Sickle Cell Disorder Flashcards

1
Q

Define Sickle Cell Disorder

A

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

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2
Q

What are the types of sickle cell disorder

A

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

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3
Q

What is the aetiology of sickle cell disorder

A

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

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4
Q

What causes the symptoms of crisis in sickle cell disease

A

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

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5
Q

What are the risk factors of sickle cell disease

A

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

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6
Q

What is the epidemiology of sickle cell disease

A

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

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7
Q

What are the early manifestation symptoms of sickle cell disorder

A

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

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8
Q

What are the general symptoms of sickle cell disorder

A

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

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9
Q

What are the symptoms in an acute sickle cell crisis

A

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)

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10
Q

What are the signs of sickle cell disorder on examination

A

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)

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11
Q

What constitutes an emergency in sickle cell disorder

A

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

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12
Q

What investigations should be done for sickle cell disorder

A

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)

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13
Q

What is the management for sickle cell disorder

A

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

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14
Q

Which vaccinations should be given to patients with sickle cell disorder

A

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

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15
Q

What are the indications for haematopoietic stem cell transplantation in SCD

A

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

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16
Q

When is referral required for sickle cell crises

A

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

17
Q

What is the management for sickle cell crises not requiring admission

A

Empirical broad-spectrum antibiotics

18
Q

What is the management for sickle cell crises

A
  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
19
Q

What is the management for priapism in sickle cell disorder

A

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.

20
Q

What are the complications of sickle cell disorder

A

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

21
Q

What is the prognosis for sickle cell disorder

A

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

22
Q

Describe aplastic crises in sickle cell disorder

A

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

23
Q

Describe acute chest syndrome

A

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%

24
Q

What are the chronic complications of sickle cell disorder

A

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