Prospective Evaluation of the Prevalence of Elevated Tricuspid Regurgitant Jet Velocity and Associated Clinical and Echocardiographic Factors in Children and Adolescents with Sickle Cell Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3388-3388
Author(s):  
Andrew D. Campbell ◽  
Caterina Minniti ◽  
Craig Sable ◽  
Greg Ensing ◽  
Niti Dham ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Children And Adolescents ◽  
Sickle Cell ◽  
Fold Increase ◽  
Systemic Hypertension ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Jet Velocity ◽  
Minute Walk

Abstract Background: Echocardiography (ECHO)-determined tricuspid regurgitation jet velocity (TRV) ≥2.5 m/s occurs in about 30% of adults with sickle cell disease(SCD)and is associated with increased mortality. The frequency and significance of high TRV in children is not known. We determined the prevalence and risk factors of elevated estimated systolic pulmonary artery pressures in 228 patients with SCD and 39 controls. Methods: Patients with SCD (Hb SS, SC, SB thalassemia or other major sickling phenotypes) aged 3 to 20 years were evaluated clinically and with ECHO and six minute walk tests at their steady state. Healthy, non-SCD controls, matched for ethnicity, sex and age, were also evaluated. Results: A comparison of patients and controls is summarized in Table 1. 184 patients (81%) had hemoglobin SS phenotype and 28 (12%) had hemoglobin SC. TRV was measurable in 214 (94%) of the patients and 34 (87%) of the controls. In a multivariate logistic regression model, each 10 mm Hg increase in systolic blood pressure was associated with an estimated 2.0-fold increase in the odds of TRV≥2.5 m/sec (P = 0.002) and a 10-fold increase in LDH with a 25-fold increase in the odds (P = 0.015). Conclusion: This study of children with SCD who have limited iron overload and limited renal dysfunction compared with the aging SCD population provides a unique window into the early pathogenesis of PH in SCD. TRV and LVMI are significantly higher in children and adolescents with SCD at steady state than age-matched control participants. Among children with SCD, TRV elevation is independently associated with systolic BP and LDH concentration. In this analysis we find a strong association with hemolysis and systemic hypertension and surprisingly no associations with vaso-occlusive events or biomarkers (VOC, ACS, HU use, WBC and platelet counts). Table I. Comparison of SCD and control subjects. Results in mean (SD) unless otherwise stated. SCD(n=228) Control (n=39) p Age in years 12 (5) 12 (5) 0.7 Female (%) 48% 46% 0.8 Systolic BP (mm Hg) 112 (11) 116 (15) 0.1 Diastolic BP (mm Hg) 64 (9) 68 (10) 0.040 Six minute walk in meters 454 (76) 498 (84) 0.006 TRV in m/sec 2.3 (0.3) 2.1 (0.3) 0.003 TRV 2.5 m/sec (%) 21% 3% 0.012 LV intern. diastolic diam Z-score 1.2(1.4) −0.3(1.2) <0.001 LV mass index 88 (25) 59 (13) <0.001 Table II. Comparison of SCD patients according to TRV category. Results in mean (SD) unless otherwise stated. Variables TRV <2.5 (n= 169) TRV ≥2.5 (n=45) p History of acute chest syndrome (%) 20% 40% 0.034 Hydroxyurea therapy 42% 44% 0.8 Hemoglobin in g/dl 9.3 (1.8) 8.9 (1.7) 0.071 LDH in U/L 393 (163) 474 (170) 0.009 Total Bilirubin in mg/dL 2.7 (1.9) 3.8 (2.2) 0.004

Hemolysis-Associated Elevation in Tricuspid Regurgitation Velocity Predicts Reduction in Six-Minute Walk Distance After Two Years of Follow up in Children and Adolescents with Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 574-574
Author(s):  
Victor R. Gordeuk ◽  
Lori Luchtman-Jones ◽  
Andrew D. Campbell ◽  
Sohail R Rana ◽  
Mehdi Nouraie ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Children And Adolescents ◽  
Sickle Cell ◽  
Cell Disease ◽  
Walk Distance ◽  
Six Minute Walk Test ◽  
Minute Walk Distance ◽  
Minute Walk

