QuestionSBA
QuestionChoice
This would be indicated in severe hypoxaemia, progression of the crisis despite simple transfusion, multi-lobar disease or a previous history of severe chest crisis
32030
c
Exchange transfusion
QuestionChoice
This may be considered later down the line if the patient is failing to maintain oxygen saturations on increasing levels of oxygen. Frequent oxygen monitoring, incentive spirometry and arterial blood gases should be done to monitor progression in such patients
32031
d
Non-invasive ventilation
QuestionChoice
This patient has a productive cough and acute chest crisis in the context of sickle cell anaemia. Recommended treatment in acute chest crises would be intravenous broad spectrum empiric coverage with a third generation cephalosporin for bacterial coverage and a macrolide for atypical organism cover
32032
e
Start oral amoxicillin
QuestionChoice
Effective pain control is key in the management of acute chest crises. Opioid analgesia can be started and titrated according to the pain ladder
32028
a
Start morphine
QuestionChoice
This would be useful in long-term management to prevent future acute chest crises
32029
b
Start hydroxyurea
QuestionComment
Typical exam question, where every option seems right...
23918
User
subscriber
NS
QuestionComment
stem doesn't exclude infections cause does it ? 

28515
QuestionComment
no, it doesn't. You would definitely give an abx, but not oral as the last answer suggests - IV.
42892
User
subscriber
Ale
User
subscriber
Hematoma Lumbar
Concept
Chapter
# Summary

Sickle cell anaemia (SCA) is an autosomal recessive condition in which a point mutation in the beta chain on chromosome 11 leads to the production of HbS (rather than HbA). HbS polymerises when deoxygenated leading to sickled red blood cells. These cells are fragile and sticky, causing vaso-occlusive crises leading to pain and ischaemia of vital organs. The most common acute presentation is painful vaso-occlusive crises, while the most dangerous is acute chest crises. Diagnosis is typically made postnatally in the UK via a national screening programme but otherwise presents with progressive anaemia in early life. Investigations may reveal microcytic anaemia with variable degrees of haemolysis, and a definitive diagnosis is achieved with haemoglobin electrophoresis +/- genetic testing. Management strategies include high-flow oxygen, IV fluids and analgesia for acute crises, hydroxycarbamide, regular exchange transfusions, vaccinations and antibiotics for chronic disease management.

# Definition

Sickle cell anaemia (SCA) is a genetic condition where normal haemoglobin (where variable HbS is present) tends to form abnormal haemoglobin molecules (HbS) upon deoxygenation leading to distortion of RBCs.

# Epidemiology

Sickle cell disease is common among individuals of Central and West African descent, where having the carrier (trait) status confers some protection against malaria. 

# Pathophysiology  

- HbS is produced when the glutamic acid at the 6th position of the β chain is replaced by valine 
- In its deoxygenated state, HbS undergoes polymerisation, forming crystals that cause polymers to form, which in turn leads to the development of RBCs with a sickle shape 
- The abnormal shape of the RBCs causes clotting in the microvasculature, which precipitates vaso-occlusive crises, leading to ischaemia of vital organs and pain
- Deformation of the RBCs leads to chronic haemolysis, which decreases the body's nitric oxide – typically needed for vasoregulation – and this leads to chronic complications such as pulmonary hypertension and leg ulcers

## Inheritance 

- Sickle cell anaemia (HbSS) is an autosomal recessive condition. The most predominant and most severe form, homozygous HbS, represents just one of the sickle cell disease syndromes.
- Other forms of sickle cell disease involve the coinheritance of HbS with other haemoglobin variants.
  - Most commonly HbC or β-thalassaemia, leading to the HbSC or HbS-βthal forms of sickle cell disease.

## Mechanism of hyposplenism

In addition, sickled red cells commonly sequester in the spleen, where they undergo phagocytosis by the reticular endothelial system, leading to extravascular haemolysis

- Initially, this leads to splenic congestion and splenomegaly
- This is followed by splenic infarction, leading to hyposplenism
- Because of splenic compromise, there is reduced immune function 
  - Individuals with sickle cell disease are prone to bacteraemia – the spleen is necessary for phagocytosis of encapsulated bacteria. This means there is vulnerability to encapsulated organisms such as Haemophilus influenzae type B.
  - Affected individuals should have up to date vaccinations for S. pneumoniae, H. influenzae B and N. meningitidis.


