Dataset Information

Clinical and Laboratory Correlates of QTc Duration in Adult and Pediatric Sickle Cell Disease.

ABSTRACT:

Background

Sickle cell disease, a common genetic disorder in African Americans, manifests an increased risk of sudden death, the basis of which is incompletely understood. Prolongation of heart rate-corrected QT (QTc) interval on the electrocardiogram, a standard clinical measure of cardiac repolarization, may contribute to sudden death by predisposing to torsades de pointes ventricular tachycardia.

Methods

We established a cohort study of 293 adult and 121 pediatric sickle cell disease patients drawn from the same geographic region as the Jackson Heart Study (JHS) cohort, in which significant correlates of QT duration have been characterized and quantitatively modeled. Herein, we establish clinical and laboratory correlates of QTc duration in our cohort using stepwise multivariate linear regression analysis. We then compared our adult sickle cell disease data to effect-size predictions from the published JHS statistical model of QT interval duration.

Results

In adult sickle cell disease, gender, diuretic use, QRS duration, serum ALT levels, anion gap, and diastolic blood pressure show positive correlation; hemoglobin levels show inverse correlation; in pediatric sickle cell disease, age, hemoglobin levels, and serum bicarbonate and creatinine levels show inverse correlation. The mean QTc in our adult sickle cell disease cohort is 7.8 milliseconds longer than in the JHS cohort, even though the JHS statistical model predicts that the mean QTc in our cohort should be > 11 milliseconds shorter than in the much older JHS cohort, a differential of > 18 milliseconds.

Conclusion

Sickle cell disease patients have substantial QTc prolongation relative to their age, driven by factors some overlapping, in adult and pediatric sickle cell disease, and distinct from those that have been defined in the general African American community.

SUBMITTER: Yu X

PROVIDER: S-EPMC10785202 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Clinical and Laboratory Correlates of QTc Duration in Adult and Pediatric Sickle Cell Disease.

Yu Xue X Majumdar Suvankar S Pollard J Daryl JD Jackson Erin E Knudson Jarrod J Wolfe Douglas D Kato Gregory J GJ Maher Joseph F JF

American journal of medicine open 20230612

<h4>Background</h4>Sickle cell disease, a common genetic disorder in African Americans, manifests an increased risk of sudden death, the basis of which is incompletely understood. Prolongation of heart rate-corrected QT (QTc) interval on the electrocardiogram, a standard clinical measure of cardiac repolarization, may contribute to sudden death by predisposing to <i>torsades de pointes</i> ventricular tachycardia.<h4>Methods</h4>We established a cohort study of 293 adult and 121 pediatric sickle ...[more]

PMID: 38222852

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Project description:BackgroundSickle cell anemia (SCA) is a monogenic hemoglobinopathy associated with severe acute and chronic complications, with the highest incidence worldwide in Sub-Saharan Africa. The wide variability in clinical manifestations suggest that a uniform response to hydroxurea may not be attained. In view of a potential treatment with hydroxyurea (HU), we assessed the variability of clinical and hematological manifestations in a cohort of adults with SCA in Kinshasa, capital of the DR Congo in Central Africa.MethodsA cross-sectional study was conducted in a hospital dedicated to SCA management in Kinshasa. Clinical history of patients was recorded, a complete physical examination performed. The diagnosis was confirmed by means of DNA analysis. A full blood count and hemolysis markers were measured. The severity of the disease was evaluated by means of a previously reported score.ResultsThe study group consisted of 166 genetically confirmed SCA patients. The SCA severity was mild in 28.9%, moderate in 64.5% and severe in 6.6%. The disease severity score increased with patient's age (p ≤ 0.001). The severity was higher in males compared to females (p = 0.012). In males, the severity score was correlated with the presence of priapism (p = 0.045), a manifestation not previously incorporated in the severity score. The severity score was inversely correlated with the fetal hemoglobin (HbF) rate (p = 0.005). Malnutrition (BMI <18.5 kg/m2) was present in 47% of patients and was related to the male sex, hip disease (aOR 3.11; p = 0.019) and severe phenotype (aOR 3.53; p = 0.012). Leg ulcers were more frequent in males than in females (p = 0.001; OR 24.3) and were correlated with the number of days of hospitalization (p = 0.029). Hip disease was related to the increasing age (p = 0.008).ConclusionIn this selected, hospital-based populations of adults with SCA, severe disease was rare, which may be due to survival bias. However, two thirds had moderate severity of the disease, mostly with a low HbF, and they may benefit from HU treatment. In the Central-African setting the separation between vaso-occlusive and hyperhemolytic sub-phenotypes was not applicable.

