Abstract
Introduction: Progress in the management of sickle cell disease (SCD) has improved life expectancy. However, stroke remains one of the most serious complications of SCD. The purpose of this single-center longitudinal descriptive study is to demonstrate that hydroxyurea (HU), apart from lowering transcranial doppler flow (TCD) velocities, improves the clinical symptoms in SCD. Furthermore, starting the children at risk for stroke concomitantly on HU and short-term transfusion ameliorates rapidly the TCD velocities and clinical symptoms.
Patients and Methods: Twenty-eight consecutive patients with a median age of 10.8 years (range 6.0–21.0 years) had biologic and clinical follow-up for a median of 9 years (range 2.5–18 y). A total of 27 patients were followed by TCD screening of the middle cerebral artery (MCA), anterior (ACA) and posterior cerebral arteries (PCA), carotid siphons (ICA) and basilar artery (BA). Twenty-one patients received hydroxyurea for a median of 5.9 years (range 4 months-9.5 years). HU was started for the following: 3 or more severe vaso-occlusive crises requiring hospitalization, abnormal MRI, TCD velocities of 200 cm/sec, and parental refusal to transfusion. Three patients had monthly red blood cell transfusion for 6 months concomitantly to HU. Myelotoxicity was controlled at two-week intervals for the first 3 months. Twenty-one patients under HU were retained for analysis. TCD velocities of a given patient were compared using the nonparametric Wilcoxon sum test.
Results: All patients improved clinically under HU treatment with decrease in the number of crises. Concerning the neurologic findings of the patients, 13 with increased TCD velocities in the MCA (median190 cm/sec) showed decreases under HU (table).
MCA flow velocities for 13 children with SCD, before and 3, 6, 12 and 24 months after starting therapy MCA flow velocity (cm/s) before 3 months 6 months 12 months 24 months NS indicates not significant; P values indicate comparison between each month under HU and before treatment. median (range) 190(156–246) 172(128–232) 172(149–244) 158(121–222) 164(150–228) P 0.03 NS 0.03 0.03
Two patients with headaches accompanying increases in TCD velocities had disappearance of the headaches 1–2 months after starting treatment. One of these had concomitant monthly transfusions for 6 months. After the end of transfusions, she remained asymptomatic under HU. One patient with stroke, severe headaches and pathologic MRI before HU had very rapid and stable recovery of symptoms under HU and short-term transfusions. She is at present 15 months after the last transfusion asymptomatic under HU therapy. None of the other 28 patients manifested any neurologic symptom during the follow-up.
DISCUSSION Our single-center longitudinal study, although limited in number, shows the benefits of HU on the neurologic outcome in pediatric SCD patients, and brings the observation that concomitant use of short-term transfusion prophylaxis and HU might produce a faster response in clinical and biologic parameters which will be stable over the years. Long-term follow-up will show if short-term transfusion prophylaxis is periodically necessary in these patients under HU.
The natural history of conditional transcranial Doppler flow velocities in children with sickle cell anaemia
