Papers by Andrew Campbell
Pediatric Blood & Cancer, 2020
BackgroundTotal splenectomy (TS) and partial splenectomy (PS) are used for children with congenit... more BackgroundTotal splenectomy (TS) and partial splenectomy (PS) are used for children with congenital hemolytic anemia (CHA), although the long‐term outcomes of these procedures are poorly defined. This report describes long‐term outcomes of children with CHA requiring TS or PS.ProcedureWe collected data from children ages 2‐17 with hereditary spherocytosis (HS) or sickle cell disease (SCD) requiring TS or PS from 1996 to 2016 from 14 sites in the Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium using a prospective, observational patient registry. We summarized hematologic outcomes, clinical outcomes, and adverse events to 5 years after surgery. Hematologic outcomes were compared using mixed effects modeling.ResultsOver the study period, 110 children with HS and 97 children with SCD underwent TS or PS. From preoperatively compared to postoperatively, children with HS increased their mean hemoglobin level by 3.4 g/dL, decreased their mean reticulocyte percentage by 6.7%, a...
OMICS: A Journal of Integrative Biology, 2020
Frontiers in Medicine
BackgroundCOVID-19 was declared a global pandemic in March 2020. Early reports were primarily in ... more BackgroundCOVID-19 was declared a global pandemic in March 2020. Early reports were primarily in adults, and sickle cell disease (SCD) was classified as a risk factor for severe COVID-19 disease. However, there are a limited number of primarily multi-center studies reporting on the clinical course of pediatric patients with SCD and COVID-19.MethodsWe conducted an observational study of all patients with SCD diagnosed with COVID-19 at our institution between March 31, 2020, and February 12, 2021. Demographic and clinical characteristics of this group were collected by retrospective chart review.ResultsA total of 55 patients were studied, including 38 children and 17 adolescents. Demographics, acute COVID-19 clinical presentation, respiratory support, laboratory findings, healthcare utilization, and SCD modifying therapies were comparable between the children and adolescents. Seventy-three percent (N = 40) of all patients required emergency department care or hospitalization. While 47...
Annals of Hematology, 2020
Ethical approval With the exception of Azienda Ospedaliera-Università di Padova, where there was ... more Ethical approval With the exception of Azienda Ospedaliera-Università di Padova, where there was a previously IRB-approved SCD Registry, IRB approval was obtained at all sites, and written informed consent was obtained from each patient and/or parent/guardian. Ethical approval for the study was sought from the Ethical and Protocol Review Committee of each participating site.
Hemoglobin, Jan 15, 2015
Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the γ-globi... more Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the γ-globin gene promoters. We report three rare cases: a child compound heterozygous for Hb S (HBB: c.20A > T) and HPFH with a novel point mutation in the (A)γ-globin gene promoter who had 42.0% Hb S, 17.0% Hb A and 38.0% Hb F; a man with Hb SC (HBB: c.19G > A) disease and a point mutation in the (G)γ-globin gene promoter who had 54.0% Hb S, 18.0% Hb C and 25.0% Hb F; a child heterozygous for Hb S and HPFH due to mutations in both the (A)γ- and (G)γ-globin gene promoters in cis [(G)γ(A)γ(β(+)) HPFH], with 67.0% Hb A, 6.5% Hb S and 25.0% Hb F.
Pediatric Cardiology, 2007
The prevalence of pulmonary hypertension (PHTN) in the pediatric sickle cell disease (SCD) popula... more The prevalence of pulmonary hypertension (PHTN) in the pediatric sickle cell disease (SCD) population is not known despite its high prevalence in adult patients. Our hypothesis was that increased pulmonary artery pressures (PAPs) would be found in SCD children and adolescents, especially those with a history of pulmonary complications: acute chest syndrome, obstructive sleep apnea, asthma, and reactive airway disease. Fifty-two SCD children, 23 of whom had underlying pulmonary disease, were screened for PHTN, which was defined as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/s. Twenty-four (46.15%) SCD patients had increased PAP (i.e., TRV ! 2.5 m/s), and 6 (11.5%) had significant PHTN (i.e., TRV ! 3.0 m/s). Pulmonary disease was marginally associated with PHTN (odds ratio 2.80 and confidence interval 0.88 to 8.86; p = 0.0795). As in adult SCD patients with PHTN, this complication was correlated with the degree of hemolysis as manifested by significantly higher lactate dehydrogenase and bilirubin, lower hemoglobin and hematocrit levels, and a strong association with Hb-SS phenotype. However, after statistical adjustment for age and sex, increased serum LDH was not associated with the development of PHTN. Further studies are needed to clarify the prevalence and mechanisms of PHTN in pediatric and adolescent patients with SCD.
