Thalassemia

Question 1

Inheritance of thalassemia

Answer 1

Autosomal recessive

Question 2

Affect of thalassemias on RBC

Answer 2

Anaemia
Microcytic RBC

Question 3

Why do thalassemias cause anaemia

Answer 3

Shsortened RBC half life and bone marrow cant keep up with RBC production

Question 4

What can increased RBC destruction cause

Answer 4

Jaundice
Increased likelihood for gallstones

Question 5

When does alpha thalassemia start affecting patient

Answer 5

First trimester of pregnancy to adulthood as require alpha chains from foetus for Hb

Question 6

When does beta thalassemia start affecting patient

Answer 6

After 4-5 months old - when beta chains start being importnat for Hb

Question 7

What genetic abnormality causes beta thalassemia major

Answer 7

2 abnormal genes

Question 8

Situations that can cause beta thalassemia intermedia

Answer 8

2 mildly abnormal genese
One very abnormal gene

Question 9

What is dominant negative beta thalassemia

Answer 9

Where the one abnormal beta chain protein inhibits function of the normal protein

Question 10

What beta thalassemia diseases require regular transfusions

Answer 10

Major = lifelong
Intermediate = regular potentiall required

Question 11

What will one gene abnormality in beta chain cause?

Answer 11

beta thalassemia trait - asymtpomatic

Question 12

What is the normal number of genes for encoding alpha chains

Answer 12

4

Question 13

What does alpha thalassemia severity depend on

Answer 13

how many genes lost

Question 14

What does 0 working alpha chains cause

Answer 14

Hb barts or hydrops fetalis - incompatible with life

Question 15

How can try and prevent alpha thalassemia complete causing hydrops fetalis

Answer 15

Intrauterine transfusion and post natal bone marrow transplant

Question 16

What does 3 working alpha genes cause

Answer 16

Asymptomatic, no anaemia, ay have slight miscrocytic RBC

Question 17

What causes HbH and what are the clinical features

Answer 17

1 working alpha gene
Microcytosis Marked anaemia
Surprisingly well often

Question 18

What does unbalaced/ineffective Hb stimulate

Answer 18

Production of more Hb
Iron absorpiton (causes Fe overlaod)

Question 19

What does overporduction of Hb cause

Answer 19

Extramedullay haemotopoeisis
Bony deformity

Question 20

What can bony deformity in thalassemia present as

Answer 20

‘hair on end’ skull radiograph
Thalassemic face - deformity
Risk of fractures

Question 21

Treatment for beta thalassemia symptomatic or physiological

Answer 21

1st line - blood transfusions - ALL beta majors
Hydroxycarbamide - beta intermedia
Lutacerpt- decrease transfusion burden in some
Bone marrow transplant
Gene therapy
Genetic counselling - select unaffected embryos
Iron chelation to mitigate overload effects

Question 22

Complications of thalassemia

Answer 22

Iron overlaod from regular blood transfusions

Question 23

iron overload complications (from transfusions)

Answer 23

Endocrine - diabetes, stunted grwoth
Cardiac arrhythmias
Hepatic toxiity - cirrhosis, HCC

Question 24

Summary of hereditary spherocytosis

Answer 24

• Often asymptomatic until increased O2 requirement
• Treatment supportive
• Folate replacement
• Increased thrombotic risk
• Increased risk of pulmonary HPTN

Question 25

G6PD deficinecy summary

Answer 25

- Acute haemolysis when exposed to oxidants - Classic = broad beans 9fava beans), many other drugs also cause haemolysis - Antimalarials, antibiotics, chemotherapy X linked (can affect females if both chromosomes affected)

Question 26

What do all inherited anaemias increase risk to?

Answer 26

- Specific risk from parvovirus B19 infection - Can cause temporary halt of RBC production -. profound anaemia

Question 27

What diseases cause iron overload due to transfusions but canot venesect as transfusion dependent eg may need iron chelation

Answer 27

, beta thalassemia major, severe beta thalassemia intermedia, sickle cell anemia, myelodysplasia, aplastic anemia

Question 28

Meds for thalassemia iron chelation

Answer 28

Deferixamine Deferrasirox

Question 29

HBH globin cells present

Answer 29

moderate anaemia and microcytic, hypochromic red cells anisopoikilocytosis (red blood cells of varying and abnormal sizes and shapes), teardrop cells and basophilic stippling.

Question 30

Test for thalassemia

Answer 30

haemoglobin electrophoresis

Question 31

When give folic acid supplementation

Answer 31

High turnover of RBC eg haemolysis

Question 32

Haemoglobin electrophoresis in alphA HbH disease

Answer 32

Reduced HbA Increased HbH = large amounts

Question 33

Haemoglobin electrophoresis in beta thalassemia trait

Answer 33

raised level of haemoglobin A2 (HbA2)

Question 34

Features of beta thalassemia major

Answer 34

Severe anaemia Bony expainsion Hepatosplenomegaly and jaundice

Question 35

What surgery can reduce blood requirement in beta thalassemia major

Answer 35

Splenectomy

Question 36

Investigation results in beta thalassemia majro

Answer 36

Full blood count: microcytic anaemia Liver function tests: isolated hyperbilirubinemia Ferritin or iron studies: normal iron levels, differentiating thalassaemia from iron deficiency anaemia Blood film: hypochromic, microcytic anaemia, nucleated red blood cells, target cells, polychromasia (reticulocytes) and basophilic stippling Haemoglobin electrophoresis or HPLC: absence of HbA, both HbF and HbA2 are elevated

Question 37

Screening for thalassemia

Answer 37

Pregnant women are offered a blood test before they reach 10 weeks gestation to identify carriers of thalassaemia. If mum is carrier father offered testing. If both parents -> chorionic villus sampling or amniocentesis->thalassaemia status. Testing for thalassaemia is also included in the newborn blood spot for babies 5-8 days old.

Question 38

What infections does splenectomy increase the risk of

Answer 38

pneumococcal, Haemophilus and meningococcal infection

Question 39

Infections seen in iron overlaod

Answer 39

klebsiella, yersinia and fungal infection

Question 40

Blood transfusion complications if regular

Answer 40

Infection Osteoporosis Transfusion reactions Alloimmunisation - transfused patient develops antibodies against red cell antigens, difficulties crossmatching and trasnfusion reactions Endocrine complications: due to iron overload, patients can develop delayed sexual maturation, infertility, thyroid dysfunction and parathyroid dysfunction. Cardiovascular complications: iron overload increase the risk of arrhythmias and heart failure due to iron-induced cardiomyopathy. Thrombosis: thalassaemia increases the risk of thrombosis. Other complications: gallstones, leg ulcers, gout and skin bronzing due to iron overload