Theme 7 Haematology: Haemaglobinopathies, Obstetric Haematology and paediatric haematology

Question 1

When do you have a haemoglobinopathy screening in pregnancy?

Answer 1

around 8 weeks

Question 2

What testing is carried out if:

1. In low prevalence area
2. In high prevalence area

Answer 2

1. family origin and FBC

2. HPLC +/- partner testing

Question 3

When is a haemoglobinopathy screening carried out post-natally?

Answer 3

at 5 days

Question 4

What is the post natal haemoglobinopathy screening test?

Answer 4

heel prick test:

• analysis of dried blood spot
• multiple conditions tested for
• goal is early detection of sickle cell disease

Question 5

State the haematological changes in pregnancy

Answer 5

• plasma volume expands by 50%
• red cell mass expands by 25%
• haemodilution occurs –> this means there is a fall in haemoglobin as the plasma volume expands faster than the red cell mass
• the MCV increases
• folic acid requirements increase
• leukocytosis (mainly a neutrophilia

Question 6

What is the most common cause of anaemia in pregnancy?

Answer 6

iron deficiency

Question 7

What happens to your platelet count during pregnancy?

Answer 7

• gestational thrombocytopenia

- platelet count drops in some women toward the end of pregnancy

Question 8

What is the coagulation state in pregnancy?

Answer 8

• pregnancy is a pro-thrombotic state
• evidence of platelet activation
• reduction in anticoagulants and fibrinolysis
• rise in thrombin generation

Question 9

Which coagulation factors are increased in pregnancy?

Answer 9

• plasma fibrinogen and FVII
• FV, VIII, X, XII
• big increase in vWF

Question 10

erythrocyte production is controlled by what?

Answer 10

erythropoietin produced in kidneys

Question 11

What is the function of the globin chain in haemoglobin

Answer 11

• protects haem from oxidation
• renders the molecule soluble
• permits variation in oxygen affinity

Question 12

Explain the genetic control of an adult globin chain

Answer 12

• alpha chains produced on chromosome 16
• beta or gamma chains produced on chromosome 11
• forms Hb-A (adult haemaglobin)

Question 13

Explain the genetic control of an foetal globin chain

Answer 13

• alpha chains produced on chromosome 16

- delta chains produced on chromosome 11 produce Hb-F

Question 14

What is a haemaglobinopathy?

Answer 14

changes in globin genes or their expression leads to disease

Question 15

What is a thalassaemia?

Answer 15

• alpha or beta
• change in globin gene expression leads to reduced rate of synthesis of normal globin chains
• pathology is due to imbalance of alpha and beta chain production

Question 16

Explain structural Hb variants

Answer 16

• usually a single base substitution in globin gene
• altered structure and function
• HbS (sickle), C, D, E

Question 17

What is the relationship between worldwide distribution of haemoglobin disorders and falciparum malaria?

Answer 17

suspected that the mutations persisted because they offer a survival advantage as the different red cell membrane in haemaglobin disorders results in resistance to malarial attack

Question 18

How do we diagnose a haemaglobinopathy?

Answer 18

• FBC
• haemaglobin electrophoresis
• isoelectric focusing
• high performance liquid chromatography (HPLC)

specialist tests:

• heat stability, isopropanol
• oxygen dissociation curve
• DNA analysis
• mass spectrometry

Question 19

When is the sickle cell trait a problem?

Answer 19

extreme hypoxia/ dehydration e.g bad anaesthesia or flying unpressurised military aircraft

Question 20

Why are sickle cells so called?

Answer 20

Hb-S polymerises to form long fibrils which distort the red cell membrane and produce the classical sickle shape

Question 21

Why do people with sickle cell disease have haemolytic anaemia?

Answer 21

the sickled red cells have a short life span in the blood so it requires a massive increase in red cell turnover to maintain haemoglobin

Question 22

What is haemolytic anaemia?