Paediatric Respiratory Reviews, 2014
Haemolytic anaemia is variable among patients with sickle cell anaemia and can be estimated by re... more Haemolytic anaemia is variable among patients with sickle cell anaemia and can be estimated by reticulocyte count, lactate dehydrogenase, aspartate aminotransferase and bilirubin levels. Using principal component analysis of these measurements we computed a haemolytic score that we used as a subphenotype in a genome-wide association study. We identified in one cohort and replicated in two additional cohorts the association of a single nucleotide polymorphism in NPRL3 (rs7203560; chr16p13Á3) (P = 6Á04 9 10 À07). This association was validated by targeted genotyping in a fourth independent cohort. The HBA1/HBA2 regulatory elements, hypersensitive sites (HS)-33, HS-40 and HS-48 are located in introns of NPRL3. Rs7203560 was in perfect linkage disequilibrium (LD) with rs9926112 (r 2 = 1) and in strong LD with rs7197554 (r 2 = 0Á75) and rs13336641 (r 2 = 0Á77); the latter is located between HS-33 and HS-40 sites and next to a CTCF binding site. The minor allele for rs7203560 was associated with the À/ 3Á7 thalassaemia gene deletion. When adjusting for HbF and / thalassaemia, the association of NPRL3 with the haemolytic score was significant (P = 0Á00375) and remained significant when examining only cases without gene deletion/ thalassaemia (P = 0Á02463). Perhaps by independently down-regulating expression of the HBA1/HBA2 genes, variants of the HBA1/HBA2 gene regulatory loci, tagged by rs7203560, reduce haemolysis in sickle cell anaemia.
The Journal of Pediatrics, 2012
Objective-To identify factors associated with frequent severe vaso-occlusive pain crises in a con... more Objective-To identify factors associated with frequent severe vaso-occlusive pain crises in a contemporary pediatric cohort of sickle cell anemia (SCA)enrolled in a prospective study of pulmonary hypertension and the hypoxic response in sickle cell disease (SCD). Study design-Clinical and laboratory characteristics of children with SCA who had ≥3 severe pain crises requiring health care in the preceding year were compared with subjects with <3 such episodes. Results-Seventy-five children (20%) reported ≥3 severe pain episodes in the preceding year, and 232 (61%) had none. Frequent pain episodes were associated with older age (OR 1.2; 95% CI 1.1-1.3; P<0.0001), α-thalassemia trait (OR 3.5; 1.6-6.7; P=0.002), higher median hemoglobin (OR 1.7; 95% CI: 1.2-2.4; P<0.003) and lower lactate dehydrogenase (LDH) concentration (OR 1.82; 95% CI: 1.07-3.11; P = 0.027). Children with high pain frequency also had an increased iron burden (serum ferritin 480 vs. 198 μg/L; P=0.006) and higher median tricuspid regurgitation jet velocity (2.41 vs. 2.31 m/s; P=0.001). Neither hydroxy urea use nor fetal hemoglobin levels were significantly different according to severe pain history. Conclusions-In our cohort of children with SCA increasing age was associated with higher frequency of severe pain episodes as were α-thalassemia, iron overload, higher hemoglobin and lower LDH concentration and higher tricuspid regurgitation velocity.
