TCD in Infants: A Report from the BABY HUG Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 952-952 ◽  
Author(s):  
Robert J. Adams ◽  
Julio Barredo ◽  
Duane R. Bonds ◽  
Clark Brown ◽  
James Casella ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Maximum Flow ◽  
Organ Damage ◽  
Sample Volume ◽  
Phase Iii ◽  
Mean Velocity ◽  
Increased Risk ◽  
The Mean ◽  
The Right

Abstract Transcranial Doppler (TCD) is useful in children with sickle cell anemia (SCA) to detect increased risk of stroke. The use of TCD in infants less than 2 years of age is less well established, but has previously been shown to be feasible. As a secondary endpoint in the BABY HUG Trial, TCD is expected to provide useful information on the possible effects of hydroxyurea (HU) in babies with SCA. BABY HUG is an NHLBI-NICHD sponsored phase III clinical trial to compare hydroxyurea to placebo to ascertain effectiveness in preventing end organ damage of the spleen and kidney. Eligible subjects underwent a baseline TCD using the Nicolet Companion (EME) 2-MHz pulsed Doppler. All infants were 8–18 months of age at enrollment, had no history of stroke and were not receiving chronic blood transfusions. Blood flow velocities were recorded using the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol with the exception of reducing the standard sample volume to 4 mm. No sedation was used. The time averaged maximum mean was measured to determine the highest velocity on either side to categorize the study as normal (all recordings <170 cm/sec), conditional (170–199cm/sec) or abnormal (≥200 cm/sec). Recordings of the middle cerebral artery (MCA) and internal carotid artery (ICA) bifurcation defined an adequate TCD. TCD was not required for study entry but subjects with an abnormal exam were not eligible for randomization and treatment. TCD exams were read by blinded reviewers at the Medical College of Georgia. TCD results were transmitted to Clinical Trials & Surveys Corporation (C-TASC) for statistical analysis. As of June 24, 2005, 70 TCD exams had been attempted. Two exams were unsuccessful (no data) because of the children’s irritability and 1 was interpreted as inadequate. Of the remaining 67 TCD exams, 66 were normal and one baby had a high conditional TCD (190 cm/sec). No subjects were found ineligible for the study due to TCD results. The mean velocity of the left MCA was 117 cm/sec ±22.9 and that of the right MCA was 114 cm/sec ±24.9. Regression analyses were performed to examine the relationship of maximum flow velocity (VMAX) to age and total hemoglobin (Hb). VMAX was inversely correlated to Hb (left p=<0.0001, right=<0.0014) and directly associated with age (left p=<.0005, right p=<0.0022). When the mean MCA velocity was regressed against age and Hb, both age (p=0.0285) and Hb (p=.0024) were significant. Adequate baseline TCD evaluation was obtained on 67 out of 70 babies. As expected, baseline TCD velocities varied inversely with the degree of anemia and directly with age; all but one was normal by childhood sickle cell disease standards. These studies provide valuable normative data for infants with SCA, and for further assessment of the effect of HU on TCD in infants with SCA as the study progresses.

Transcranial Doppler (TCD) Ultrasonography in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1436-1436 ◽  
Author(s):  
Winfred Wang ◽  
Renee C Rees ◽  
Scott T. Miller ◽  
R. Clark Brown ◽  
James F. Casella ◽  
...  
Keyword(s):  
Regression Model ◽  
Multiple Regression ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transcranial Doppler ◽  
Reticulocyte Count ◽  
Multiple Regression Model ◽  
Phase Iii ◽  
Mean Velocity ◽  
The Mean