Abstract Abstract 574 Background. Elevated tricuspid regurgitation velocity (TRV) as determined by echocardiography correlates with elevated systolic pulmonary artery pressure and is associated with increased morbidity and mortality in adults with sickle cell disease. The importance of elevated TRV in children and adolescents with sickle cell disease is not known. The Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study is an ongoing, longitudinal and observational multicenter study of children with sickle cell disease. Methods. Baseline echocardiography and six-minute walk test were performed prospectively in 361 children and adolescents with sickle cell disease at steady state and then repeat studies were performed in 209 after a median of 22 months of follow up (range 10 months to 36 months), also at steady state. A hemolytic component was derived by principal component analysis of baseline values for reticulocyte count, lactate dehydrogenase, aspartate aminotransferase and total bilirubin. Results. TRV or six-minute walk test were measured at both baseline and follow-up in 193 patients. Twenty-one of these 193 patients had elevated TRV of 2.60 m/sec or higher at baseline. Elevated baseline TRV was associated with high hemolytic rate in 15 patients, defined as hemolytic component above the median for the population studied, and with lower hemolytic rate in six patients. Elevated baseline TRV with high hemolytic rate predicted elevated TRV at follow up (odds ratio 7.7; 95% confidence interval [CI] 2.5 to 24.2; P <0.001) but elevated baseline TRV with lower hemolytic rate did not (odds ratio 1.6; 95% CI 0.2 to 14.1; P = 0.7). Elevated baseline TRV with high hemolytic rate also predicted a decline in the six-minute walk distance by 10% or more at follow-up (hazard ratio 3.9; 95% CI 1.4 to 10.7; P = 0.009). In contrast, higher cardiac output as measured by the left ventricular end diastolic dimension z-score was associated with reduced risk for a decline in the walk distance (hazard ratio 0.7; 95%CI 0.6 to 0.9; P = 0.006). Conclusion. Steady-state TRV elevation in association with a high hemolytic rate occurs on screening in about 8% of children and adolescents with sickle cell disease and is predictive of elevated TRV and reduced six-minute walk distance after approximately two years of follow. Such children may be at risk for adverse clinical consequences of pulmonary hypertension as young adults. Further studies are indicated to identify the molecular mechanisms and to develop appropriate medical management for children and adolescents with this complication. Disclosures: No relevant conflicts of interest to declare.

Correlations Between Cytokines and Elevated Tricuspid Regurgitant Jet Velocity in Children and Adolescents with Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2484-2484
Author(s):  
Xiaomei Niu ◽  
Mehdi Nouraie ◽  
Caterina Minniti ◽  
Craig Sable ◽  
Andrew Campbell ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Growth Factor ◽  
Sickle Cell Disease ◽  
Children And Adolescents ◽  
Sickle Cell ◽  
Plasma Concentrations ◽  
Interferon Γ ◽  
Cell Disease ◽  
Jet Velocity ◽  
Factor Α