Blood Cells, Molecules, and Diseases, 2007
Blood Cells, Molecules, and Diseases, 2007
Archives of Pediatrics & Adolescent Medicine, 2006
To describe the inpatient length of stay and related charges for adults in the United States with... more To describe the inpatient length of stay and related charges for adults in the United States with childhood-onset chronic disease and to examine patterns with respect to different hospital settings. Design: We analyzed data from the 2002 Nationwide Inpatient Sample, a nationally representative data set of hospital discharges. We performed a case-mixadjusted, sample-weighted regression analysis as well as descriptive statistics of hospital use among adults with childhood-onset chronic disease. Setting: United States. Participants: We identified hospitalizations for persons aged 18 years or older with a diagnosis of complex congenital heart disease, cystic fibrosis, sickle cell disease, or spina bifida. Main Exposure: Childhood chronic illness. Main Outcome Measures: Length of stay and total charges among pediatric, adult, and mixed hospitals. Results: In multivariate adjusted analyses, patients with complex congenital heart disease and cystic fibrosis had a significantly longer length of stay in pediatric hospitals than in adult or mixed hospitals (PϽ.001); no similar difference was found for sickle cell disease and spina bifida. For all of the 4 conditions, hospital charges were significantly greater in pediatric hospitals than in adult or mixed hospitals (PϽ.001 for cystic fibrosis, complex congenital heart disease, and sickle cell disease, and PϽ.01 for spina bifida). Conclusions: The vast majority of persons who have survived to adulthood with complex congenital heart disease, cystic fibrosis, spina bifida, or sickle cell disease are hospitalized in hospitals that predominantly care for adults, where charges for care appear to be lower than in pediatric hospitals.
Medicina, 2019
Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defe... more Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defense system and consequently lead to oxidative stress and associated complications in sickle cell disease (SCD) patients. Iron levels have been reported to increase in sickle cell patients due to frequent blood transfusion, chronic intravenous haemolysis and increased absorption of iron from the gastrointestinal tract. These elevated levels of iron may also lead to extensive oxidative damage. The current study evaluated serum levels of iron, copper and zinc in SCD patients and “healthy” controls. Materials and Methods: The study was a cross-sectional one, comprising 90 SCD patients with Haemoglobin SS and Haemoglobin SC genotypes and 50 HbAA “healthy” controls. Serum levels of iron, copper and zinc were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd, VIC, Australia). Copper and zinc ratios were calculated and analyzed. Results...
Medical Sciences, 2019
Oxidative stress plays a very significant role in the pathophysiology of sickle cell disease (SCD... more Oxidative stress plays a very significant role in the pathophysiology of sickle cell disease (SCD) and associated complications. Oxidative stress, which is often experienced by SCD patients as a result of continuous production of reactive oxygen species (ROS), may lead to endothelial dysfunction and acute inflammation. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), often play a protective role. The current study aimed at determining the oxidative profile of persons with SCD at a tertiary hospital in Ghana. This was a case-control study involving 90 patients with SCD (34 HbSS patients at steady state, 30 HbSC at steady state, 15 HbSS with vaso-occlusive crisis, 11 HbSC with vaso-occlusive crisis), and 50 HbAA control group. Whole blood samples were collected from the study participants and analyzed for full blood counts. The blood samples were assayed for SOD and CAT as a measure of antioxidant defense, while lipid peroxidation was quantified as malondial...
Medical sciences (Basel, Switzerland), Jan 20, 2018
Nitric Oxide (NO) and soluble adhesion molecules are promising biomarkers, which predict endothel... more Nitric Oxide (NO) and soluble adhesion molecules are promising biomarkers, which predict endothelial dysfunction in sickle cell disease (SCD). Several studies have investigated the relationship between NO (as well as its metabolites) and endothelial adhesion molecules in SCD. However, these studies were done mainly in the developed world, and it is difficult to extrapolate the findings to SCD populations in other geographical regions such as Africa due to significant disparities in the results. The aim of the current study was to determine the correlation between levels of nitric oxide metabolites (NOx) and adhesion molecules in SCD patients in a tertiary hospital in Ghana. A case control cross-sectional study involving 100 SCD (made up of HbSS and HbSC patients) and 60 healthy controls was conducted. Concentrations of NOx and soluble endothelial adhesion molecules (ICAM-1, VCAM-1 and E-selectin) were measured in all the study participants (n = 160) by the Griess reagent system and ...