Abstract Introduction: Transcranial Doppler ultrasound (TCD) is used in children with sickle cell anemia (SCA) to detect stroke risk. TCD screening is mostly employed in children between 2–16 yrs of age; its use in infants <2 yr of age is less well established. BABY HUG is an NHLBI-NICHD sponsored Phase III clinical trial in infants with SCA comparing hydroxyurea (HU) to placebo to ascertain efficacy of HU in preventing damage to the spleen and kidney (NCT00006400). As a secondary endpoint in this trial, TCD was done to determine possible effects of HU in babies with SCA. We reviewed the baseline TCD data of infants obtained during eligibility screening in BABY HUG. Methods: All subjects underwent a baseline TCD using the Nicolet Companion (EME) 2-MHz pulsed Doppler. All infants were 7–17 months of age during screening, had no history of stroke and were not receiving chronic blood transfusion. Blood flow velocities were recorded using the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol with the exception of reducing the standard sample volume to 4 mm. No sedation was used. The time averaged maximum mean velocity (TAMM) was measured to determine the highest velocity on either side to categorize the study as normal (highest velocity <170 cm/sec), conditional (170 – 199) or abnormal (≥200). Recordings of both middle cerebral (MCA) and internal carotid (ICA) arteries defined an adequate TCD. Eligibility for BABY HUG required at least an attempted TCD. TCD exams were read by blinded reviewers at the Medical College of Georgia and results transmitted to Clinical Trials & Surveys Corp. for statistical analysis. Results: TCD exams were attempted on 204 infants. Six exams were unsuccessful (no data) because of the subjects’ lack of cooperation and 11 TCD’s were inadequate. Of the remaining (187) TCD exams, 183 were normal and four included at least one conditional velocity. No subjects were found ineligible for the trial due to an abnormal TCD result. The mean velocity of the left MCA was 114.0 cm/sec ± 22.1 and that of the right MCA was 111.7 cm/sec ± 23.1. The top two deciles of the maximum TAMM reading for each child were 149 cm/sec and 141 cm/sec. Both age and total hemoglobin (Hb) were significantly associated (p<0.0001) with the mean MCA velocity in a multiple regression model. Analysis of the maximum TAMM for each child versus age, total Hb, Hb F, reticulocyte count, and Bayley Scales of Infant Devlopment II in a multiple regression model showed that only age (positively, p=0.0001), reticulocyte count (positively, p=0.015), and total Hb (negatively, p=0.0025) were significantly associated with the maximum TAMM. Conclusions: Adequate baseline TCD evaluation was obtained on 187 of 204 (92%) subjects. All but 4 were normal by STOP criteria as compared to approximately 10% abnormal and 18% conditional in STOP screening of older children. Using multivariate analysis, baseline TCD velocities varied inversely with the degree of anemia, as expected, but in addition varied directly with age The lack of significant TCD abnormalities is interesting, given the presence of silent infarcts in 13% of this group of children (Pediatr Blood Canc, 2008). When post-treatment TCD data collection is completed, it may become apparent whether: lower TCD velocities reflect a lack of stenotic vascular disease in infants; infants with TAMMs in the upper deciles will be more likely to have abnormal/conditional velocities as they grow older; and HU will have an impact on TAMM.

Evaluation of Splenic Function in Infants with Sickle Cell Anemia in the BABY HUG Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3587-3587
Author(s):  
Zora R. Rogers ◽  
Renee R. Rees ◽  
Winfred C. Wang ◽  
Daner Li ◽  
Rathi V. Iyer ◽  
...  
Keyword(s):  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Geometric Mean ◽  
Organ Damage ◽  
Phase Iii ◽  
Qualitative Assessment ◽  
Splenic Function ◽  
Clinical Complications ◽  
Normal Mean

Abstract Organ damage in children with sickle cell anemia [SCA] begins with the spleen. Hydroxyurea [HU] decreases clinical complications and mortality in severely affected adults with SCA, and has proven hematologic benefits in children. To critically assess the efficacy of HU in preventing chronic organ damage, the Pediatric Hydroxyurea Phase III Clinical Trial [BABY HUG], an NHLBI sponsored double-blinded placebo-controlled multi-center trial, was initiated. One objective of the Feasibility and Safety Pilot is to evaluate novel strategies for assessment of splenic function in young children with SCA. To date 23 subjects (13 male; median age 12.9 mos, range 10.3–17.6 mos) have been recruited without regard to disease severity. Pretreatment spleen function determined by Tc-99m sulfur colloid liver-spleen [LS] scan was compared to pocked erythrocyte [PIT] counts and flow cytometric quantitation of Howell-Jolly Bodies [HJB]. Results were correlated with total [Hgb] and % fetal [HbF] hemoglobin, white blood cell [WBC] and platelet [PLT] counts. Splenic uptake of Tc-99m was qualitatively graded as normal, decreased, or absent by two nuclear medicine physicians. Of 17 LS scans reviewed 3 had normal (mean age 12.2 mos) and 14 decreased (mean age 14.6 mos) spleen function. LS scans were also imaged quantitatively by determining the geometric mean total counts over the spleen. Although there was a trend for qualitative LS scan results to discriminate splenic function among patients (p=.08), quantitative spleen counts demonstrated a stronger relationship between lower uptake and reduced splenic function. A logarithmic transformation was applied to each measure (except age) to improve linearity with other variables and stabilize the variance of the transformed data. PIT counts (p<.0001) and WBC counts (p=.023) were significantly linearly associated with age. Age was inversely related to Hgb (p=.005) and %HbF (p=.009), but not associated with PLT (p=.54) or HJB (p=.38). Quantitative spleen counts were related inversely to age (p<.01), PIT counts (p=.02), and WBC (p=.026); linearly to %HbF (p=.0003) and Hgb (p=.04); and had no relationship with HJB (p=.39) or PLT (p=.68). In multivariate analysis with age and PIT counts, the decline in spleen counts had the strongest association with %HbF (p=.006). A PIT count of 3.5%, which classically divides normal from decreased spleen function, separated spleen counts into significantly different groups (p<.001). No similar relationship existed for HbF 25% (p=.059), Hgb 8 g/dl (p=.15), or HJB 300/million rbc (p=.28). These preliminary data indicate that the decline of splenic function with age in young children with SCA can be effectively assessed by multiple techniques in a multi-center study. Compared to the traditional qualitative assessment, quantitative evaluation of the LS scan will allow more informative gradation of the decline in splenic function for the BABY HUG study. Surrogate measures such as PIT counts and %HbF are associated with LS scan results, and may prove to be informative non-invasive markers predictive of splenic function.