# Signs and Symptoms

## Vaso-occlusive crises

Painful vaso-occlusive crises are the most common acute presentation of sickle cell anaemia

- Primarily caused by microvascular obstruction due to RBC sickling and inflammation
- May be triggered by local hypoxia (eg. in cold weather)

## Acute chest crisis

Acute chest crises are the most dangerous acute presentation

- 3% mortality rate, causing 25% of sickle cell-related deaths 
- The cause is often unknown (maybe infectious)
- Patients present with tachypnoea, wheeze, and cough, with hypoxia and pulmonary infiltrates on chest X-ray

## Other complications 

- Splenic infarction and subsequent immunocompromise
- Sequestration crisis
- Osteomyelitis
- Stroke
- Dactylitis
- Poor growth
- Chronic renal disease
- Gallstones
- Retinal disorders
- Priapism
- Pulmonary fibrosis and pulmonary hypertension
- Iron overload from repeated blood transfusions
- Red cell aplasia (due to parvovirus B19 infection in the presence of chronic haemolytic anaemia)

**Clinical severity** is highly variable: some patients have few symptoms; others have severe and frequent crises, haemolytic anaemia and end-organ damage

- This is due to a range of factors such as the amount of HbF (foetal haemoglobin) – higher levels of HbF reduce the severity of clinical complications
- Patients with Hb SC disease have milder anaemia and suffer fewer crises than people with Hb SS disease 
- Patients with Hb SC disease are however more prone to sickle cell retinopathy 
  - Ophthalmological review is needed annually for all patients with Hb SC disease

# Investigations

- Bedside - peak flow, which is essential for monitoring patients with chest crisis
- **FBC** may show microcytic anaemia with variable degrees of haemolysis 
  - Reticulocytosis and unconjugated hyperbilirubinemia may be noted

- Typical **blood film** findings include: 
  - characteristic sickle cells
  - target cells
  - reticulocytosis with polychromasia 
  - features of functional hyposplenism (Howell–Jolly bodies, nucleated red cells)

Definitive diagnosis is with **haemoglobin electrophoresis** +/– genetic testing. However, many labs use high-performance liquid chromatography (HPLC) and/or isoelectric focusing (IEF) instead of HB electrophoresis. 

[lightgallery]

## Screening for sickle cell disease

- Sickle cell disease in the UK is typically diagnosed postnatally (by the national screening programme)
- Additionally, all patients of African or Caribbean descent should have a sickle cell test prior to surgery 
- Otherwise, it can present with progressive anaemia in early life when levels of foetal haemoglobin (which contains γ-chains) fall and are replaced by HbS (containing the variant β-globin)

# Management 

## Acute sickle cell crisis

Treatments include: 

- High-flow oxygen 
- IV fluids and analgesia
- Top-up transfusions – required in some severe cases

Note: ABO-compatible red cells matched for Rhesus and Kell antigens should be given as this will inhibit the development of antibodies that can otherwise complicate future transfusions.


## Chronic sickle cell disease

* **Hydroxycarbamide** if frequent crises occur
  * Increases foetal haemoglobin concentrations – needs to be balanced with risks of marrow suppression, reduced fertility and risk of teratogenicity

* Alternatively regular exchange transfusions may be required for frequent sickle cell crises, acute chest syndrome, priapism and stroke prevention 
* **Vaccinations** and **antibiotic prophylaxis** – in view of hyposplenism and subsequent immunocompromise
* Newer therapies include: 
  * crizaniluzumab (p-selectin inhibitor) for treatment of pain crises 
  * voxelotor (haemoglobin oxygen-affinity modulator) for haemolytic complications

* Bone marrow transplant and gene-editing techniques are now becoming possible curative options for some patients

# NICE Guidelines

[Click here to see information on NICE CKS on sickle cell](https://cks.nice.org.uk/topics/sickle-cell-disease/)
377
Picture
A bloodfilm showing sickle cell disease.
777
Sickle cell.jpeg
images/s98h68ab1665036171705.jpg
images/s98h68ab1665036171705_256.jpg
images/s98h68ab1665036171705_512.jpg
rPcBBYApv8aNqGiGeXqJeMNvCG6W
377
Sickle cell disease
Topic
8
Haematology
Video
Concept
377
Sickle cell disease
356
zzeXMCS
images/videos/hematology.png
Sickle cell disease
Video
Concept
377
Sickle cell disease
302
L3XLqqB
images/videos/surgery.png
Quesmed Tutorial: Acute Abdomen
6406
Effective pain management with opioids is crucial in treating acute chest crises in patients with sickle cell disease.
A 19 year old male is admitted with a 1 day history of sudden onset severe chest pain and productive cough. He has a known history of sickle cell disease.

Vitals on admission:

- T 38.5°C
- BP 100/60
- Pulse 105
- Respiratory rate 25
- SpO<sub>2</sub> 98% on 4L oxygen

CXR reveals bilateral lower zone shadowing. What is the next best step?
a