Answer 22

a disorder in which red blood cells are destroyed faster than they are made

Question 23

In sickle cell disease, what will you expect to see on:

1. Blood count
2. Blood film
3. Hb electrophoresis

Answer 23

1. anaemia
2. visible sickle cells and hyposplenism
3. Hb-S > 95%, Hb-A 0%

Question 24

How might a patient with sickle cell disease present?

Answer 24

• usually 3-6 months old

- may present with jaundice, physically enlarged spleen until hyposplenism in the first decade

Question 25

What are the acute complications of sickle cell disease?

Answer 25

- vaso-occlusive crisis --> hands and feet pain (dactylitis), chest syndrome, abdominal pain, bone infarction, priapism (painful erection) - septicaemia due to underactive spleen - aplastic crisis - sequestration crisis - rapid pooling of red cells and enlargement of organ

Question 26

What are the chronic complications of sickle cell disease?

Answer 26

- hyposplenism: due to infarction and atrophy of spleen - renal disease - avascular necrosis - chronic renal failure/ dialysis

Question 27

When should you transfuse patients with sickle cell?

Answer 27

in acute chest crisis, acute stroke, pre-operative and splenic sequestration

Question 28

What is the main medical therapy for sickle cell?

Answer 28

hydroxycarbamide - increases % of HbF in blood - acts as an anti-inflammatory

Question 29

What are the most common single gene disorders?

Answer 29

thalassaemia

Question 30

What are the different types of thalassaemias?

Answer 30

• Divided into a, B, δβ , and γδβ according to which globin chain is reduced

Question 31

What is the pathology of B-thalassaemia?

Answer 31

- reduced rate of production of beta globin chains | - pathology caused by excess alpha chains

Question 32

What will a blood picture look like from a patient with B-thalassaemia?

Answer 32

- resembles iron deficiency - small, pale red cells - MCV reduced

Question 33

What are the medical complications of thalassaemia intermedia?

Answer 33

- pulmonary hypertension - extra medullary haematopoiesis - bone changes and osteoporosis - endocrine and fertility - leg ulcers

Question 34

What are the signs and symptoms of B-thalassaemia major?

Answer 34

- very severe anaemia - short stature and distorted limb growth due to premature closure of epiphyses in long bones - child will be pale and failure to thrive - enlarged liver and spleen

Question 35

Explain the pathology of B-thalassaemia major

Answer 35

- anaemia arises because there is alpha chain excess -this causes ineffective erythropoiesis (red cells die in marrow) - so there is a shortened red cell lifespan (haemolysis)

Question 36

What does a thalassaemic face look like?

Answer 36

- maxillary hyperthrophy - abnormal dentition - frontal bossing due to expanded bone marrow

Question 37

What is an "hair on end" skull

Answer 37

- in X-ray of skull of thalassaemic patients | - due to widening of diploic cavities by marrow expansion

Question 38

Why do we use a transfusion to treat B-thalassaemia major?

Answer 38

- to maintain mean Hb 120g/l | - suppresses marrow red cell production and prevents skeletal deformity and liver/spleen enlargement

Question 39

What are the complications of transfusion?

Answer 39

- transmission of infection - iron overload - allo-immunisation - formation of allo antibodies that make it harder to cross-match blood and infection

Question 40

What is the biggest cause of death in patients with thalassaemia?

Answer 40

heart failure

Question 41

How is iron overload prevented in thalassaemic patients?

Answer 41

- iron chelation therapy | - desferrioxamine

Question 42

In antenatal screening for haemoglobin disorders, what are the options if antenatal test is positive?

Answer 42

- pre-implantation diagnostic testing - choriovillus biopsy - termination

Question 43

How do healthy neonates and children differ haematologically from adults?

Answer 43

- neutrophils are increased in babies - eosinophils and basophils do not change much in quantity - you have the adequate number of platelets in a baby at 20 weeks

Question 44

When are blood cells first made

Answer 44

day 18 in the yolk sac

Question 45

What are the acquired causes of anaemia in childhood?

Answer 45

- physiological - infection - tumours - trauma - iatrogenic - any systems

Question 46

What is the most common cause of anaemia in children?

Answer 46

iron deficiency