Learning objectives
- Understand the inheritance of Sickle cell disease
- Understand Sickle cell disease and stroke presentations
- Understand diagnostics and treatment strategies
- Discuss complications and management
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About
- Stroke is a Major complication of sickle cell disease
- The naive clinician may assume that sickle cell anaemia is associated predominantly with sickling within small vessels as the mechanism of stroke but this would be wrong.
- There is a poorly understood strong predisposition to large vessel intracranial disease with narrowing and occlusion of the internal carotids and middle cerebral vessels.
- The prevalence of Cerebral infarction by the age of 20 is 11%. Sickle cell related stroke disease often commences in childhood after the age of 2. Sickle cell disease is in fact the most common cause of stroke in children.
Age adjusted prevalencelink
| Sickle cell | Prevalence |
|---|
| Sickle cell disease (homozygous) | 4.01% |
| S-β0 thalassemia | 2.43% |
| S-β+thalassemia | 1.29% |
| SC disease | 0.84% |
Sickle cell disease
- Sickle cell disease (SCD) is a group of inherited red blood cell disorders.
- People with SCD have abnormal haemoglobin, called haemoglobin S
- Those with SCD inherit two abnormal haemoglobin genes, one from each parent.
- These make haemoglobin S. When a person has two haemoglobin S genes, this is sickle cell anaemia the most severe kind of SCD.
- Haemoglobin SC disease and haemoglobin Sβ thalassemia (thal-uh-SEE-me-uh) are two other common forms of SCD.
Manifestation
| Manifestations of Stroke and Sickle cell disease |
|---|
| Large vessel stroke disease : occlusion of MCA/ACA |
| Small vessel stroke disease |
| Silent infarction is common |
| Moya moya type syndrome |
| Haemorrhagic stroke |
Aetiology
- Strokes are due to a culmination of large and small vessel disease and altered cerebral autoregulation
- Some are typically due to large-artery vasculopathy of the intracranial internal carotid arteries and proximal MCAs and occasionally the ACAs.
- Silent infarcts may be seen on MRI T2 may be seen in 21.8% of children between 6 and 19 years of age with SCD-SS
- Children with Transcranial doppler showing high velocities (suggests narrowing) of the MCA at increased risk.
- Red cell adherence to the endothelium mediated by von Willebrand's protein my be important.
- There may be collateralisation and a Moyamoya syndrome picture can develop.
- There is a risk of both Cerebral infarction and haemorrhage.
Clinical
- SCD itself will cause fatigue, anaemia, haemolysis, sickling crises.
- Stroke related presentations will be related to ischaemia and strokes involving the large vessel MCAs and Carotid territory infarcts with related clinical syndromes in children.
- Penetrating small vessel strokes are often silent. Watershed infarction also seen.
Investigations
- FBC: anaemia. U&E, LFT: Evidence of haemolysis
- Hb Electrophoresis: HbSS or HbSC
- Transcranial Doppler of the MCA: Useful for detecting intracranial stenoses and a velocity > 200 cm/second suggests at risk and at risk children should have annual screening as this is a major stroke risk factor.
- Non-Contrast CT acutely can determine if there is infarction and/or haemorrhage
- MRI/A for more detailed assessment: this may show occlusive intracranial internal carotid disease. There may be frank large vessel infarcts on borderzone lesions.
- Hb Electrophoresis
Management
- ABC. Stroke Unit. Oxygen to achieve SAO2 94-98% and IV fluids as needed. Urgent Haematology consult. The role and risk and benefits of thrombolysis and thrombectomy is unclear.
- Acutely needs Manual or automated exchange transfusion to keep HbS at <30% and keeping Hb > 10g/dl suppresses erythropoiesis.
- Exchange transfusion: The STOP study showed that high risk children defined by high flow (> 200 cm/sec) on transcranial doppler benefited significantly from a programme of chronic transfusion. However chronic transfusions can be associated with risk of iron overload. Target is a HbS level < 30% of total Haemoglobin.
- Aspirin and Hydroxyurea (Hydroxycarbamide) may be considered and increases HbF. Hydroxycarbamide increases HbF. Aspirin is commonly also used but it may increase risk of haemorrhage.
- Prevention with prophylactic chronic transfusions is advised but associated with severe iron overload which may require chelation therapies.
- Stem cell transplantation is only long-term cure but is associated with multiple possible serious complications.
- Revascularisation surgery may be considered in those with a typical Moyamoya arteriopathy.
Further reading
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