Impact of <i>VEGFA</i> −583C &gt; T polymorphism on serum VEGF levels and the susceptibility to acute chest syndrome in pediatric patients with sickle cell disease

Redha, Noor; Mahdi, Najat; Al-Habboubi, Hebah H.; Almawi, Wassim Y.

doi:10.1002/pbc.25158

Cited by 10 publications

(6 citation statements)

References 16 publications

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“…Recently, several diagnostic studies have investigated predicting susceptibility to ACS in SCD patients, such as using immunohistochemistry to evaluate platelet activation of plasma marker CD40 ligand together with thrombospondin, or using cytogenetics to study certain glycoprotein polymorphisms of vasculogenesis in embryological bases, which typify a raw and promising potential marker to evaluate susceptibility to ACS in sickle cell anemia patients. [1516] However, to the best of the authors’ knowledge, few studies have extrapolated the associated extrapulmonary radiological characteristics for improving bedside imaging diagnosis of ACS. [1718] Improving the imaging diagnosis of ACS will enable timely implementation of treatment to minimize complications.…”

Section: Discussionmentioning

confidence: 99%

Radiological patterns in sickle cell disease patients with acute chest syndrome: Are there age-related differences?

Al-Sharydah

Alshahrani

Al-Dhaferi

et al. 2019

Saudi J Med Med Sci

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Background: Acute chest syndrome is a major cause of pulmonary disease and mortality in sickle cell disease patients. Its diagnosis can be delayed due to differing imaging patterns between children and adults. Objective: The purpose of this study was to describe the pulmonary and extrapulmonary imaging findings in sickle cell disease patients with acute chest syndrome and determine differences in findings between adult and pediatric patients. Patients and Methods: This retrospective study analyzed the data of all sickle cell disease patients who were admitted with a diagnosis of acute chest syndrome to King Fahd Hospital of the University, Al Khobar, Saudi Arabia, between January and June 2015 ( n = 150). After grouping the patients into adults and pediatrics, the pulmonary and extrapulmonary characteristics were identified and the digital radiography, computed tomography and laboratory findings were compared. Results: A total of 116 patients with 163 acute chest syndrome episodes met the inclusion criteria, of which 69 (60%) were adults. In both adult and pediatric patients, the most frequent pulmonary finding was consolidation of the lung parenchyma. The right lung was most frequently involved: the lower lobe in adult patients and the middle lobe in pediatric patients. In addition, pleural effusion was observed in both age groups. Extrapulmonary radiological findings, such as avascular necrosis and cardiomegaly, were significantly more common in adult patients than in pediatric patients ( P < 0.05). Compared with adults, pediatric patients had significantly lower hemoglobin levels ( P = 0.001) and oxygen tension fraction in arterial blood ( P = 0.007). Conclusions: Pediatric and adult sickle cell disease patients with acute chest syndrome typically exhibited similar pulmonary characteristics, whereas extrapulmonary findings were more prominent in adult patients. Furthermore, low levels of hemoglobin and oxygen tension fraction were dependent predictors of acute chest syndrome.

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Section: Discussionmentioning

confidence: 99%

Radiological patterns in sickle cell disease patients with acute chest syndrome: Are there age-related differences?

Al-Sharydah

Alshahrani

Al-Dhaferi

et al. 2019

Saudi J Med Med Sci

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“…Some biomarkers linked to known aspects of SCD pathophysiology may be increased during a pain event: elevated C-reactive protein 128 or substance P (SP) 129 as markers of inflammation; microparticles 130 or cell-free DNA 131 as markers of increased tissue infarction; or plasma-free heme, 132 plasma arginine, 133,134 and exhaled nitric oxide 135 as markers of hemolysis. nitric oxide, endothelial progenitor cells, 136 soluble VCAM, 137 and vascular endothelial growth factor 138,139 may also capture vascular damage and adhesion aspects of a pain crisis. None of these have been shown to be clinically useful or are suitable as important end points in studies of pain.…”

Section: Measures Of Underlying Pain Mechanisms: Pain/ Vaso-occlusivementioning

confidence: 99%

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

Farrell

Panepinto

Carroll³

et al. 2019

Blood Advances

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To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

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“…Acute chest syndrome continues to contribute to significant morbidity and mortality in children and adults with SCD [47]; therefore, the discovery of genetic modifiers of this complication has the potential for high impact and the design of precision medicine. Redha et al [48] investigated the association of the vascular endothelial growth factor A (VEGFA) 583C/ T mutation with acute chest rates in children with SCD. The presence of the 583T/T genotype was associated with increased serum VEGF levels while the VEGFA 583C/T caused reduced VEGF serum levels.…”

Section: Acute Chest Syndrome/pulmonary Hypertensionmentioning

confidence: 99%

“…A great urgency exists to identify genetic factors associated with risk for acute chest syndrome, the leading cause of morbidity and mortality in children and adults with SCD. Mutations in VEGF [48] and the HMOX1 [49] genes hold promise since they serve as markers of endothelial damage and hemolysis associated with the release of free heme in the vascular space, respectively. Long-term repeated episodes of acute chest syndrome can lead to pulmonary hypertension and early death.…”

Section: Precision Medicine For Sickle Cell Diseasementioning

confidence: 99%

Precision Medicine for Sickle Cell Disease: Discovery of Genetic Targets for Drug Development

Pace¹,

Lopez²,

Zhu³

et al. 2016

Sickle Cell Disease - Pain and Common Chronic Complications

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Sickle cell disease (SCD) consists of inherited monogenic hemoglobin disorders affecting over three million people worldwide. Efforts to establish precision medicine based on the discovery of genetic polymorphisms associated with disease severity are ongoing to inform strategies for novel drug design. Numerous gene mutations have been associated with the clinical complications of SCD such as frequency of pain episodes, acute chest syndrome, and stroke among others. However, these discoveries have not produced additional treatment options. To date, Hydroxyurea remains the only Food and Drug Administration-approved agent for treating adults with SCD; recently it was demonstrated to be safe and effective in children. The main action of Hydroxyurea is the induction of fetal hemoglobin, a potent modifier of SCD clinical severity. Three inherited gene loci including XmnI-HBG2, HBS1L-MYB and BCL11A have been linked to HBG expression, however the greatest progress has been made to develop BCL11A as a therapeutic target. With the expanded availability of next generation sequencing, there exist opportunities to discover additional genetic modifiers of SCD. The progress made over the last two decades to define markers of disease severity and the implications for achieving precision medicine to treat the complications of SCD will be discussed.

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Impact of VEGFA −583C > T polymorphism on serum VEGF levels and the susceptibility to acute chest syndrome in pediatric patients with sickle cell disease

Cited by 10 publications

References 16 publications

Radiological patterns in sickle cell disease patients with acute chest syndrome: Are there age-related differences?

Radiological patterns in sickle cell disease patients with acute chest syndrome: Are there age-related differences?

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

Precision Medicine for Sickle Cell Disease: Discovery of Genetic Targets for Drug Development

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