Transcranial Doppler velocity and brain MRI/MRA changes in children with sickle cell anemia on chronic transfusions to prevent primary stroke.

BACKGROUND: Chronic transfusions help prevent primary stroke in children with sickle cell anemia (SCA) and abnormal transcranial Doppler (TCD) velocities. However, the effects of transfusions on TCD velocities and brain MRI/MRA findings are incompletely described. PROCEDURE: We reviewed TCD and brain MRI/MRA results in 27 children with SCA and abnormal TCD velocities receiving transfusions to prevent primary stroke. All TCDs were performed by a single examiner, immediately prior to a scheduled transfusion. We also examined the effects of laboratory and clinical parameters on TCD responses to transfusion therapy. RESULTS: For the whole cohort, the average pre-transfusion HbS on transfusions was 31.7 ± 12.3%. The most significant decline in TCD velocities occurred within 10 months of starting transfusions. Follow-up TCD values trended upward with increasing pre-transfusion %HbS levels while on treatment. Half of the children had persistent conditional/abnormal TCD velocities despite transfusions and 28% had new/progressive stenosis on MRA, but none had primary stroke during 73 patient-years of follow-up. CONCLUSIONS: For children with SCA and abnormal TCD velocities, transfusions lower TCD velocities and help prevent stroke, but do not always result in normal velocities or protect against progression of cerebral vasculopathy. Improved adherence to transfusion goals may improve on-treatment TCD velocities.

The natural history of conditional transcranial Doppler flow velocities in children with sickle cell anaemia.

Children with sickle cell anaemia (SCA) and conditional transcranial Doppler (TCD) [time-averaged mean velocity (TAMV) 170-199 cm/s] have increased risk of primary stroke, but receive no specific therapy. Some will convert to abnormal velocities (TAMV >/=200 cm/s) with further increase in stroke risk. In 2003, our centre initiated universal TCD screening, targeting all children (aged 2-16 years) with SCA. TCD examinations were repeated at intervals based on initial results. To determine rates and risk factors for TCD conversion, we reviewed all examinations since 2003, excluding patients receiving hydroxycarbamide (hydroxyurea) or transfusions. Of the eligible population, 274 children (98%) were screened at a median age of 7.1 years (range 1.7-18.2). Fifty-four patients (20%) had conditional TAMV either on initial screening or a subsequent examination. The 18-month cumulative incidence of conversion from conditional to abnormal TAMV was 23%. Age, initial TAMV, laboratory values, blood pressure and oxygen saturation were not significantly associated with conversion. Our cohort provides systematic longitudinal evaluation of an unselected paediatric population universally screened and retested at regular intervals. Our data document a high conversion rate to abnormal velocities among untreated children with SCA. Therapy should be considered for the prevention of conversion to abnormal TCD velocities.

Evaluation of a comprehensive transcranial doppler screening program for children with sickle cell anemia.

BACKGROUND: Although transcranial Doppler ultrasonography (TCD) screening is effective in identifying children with sickle cell anemia (SCA) who are at high risk of stroke, not all children are screened. In 2003, we instituted a comprehensive TCD screening program designed to screen all at-risk children treated at our sickle cell center. PROCEDURE: We evaluated the efficacy of our program by comparing the number of patients screened per year and incidence of first stroke across three periods defined by TCD usage: (1) pre-dating TCD screening, (2) sporadic TCD screening, and (3) comprehensive TCD screening. RESULTS: During Period 2, an average of 52 patients/year were screened. In Period 3, an average of 95 patients/year were screened representing 99% of the at-risk population. Eighteen strokes occurred in Period 1, 22 in Period 2 and three in Period 3. The first stroke incidence was significantly lower in Period 3 compared to Periods 1 and 2 (P = 0.047). Furthermore, of the 25 patients in Periods 2 and 3 who had stroke, only six had received TCD screening (four in Period 2, two in Period 3). These six either declined prophylactic transfusion therapy (n = 2), had co-existing stroke risk factors (n = 2), or did not return for appropriate TCD follow-up (n = 2). Therefore, strokes that occurred were not the result of a failure of TCD screening per se. CONCLUSIONS: It is possible to perform TCD screening of most children with SCA. TCD screening is effective in reducing first stroke incidence in these children.