Efficacy of Hydroxyurea To Prevent Organ Damage in Young Children with Sickle Cell Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3386-3386 ◽  
Author(s):  
Courtney D. Thornburg ◽  
Natalia Dixon ◽  
Shelly Burgett ◽  
Nicole A. Mortier ◽  
Sherri A. Zimmerman ◽  
...  
Keyword(s):  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Brain Mri ◽  
Organ Damage ◽  
Study Entry ◽  
Acute Chest Syndrome ◽  
Time Interval ◽  
Splenic Sequestration ◽  
Increased Risk

Abstract Hydroxyurea (HU) prevents many acute complications of sickle cell anemia (SCA) in adults and children, but its potential to delay or prevent chronic organ damage has not been defined. The objectives of this prospective IRB-approved study were to assess the safety and efficacy of HU in young children with SCA (age 18 mon–5 years) and to determine whether 2 years of therapy preserves renal function, reduces transcranial doppler ultrasound (TCD) values, and prevents development of brain ischemia as evidenced by magnetic resonance imaging/angiography (MRI/MRA). Fourteen children with SCA (11 male, 3 female; mean age 35±11 mon) enrolled and underwent evaluation including blood counts, %HbF measurement, determination of the glomerular filtration rate (GFR) by radionuclide DTPA clearance and Schwartz estimate, TCD mean cerebral artery (MCA) velocities, and brain MRI/MRA. HU was started at 20 mg/kg/day and escalated by 5mg/kg/day every 8 weeks to a maximum tolerated dose (MTD) or 30 mg/kg/day (mean dose 28±4 mg/kg). Children were evaluated initially every 4 weeks. All baseline tests were repeated at study exit (mean time 25±3 months). HU was tolerated well by all children. Hematological changes occurred as expected, with significant increases observed in hemoglobin concentration, MCV, and %HbF and significant decreases in reticulocytes, WBC, and neutrophils. The average GFR value did not rise as expected in this age range; the DTPA GFR decreased by 5.1 mL/min/1.73 m2 (p=0.26) with only 3 of 11 exit studies exceeding 150 mL/min/1.73 m2 and the Schwartz estimate increased by 16.5 mL/min/1.73 m2 (p=0.17). During HU therapy, the average TCD values significantly decreased with a mean decrease of 26±28 cm/sec in the right MCA (p<.01) and mean decrease of 27±33 in the left MCA (p<.05). At study entry, 3 children had conditional TCD velocities, but all were normal at study exit. One child had mild small vessel ischemic changes on MRI at study entry that were unchanged at study exit. Two children had mild MRA changes that were stable or improved at the end of the study. All children had normal or improved rates of growth and development during therapy. Two children required PRBC transfusion for acute events (acute chest syndrome and hypoplastic anemia during a viral illness). There was one episode of Moraxella catarrhalis bacteremia that was unrelated to myelosuppression and responded to antibiotic therapy. One child was removed from study at week 82 due to the development of thrombocytopenia and hypersplenism, another had acute splenic sequestration but continued HU without recurrence, and a third child with previous acute splenic sequestration did not have recurrence during the study. In conclusion, HU therapy appears to be well tolerated in young children with SCA. In addition to providing beneficial changes in hematological parameters, HU has salutary effects on both the kidney and brain. HU therapy was associated with a stable GFR value during a time interval when hyperfiltration develops, and led to significant decreases in TCD velocities. However, preservation of splenic tissue could lead to an increased risk of splenic complications. Follow-up studies are warranted to determine if long-term HU therapy can preserve or restore organ function in this patient population.

