Hydroxyurea therapy lowers TCD velocities in children with sickle cell disease

INTRODUCTION: Hydroxyurea (HU) improves hematologic parameters and decreases adverse events in patients with sickle cell disease (SCD). HU has been proposed as an alternative to chronic transfusions for secondary stroke prevention. Transcranial doppler (TCD) is an accepted method of stroke risk stratification in patients with SCD. We sought to determine if HU affects TCD velocities in children with SCD. METHODS: A cohort of 24 children with HbSS with a baseline TCDi prior to HU and a follow-up after at least 6 months of therapy was analyzed. Twenty-four age-matched children with HbSS formed the control group. Differences in hematologic parameters before and after HU therapy were evaluated. RESULTS: TCDi velocities decreased in the HU-treated patients. The adjusted mean change in TCDi velocities was -13.0 cm/sec (95% CI -20.19, -5.92) in the HU-treated group and +4.72 cm/sec (95% CI -3.24, 12.69) in the controls. Changes in TCDi between the two groups were statistically significant (P < 0.001). Changes in hematologic parameters were not predictive of changes in TCDi velocities in the treated patients. Four out of five patients with TCDi velocities >170 cm/sec had normalization of TCDi velocities on HU. Mean change was -34.75 cm/sec in this subgroup. No patients experienced cerebrovascular accidents (CVA) while on HU. CONCLUSIONS: HU-treated patients experienced statistically significant decreases in TCDi velocities compared to age-matched controls. Changes in hematologic parameters were not predictive of changes in TCDi velocities in the treated group. The decrease in TCDi velocities is not a consequence of changes in hematologic values in patients treated with HU.     

Acute silent cerebral infarction in children with sickle cell anemia

Silent cerebral infarctions (SCI) occur in up to 35% of children with sickle cell anemia (HbSS) but are rarely recognized during the initial 10–14 days when diffusion weighted magnetic resonance imaging (MRI) can differentiate acute infarctions from remote events. We report acute SCI in seven children with HbSS who had areas of restricted diffusion on MRI without persistent focal neurologic deficits. Four had acute SCI identified following acute anemic events. Our observations suggest that SCI are detectible in the acute phase, present with subtle neurologic symptoms, result in permanent neurologic injury, and may be caused by acute anemic events. Pediatr Blood Cancer 2010;54:461–464. © 2009 Wiley‐Liss, Inc.     

Secondary benefit of maintaining normal transcranial Doppler velocities when using hydroxyurea for prevention of severe sickle cell anemia

In a retrospective cohort study, we tested the hypothesis that when prescribing hydroxyurea (HU) to children with sickle cell anemia (SCA) to prevent vaso‐occlusive events, there will be a secondary benefit of maintaining low transcranial Doppler (TCD) velocity, measured by imaging technique (TCDi). HU was prescribed for 90.9% (110 of 120) of children with SCA ≥5 years of age and followed for a median of 4.4 years, with 70% (n = 77) receiving at least one TCDi evaluation after starting HU. No child prescribed HU had a conditional or abnormal TCDi measurement. HU initiation for disease severity prevention decreases the prevalence of abnormal TCDi velocities.     

Early blood transfusions protect against microalbuminuria in children with sickle cell disease

BACKGROUND: Microalbuminuria (MA) is an early indicator for glomerulopathy in sickle cell disease (SCD). PROCEDURE: We reviewed the medical records of asymptomatic patients ages 4-20 with sickle hemoglobinopathies, who were screened for MA in order to find out its prevalence and risk factors. RESULTS: Nineteen of 120 (15.8%) screened patients had MA detected by spot urine (mean albumin absolute value 6.95 +/- 0.56 mg/dl) and abnormal albumin to creatinine ratios (79.8 +/- 0.62 mg/g creatinine). Twenty four-hour urine collections confirmed 57% of MA cases by spot urine. There was no difference in hyperfiltration between positive and negative patients. From the MA-positive patients, 15 had SS (16.8% of SS group) and 4 had SC (18% of SC group). Nineteen percent of children 10 years of age or older had MA, as compared to 8% of the younger children (P = 0.018), demonstrating that increasing age is a risk factor for MA. There was a positive correlation between MA and acute chest syndrome. Young age at start of chronic transfusions was inversely related to MA and therefore renoprotective (P = 0.03). We did not see a protective effect in the group of patients taking hydroxyurea for a relatively short time, mean age at start of treatment 12 +/- 5 years; however the sample was small. CONCLUSIONS: We conclude that: (1) children with sickle cell hemoglobinopathies 10 years or older should be screened for MA and (2) chronic transfusions starting at an early age may be renoprotective.     

Reversible posterior leuko‐encephalopathy in children with sickle cell disease

Children with sickle cell disease (SCD) have high risk of neurologic morbidity and mortality, such as strokes, silent infarcts and TIA's. A retrospective review of magnetic resonance imaging and magnetic resonance angiography identified eight children with radiological and clinical characteristics of reversible posterior encephalopathy (RPLS). These patients had no evidence of previous cerebral infarcts or vasculopathy. Three have died during the 5‐year follow up; one developed a stroke and one a conditional TCD. RPLS needs to be considered in the differential diagnosis of children with SCD that present with acute neurological changes, especially if they are already been hospitalized. Pediatr Blood Cancer 2009;52:373–375. © 2008 Wiley‐Liss, Inc.     

Transcranial Doppler in hemoglobin SC disease

Background: Stroke is a severe clinical disorder in sickle cell disease (SCD), and few studies have evaluated transcranial Doppler (TCD) flow velocities in hemoglobin SC disease (HbSC). The guidelines for stroke risk are based on evaluations in sickle cell anemia (SCA) or HbS/β thalassemia. Procedure: In this study, we compare cerebral blood flow in patients with SCD stratified by genotypes. A total of 1,664 pediatric patients with SCD underwent TCD velocity screening, and the time‐averaged maximum mean velocity (TAMM) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). Results: Abnormal velocities were not identified in the ACA; therefore, we only use ICA and MCA velocities. TAMM from the left and right in the ICA and MCA was 134.3 ± 32.0 and 134.4 ± 32.6 cm/s in patients with SCA, and 105.2 ± 20.6 and 104.7 ± 20.0 cm/s in the patients with HbSC, respectively. Mean TAMM between right and left ICA/MCA was 134.5 ± 30.5 cm/s in the SCA group, and 104.9 ± 19.3 cm/s in the HbSC group. Notably, our data show that TCD velocities were significantly lower among the patients with HbSC compared to SCA. TAMM was negatively correlated with hemoglobin and hematocrit in both genotypes. Conclusion: These results suggest that a different cut‐off value for abnormal TCD velocities could be considered for patients with HbSC. Additional studies are warranted to determine the actual risk of stroke in HbSC genotype associated with this possible TCD risk value.     

Diverse manifestations of acute sickle cell hepatopathy in pediatric patients with sickle cell disease: A case series

The hepatic complications of sickle cell disease (SCD) are associated with increased morbidity and mortality in adults; children usually survive but may suffer significant sequelae. Few diagnostic tools differentiate the various hepatic manifestations of SCD. Why patients exhibit one hepatic pathology versus another is unclear. We report four pediatric patients with hemoglobin SS disease with diverse manifestations of acute hepatic involvement including acute sickle hepatic crisis, hepatic sequestration, sickle cell intrahepatic cholestasis, and a non‐SCD cause of hepatopathy in a patient with viral hepatitis. These complications require a systematic approach to extensive evaluation and coordinated multidisciplinary care.