BackgroundSickle cell anemia (SCA) patients exhibit sub-phenotypes associated to hemolysis and vaso-occlusion. The disease has a chronic inflammatory nature that has been also associated to alterations in the lipid profile. This study aims to analyze hematological and biochemical parameters to provide knowledge about the SCA sub-phenotypes previously described and suggest a dyslipidemic sub-phenotype.MethodsA cross-sectional study was conducted from 2013 to 2014, and 99 SCA patients in steady state were enrolled. We assessed correlations and associations with hematological and biochemical data and investigated the co-inheritance of -α3.7Kb-thalassemia (-α3.7Kb-thal). Correlation analyses were performed using Spearman and Pearson coefficient. The median of quantitative variables between two groups was compared using t-test and Mann-Whitney. P-values <0.05 were considered statistically significant.ResultsWe found significant association of high lactate dehydrogenase levels with decreased red blood cell count and hematocrit as well as high levels of total and indirect bilirubin. SCA patients with low nitric oxide metabolites had high total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and reduced very low-density cholesterol, triglycerides, direct bilirubin level and reticulocyte counts. In SCA patients with high-density lipoprotein cholesterol greater than 40 mg/dL, we observed increased red blood cell count, hemoglobin, hematocrit, and fetal hemoglobin and decreased nitric oxide metabolites levels. The presence of -α3.7Kb-thal was associated with high red blood cell count and low mean corpuscular volume, mean corpuscular hemoglobin, platelet count and total and indirect bilirubin levels.ConclusionsOur results provide additional information about the association between biomarkers and co-inheritance of -α3.7Kb-thal in SCA, and suggest the role of dyslipidemia and nitric oxide metabolites in the characterization of this sub-phenotype.
BackgroundIn this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes.MethodsWe conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the βS-globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (−α3.7Kb-thal), as well as the occurrence of clinical events in both SCD genotypes.ResultsLaboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α3.7Kb-thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients.ConclusionsOur data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.
Sickle cell anemia is a severe monogenic disorder characterized by the homozygous state of a single beta globin gene mutation, with heterogeneous clinic characteristics, associated with pro-inflammatory profile, oxidant state and hypercoagulable state. Vessels occlusion is likely initiated by intimal proliferation and amplified by inflammation, excessive adhesion of cells to activated endothelium and vascular tone dysregulation, normally modulated by NFkB pathway both endothelium cells as leukocytes. Herein, we investigated the gene expression of tissue factor (Factor III), oxide nitric synthase (NOS) and endothelial protein C receptor (EPCR) associating with biomarkers of prognosis like hemolysis markers, pro-inflammatory and anti-inflammatory profile. Forty two steady-state sickle cell disease (SCD) patients (16.5 ± 13.5 years, 20 female) from Northeast Brazil were enrolled in this study and were diagnosed in attendance of the outpatients’ clinic of the Sickle Cell Disease Center of Itabuna (CERDOFI). The control group was compound by 20 healthy Brazilian individuals with hemoglobin AA pattern matched by age, years and ethnic origin. The study was approved by the UESC ethical committee and informed consents were signed by patients or official responsible. Using real time quantitative PCR, we analyzed tissue factor, NOS and EPCR gene expression. We also measured hematological and hemoglobin parameters by electronic cell counter and HPLC respectively, biochemical profile was evaluated by colorimetric methodology and cytokine by flow cytometry. The statistical analysis was performed using the Kolmogorov–Smirnov test to access distribution of quantitative variables. Mean values of quantitative variables between groups were compared using an unpaired t-test for data distributed normally and a Mann–Whitney test for non-normal data. Oxide nitric synthase gene expression was increased in SCD patients 1.58-fold compared with healthy controls and higher tissue factor and EPCR gene expression were detected in patients than healthy controls, 4.82-fold and 5.46-fold respectively. The SCD cohort comprised pediatric and adult patients, and the medical history data was search from patient’s records where 95% of patients presented painful crisis at least once. Tissue factor gene expression was positive correlated with expression of NOS (p=0.005) and EPCR (p=0.0001). The increase tissue factor gene expression was detected in patients with high serum levels of bilirubin (p=0.026). Tissue factor gene expression above 75th percentile was associated high concentration of serum creatine kinase and serum calcium (p<0.005) in SCD patients. Our study reveals that genes associate to hemostasis and vascular integrity are upregulated in SCD patients, probably associated to chronic oxidative stress and pro-inflammatory state. Enhanced tissue factor, NOS and EPCR gene expression may influences in the pathophysiology of SCD. Studies tissue factor, NOS and EPCR should be carried out in order to explore mechanism, clarify participation and contributing to search of therapeutic strategies on prevention of vascular events among SCD patients. Disclosures: No relevant conflicts of interest to declare.
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