Influence of Hemoglobin Level on Clinical Findings In Infants with Sickle Cell Anemia: Data From BABY HUG

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1631-1631 ◽  
Author(s):  
Jeffrey D. Lebensburger ◽  
Scott T Miller ◽  
Thomas H. Howard ◽  
James F. Casella ◽  
R. Clark Brown ◽  
...  
Keyword(s):  
Platelet Count ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Organ Damage ◽  
Hemoglobin Level ◽  
Phase Iii ◽  
Acute Chest Syndrome ◽  
Severe Anemia ◽  
Laboratory Findings ◽  
Baseline Hemoglobin

Abstract Abstract 1631 Introduction: Infants with sickle cell anemia (SCA) are at risk for organ damage and clinical events. Risk may vary depending on steady state hemoglobin level. BABY HUG (ClinicalTrials.org, NCT00006400), a NHLBI-NICHD supported phase III randomized placebo-controlled trial, examined the ability of hydroxyurea (HU) to reduce end organ damage to the kidneys and spleen and attenuate other complications of SCA in infants. In this secondary study, we investigated whether placebo-treated subgroups defined by extremes of baseline hemoglobin level differed from one another in frequency of sickle cell-related complications and other laboratory findings, and then compared these data to the entire group of infants treated with HU. Methods: BABY HUG subjects randomized at ages 9 – 18 mo were treated with hydroxyurea (20 mg/kg/d) (N=96) or with placebo (N=97) for 2 years. Those randomized to placebo were classified according to their age-adjusted baseline hemoglobin level and subgroups in the lowest (n=24) and highest (n=24) quartiles compared. (Demarcating Hb values were: age 9 to <12 mo, <8.0 vs. >10.2gm/dL; age12 – 18 mo, <8.1 vs. >9.9gm/dL.) Results: BABY HUG primary endpoints of spleen (splenic uptake of 99mTc sulfur colloid on liver-spleen scan) and kidney (GFR by DTPA clearance) function did not differ in placebo group subjects who were in the lowest and highest quartile hemoglobin levels. However, those in the lowest hemoglobin quartile had a higher incidence of acute chest syndrome (ACS) than those in the highest quartile (0.31 vs. 0.02 events/person-year, RR 14.4, p=0.01) and this difference was significantly attenuated by HU (0.05 events/person-year). The relative risk for developing a pain crisis did not differ between the two placebo subgroups (2.2 vs. 2.1 events/person-year), but HU significantly reduced pain frequency compared to either subgroup (0.94 events/person-year, p<0.001). Subjects in the lowest hemoglobin quartile had higher baseline mean TCD velocities than those in the highest quartile (126.2 vs. 112.4 cm/sec, p=0.008). These differences persisted over the two-year period of study, with exit values of 164.9 and 139.6 cm/sec, respectively (p=0.003). By comparison mean TCD velocity in the HU-treated group was 124.5 cm/sec at baseline and 145.6 at exit. Results of neurocognitive testing were not statistically different between groups; however, a trend toward a lower performance developmental index (PDI, p=0.07), but not a lower mental development index (MDI, p=0.15), was observed in subjects with the lowest hemoglobin levels. Subjects in the lowest quartile also had a higher mean WBC (18.0 vs. 11.4 × 109/L, p<0.001), absolute neutrophil count (5.3 vs. 3.6 × 109/L, p=0.001), and platelet count (416 vs. 315 × 109/L, p=0.0001) compared to those with the highest hemoglobin. The laboratory findings of patients receiving HU also were significantly lower than those of subjects in the lowest hemoglobin group and similar to those in the highest hemoglobin group. Conclusions: Severe anemia in very young patients with SCA was associated with elevated WBC and platelet counts and higher TCD velocities. Interestingly, severe anemia also was associated with increased frequency of ACS, in contrast to the association of ACS with higher hemoglobin levels in older patients. Future studies will need to confirm this relationship and clarify to what extent associated findings (e.g., hyposplenia, elevated WBC or platelet count) contribute to this susceptibility. Severe anemia in young SCA patients is a negative prognostic factor that is significantly impacted by early hydroxyurea therapy. Disclosures: Off Label Use: Hydroxyurea is not approved by FDA for infants with sickle cell disease. Miller:NIH/NHLBI; Emmaus Med Inc, Novartis Pharmaceutical; St Jude Childrens Hospital: Research Funding.

Interleukin 8 Level, Reticulocyte Counting and aPTT Ratio in Brazilian Sickle Cell Anemia Patients with Leg Ulcers

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4835-4835
Author(s):  
Magnun N N Santos ◽  
Eliel Wagner Faber ◽  
Dulcinéia Martins Albuquerque ◽  
Romulo Tadeu Dias Oliveira ◽  
Marcos André Cavalcanti Bezerra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Organ Damage ◽  
Northeastern Brazil ◽  
Leg Ulcers ◽  
Increased Risk ◽  
History Of