Abstract Background:The pathogenesis of pulmonary hypertension in sickle cell disease is not fully defined. We have found independent associations of hemolysis and hemoglobin oxygen desaturation with elevated tricuspid regurgitant jet velocity in a prospective multicenter study of 310 children and adolescents with sickle cell disease. The present report includes a subset of these patients in whom we investigated the association with jet velocity of an array of cytokines and biomediators that have previously been associated with vasculopathy and primary or secondary hypertension. Methods:Jet velocity was prospectively determined by Doppler echocardiograph in 237 children and adolescents with sickle cell disease at steady state. Elevated jet velocity was defined as ≥2.6 m/sec based on the mean + 2 SD in control subjects matched by age, sex and ethnicity to every sixth patient. Plasma concentrations of interleukins-6, 8 and10, interferon-γ, tumor necrosis factor-α, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF-BB) and Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES) were determined by a multiplex cytokine kit and the Bio-Plex suspension array system (Bio-Rad, Hercules, CA). Plasma concentrations of endothelin-1 and serum concentrations of erythropoietin were analyzed by ELISA (R&D Systems, Minneapolis, MN). Levels of significance were adjusted for multiple comparisons. A hemolytic index was derived by principle component analysis of reticulocyte count, aspartate aminotransferase, total bilirubin and lactate dehydrogenase. Oxygen saturation of hemoglobin was determined by pulse oximetry. Results:Interleukins-8 and 10, VEGF and erythropoietin were significantly increased in sickle cell disease patients compared with controls while RANTES was significantly decreased. Among patients with sickle cell disease, interleukins-6 and 8, interferon-γ, tumor necrosis factor-α, PDGF-bb, erythropoietin and RANTES had significant positive correlations with jet velocity in bivariate analyses. Of these, only interleukin-8 and erythropoietin correlated significantly with the hemolytic index in bivariate analyses. By logistic regression, interleukin-6 (p = 0.020) and PDGF-bb (P = 0.003) were independently associated with increased odds of elevated jet velocity while VEGF was independently associated with decreased odds (P = 0.004). These associations persisted after adjustment either for the degree of hemolysis or for hemoglobin oxygen saturation. Conclusion: Similar to observations in primary and experimental pulmonary hypertension, altered expression of interleukin-6, PDGF-bb and VEGF may be associated with the development of pulmonary hypertension in children with sickle cell disease. At least some of these effects may be additive to those of hemolysis and hypoxia. Further investigations of these pathways may be appropriate in the search for new therapeutic modalities.

scholarly journals Inpatient Utilization Among Children and Adolescents with Sickle Cell Disease: Analysis of a Large Populated-Based Retrospective Cohort

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3262-3262 ◽  
Author(s):  
Rodney Theodore ◽  
Vaughn Barry ◽  
Maa-Ohui Quarmyne ◽  
Carlton Dampier ◽  
Peter A. Lane
Keyword(s):  
Sickle Cell Disease ◽  
Children And Adolescents ◽  
Hospital Discharge ◽  
Sickle Cell ◽  
Hospitalization Rate ◽  
Hospital Utilization ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Readmission Rates ◽  
Hospitalization Rates