Project description:BackgroundSickle cell disease (SCD) is a multisystem disorder characterized by a wide spectrum of clinical manifestations and severity. Studies investigating potential effects of co-morbid human immunodeficiency virus (HIV) and SCD have produced conflicting results, and additional investigations are needed to elucidate whether the interaction between the two disease states might impact both HIV and SCD clinical outcomes. The association of HIV infection with clinical and laboratory characteristics of patients with SCD was assessed.MethodsThis nested case-control study included individuals with SCD with HIV treated at six Brazilian SCD centers. Clinical and laboratory data were abstracted from medical records. HIV positive participants were compared to age, gender, center, and SCD genotype matched HIV negative participants (ratio 1:4). Individual clinical outcomes as well as a composite outcome of any SCD complication and a composite outcome of any HIV-related complication were compared between the two groups.ResultsFifteen HIV positive participants were included, 12 (80%) alive and 3 (20%) deceased. Most of the HIV positive patients had HbSS (60%; n = 9), 53% (n = 8) were female, and mean age was 30 ± 13 years. The frequency of individual SCD complications of acute chest syndrome/pneumonia, sepsis/bacteremia, pyelonephritis, ischemic stroke, hemorrhagic stroke, abnormal transcranial Doppler (TCD), and pulmonary hypertension was higher in HIV positive participants when compared to HIV negative, although analyzed individually none were statistically significant. HIV positive participants had significantly higher risk of any SCD complication and of a composite HIV-related complication compared to the HIV negative group (HR = 4.6; 95%CI 1.1-19.6; P = 0.04 and HR = 7.7; 95%CI 1.5-40.2; P = 0.02, respectively). There was a non-significant trend towards higher risk of any infections in participants with HIV positive (HR = 3.5; 95%CI 0.92-13.4; P = 0.07). Laboratory parameters levels were not significantly different in individuals with and without HIV.ConclusionsIn summary, our study in SCD patients shows that those with HIV have an increased risk of any SCD complication and HIV-related complications, as well as a suggestive but not significantly increased risk of infections.

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Project description:IntroductionSickle cell disease (SCD) is a genetic blood disorder caused by a mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin. This mutation leads to the production of abnormal hemoglobin S (HbS), causing red blood cells to deform into a sickle shape. These deformed cells can block blood flow, leading to complications like chronic hemolysis, anemia, severe pain episodes, and organ damage. SCD genotypes include HbSS, HbSC (HbC is an abnormal variant of hemoglobin), and HbS/β-thalassemia. Sickle cell trait (SCT), HbAS, represents the carrier state, while other hemoglobin variants include HbCC, HbAC, and the normal HbAA. Over 7.5 million people worldwide live with SCD, with a high mortality rate in sub-Saharan Africa, including Ghana. Despite its prevalence, SCD is underdiagnosed and poorly managed, especially in children. Characterized by intravascular hemolysis, SCD leads to oxidative stress, endothelial activation, and systemic inflammation. Identifying circulating blood biomarkers indicative of organ damage and systemic processes is vital for understanding SCD and improving patient management. However, research on biomarkers in pediatric SCD is limited and few have been identified and validated. This study explores specific circulating biomarkers in pediatric SCD in Ghana (West Africa), hypothesizing that inflammatory and neuronal injury markers in children with SCD could predict disease outcomes.MethodsClinical data were collected from 377 children aged 3-8 years with various Hb genotypes, including SCD and SCT, at Korle-Bu Teaching Hospital in Accra, Ghana (2021-2022). A total of 80 age- and sex-matched subjects were identified. A cross-sectional study utilized a multiplexed immunoassay procedure to evaluate serum biomarkers, including cytokines, chemokines, vascular injury markers, systemic inflammation markers, cell-free heme scavengers, brain-derived neurotrophic factor (BDNF), and angiogenic factors.ResultsElevated levels of BDNF, Ang-2, CXCL10, CCL11, TNF-α, IL-6, IL-10, IL12p40, ICAM-1, VCAM-1, Tie-2, and VEGFA were observed in HbSS subjects, correlating with hemoglobin level, leukocyte, and erythrocyte counts. Heme scavengers like HO-1, hemopexin, and haptoglobin also correlated with these parameters. ROC and AUC analyses demonstrated the potential of these biomarkers in predicting SCD outcomes.ConclusionThese findings suggest that there are significant differences between biomarker expression among the different genotypes examined. We conclude that a predictive algorithm based on these biomarkers could be developed and validated through longitudinal assessment of within-genotype differences and correlation of the data with disease severity or outcomes. With such a tool one can enhance SCD management and improve patient outcomes. This approach may pave the way for personalized interventions and better clinical care for pediatric SCD patients.

Dataset Information

Clinical and Laboratory Correlates of QTc Duration in Adult and Pediatric Sickle Cell Disease.

Background

Methods

Results

Conclusion

Publications

Clinical and Laboratory Correlates of QTc Duration in Adult and Pediatric Sickle Cell Disease.

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