Abstract Abstract 4835 Background: Sickle cell anemia (SCA) is characterized by a chronic inflammatory state in which oxidative stress, particularly in the endothelium, exerts a strong influence on the pathogenesis of vaso-occlusion and may be implicated in patients' clinical heterogeneity and survival. It has been suggested that the cytokine production profile of cells involved in the immune response may vary among patients with SCA. Leg ulcers (LU) represent a severe complication in these patients, and this condition has been associated with specific end-organ damage and an increase in morbidity and mortality. Recent studies have shown that venous obstruction, endothelial dysfunction, coagulopathy and infections are implicated in the complex pathogenesis of LU. Aims: To determine IL-1β, IL-6 and IL-8 plasma levels and gene expression rates as well as hematological and coagulation parameters and correlate these with the history of LU in adult SCA patients followed up at HEMOPE, in the state of Pernambuco, northeastern Brazil. Methods: Peripheral blood samples from 92 patients (median age 27 years; 42 female; 52 male; all Afro-descendants) in the steady state who had been diagnosed with SCA (HbSS), had not received a transfusion and were not using hydroxyurea were analyzed. Plasma levels of cytokines were determined by ELISA, and the gene expression rates by qRT-PCR. The patients' clinical and laboratorial characteristics were obtained from their medical charts. Statistical analysis was performed using the SAS System for Windows version 9.2. Results: Median age was higher in patients with a history of LU than in those without a history (33.1 vs. 28.4; p = 0.04). Although no statistically significant (p = 0.5) differences in IL-8 gene expression rates were observed, IL-8 plasma levels were significantly higher in patients with a history of LU than in patients without a history (23.8 vs. 7.7; p = 0.01) (Figure 1). Thus, patients with high levels of IL-8 had an increased risk for the occurrence of leg ulcers (OR = 1.01; 95% CI = 1.00–1.02). The ROC curve showed that IL-8 levels higher than 8.55 pg/mL could indicate the presence of LU (accuracy = 71.6%; sensitivity = 73.7%; specificity = 68.5%). The laboratory tests revealed reticulocyte counts and activated partial thromboplastin time (aPTT) ratios (R) that were significantly higher in patients with a history of LU than in those without a history (11.8 vs. 8.4, p = 0.01; 1.1 vs. 0.9, p = 0.04, respectively). Both the higher reticulocyte counts and R values were associated with increased risk for the occurrence of leg ulcers in these patients (OR = 1.12, 95% CI = 1.02 – 1.20; OR = 24.28, 95% CI = 1.20 – 486.09, respectively). Conclusion: In this study, patients who had had LU at some time in their lives showed significantly higher IL-8 levels, reticulocyte counts and R values than patients who had never had LU. Our results therefore suggest a relationship between the parameters described above and LU in patients with SCA. These parameters could perhaps be used, in association with different genetic modulators that may contribute to different clinical phenotypes observed in this disease, as markers of this clinical manifestation of SCA or of a propensity to develop it. Financial Support: CAPES (Brazil)/FAPESP/CNPq/INCTS Disclosures: No relevant conflicts of interest to declare.

scholarly journals Characteristics of Children with Abnormal TCD in the Modern Era: Results from the Displace Consortium

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2270-2270
Author(s):  
Julie Kanter ◽  
Mary Dooley ◽  
Logan P Sirline ◽  
Martina Mueller ◽  
Shannon Phillips ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Prevention ◽  
High Risk Group ◽  
Phase Iii ◽  
Dissemination And Implementation ◽  
Advisory Committees ◽  
Transfusion Therapy ◽  
The Mean