Abstract Background: Sickle cell disease (SCD) is characterized by marked heterogeneity in clinical outcomes, severity and utilization of health care services. This heterogeneity is particularly evident with regards to utilization of inpatient hospital services. Some children with SCD are frequently admitted to the hospital while others are rarely or never admitted. In addition, rates of readmission within 30 days of hospital discharge are high in SCD. The causes of this variable utilization and high rates of readmission are not well understood. Objectives: We sought to determine rates and primary causes of SCD-related hospital utilization among children and adolescents with SCD and to determine whether rates of hospitalization and of 7-, 14- and 30-day readmissions varied by age, SCD genotype, gender and cause of hospitalization. Methods: Children who lived in the 28-county greater metro Atlanta area with a confirmed SCD diagnosis and who received care at the ChildrenÕs Healthcare of Atlanta (CHOA) SCD program between January 1, 2010 through December 31, 2014 were included. The earliest and latest encounter during the five-year period was used to determine total length of observation for each patient. To ensure a substantial period of observation, individuals with two consecutive encounters >18 months apart or with < 2 yr of observation were excluded. SCD genotype (SS, SC, and Sβ0 and Sβ+ thalassemia) was confirmed for each patient by review of hematologic and clinical data, including results of diagnostic hemoglobin electrophoresis; those with rare SCD genotypes (e.g. SD, SE) were excluded. The primary cause for each admission was determined through medical chart review and classified into 4 mutually exclusive hierarchical categories in the following descending order: acute chest syndrome (ACS), pain crisis, fever/infection, and other complications of SCD (i.e. an admission for both pain and ACS was categorized as ACS). Scheduled hospitalizations for elective procedures (e.g. splenectomy, cholecystectomy, venous catheter placement) were excluded. A readmission was defined as a hospitalization occurring within 7, 14, or 30 days of a previous hospital discharge. Results: The analysis included 1,331 individuals with 5,362 person-years of observation; 68% had SS/Sβ0 thal genotypes, 49% were male. Age at the time of the earliest encounter ranged from 2 months to 19 years; average length of observation was 4.02 years (min, max= 2, 5). Total n of hospital admissions was 5,317; 19.4% were never hospitalized, and 44.8% were hospitalized less than once per year. The most common primary cause for hospital admission was pain (53.1% of admissions). Overall and cause-specific hospitalization rates varied by age and genotype (Figure) with overall hospitalization rates lowest among children 4-9 years old compared to other ages (0.68 vs. 1.00 admissions per person-year) and highest among those with SS or Sβ0 thal compared to those with SC or Sβ+ thal (0.97 vs. 0.68 admissions per person-year). Hospitalization rates associated with pain increased with age while rates for fever/infection decreased with age. Of the 1,073 patients who were admitted, 356 were readmitted within 30 days of a previous admission at least once. All-cause 7-, 14- and 30-day readmission rates were 5.6%, 10.0% and 18.2%, respectively. 30-day readmission rates were lower among younger age groups (15.7% for age 1-3 yr, 15.3% for 4-6 yr, 15.8% for 7-9 yr) but higher in older patients (18.3% for 10-12yr, 19.9% for 13-15yr, and 23.3% for 16-18yr). Readmission rates were highest following index admissions for pain (20.4%) and lowest for ACS (11.3%). Gender was not associated with readmission or cause of readmission. Conclusion: SCD-related hospitalization rates were highest in early life and in later adolescence with admissions for fever/infection most common in younger children and admissions for pain crises in older children. Rates of readmission strongly correlated with age and were highest following admissions for pain. These data highlight to need to develop and implement improved strategies prevention and treatment of pain in children and adolescents with SCD. Further studies should also explore individual and/or family factors that may contribute to the high rates of hospital utilization and 30-day readmissions that occur among a relatively small percentage of patients. Figure 1. Hospitalization rate per person-year by type of admission and age Figure 1. Hospitalization rate per person-year by type of admission and age Disclosures No relevant conflicts of interest to declare.

Splenectomy in Jamaican children with sickle cell disease: Outcome of selective blood transfusion

2020 ◽  
pp. 004947552097461
Author(s):  
Odayne Steele ◽  
Alfred L Duncan ◽  
Larnelle N Simms ◽  
Shani A Duncan ◽  
Simone E. Dundas Byles ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Operative Morbidity ◽  
Open Splenectomy ◽  
Bank Reserves ◽  
Transfusion Protocol

We reviewed the post-operative morbidity and mortality of open splenectomy undertaken in conjunction with selective blood transfusion in Jamaican children with sickle cell disease. Data were collected on 150 splenectomies performed between November 1994 and October 2017. Selective blood transfusion involved raising haemoglobin levels to approximately 100 g/L in patients with admission haemoglobin ≥10 g/L below steady state. There was no mortality. Mean post-operative stay was 3.2 days with a median of three days. Total morbidity was 19/150 cases (12.7%), with acute chest syndrome accounting for 11/19 (57.9%). Among the non-transfused, acute chest syndrome occurred in 10/117 cases (8.5%), while among transfused, acute chest syndrome occurred in 1/33 cases (2.9%). We recommend this selective blood transfusion protocol for patients with sickle cell disease to surgeons who undertake splenectomies in settings where blood bank reserves are perennially low.

scholarly journals Hydroxyurea Effectiveness in Children and Adolescents with Sickle Cell Anemia: A Large Retrospective, Population-Based Cohort Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2179-2179 ◽  
Author(s):  
Maa-Ohui Quarmyne ◽  
Wei Dong ◽  
Vaughn Barry ◽  
Rodney Theodore ◽  
Olufolake A. Adisa ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Sickle Cell Disease ◽  
Children And Adolescents ◽  
Selection Bias ◽  
Sickle Cell ◽  
Poisson Regression ◽  
Clinical Effectiveness ◽  
Population Based ◽  
Acute Chest Syndrome ◽  
Cell Disease

