Haemoglobinoapthies

Question 1

Thalassaemia: definition

Answer 1

group of inherited disorders characterised by abnormal haemoglobin production

severity of disease depends on how many of the four genes for alpha globin or two genes for beta globin are defective. This results in alpha thalassaemia and beta thalassaemia, respectively.

Question 2

Alpha thalassaemia inheritance pattern

Answer 2

autosomal recessive inheritance pattern.

Question 3

Alpha-thalassaemia

Answer 3

non-functioning copies related to the four alpha globin genes

Patients with two defective copies have have a mild asymptomatic anaemia anaemia – the so-called alpha thalassaemia trait

Symptomatic disease results when two or more copies of the gene are lost –> Hb H disease

Question 4

A-thalassaemia features

Answer 4

Jaundice
Fatigue
Facial bone deformities

Question 5

Diagnosis of Alpha thalassaemia

Answer 5

genetic testing
FBC - IDA

Question 6

A-thalassaemia mx

Answer 6

blood transfusions and stem cell transplantation. Another option is splenectomy

Question 7

Beta thalassaemia inheritance mode

Answer 7

It has an autosomal recessive inheritance pattern.

Question 8

Pathophysiology of Beta thalassaemia major and minor

Answer 8

B thalassaemia = non-functioning copies of the two beta globin genes

Minor = 1 defective
Major = 2 defective

Question 9

B thalassaemia minor: features

Answer 9

Isolated microcytosis and mild anaemia.

Patients are typically asymptomatic.

Question 10

B thalassaemia major: features

Answer 10

Severe symptomatic anaemia at 3-9 months HbF to HbA
Frontal bossing
Maxillary overgrowth
Extramedullary hematopoiesis (hepatosplenomegaly).

Prognosis is usually death by heart failure if it goes undiagnosed.

Question 11

B - thalassaemia mx

Answer 11

regular blood transfusions.

Iron chelating agents e.g. deferoxamine –> reducing the risk of iron overload toxicity (affects the heart, joints, liver and endocrine glands

Question 12

Locus of 2 separate alpha-globulin genes

Answer 12

Both in chromosome 16

Question 13

Locus of beta globulin gene

Answer 13

chromosome 11

Question 14

SCD: genetics

Answer 14

glutamate is substituted by non-polar valine in each of the two beta chains (codon 6). This decreases the water solubility of deoxy-Hb

HbAS - sickle cell trait
HBSS - homozygous sickle cell disease

Question 15

PaO2 of sickling: HbAS vs HbSS

Answer 15

HbAS patients sickle at p02 2.5 - 4 kPa
HbSS patients at p02 5 - 6 kPa

Question 16

SCD: aetiology

Answer 16

Sickled red bloods cells can clump together, obstruct blood flow and hemolyse.
They are associated with varying degrees of anaemia.
Obstruction of small blood capillaries can cause painful crises, damage to major organs, and increased vulnerability to severe infections.

Question 17

SCD: complications

Answer 17

Vaso-occlusive crises
Anaemia
Aplastic crisis - typically from parvovirus-B19 infections
Splenic sequestration
Priapism - this is an emergency and urology should be contacted urgently

Stroke
Dactylitis in infants and children
Pulmonary hypertension
Growth and developmental delay
Prolferative retinopathy and retinal haemorrhages
Leg ulcers
Iron overload - due to repeated transfusions
Jaundice
Avascular necrosis of the hip or shoulder

Question 18

Vaso-occlusive crises

Answer 18

painful complication of sickle cell disease

precipitated by infection, dehydration, deoxygenation

Sickled red blood cells clump together and occlude vessels –> ischaemia

Severe –> acute chest syndrome which occurs as a result of infarction in the lung parenchyma

Question 19

Mx of VOC

Answer 19

1. Strong pain relief (IV opiates) is a priority
2. Oxygen as required and IV fluids are normally given in addition to this

Treat any suspected infections

Top-up transfusions may be required

Haematology input should be sought

Acute chest syndrome - Incentive spirometry and physiotherapy (minimise risk of atelactasis)

Question 20

LT management of SCD

MAINSTAY –> Top-up […], […] […] and iron […]

Immunisations: […] and […]

Prophylactic penicillin if […]

Genetic counselling available

Answer 20

transfusions, folic acid, chelation

influenza, pneumococcal

asplenic

Question 21

1. […] crises - vessels
   aka painful crises or […]-[…] crises
   clinical diagnosis
2. […] crises - organs
   e.g. spleen or lungs –>pooling of […] with worsening of the anaemia
   - increased […] count
3. […] […] syndrome
   vaso-occlusion within the […] microvasculature → infarction in the […] […]
   dyspnoea, chest pain, pulmonary infiltrates on chest x-ray, low pO2
4. […] crises
   caused by infection with […] […]
   sudden fall in haemoglobin
   bone marrow […] causes a reduced […] count
5. […] crises
   rare
   fall in haemoglobin due an increased rate of […]

Answer 21

1. Thrombotic crises - vessels
   aka painful crises or vaso-occlusive crises
   clinical diagnosis
2. Sequestration crises - organs
   e.g. spleen or lungs –>pooling of blood with worsening of the anaemia
   - increased reticulocyte count
3. Acute chest syndrome
   vaso-occlusion within the pulmonary microvasculature → infarction in the lung parenchyma
   dyspnoea, chest pain, pulmonary infiltrates on chest x-ray, low pO2
4. Aplastic crises
   caused by infection with parvovirus B-19
   sudden fall in haemoglobin
   bone marrow suppression causes a reduced reticulocyte count
5. Haemolytic crises
   rare
   fall in haemoglobin due an increased rate of haemolysis

Question 22

Management of acute chest syndrome

Answer 22

pain relief
respiratory support e.g. oxygen therapy
antibiotics: infection may precipitate acute chest syndrome and the clinical findings (respiratory symptoms with pulmonary infiltrates) can be difficult to distinguish from pneumonia
transfusion: improves oxygenation
the most common cause of death after childhood