Background: Stroke is one of the most devastating complications of sickle cell anemia (SCA). In 1998, the Stroke Prevention Trial in Sickle Cell Anemia (STOP), demonstrated that a high-risk group of children with SCA could be identified using Transcranial Doppler ultrasound(TCD) and that chronic red cell transfusion therapy (CRCT) could reduce the risk of first ischemic stroke in this group by over 90% (Adams, et al NEJM 1998).At STOP studyenrollment, 9.7% of children with SCA were identified as having an abnormal TCD. Baby HUG, (NCT00006400), an NHLBI supported phase III trial showed that severe anemia in SCA was associated with elevated white blood cell (WBC) and higher TCD velocities (Lebensburger, et al Blood 2010 ). It is unclear if lower hemoglobin (Hb) and/or higher WBC are causative of elevated TCD velocities or correlative biomarkers. As new disease therapies become available, it is important to know the current rate of abnormal TCD and characteristics of those patients. The DISPLACE (Dissemination and Implementation Looking at the Care Environment) project is a multicenter, NHLBI-funded study whose primary purpose is to identify barriers to implementation of stroke screening in SCA and test novel methods for improving outcomes. DISPLACE is a 3-part study: retrospective assessment of current practice, qualitative review of barriers and facilitators to screening and a cluster-randomized intervention implementation project to improve stroke screening. Part 1 of the study showedthat TCD screening rates varied widely among institutions ranging from 30-75.2% (mean 48.4%, median 47%). We are now reporting on the rate of abnormal TCD and the characteristics and outcomes of patients with abnormal TCD. Methods: DISPLACE is a consortium of 28 US centers. Each site performed a rigorous retrospective chart review of children with SCA aged 2-16 years from 2012-2016. To be eligible for inclusion, children must have been seen at their institution at least 2x during the study period and have confirmation of SCA. A custom electronic data capture (EDC) system facilitated entry of de-identified data including demographics, TCD and MRI results, medications, transfusions, and laboratory values. For children with SCA who had TCD or central nervous system imaging prior to 2012, these results were also entered into the EDC. TCD results were recorded in the EDC as normal, conditional or abnormal based on their institutional interpretation. Labs and vitals were entered for each patient in closest proximity to each TCD. Confirmation and adjudication of each abnormal TCD and associated outcomes were performed. Stroke status was also recorded as well as presence or absence of CRCT. Results: In total, 5247 children with SCA are included in the database of whom 5225 should have received a TCD. Of this cohort, 4210 children (80.6%) had at least one TCD recorded in the database. Within this group, 207 (4.9%) of children had an abnormal TCD and 816 (19.4%) had a conditional TCD. For those children who underwent TCD during the study (2012-2016) period, there were 105 (2.9%) abnormal TCD and 501 (13.6%) conditional TCD (Table 1). The mean age of children at the time of abnormal TCD was 6.6 years (range 2-16 yr). The majority of children were <10 yr at first abnormal TCD. Over 30% of patients with an abnormal TCD were identified as receiving hydroxyurea.The mean Hb associated with an abnormal TCD was 7.8 +/- 1.1g/dl (range 5.7-10.6) and the mean WBC was 13 x109/L+/- 3.6 (range 3.9-23.4) (Table 2). Of the 105 patients with abn TCD during the study period, 18% had a stroke. Of the total 5247 patients in the database, 3093 (59%) had been prescribed hydroxyurea (HU) and 999 (19%) were prescribed CRCT. CRCT was prescribed most often for abnormal TCD (37%) or secondary stroke prevention (31%). Discussion: DISPLACE is the largest contemporary cohort of children with SCA. The incidence of abnormal TCD in the DISPLACE cohort is significantly lower than at randomization in the STOP study. The number of children receiving CRCT is higher than expected which may partly account for the decrease in frequency of abnormal TCD. Many patients with abnormal TCD were receiving HU when their TCD was abnormal and were started on CRCT. Additionally, while the outcomes of children with conditional TCD are still being evaluated, many of those children reverted to normal TCD without intervention. These data may also help us redefine the use and interventions needed for abnormal TCD. Disclosures Kanter: NHLBI: Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy; SCDAA: Membership on an entity's Board of Directors or advisory committees; Guidepoint Global: Consultancy; GLG: Consultancy; Sangamo: Consultancy, Honoraria; Modus: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Imara: Consultancy; Cowen: Consultancy; Jeffries: Consultancy; Medscape: Honoraria; Rockpointe: Honoraria; Peerview: Honoraria. Adams:GBT: Consultancy, Other: consultancy to companies GBT and Blueburd Bio; Bluebird: Consultancy.

Urine Concentrating Ability in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1413-1413
Author(s):  
Scott T. Miller ◽  
Winfred C. Wang ◽  
Rathi V. Iyer ◽  
Sohail R Rana ◽  
Peter A. Lane ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Study Drug ◽  
Organ Damage ◽  
Phase Iii ◽  
Urine Specimen ◽  
Double Blind ◽  
Young Infants ◽  
Paired Serum Sample ◽  
Urine Concentrating Ability

Abstract A urine concentrating defect is quite common in sickle cell anemia (SCA), has its onset in early childhood, and may be reversible (with transfusion) until age 10 years. BABY HUG is an NHLBI-NICHD sponsored double-blind, placebo-controlled Phase III Clinical Trial (NCT00006400) designed to assess efficacy of hydroxyurea in preventing organ damage in young children with SCA (Hb SS or SβO thalassemia); primary endpoints are spleen function and glomerular filtration rate (GFR). Two hundred thirty-three infants, recruited without regard to disease severity, underwent eligibility screening. To assess urine concentrating ability as a secondary endpoint, parents were instructed to collect and save timed urine specimens from subjects after 4 to 10 hours of fluid deprivation (NPO) overnight for osmolality (OSM) determination. More prolonged deprivation was avoided due to safety concerns. A paired serum sample for OSM, urea nitrogen (BUN), and creatinine was obtained the next morning. All specimens were analyzed in a central laboratory. The analyses included 184 infants with a urine specimen and a reported period of fluid deprivation of at least four hours; 178 had concurrent sera. Mean age was 13.0±2.7 mo (range 7.5 – 17.9 mo) and mean duration of fluid deprivation was 7.4±2.4 hr (4–13 hr). Mean serum OSM was 286±6 mOsm/kg H2O and independent of age, height, weight, or duration NPO. Urine OSM (mean 410±152, median 433, range 58–794 mOsm/kg H2O) was significantly greater than serum osmolality (p&lt;0.0001) and correlated with duration NPO (p=0.001). One hundred forty-two infants (77.2%) concentrated urine (urine OSM &gt; [mean serum OSM + 1 SD]); twenty-two (12.0%) had urine/serum OSM ratio &gt; 2 and 54 (29.4%) had urine OSM &gt; 500 mOsm/L. In addition, five infants (2.7%) were isosthenuric (urine OSM within mean serum OSM ± 1 SD) and 37 (20.1%) hyposthenuric (&gt; 1 SD below mean serum OSM) despite instructions to withhold fluid. Urine OSM was associated with increasing 99mTc-DTPA GFR (p=0.024) and BUN (p&lt;0.0001), but not with serum OSM, age, height, weight or serum creatinine. We conclude that even with a variable, often limited, fluid deprivation challenge, 75 percent of young infants with SCD were able to concentrate urine. We anticipate that at the end of each infant’s two-year study drug treatment period parents will be more successful in achieving the recommended fluid deprivation and urine collection and that differences in concentrating ability between those taking hydroxyurea and those taking placebo will be discernable.