Abstract Background: The clinical efficacy of hydroxyurea (HU) in patients with sickle cell anemia (SCA) is well established. In clinical trials, HU has been demonstrated to alter the clinical course of SCA; HU decreases rates of pain, dactylitis, acute chest syndrome (ACS), transfusions, hospitalizations and improves hemoglobin levels. Other studies have shown that HU improves quality of life and decreases mortality. While evidence of efficacy has been well demonstrated, published data about clinical effectiveness is limited. Additionally, attempts to compare outcomes of patients taking HU to those not taking HU have been limited by the inherent selection bias for greater disease severity in patients on HU. We sought to examine the clinical effectiveness of HU in the large population of patients with sickle cell disease (SCD) at Children's Healthcare of Atlanta (CHOA). The program provides comprehensive care to >1,700 active patients; because they include about 95% of all children and adolescents with SCD in the greater Atlanta Metropolitan Area, the program provides a population-based sample. Currently 57% of the 922 children ≥ 1 yr of age with SCA (SS and Sβ0 thalassemia) who are not on chronic transfusions are receiving HU. Methods: Using a retrospective cohort, pre-post treatment study design to control for disease severity selection bias we evaluated the clinical effectiveness of HU in patients with SCA who received care at CHOA and who first initiated HU in 2009-2011. Children on chronic transfusions, or children with inadequate follow up data and/or who ever took HU in the 3 years prior were excluded. Clinical guidelines for dosing HU have been standardized locally and recommend initial dosage of 20mg/kg/day, followed by dose escalation every 2 months to maximum tolerated dose. For each patient, healthcare utilization, laboratory values and clinical outcomes for the 2-year period prior to HU initiation were compared to those for two years after initiation. Medians were compared using the Wilcoxon Signed Rank test and means using T test. Rate ratios were computed using unadjusted Poisson regression. Interactions testing whether the effect of HU varied by age, sex, or insurance status, were assessed using multivariable Poisson regression. Results: Of 211 children with SCA who initiated HU in 2009-2011, 134 met eligibility criteria. After initiation of HU, the rate of hospitalization was 0.53 the rate before HU, a 47% reduction (Table). The number of inpatient days, emergency room (ER) visits, pain encounters, episodes of acute chest syndrome (ACS), and transfusions were also significantly reduced (Table). The hemoglobin level (mean +/- SD) pre- and post-HU initiation was 7.3+/-2.7 g /dl and 8.1+/- 2.9 respectively; an increase of 0.8+/-1.1, p<0.0001. Similarly, pre-HU mean corpuscular volume increased from 82.9+/-7.5 fl pre-HU to 95.7+/-10.7 post-HU; an increase of 12.8+/-7.2, p <0.0001. There was a statistically significant interaction between the effect of HU and age of initiation of the drug on hospitalization rates; patients < 7 years of age had a greater reduction in hospitalizations than older children (58% vs 33%, p=0.03). The effect of HU on hospitalizations did not vary by sex or insurance type. Table 1. Effect of HU initiation on clinical outcomes using Poisson Regression Rate Ratio (Confidence Limits) P Value Hospitalizations 0.53 (0.43 - 0.66) <0.0001 Inpatient Days 0.50 (0.40 - 0.63) <0.0001 ER visits 0.57 (0.49 - 0.67) <0.0001 Pain Encounters 0.64 (0.51 - 0.81) 0.0001 ACS 0.57 (0.39 - 0.83) 0.0036 Blood Exposure 0.43 (0.29 - 0.64) <0.0001 Conclusions: HU is clinically effective in children and adolescents with SCA. HU decreased hospitalizations, ER visits, pain encounters, ACS, use of transfusions and improved hemoglobin levels. HU effectiveness was similar across gender, insurance types and age, although there was a slightly greater reduction in hospitalizations in younger patients. These results are important as they parallel results obtained from HU efficacy studies, thus demonstrating that in 'real life' settings, even without the additional monitoring and adherence incentives of clinical trials, HU improves short-term outcomes in pediatric SCA. Disclosures Off Label Use: Hydroxyurea use as disease modifying therapy in pediatric patients with sickle cell disease.

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