Introduction: India has been identified as having the second largest number of births with sickle cell anemia (SCA) in the world after Africa, with estimated 44,400 new-borns affected per year. SCD was previously reported to have a milder course in children from India, with less severe disease among aboriginal tribal populations than in non-tribal populations. Recent reports indicate the occurrence of severe manifestations of SCD in both tribal and non-tribal populations in India. Stroke is one of the serious complications of SCD, but there are no data on transcranial Doppler (TCD) screening for evaluating children with SCD in India who may be at high risk for strokes.

The objective of this study was to assess the feasibility of using TCD to measure time averaged maximum of the mean velocities (TAMMV) in the intracranial arteries in children attending a tertiary centre in central India.

Methods:

STUDY DESIGN: A cross sectional study was conducted in consecutively recruited stable children of either sex with homozygous SCA proven by electrophoresis and high performance liquid chromatography in the age group of 1-26 years. Patients who were febrile, acutely ill, hypoxic or asleep were not included in the study as these conditions can falsely elevate the intracranial blood flow velocities. Patients with hemoglobinopathies other than HbSS or S/b0 Thalassemia and those with a history of congenital neurological illness were excluded.

DETERMINATION OF TCD VELOCITY: TCD was performed in a tertiary care center in Nagpur using either an imaging machine (Lasiq s8) in the department of radiology or a portable non-imaging TCD (Compumedics); for both a probe of frequency 2Mhz was used. Maximum values for TAMMV in the Middle (MCA) and Anterior (ACA) cerebral arteries were measured in all; for the non-imaging TCD values for posterior cerebral artery (PCA) and basilar artery were also obtained. The results of the first scan performed on these individuals were included in this study. Using values similar to the STOP trial, TAMMV of each of these vessels were categorized as follows: Normal <= 170cm/s; Conditional - between 170 and 199 cm/s; Abnormal >= 200 cm/s; Low <50 cm/s and unobtainable.

MEASUREMENT OF HAEMATOLOGICAL VALUES: Laboratory parameters such as Hemoglobin, white blood cell count (WBC), Mean corpuscular volume (MCV) and hemoglobin F (HbF) levels of the patients in the study were also included if the parameters were available on the day of TCD or within 90 days of TCD study.

MEASUREMENT OF HEIGHT, WEIGHT AND BMI: The height and weight of each of the patients on the day of TCD or within a period of 60 days from the TCD were measured and the body mass index (BMI) was calculated.

Results

One hundred and twenty children and youth aged 1-26 (median 7) years, 67 male (56%), were recruited. Of the 120 patients, 106 (88.5%) belonged to the Scheduled Caste category, 3 (2.5%) to the Scheduled Tribe category and 11 (9.1%) to the Other Classes category. Three (2.5%) had had a clinical stroke and 8 (7%) had had seizures, one of whom also had a stroke.

Twenty-seven (23%) children had TAMMV outside the normal range. Five had abnormal TAMMV in the MCA (n=4) and/or ACA (n=1), 8 had conditional TAMMV in the MCA (n=7) and/or ACA (n=1) while 14 patients had low (n=12) or unobtainable (n=2) TAMMV in the MCA. One child with stroke had low TAMMV and one had conditional TAMMV while the third had normal TAMMV. Of the 7 with isolated seizures, one had low TAMMV and one had conditional TAMMV while the remaining 5 were normal.

BMI was 8.6-25.3 (median 14.1), height/weight was 3.4-10.3 (median 6.5), hemoglobin was 43-134 (median 81) g/L, oxygen saturation 87-100 (median 99)%, HbF was 1.9-60 (median 21) g/dL, MCV was 59.1-96.7 (median 83.2) fl, WBC was 2.3-35.9 (median 10.1)*109.

Those with TAMMV outside the normal range were not different from those with normal TAMMV in terms of age, BMI, Height/weight, or recent hemoglobin, oxygen saturation, HbF, MCV, or WBC.

Discussion

This study demonstrates the feasibility and importance of TCD screening in Indian SCD population. TAMMV on TCD was outside the normal range in nearly a quarter of children with SCD, as has been reported in studies in other populations. The findings of this study may not be representative of stroke risk in tribal populations since they were underrepresented in this study. These data provide the rationale for implementing systematic screening with TCD to reduce the risk of stroke in children affected by SCD in India.

Disclosures

Darbari:Novartis: Membership on an entity's Board of Directors or advisory committees; Hilton Publishing: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: one day advisory board meeting .

Author notes

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Asterisk with author names denotes non-ASH members.