Dr Fazal-i-Akbar Danish
Antrim Area Hospital, Antrim, Ireland
Title: Primary prevention of ischemic stroke, hemorrhagic stroke & silent cerebral infarction in children with high-risk sickle cell disease genotypes
Submitted Date: 1/15/2020
Biography
Abstract
Introduction:By age 20 years, almost 11% patients with untreated Sickle Cell Disease (SCD), especially those with high-risk SCD genotypes (HbSS or HbS-beta0 thalassemia) will have developed a clinically-apparent stroke. By age 45 years, almost 25% cases will have a stroke, which may be ischaemic, haemorrhagic, or silent cerebral infarction (SCI).rnrnMethod:rnrnA comprehensive search of PubMed & EMBASE from January 2000 to November 2019 was made using 4 search items: sickle cell disease, stroke, chronic transfusion therapy & hydroxyurea. The search items were combined using the Boolean operator. A further search was made of the society guidelines of American Heart Association/American Stroke Association, Canadian Stroke Association, Cochrane library, & ClinicalTrials. gov with no language restriction. rnrnResults: The mainstay of primary stroke prevention in children with high-risk SCD genotypes is serial screening with Transcranial Doppler (TCD) studies from ages 2 to 16. TCD measures the mean blood flow velocity in the large intracranial vessels. Abnormally high TCD velocities thus suggest probable vascular stenosis & consequent impending risk of stroke (a TCD velocity of ≥200 cm/sec signifies an ischaemic stroke risk of up to 40%). In children with two TCD velocity measurements of ≥200 cm/sec within a period of 1-2 weeks’ warrant further investigations with magnetic resonance imaging (MRI) & magnetic resonance angiography (MRA), plus onward institution of (often indefinite) chronic transfusion therapy. Chronic transfusion therapy may also be appropriate in children with abnormally low TCD velocities (<50-70 cm/sec), especially if screening MRI shows SCI &/or MRA demonstrates large artery stenosis. The goals of chronic transfusion therapy are to lower & maintain HbSS levels at 30% of total haemoglobin & to maintain a pretransfusion haemoglobin concentration of approximately 9 g/dL. Additionally, with chronic transfusion therapy the TCD velocities are expected to improve/normalize thus substantially reducing potential stroke risk to as low as 2% per 20-month period. Hydroxyurea per se has not been studied for primary stroke prevention in this clinical setting because of the time it takes to confer maximum therapeutic benefit (usually up to several months). Prospectively, in children who have completed at least 2 years of chronic transfusion therapy with successive TCD studies confirming normalization of velocities may be considered for transition to hydroxyurea therapy. The transition should be done as it was accomplished in the TWiTCH trial with a period of overlapping transfusions while hydroxyurea is escalated to the maximum tolerated dose, serial monitoring of TCD velocities & regular assessment of hematologic response to hydroxyurea. Hydroxyurea may also be considered in patients who will not have access to &/or fail to tolerate indefinite blood transfusions.Conclusion:In patients commenced on chronic transfusion therapy, serial TCD assessments should be performed every 6-12 months & MRI/MRA imaging every 2-3 years (TCD screening is ineffective in identifying increased risk for SCI). If serial assessments demonstrate persistently abnormal TCD velocities & progressive stenotic vasculopathy despite chronic transfusion therapy, the recommended approach would either be continuation of chronic transfusions or possible commencement of dual therapy with transfusions & hydroxyurea.