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Sickle cell disease and Stroke


Learning objectives

  • Learning
  • Understand
  • Integrate
  • Reflect

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 prevalence
Sickle cellPrevalence
Sickle cell disease (homozygous) 4.01%
S-ß0 thalassemia 2.43%
S-ß+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 Sß 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
Moyamoya 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