Mortality in Children and Adolescents With Sickle Cell Disease

PEDIATRICS ◽  
1989 ◽  
Vol 84 (3) ◽  
pp. 500-508 ◽  
Author(s):  
Sanford L. Leikin ◽  
Dianne Gallagher ◽  
Thomas R. Kinney ◽  
Desirée Sloane ◽  
Panpit Klug ◽  
...  

A study of the natural history of sickle hemoglobinopathies was begun in March 1979. By August 1987, a total of 2824 patients <20 years of age were enrolled. There have been 14 670 person-years of followup. Seventy-three deaths have occurred. Most of the deaths were in patients with hemoglobin SS. The peak incidence of death was between 1 and 3 years of age, and the major cause in these young patients was infection. Cerebrovascular accidents and traumatic events exceeded infections as a cause of death in patients > 10 years of age. There was limited success in identifying risk factors for death. Comparison of this study's overall mortality of 2.6% (0.5 deaths per 100 person-years) with previous reports indicates improvement of survival in US patients <20 years of age with sickle hemoglobinopathies. This improvement is most likely due to parental education and counseling about the illness and the early institution of antibotics in suspected infections.

1998 ◽  
Vol 10 (1) ◽  
pp. 49-52 ◽  
Author(s):  
Carolyn Hoppe ◽  
Lori Styles ◽  
Elliott Vichinsky

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-20
Author(s):  
Victoria Brooks ◽  
Oluwalonimi Adebowale ◽  
Victor R. Gordeuk ◽  
Sergei Nekhai ◽  
James G. Taylor

Background: Blood transfusion is a common therapy for sickle cell disease (SCD). Although, highly effective, a major limitation is development of alloantibodies to minor blood group antigens on donor red cells. Alloimmunization has a prevalence of 2-5% for transfusions in the general population, but it is significantly higher in SCD. Risk factors for alloimmunization have been poorly characterized, although number of lifetime transfusions is an important risk factor. Alloimmunization has been clinically observed in children with a prevalence of about 7%. With development of each antibody, blood donor matching becomes increasingly difficult and expensive with an increased risk for transfusion reactions and diminished availability of compatible red cell units for treatment of SCD. The ability to identify risk factors for developing alloantibodies would be beneficial for clinicians. To identify markers for alloimmunization in SCD, we have analyzed children and adults who developed this complication. Methods: We analyzed The Pulmonary Hypertension and Hypoxic Response in Sickle Cell Disease (PUSH) study, which enrolled n=468 pediatric and n=59 adult SCD subjects. In both children and adults, alloimmunization cases were defined as a history of at least 1 alloantibody. Controls in both cohorts were defined as subjects with no history of alloantibodies and receipt of more than 10 lifetime red cell transfusions. All others within the study who did not meet these criteria were assigned to a third comparison group. To identify differences between cases, controls and all others, we performed univariate analyses (using ANOVA or Kruskal Wallace where appropriate) for clinical parameters and laboratories. Case control comparisons were also performed for selected variables and plasma levels for 11 cytokines. Results were further analyzed using regression modeling. Results: The overall prevalence of alloimmunization was 7.3% among children (34/468 subjects; median age 12, range 3-20 years) compared to 28.8% in adults (17/59 subjects; median age 37, range 18-73 years). When only considering those with >10 lifetime transfusions, the prevalence was considerably higher at 29.3% and 54.8% in children and adults, respectively. At the same time, 8 pediatric (23.5%) and 5 adult (29.4%) alloimmunization cases had received fewer than 10 transfusions. In a 3-way pediatric cohort comparison (cases, controls and all others), risk factors associated with alloimmunization included SS genotype, older age and markers of more severe disease (higher ferritin, WBCs, platelets and total bilirubin). Comparison of cases to controls showed alkaline phosphatase (P=0.05) was significantly lower in cases, whereas AST (P=0.02) was significantly higher even with adjustment for age. Levels of plasma cytokines MCP-1 (P=0.01) and IFNgamma (P=0.08) were lower in cases from a subset of the pediatric cohort. In adults, only 4/59 (6.8%) subjects had never received a lifetime transfusion (all non-SS). In the adult 3-way comparisons, only SS genotype and higher ferritin were associated with alloimmunization. The adult case control analysis showed higher absolute monocyte count (P=0.02), absolute eosinophil count (P=0.04) and absolute basophil count (P=0.008) in association with alloimmunization cases. In addition, alkaline phosphatase was again significantly lower among cases (P=0.02) as seen in the pediatric cohort. There were no significant differences in cytokine levels among adults. Conclusions: When considering only transfused SCD patients, the prevalence of alloimmunization is higher than 30%. As seen in prior studies, higher lifetime red cell transfusions are an important risk factor especially among adults where most patients have received transfusions. Children who develop alloantibodies appear to have laboratory markers of more severe disease, but this is not observed in adults. A novel association observed across both pediatric and adult subjects is a significantly lower serum alkaline phosphatase in those with alloantibodies. The results of this study suggest a need for improved tracking of red cell transfusion therapy in the US for SCD patients due to a high prevalence of alloimmunization. Further study is also needed to elucidate the significance of the alkaline phosphatase association. Disclosures Gordeuk: CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Ironwood: Research Funding; Imara: Research Funding.


