Introduction
Although a monogenic blood disorder, sickle cell disease (SCD) presents with a progressive vasculopathy triggered by free heme, which causes activation of endothelial cells, reticulocytes, neutrophils and platelets1,2. Consequent nitric oxide depletion leads to vasoconstriction, upregulation of adhesion molecules and endothelial intima proliferation3,4. As a direct consequence of this, SCD patients are prone to several complications including chronic lung disease, leg ulcers and stroke5. The latter is the most devastating of the complications and it is ischemic in affected children, in whom it occurs in about 11% before the age of 20 years if no specific intervention is instituted6. Arterial stenosis usually occurs in the large vessels of the Circle of Willis, especially the internal carotid, the middle and anterior cerebral arteries.
Stroke tends to be recurrent in SCD; therefore, there is a need for primary and secondary prevention by identifying patients at risk6. Transcranial Doppler ultrasound imaging (TCDI) is used for screening children with SCD and the STOP guidelines call for patients with abnormal time-averaged mean of the maximum velocity (TAMMV) of >200 cm/s to start prophylactic blood transfusions to reduce the concentration of HbS7. Hydroxyurea has also been shown to be effective for primary stroke prevention, especially in resource-poor populations8.
Kuwaiti patients with SCD uniformly carry the Arab/India (A/I) haplotype and have elevated HbF levels9,10. Stroke is relatively rare in these patients, just as has been reported for other Arab Gulf patients with SCD11. A previous TCDI study carried out in Kuwait about 10 years ago did not identify any patients with abnormal or conditional TAMMV in any of the cerebral arteries12. The present study was therefore designed to repeat TCDI as a follow up on the same patients to see if or how their parameters have changed in the intervening years. Would the TAMMV values remain in the normal range or would the effects of cumulative vasculopathy be evident in elevated velocities? Or will the effects of age produce lower velocities than in the initial study?