Use of hydroxyurea in prevention of stroke in children with sickle cell disease

Abstract

We carefully read the paper by Zimmerman and colleagues 1 about the possible effect of hydroxyurea on the transcranial doppler flow velocities in children with sickle cell disease. We reviewed the transcranial dopplers (TCD) performed on the children with sickle cell disease in our hospital from 0 to 25 years old, treated or not treated with hydroxyurea, and we compared the trend of the time-averaged maximum velocity (TAMV) measured in the middle cerebral arteries and the incidence of stroke.Among our 119 patients, we found that in the patients not treated with hydroxyurea, the velocity increased with age to a maximum between 6 and 9 years old (P Ͻ .05). This significant increase does not appear in the patients treated with hydroxyurea ( Figure 1). Following the 85 patients who had repeated TCD after a mean duration of 3.1 (Ϯ 1.5) years, we noticed that the velocity was increasing in the patients whose first TCD was normal (148 Ϯ 16 cm/s to 172 Ϯ 21 cm/s, n ϭ 34, P Ͻ .01), stabilizing in the patients whose first TCD was conditional (181 Ϯ 8 cm/s to 181 Ϯ 25 cm/s, n ϭ 30, P ϭ .75); and decreasing in the patients whose first TCD was abnormal and who were thereafter treated by hydroxyurea between the first and the second TCD (235 Ϯ 18 cm/s to 202 Ϯ 34 cm/s, n ϭ 21, P Ͻ .01). In these 21 patients with an abnormal first TCD, the velocities decreased to the normal/conditional range in 8 of them. This strengthens the observation of Zimmerman and colleagues 1 that children with the highest baseline doppler velocity had the greatest decrease in response to hydroxyurea.In the 80 patients treated with hydroxyurea with a follow-up of 555 patient-years, 2 presented stroke, and of the 4 patients with a previous history of stroke, only one presented a new episode for a follow-up of 35 patient-years. For the 23 patients receiving hydroxyurea based on an abnormal TCD and no other clinical risk, no stroke was recorded for 84 patient-years. Seventeen of these 23 patients (mean age 5.5 Ϯ 1.8 years) had repeated TCD after a mean duration of hydroxyurea treatment of 31 (Ϯ 14) months. Their mean velocity dropped from 231 (Ϯ 22) cm/s to 208 (Ϯ 24) cm/s (P Ͻ .01). Magnetic resonance angiography (MRA) from 14 of these patients showed vascular stenosis in 6 of them. This stenosis persisted in 2 of the 5 patients on repeated MRA performed after a mean time of 4 (Ϯ 1) years.Concerning the secondary prevention of stroke, the recurrence rate of stroke in our patients treated with hydroxyurea was 2.9 for 100 patient-years, similar to that recorded in chronically transfused patients. 2,3 However, in the primary prevention of stroke, the incidence of first stroke in our patients with hydroxyurea was 0.36 for 100 patient-years, lower than in nontransfused patients of other larger cohorts 4 and lower than in the cohort of Zimmerman and colleagues (0.52 for 100 patient-years), 1 without using maximum tolerated dose of hydroxyurea. 5 Our preliminary results therefore indicate that, in the patients at risk for stroke on the basis of transcranial do...

Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack

“…Early studies suggested that hydroxyurea might replace regular blood transfusion therapy [720][721][722][723] ; however, an RCT called Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) found no strokes with chronic transfusion but 10% with hydroxyurea, which resulted in termination of the trial. 724 In situations in which transfusion is not available, a nonrandomized group comparison study of patients with an initial stroke suggested that patients who do not receive hydroxyurea at the maximum tolerated dose are at increased risk for recurrent stroke (HR, 9.4; 95% CI, 1.5-70.6).…”

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…Recognizing this significant barrier, several investigators evaluated hydroxyurea therapy as an alternative to regular transfusions for stroke prevention. Based on several studies that consistently demonstrated a decrease in TCD measurements with hydroxyurea therapy [66][67][68][69][70][71], the NHLBI sponsored the Transcranial Doppler With Transfusions Switching to Hydroxyurea (TWiTCH) trial. For primary stroke prevention, the TWiTCH trial randomly allotted children with hemoglobin SS and hemoglobin S/beta-0-thalassemia with elevated TCD velocities without strokes and were on a regimen of regular transfusions to receive either regular blood transfusion therapy or hydroxyurea therapy escalated to maximum tolerated dose.…”

Stroke in patients with sickle cell disease

“…Therefore, chronic red cell transfusion therapy remains the mainstay of secondary stroke prevention. See tablE 2 for a summary of stroke recurrence rates with hydroxyurea [104][105][106][107][108][109]. Moyamoya disease, if identified, predicts a high risk of recurrent stroke in patients with SCD in spite of optimal transfusion therapy [41].…”