1993 ◽  
Vol 152 (3) ◽  
pp. 201-204 ◽  
Author(s):  
M. de Montalembert ◽  
◽  
P. Beauvais ◽  
D. Bachir ◽  
F. Galacteros ◽  
...  

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4760-4760 ◽  
Author(s):  
Najibah Aliyu Galadanci ◽  
Wayne Liang ◽  
Muktar Aliyu ◽  
Binta Wudil Jibir ◽  
Ibraheem Karaye ◽  
...  

Abstract Abstract 4760 Background: Nigeria has the largest population of children and adults with sickle cell disease (SCD) in the world. Approximately 150,000 children are born with SCD each year (incident cases) in Nigeria, compared to a total of approximately 100,000 children and adults living with SCD in the United States (prevalent cases). Pulmonary complications, including asthma and asthma-like symptoms are leading causes of morbidity and mortality in SCD. However, the natural history, risk factors and biological basis of asthma and SCD-associated asthma-like symptoms in SCD are poorly defined. The primary aim of this study is to determine the prevalence of asthma and asthma-like symptoms among children with and without SCD in Nigeria. In a 1:1 case-control study design, we tested the hypothesis that children with SCD would have a higher rate of asthma-like symptoms when compared to children without SCD. Methods: We enrolled 250 cases with SCD and controls, children without SCD, from patients presenting for routine medical care at the Murtala Mohammed Specialist Hospital (MMSH) in Kano, Nigeria over a 4-month period (12/2011 to 04/2012). A structured questionnaire was employed to capture participants' demographic information, medical history (including history of asthma symptoms and allergies), environmental factors (e.g., cooking, presence of animals in the home) and parental behavior (e.g., smoking). Asthma symptoms were identified based on responses to questions adapted from the American Thoracic Society Division of Lung Disease (ATS-DLD-78) questionnaire. Chi-square test of association was used for categorical variables; Wilcoxon rank-sum tests and Kruskal-Wallis U test were used for continuous and ordinal variables. Results: No differences in sex, ethnicity, or place of residence were noted between cases and controls. The average age for the cases was 5.7 years and for controls was 2.8 years (P<0.01). In both cases and controls, affirmative responses to ATS-DLD questions were unrelated to age. Cases were more likely than controls to report a history of cough that worsens with a cold (28.0% vs. 16.8%, P<0.01), cough without a cold (16.0% vs. 9.6%, P=0.03), chest congestion that worsens with a cold (8.0% vs. 1.2%, P<0.01), wheezing that worsens with a cold (19.6% vs. 6.4%, P<0.01), and wheezing without a cold (5.6% vs. 1.6%, P=0.02). Participants with SCD were more likely to have eczema (4.4% vs. 0.4%, P<0.01). Surprisingly, despite the high prevalence of asthma-like symptoms in cases when compared to controls, the prevalence of physician diagnosis of asthma was low in both groups. Only two children were reported as having asthma among cases, compared to none in the control group. No participant reported a history of wheezing attacks with shortness of breath. No difference between cases and controls existed in the distribution of risk factors for asthma, namely: mode of delivery, gestational age at delivery, parental history of asthma, maternal smoking during pregnancy, and exposure to smoking as a child. No association was observed between respiratory symptoms in either group and age, household income, household size, mode of delivery, gestational age, parental history of asthma, or use of firewood/charcoal. Subgroup analysis was performed on participants 4 years of age and older (163 cases and 96 controls). No substantial differences in the results were noted when compared to the entire cohort of 250 cases and controls (results not shown). Conclusions/Recommendation: Nigerian children with SCD have a much higher prevalence of asthma-like symptoms when compared to controls. Despite asthma symptoms being common, a diagnosis of asthma is rare in both cases and controls, suggesting under-ascertainment of an asthma diagnosis. Future work in low income countries directed towards improving co-morbid respiratory disease in children with SCD should focus on the presence of asthma-like symptoms and not a physician diagnosis of asthma. Better understanding of the biological basis for why children with SCD have a higher rate of asthma-like symptoms and atopy may lead to targeted therapy. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3117-3117
Author(s):  
Sherraine Della-Moretta ◽  
William Marshall ◽  
Rui Li ◽  
Erin Cleary ◽  
Philip Samuels ◽  
...  