scholarly journals Impact of TCD Screening Protocol on the Incidence of Hemorrhagic Stroke in Children and Young Adults with Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3402-3402 ◽  
Author(s):  
Julie Kanter ◽  
Janet Kwiatkowski ◽  
Heather J. Fullerton ◽  
Jenifer Voeks ◽  
Ellen Debenham ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Prevention ◽  
Hemorrhagic Stroke ◽  
Cell Disease ◽  
Increased Risk ◽  
The Mean ◽  
The Impact

Abstract Background: Primary hemorrhagic stroke is a rare complication of sickle cell disease (SCD) that usually occurs in adults. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) established routine transcranial Doppler ultrasound (TCD) screening with indefinite chronic red cell transfusions (CRCT) for patients with abnormal TCD as standard of care. Despite a notable improvement in the incidence of infarctive stroke in children with SCD after the introduction of TCD screening protocols, it is unclear how this protocol will affect the rate of hemorrhagic stroke. Presumably, early TCD screening and subsequent initiation of CRCT in high risk patients will prevent the progression of cerebral vasculopathy, which should decrease the risk of hemorrhagic stroke; however this has not been proven. Using the large multicenter cohort of children who participated in STOP and/or STOP 2 trials, we sought to assess whether the rate of hemorrhagic stroke was impacted by the use of TCD screening and/or CRCT. Subjects and Methods: Between 1995 and 2005, STOP and STOP 2 (STOP/2) were conducted at 26 sites in the US and Canada. These studies included 3835 children, ages 2 to 16 y with SCD type SS or S-beta-0-thalassemia. Participation in STOP/2 required at least a single screening TCD for randomization. Patients on STOP 2 also had an observational arm for children started on CRCT who had an abnormal TCD. The Post-STOP study was designed to follow-up the outcomes of children who participated in one or both of trials. For all participants the date of their last encounter in STOP/2 was defined as the start of their Post-STOP period. 19 of the 26 original study sites participated in Post-STOP, contributing a total of 3539 (92%) of the STOP/2 subjects. After exit from STOP/2, these children received TCD screening and treatment according to local practices. Data abstractors visited each clinical site and obtained retrospective data from STOP/2 study exit to 2012-2014 including follow-up TCD and brain imaging results, clinical information, and laboratory results. Two separate neurologists, blinded to STOP/2 status and prior TCD and neuroimaging results adjudicated all suspected strokes. Results: Follow-up data were available for 2850 of the 3539 subjects (81%). Twelve children who had a stroke during the STOP study period were further excluded from this analysis resulting 2838 subjects. The mean age at the start of Post-STOP was 10.5 years and mean duration of follow-up after exiting STOP/2 until time of last medical encounter was 9.1 years. A total of 31 patients had a primary hemorrhagic stroke during the Post-STOP observation period (incidence 0.12 per 100 pt years). The mean age at time of stroke was 16.2+5.6 (median 15.3 range (4.8-30.2) years of age. Of those 31 patients, only 52% had a TCD during Post-STOP prior to the event. Seven of those children who underwent screening had documentation of an abnormal TCD prior to the event (5 during STOP era and/or 3 Post-STOP). However, only 1/7 patients (14%) were documented on CRCT at the time of the stroke (4 patients were receiving HU and 2 patients had unknown treatment). Discussion: Although less common than infarctive stroke, patients with SCD are at increased risk for hemorrhagic stroke. There is an increased risk of mortality for patients who suffer from hemorrhagic stroke (up to 26% in some reports in the 2 weeks after the event). It is unclear if TCD screening and subsequent initiation of CRCT will impact the rate of hemorrhagic stroke in the long term. In our results, a similar incidence of primary hemorrhagic stroke was noted although the patients were overall younger than previously reported (16.5+/- 5.5 years versus 20-29 years in Cooperative Study of Sickle Cell Disease). Many patients who had a hemorrhagic stroke (48%) had not undergone TCD screening during the Post-Stop period. Additionally, although a safe stopping point for CRCT has not been established in patients who have had an abnormal TCD, only 1 patient was documented on CRCT at the time of the event (14%). Thus, it is unclear at this time whether TCD screening and subsequent, lifelong continuation of CRCT could have prevented these other events. Clearly, these results demonstrate that improved implementation of STOP protocol is needed as well as further evaluation of the impact of this protocol on the incidence of hemorrhagic stroke. Disclosures No relevant conflicts of interest to declare.

