Sickle Cell Disorder

Question 1

Define Sickle Cell Disorder

Answer 1

A chronic condition characterised by sickling of red blood cells, caused by inheritance of haemoglobin S (Hb S)

Question 2

What are the types of sickle cell disorder

Answer 2

Sickle cell anaemia = Hb SS (homozygous)
Sickle cell trait = Hb AS (heterozygous)
Sickle cell disease = Anything involving sickling: compound heterozygosity for Hb S and C and HbS and beta-thalassaemia

Question 3

What is the aetiology of sickle cell disorder

Answer 3

Autosomal recessive inherited point mutation at codon 6 of the beta globin chain gene (glutamic acid → valine) of chromosome 11
The change from polar and soluble to non-polar and insoluble causes HbS to polymerise and form tactoids
RBC becomes distorted, dehydrated and adhered to the vascular endothelium
RBCs block vessels, damaging them and sequester in liver and spleen
Shortened lifespan (20 days) + low affinity HbA release O2 readily → EPO drive lower → anaemia

Question 4

What causes the symptoms of crisis in sickle cell disease

Answer 4

Symptoms are due to a shortened lifespan of RBCs, leading to haemolysis + vessel occlusion
Painful Crises are Stimulated by:
- Infection
- Exertion
- Dehydration
- Hypoxia
- Psychological stress
- Acidosis

Question 5

What are the risk factors of sickle cell disease

Answer 5

FHx or carriers
Coinheritance of Gilbert syndrome(UGT 1A1 TA7/TA7 genotype)

Question 6

What is the epidemiology of sickle cell disease

Answer 6

Rarely presents before 4-6 months
Distribution matches that of endemic plasmodium falciparum malaria - Gene will provide protection against malaria
Up to 25% Africans (sub-Saharan) and 10% Caribbeans carry the sickle gene
Common in Africa, Caribbean, Middle East
Around 300,000 births affected worldwide annually
Most common monogenic disorders

Question 7

What are the early manifestation symptoms of sickle cell disorder

Answer 7

May be diagnosed on Guthrie spot

Dactylitis (pain in bones) in the small bones of hands and feet
Splenic sequestration (pallor, tachycardia, shock)
Infection e.g. S. pneumoniae

Question 8

What are the general symptoms of sickle cell disorder

Answer 8

Anaemia: fatigue, SOB, pallor, dizziness
Recurrent infection (due to autosplenectomy) e.g. with pneumococcus, influenza etc.
Chronic/recurrent leg ulcers
Gallstones: RUQ pain, especially after eating
Dactylitis in ribs, spine, pelvis and long bones in adults
Myalgia and arthralgia
Chronic cholecystitis

Question 9

What are the symptoms in an acute sickle cell crisis

Answer 9

Pain crisis due to vaso-occlusion by erythrocytes → ischaemic tissue damage:
- Painful, swollen joints (bone infarction, acute pain crisis)
- Dactylitis
- Acute osteomyelitis
- Abdominal pain (gallstones, ascending cholangitis, acute cholecystitis, empyema, acute pancreatitis)

Question 10

What are the signs of sickle cell disorder on examination

Answer 10

Obs: Fever
General
- Anaemia: pallor, SOB
- Maxillary hypertrophy with overbite (extramedullary haematopoeisis)
- Jaundice (gallstones)
- Dehydration (renal damage)
- Cotton wool spots on retina (vaso-occlusive)

Abdominal
- Splenomegaly in early disease (sequestration crisis) -> will shrink as the patient gets older
- Tender hepatomegaly (acute hepatitis)
- Abdominal distension (acute hepatitis)
- Priapism

Joints
- Dactylitis
- Osteomyelitis
- Short digits or joint/muscle tenderness and swelling (vaso-occlusive crisis)

Question 11

What constitutes an emergency in sickle cell disorder

Answer 11

Septic shock (BP <90/60)
Neurological signs or symptoms
SpO2 <92% on air
Symptoms/signs of anaemia with Hb <5 or fall >3g/dl from baseline
Priapism >4 hours

