Haemoglobinopathy - Sickle Cell Anaemia

Question 1

What is Sickle Cell Anaemia?

Answer 1

A genetic autosomal recessive condition that cause sickle (crescent)-shaped RBCs due to an abnormal gene for B-globin on chromosome 11.

Question 2

What is Sickle Cell Trait?

Answer 2

One faulty copy of the gene - usually asymptomatic.

Question 3

Epidemiology of Sickle Cell Disease (2).

Answer 3

1. Commoner in areas traditionally affected by Malaria e.g. Africa, India, Middle East and Caribbean.
2. Sickle Cell Trait reduces severity of malaria (selective advantage) so is at a higher proportion.

Question 4

Types of Haemoglobin (3).

Answer 4

1. Fetal Haemoglobin (HbF) replaced by Haemoglobin A (HbA) at 6 weeks of age.
2. Faulty Variant - Haemoglobin S (HbS).

Question 5

Pathophysiology of Sickle Cell Disease (4).

Answer 5

1. The polar amino acid Glutamate is substituted by the non-polar amino acid Valine, which reduces the water solubility of deoxygenated Haemoglobin S.
2. The molecules polymerise.
3. RBCs sickle at low Oxygen pressure.
4. They are fragile and can haemolyse to block small blood vessels and cause infarction.

Question 6

Bloods in Sickle Cell Anaemia.

Answer 6

Microcytic Anaemia with Variable Degrees of Haemolysis.

Question 7

Blood Film Findings in Sickle Cell Anaemia (4).

Answer 7

1. Sickle Cells.
2. Target Cells.
3. Reticulocytosis with Polychromasia.
4. Features of Functional Hyposplenism e.g. Howell-Jolly Bodies, Nucleated RBCs.

Question 8

When are patients with Sickle Cell Anaemia diagnosed (2)?

Answer 8

1. Pregnant Women - Testing for those At-Risk.
2. Newborn Screening Heel Prick Test at 5 Days.

Question 9

What is used to diagnose Sickle Cell Anaemia definitively?

Answer 9

Definitive = Haemoglobin Electrophoresis with/out genetic testing.

Question 10

General Management of Sickle Cell Anaemia (8).

Answer 10

1. Avoid Triggers e.g. Dehydration.
2. Vaccinations.
3. Antibiotic Prophylaxis with Penicillin V (Phenoxymethylpenicillin).
4. Hydrocarbamide.
5. Blood Transfusion (Severe).
6. Bone Marrow Transplant (Curative).
7. Analgesia and Oxygen.
8. Hydroxyurea.

Question 11

Why is Hydroxycarbamide used?

Answer 11

Stimulate production of HbF. HbF does not lead to sickling of RBCs so protective effect against sickle crises.

Question 12

Why is Hydroxyurea used?

Answer 12

It increases HbF levels and used in prophylaxis to prevent painful episodes.

Question 13

Vaccinations in Sickle Cell Anaemia.

Answer 13

Pneumococcal Polysaccharide Vaccine every 5 years.

Question 14

What is a Sickle Cell Crisis?

Answer 14

A spectrum of acute crises related to Sickle Cell Disease, ranging from mild to life threatening that can occur spontaneously or due to triggers.

Question 15

Triggers of Sickle Cell Crises (4).

Answer 15

1. Infection.
2. Dehydration.
3. Cold.
4. Significant Life Events.

Question 16

Management of Sickle Cell Crises (3).

Answer 16

SUPPORTIVE :
1. Low Threshold for Admission.
2. Infection Treatment.
3. Warm, Well-Hydrated, Pain-Free.

Question 17

What is a Vaso-Occlusive Crisis?

Answer 17

A painful thrombotic crisis where the RBCs clog capillaries to cause distal ischaemia.

Question 18

Clinical Features of Vaso-Occlusive Crisis (4).

Answer 18

1. Pain.
2. Fever.
3. Triggering Infection Features.
4. Priapism (Painful and Persistent Erection).

Question 19

What causes Priapism and how is it treated?

Answer 19

A urological emergency where blood is trapped in the penis - treated with aspiration of blood from the penis.

Question 20

What is Splenic Sequestration Crisis?

Answer 20

RBCs block blood flow within the spleen - an emergency.

Question 21

Clinical Features of Splenic Sequestration Crisis (2).

Answer 21

1. Acutely Enlarged and Painful Spleen.
2. Severe Anaemia and Circulatory Collapse (Pooling of Blood).

Question 22

Management of Splenic Sequestration Crisis (3).

Answer 22

SUPPORTIVE :
1. Blood Transfusions.
2. Fluid Resuscitation.
3. Splenectomy (if Recurrent due to risk of splenic infarction and susceptibility to infections).

Question 23

Blood Finding in Sequestration Crisis.

Answer 23

Increased Reticulocyte Count.

Question 24

What is an Aplastic Crisis?

Answer 24

Temporary loss of the creation of new RBCs leading to significant anaemia.

Question 25

Commonest Trigger of Aplastic Crisis.

Answer 25

Parvovirus B19.

Question 26

Management of Aplastic Crisis.

Answer 26

Supportive Blood Transfusions - it usually resolves spontaneously within a week.

Question 27

Blood Finding in Aplastic Crisis.

Answer 27

1. Sudden fall in Haemoglobin.
2. Bone Marrow Suppression - Reduced Reticulocyte Count.

Question 28

Pathophysiology of Acute Chest Syndrome.

Answer 28

Vaso-occlusion within the pulmonary microvasculature resulting in infarction in the lung parenchyma.

Question 29

Aetiology of Acute Chest Syndrome.

Answer 29

1. Infection e.g. Pneumonia or Bronchiolitis.
2. Non-Infective Causes e.g. Pulmonary Vaso-Occlusion/Fat Emboli.

Question 30

Diagnosis of Acute Chest Syndrome (2).

Answer 30

1. Fever or Respiratory Symptoms e.g. Dyspnoea, Chest Pain, low pO2.
2. New Infiltrates on CXR.

Question 31

Management of Acute Chest Syndrome (4).

Answer 31

SUPPORTIVE and Underlying Cause :
1. Antibiotics/Antivirals = Infection.
2. Blood Transfusion = Anaemia.
3. Incentive Spirometry = Encourage Effective and Deep Breathing.
4. Artificial Ventilation.