Is There an Increased Risk of Haemophilus influenzae Septicemia in Children with Sickle Cell Anemia?

PEDIATRICS ◽  
1983 ◽  
Vol 71 (6) ◽  
pp. 927-931
Author(s):  
Darleen Powars ◽  
Gary Overturf ◽  
Ernest Turner
Keyword(s):  
Haemophilus Influenzae ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Course ◽  
Febrile Child ◽  
Low Grade ◽  
Upper Respiratory Tract ◽  
Pneumococcal Infections ◽  
Increased Risk ◽  
Upper Respiratory

The risk of Haemophilus influenzae septicemia/meningitis to children who have sickle cell anemia (SS) has been determined to be greater than that seen among normal infants. Of ten bacteriologically proven cases, eight episodes of infection were observed among 234 children with sickle cell anemia (645 person-years), who were less than 5 years of age. There was one case per 69 infants with sickle cell anemia who were less than 18 months old and one case per 36 children with sickle cell anemia between 19 and 59 months of age. Unexpectedly, two infections occurred among 224 children (824 person-years), aged 5 to 9 years; both died. Contrary to the rapid clinical course of pneumococcal infections in children with sickle cell anemia H influenzae septicemia was regularly heralded by a greater than 24-hour prodrome of upper respiratory tract infection, low-grade fever, and otitis media. Three (30%) preventable deaths occurred. Antibiotic therapy for the febrile child with sickle cell anemia must be predicated on the known 400-fold increased risk of pneumococcal septicemia in those less than 5 years old and the fourfold risk of H influenzae septicemia in those less than 9 years of age.

scholarly journals Prevalence of Pulmonary Hypertension in Sickle Cell Anemiai Patient in KSA

2021 ◽  
pp. 214-220
Author(s):  
Eman AbdulAziz Balbaid ◽  
Manal abdulaziz Murad ◽  
Hoda Jehad Abousada ◽  
Abdurrahman Yousuf Banjar ◽  
Mashael Abdulghani Taj ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Nervous System ◽  
Saudi Arabia ◽  
Risk Factor ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Cardiac Disease ◽  
Kingdom Of Saudi Arabia ◽  
Cross Sectional ◽  
Increased Risk

Introduction: Pulmonary hypertension (PH) is a relatively common and severe complication of SCI and an independent risk factor for mortality. Sickle cell disease is considered one of the most common diseases in the Kingdom of Saudi Arabia. When a healthy disease related to cardiovascular health is highlighted, sickle cell anemia may be the most common and related disease in high pulmonary pressure. In this study, we aimed to determine prevalence of PHTN in SCA patient, and associated risk factors with it.   Methodology: This is an analytical cross-sectional study conducted in kingdom of Saudi Arabia (General population, SCA patient and CVD patient), from 29/7/2020 till 15/11/2020. The study was depending on online self-reported questionnaire that included assessing the demographic factors as gender, nationality besides, disease-related information:  SCA patient , CVD patient and DM patient. Results: we received 794 responses to our questionnaire where 93.5% of them were Saudi Arabian.  The prevalence of sickle cell anemia is 8.8%. Male represented 29.8% of patients while female represented 52.2% of patients. In SCA patients, the prevalence of PHTN was 31.8%. Moreover, it was found that having cardiac disease is considered a risk factor for developing PHTN where 37.7% of patients having cardiac disease had PHTN compared with 6.2% of health patients (OD: 9.16, 95% CI: 5.5479 to 15.13, P=0.000) while diabetes mellitus increase risk for developing PHTN by more than seven fold (OD: 7.6, 95% CI; 4.7175 to 12.4, P=0.000) and disorder of nervous system by 12 folds (OD: 12.7; 95% CI: 7.6658 to 21.09, P=0.000). Conclusion: we had found that the prevalence if SCA among Saudi Arabia is 8.8% with a higher prevalence in female than male. Moreover, the prevalence of PHTN in SCA patients was high about 31.8% which is much higher than its prevalence in normal individuals. Moreover, it was found that having cardiac disease is considered a risk factor for developing PHTN besides, having diabetic condition and disorder of nervous system which increased risk for developing PHTN in SCA by nine, seven and 12-fold respectively.

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