Question 12

What investigations should be done for sickle cell disorder

Answer 12

Bloods
- FBC + reticulocytes: leucocytosis, anaemia, high reticulocytes
- Blood film: sickled cells, boat cells, Howell jolly bodies (hyposplenism), target cells (hyposplenism)
- Solubility test: solution turgid, <10-15% HbS → if positive then electrophoresis
- Electrophoresis: Presence of HbS and/or HbA
- High performance liquid chromatography (HPLC): HbF predominates, HbA/HbS

Other
- X-ray hip: exclude avascular necrosis (Infarctions seen by irregular margins or moth-eaten destruction with overlying periosteal new bone formation)
- CXR (Acute chest syndrome)

Question 13

What is the management for sickle cell disorder

Answer 13

Conservative
Education
Crisis trigger avoidance e.g. cold, windy, excessive activity, dehydration
Coping: distraction techniques
Maintain fluid intake, hygiene and nutrition
Genetic counselling for family
Psychological support

Medical
Vaccination
Hydroxyurea (increased HbF levels and reduces frequency and duration of crises)
Folic acid
Prophylactic antibiotics (for <3yo or >5 with severe infections)
Analgesia

Surgical
bone marrow transplant
Joint replacement in avascular necrosis

Question 14

Which vaccinations should be given to patients with sickle cell disorder

Answer 14

Pneumococcal polysaccharide vaccine at 2 years
Influenza annually from 6 months
Meningitis ACWY

Question 15

What are the indications for haematopoietic stem cell transplantation in SCD

Answer 15

CNS disease
Recurrent severe vaso-occlusive crisis
Recurrent acute chest syndrome when hydroxyurea fails

Question 16

When is referral required for sickle cell crises

Answer 16

Severe pain not controlled by analgesia
Dehydration (vomiting or diarrhoea)
Severe sepsis
New neurological symptoms or signs
Symptoms or signs of acute fall in Hb
Acute enlargement of spleen or liver over 24h, particularly in young children
Marked increased in jaundice
Any change in vision
Haematuria
Fulminant priapism >2 hours

Question 17

What is the management for sickle cell crises not requiring admission

Answer 17

Empirical broad-spectrum antibiotics

Question 18

What is the management for sickle cell crises

Answer 18

1. Oxygen if hypoxic
2. Pain relief (opioids, most commonly diamorphine), oral opioids for children
3. Hydration - IV fluids or oral depending on severity
4. Keep warm
5. Antihistamine
6. Exclude infection:
   - Blood and urine cultures
   - CXR
7. Give antibiotics

Question 19

What is the management for priapism in sickle cell disorder

Answer 19

Advice: gentle exercise, warm baths, analgesia, trying to urinate, keeping warm, keeping hydrated at bedtime
Go to hospital if >1 hour
First line: alpha-adrenergic agonists (etilefrine) and anti-androgens.

Question 20

What are the complications of sickle cell disorder

Answer 20

Acute chest syndrome
Acute painful crises
Hyposthenuria (impaired concentration)
Priapism
Proliferative retinopathy
Haem: Aplastic crises, anaemia, Stroke
Kidney: Papillary necrosis (haematuria), Nephropathy, Renal failure
Infections: pneumococcus, sepsis, osteomyelitis

Question 21

What is the prognosis for sickle cell disorder

Answer 21

Variable in severity and onset of acute and chronic complications is unpredictable
Childhood mortality is relatively rare with 99% of children in the UK surviving to adulthood, however, in Africa 50–90% of children die before the age of 5 years.
Chronic organ damage due to sickle cell results in many medical complications, although some prophylactic treatments can reduce incidence

Question 22

Describe aplastic crises in sickle cell disorder

Answer 22

caused by infection with parvovirus
sudden fall in haemoglobin without a rise in reticulocytes

Question 23

Describe acute chest syndrome

Answer 23

New pulmonary infiltrate on the chest X-ray with fever, cough, chest pain and tachypnoea Incidence: SS > SC > Sβ Thalassaemia
most common cause of death after childhood
Mechanical ventilation = 15%
Mortality > 18 = 9%

Question 24

What are the chronic complications of sickle cell disorder

Answer 24

Growth and developmental delay
Learning and behaviour issues
Pulmonary hypertension
CKD
Auto-splenectomy (scarring and fibrosis)