Abstract Background Approximately 100,000 Americans are affected by sickle cell disease (SCD), an inherited hematologic disorder. In women with sickle cell disease, pregnancy is associated with increased maternal and fetal adverse outcomes (Elenga et al). However, there is a paucity of data on risk factors for adverse events in this population. This retrospective study seeks to add to the deficient repertoire of information regarding maternal and fetal outcomes in patients with sickle cell disease and their children. Methods We retrospectively evaluated pregnancy outcomes of women with SCD who had previously undergone echocardiography from the year 2000-2021. The associations between clinical variables and adverse hematologic (AHE), cardiac (ACE), obstetric (AOE) and fetal/neonatal (ANE) events were evaluated by the Generalized Linear Model (GLM). The adverse hematologic events were vaso-occlusive crisis (VOC) antepartum and postpartum, acute chest syndrome, venous thromboembolism antepartum and postpartum, and transfusion antepartum. Results We identified 43 women/59 pregnancies with a median maternal age 27 years old (interquartile range [IQR] 20), pre-pregnancy BMI 25 kg/m2 (IQR 16). Maternal sickle cell genotype was SS in 31 (72%) women/37 (63%) pregnancies, SC in 8 (18%) women/18 (31%) pregnancies, and other genotype in 4 (9%) women/4 (7%) pregnancies. Prior venous thromboembolism was present in 12 (27%) women/15 (25%) pregnancies and prior acute chest syndrome (ACS) in 33 (80%) women/41 (75%) pregnancies. In the year before pregnancy, 24 (56%) women were admitted at least once for VOC. There were no maternal deaths during pregnancy or up to 1 year postpartum. AHE (n = 171) occurred in 43 (73%) pregnancies (Figure A), with a median of 2 (range 0-13) AHE per pregnancy. AHE were more common with genotype SS, history of ACS, history of ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, tricuspid regurgitation velocity (TRV) &gt;2.5 m/s on echocardiogram, and increased maternal age, and less common with increased hemoglobin (Figure B). ACE were rare (n = 3) (Figure A) and weakly associated with increased maternal age (Figure C). AOE (n = 37) occurred in 27 (45%) pregnancies (Figure A) and were associated with lower pre-pregnancy maternal BMI (Figure D). ANE (n = 54) occurred in 27 (46%) of pregnancies, and were associated with maternal hypertensive disorders of pregnancy (Figure E). Conclusions We found that AHE during pregnancy in women with SCD were associated with genotype SS, history of ACS, ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, higher maternal age, and inversely related to hemoglobin. In addition, AHE during pregnancy were associated with TRV &gt;2.5 m/s on echocardiogram, which has not been previously shown in women with SCD. These data may be useful to identify women at increased risk during pregnancy. Data show that patients with sickle cell disease who have more disease-related complications including history of acute chest syndrome, frequent pain crisis, elevated TRV on echocardiogram, and lower hemoglobin are at greater risk for AHE. This suggests that disease severity is directly related to outcomes. The association between increased maternal age and ACE has been demonstrated in the past in women without SCD (DeViti et al). The same can be noted for the association of AOE with lower maternal BMI (Verma et al), and ANE being associated with maternal hypertensive disorders of pregnancy (Lugobe et al). In the future, prevention of these complications will be key. Future directions include determining the effect of disease-modifying therapy on these outcomes, though safety during pregnancy has not yet been demonstrated for more novel agents such as voxelotor and crizanlizumab. With more information on these risk factors, we hope that modification and treatment can result in better outcomes. Figure 1 Figure 1. Disclosures Desai: Pfizer: Other: Publication Fee, Research Funding; Foundation for Sickle Cell Research: Honoraria; Forma: Consultancy; Novartis: Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding.


2021 ◽  
Vol 5 (13) ◽  
pp. 2717-2724
Author(s):  
Lana Mucalo ◽  
Amanda M. Brandow ◽  
Mahua Dasgupta ◽  
Sadie F. Mason ◽  
Pippa M. Simpson ◽  
...  

Patients with sickle cell disease (SCD) are at high risk of developing serious infections, therefore, understanding the impact that severe acute respiratory syndrome coronavirus 2 infection has on this population is important. We sought to identify factors associated with hospitalization and serious COVID-19 illness in children and adults with SCD.We established the international SECURE-SCD Registry to collect data on patients with SCD and COVID-19 illness. We used multivariable logistic models to estimate the independent effects of age, sex, genotype, hydroxyurea, and SCD-related and -nonrelated comorbidities on hospitalization, serious COVID-19 illness, and pain as a presenting symptom during COVID-19 illness. As of 23 March 2021, 750 COVID-19 illness cases in patients with SCD were reported to the registry. We identified history of pain (relative risk [RR], 2.15; P &lt; .0001) and SCD heart/lung comorbidities (RR, 1.61; P = .0001) as risk factors for hospitalization in children. History of pain (RR, 1.78; P = .002) was also a risk factor for hospitalization in adults. Children with history of pain (RR, 3.09; P = .009), SCD heart/lung comorbidities (RR, 1.76; P = .03), and SCD renal comorbidities (RR, 3.67; P &lt; .0001) and adults with history of pain (RR 1.94, P = .02) were at higher risk of developing serious COVID-19 illness. History of pain and SCD renal comorbidities also increased risk of pain during COVID-19 in children; history of pain, SCD heart/lung comorbidities, and female sex increased risk of pain during COVID-19 in adults. Hydroxyurea showed no effect on hospitalization and COVID-19 severity, but it lowered the risk of presenting with pain in adults during COVID-19.


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