Vascular health and risk management, 2018
Nitric oxide (NO) plays a fundamental role in maintaining normal vasomotor tone. Recent clinical ... more Nitric oxide (NO) plays a fundamental role in maintaining normal vasomotor tone. Recent clinical and experimental data suggest that NO may play a role in the pathogenesis and therapy of sickle cell disease (SCD). The aim of this study was to determine NO metabolites (NOx) in SCD patients at steady state and in vaso-occlusive crisis (VOC), as well as those with hemolytic clinical sub-phenotype that includes leg ulcers and priapism. This was a case-control cross-sectional study conducted on a total of 694 subjects including 148 comparison group HbAA, 208 HbSS SCD patients in steady state, 82 HbSC SCD patients in steady state, 156 HbSS SCD patients in VOC, 34 HbSC SCD patients in VOC, 34 HbSS SCD patients in post VOC, 21 HbSS SCD patients with leg ulcer and 11 HbSS SCD patients with priapism, with age ranging from 15 to 65 years. Laboratory diagnosis of SCD was done at the Sickle Cell Clinic of the Korle-Bu Teaching Hospital. Plasma nitric oxide metabolites were measured using Griess r...
Medical sciences (Basel, Switzerland), Jan 27, 2018
Sickle cell disease (SCD) is an inherited blood disorder that can result in vasculopathy and end ... more Sickle cell disease (SCD) is an inherited blood disorder that can result in vasculopathy and end organ damage. Angiogenesis has been implicated as a key contributing factor to vascular mediated tissue injury in SCD. The relative plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) greatly influence angiogenesis. Dysregulation of these growth factors, leading to a pro-angiogenic state in SCD patients, has been documented in the developed world but there is very little data in Africa. There is the need, therefore, for studies in Ghanaian SCD patients. The aim of this study was to assess plasma levels of Ang-1, Ang-2, and VEGF in homozygous (HbSS) SCD patients with or without complications and healthy controls (HbAA) in Ghana. The study was a case-control study involving 544 participants: 396 HbSS SCD patients and 148 HbAA healthy controls. The study was conducted at the Center for Clinical Genetics (Sickle Cell Clinic) and Accr...
Pediatric Blood & Cancer, 2017
Objective: To identify characteristics of pediatric sickle cell disease (SCD) hospitalizations, a... more Objective: To identify characteristics of pediatric sickle cell disease (SCD) hospitalizations, and to examine admission demographics and medical expenditures. Methods: Admissions with SCD were identified from the 2009 and 2012 releases of the Healthcare and Cost Utilization Project's Kids Inpatient Database. Disease-specific secondary diagnoses including; acute chest syndrome (ACS), vaso-occlusive pain crisis (VOC), splenic sequestration, and stroke/transient ischemic attack were analyzed for patient and hospital demographics. Analytical endpoints included total healthcare expenditures and mortality. Results: We reviewed 75,234 inpatient hospitalizations with a diagnosis of SCD. Over $900,000,000 was spent annually in associated healthcare expenditure. The median length of hospitalization stay (LOS) for all admissions was 3 days (IQR 2-5 days). VOC was the most frequent secondary diagnosis, recording 48,698 total hospitalizations and a median LOS of 3 days (IQR 2-6 days). Of the 8,490 hospitalizations with ACS, the infant population had a significantly higher mortality rate compared to other age groups (2% vs. 0.3%, p < 0.001). Cerebral vascular accidents incurred the second highest median hospitalization cost ($18,956), behind ACS ($22,631). A high proportion of Caucasian patients died during hospitalization for VOC (0.4% vs 0.1%, p=0.014) and ACS (4% vs 0.2%, p < 0.001) when compared to non-Caucasians. Conclusion: Inpatient hospitalizations for secondary manifestations of pediatric SCD were associated with significant healthcare expenditures. Patients with an increased statistical risk for death during hospitalization included Caucasians with SCD complications of ACS and VOC, and patients <1-year-old with ACS. Further research is needed to substantiate the associated clinical significance of these findings.
British Journal of Haematology, 2016
This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Human immunology, Jan 15, 2015
Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is conside... more Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p=0.02), -DQ3 (p=0.02) and -DQ5 (p=0.01) alleles were significantly hig...
Blood Cells, Molecules, and Diseases, 2015
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Papers by Andrew Campbell