

Question 14

what happens in a sequestration crisis in sickle cell disease

Answer 14

blood gets blocked in organs like the spleen due to sickling, but get a reticulocyte response as bone marrow is not affected (unlike in a aplastic crisis)

Question 15

what is the pathophysiology of SCD

Answer 15

autosomal recessive point mutation of glu –> val on chromosome 11 which makes HbS and this is means it can sickle in stress (infection, cold, hypoxia, dehydration)

Question 16

how might SCD present

Answer 16

anaemia, jaundice, in criss, recurrent infection, splenomegaly

Question 17

key Ix for SCD

Answer 17

FBC (see high reticulocytes), blood film, Hb electrophoresis
-newborn screening

Question 18

Mx of SCD

Answer 18

-avoid triggers of vasoocclusion like dehydration/ exhaustion
-abx prophylaxis and vaccinations
-may need transfusion
-hydroxycarbamide can be used to increase HbF

Question 19

complications of SCD

Answer 19

chronic pain, priapism, CKD, hyposplenism, avascular necrosis

Question 20

what is the most common inherited clotting disorder

Answer 20

von willebrands disease (1%) of population

Question 21

how does vWF normally present

Answer 21

commonly asymptomatic but can present with epistaxis, heavy menstrual bleeding

Question 22

what is vWF normal role

Answer 22

mediates platelet aggregation to damaged endothelium and it has a role in the intrinsic (APTT) pathway where it is a carrier for factor VIII

Question 23

what would bloods show for von willebrand disease

Answer 23

FBC normal, APTT normal or increased due to vWF being a carrier for FVIII, PT normal, fibrinogen normal

Question 24

Mx of von willebrand disease

Answer 24

lifestyle - avoid things which increase the bleed risk, desmopressin

Question 25

why can desmopressin be used to treat von willebrand disease

Answer 25

it increases the clotting factors in the blood

Question 26

what kind of haemolysis do you get in hereditary spherocytosis

Answer 26

extravascular haemolysis as the spherocytes are removed from the circulation and then get destroyed by the spleen

Question 27

what is the key diagnostic test for hereditary spherocytosis

Answer 27

MCHC (which is ELEVATED) due to the reduction in SA:vol

Question 28

Mx of hereditary spherocytosis

Answer 28

same as for all the haemoglobinopathies
-tranfusions
-folic acid supplementation –> to keep up with the rate of production of the RBC
-splenectomy

Question 29

characteristics of a warm haemolytic anaemia

Answer 29

CLL and autoimmune
-IgG and extravascular (extravascular means it happens in the spleen)
-Tx underlying condition or can treat with steroids or rituximab

Question 30

characteristics of a cold haemolytic anaemia

Answer 30

IgM mediated, intravascular
-malignancy and infection!!
-present with raynauds like symptoms
-harder to treat

Question 31

what is an example of an alloimmune haemolytic anaemia

Answer 31

ABO incompatibility reaction

Question 32

what is the firstline investigation for a haemolytic anaemia

Answer 32

direct Coombs test (add Coombs reagent and look for agglutination)

Question 33

what is the level of haptoglobin in a haemolytic anaemia

Answer 33

low as it mops up all the free Hb

Question 34

complications of haemolytic anaemias

Answer 34

high output heart failure, pigmented gallstones and pruritus

Question 35

what is it helpful to do if the cause of a haemolytic anaemia is unknown

Answer 35

a blood smear

Question 36

what is haemolytic anaemia triggered by in a G6PDH deficiency

Answer 36

medications, fava beans or infections (which cause oxidative stress to cells and cells do not have any NADPH to then repair)

Question 37

Investigations for G6PDH deficiency

Answer 37

G6PDH assay