scholarly journals Oxidative Profile of Patients with Sickle Cell Disease

2019 ◽  
Vol 7 (2) ◽  
pp. 17 ◽  
Author(s):  
Charles Antwi-Boasiako ◽  
Gifty Dankwah ◽  
Robert Aryee ◽  
Charles Hayfron-Benjamin ◽  
Eric Donkor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Continuous Production ◽  
Tertiary Hospital ◽  
Control Group ◽  
Cell Disease ◽  
Blood Samples

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 malondialdehyde (MDA). The results showed that the levels of SOD and CAT were significantly lower in SCD patients as compared to the control group. Patients with HbSS vaso-occlusive crisis had the lowest levels of SOD and CAT. The difference in SOD levels between HbSS at steady state and HbSC with vaso-occlusive crisis was, however, not significant (p = 0.228). The MDA level was significantly higher in SCD patients compared to the control group. This study concludes that the levels of various antioxidant enzymes (erythrocyte SOD and erythrocyte CAT) and oxidative marker (MDA) and are altered in SCD patients.

scholarly journals Biochemical Assessment of the Liver in SCD in a Tertiary Hospital in South-South, Nigeria

2019 ◽  
pp. 1-6 ◽  
Author(s):  
Kingsley Akaba ◽  
Ofem Enang ◽  
Bassey Okon Bassey ◽  
Oluwakorede Babatope ◽  
Omolabake Riman
Keyword(s):  
Steady State ◽  
Liver Disease ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Biochemical Parameters ◽  
Liver Function Tests ◽  
Tertiary Hospital ◽  
Control Group ◽  
Cell Disease ◽  
Apparently Healthy

Background: Sickle cell disease (SCD) is often associated with liver disease. The constant state of haemolysis, multiple blood transfusion, viral hepatitis, hepatic sinusoidal congestion, haemosiderosis and cholestasis, are all conditions which may eventually evolve into liver disease. Sickle cell disease is a heterogeneous group of disorders that is usually associated with an autosomal recessive structural haemoglobin disorder. Biochemical abnormalities have been associated with SCD and it is usually more pronounced in vaso occlusive crises; an acute bone crisis and common painful complication of SCD, than in steady state. Aim: The aim of the study was to assess some biochemical parameters in relation to SCD patients in our environment with a view to improving the monitoring and management of these patients.  Methodology: The study was a comparative hospital based research carried out at the University of Calabar Teaching Hospital (UCTH), Calabar, South-South Nigeria. Liver function tests were carried out on 60 SCA both in steady state and in crisis and also on 50 apparently healthy adults.  The data collected were analyzed using statistical data for social sciences (SPSS) Version 22 for windows. Pearson linear correlation and simple inferential statistical methods were employed for data analysis, a P ≤ 0.05 was considered to be statistically significant. Result: The serum concentrations of AST, ALT, ALP, LDH, Total and conjugated bilirubin were seen to be elevated in VOC compared to in steady state and with the apparently healthy control group. The AST/ALT ratio was also observed to be elevated in VOC as compared with the steady state and the control. Significant product moment correlation was observed in the biochemical parameters both in steady state and in VOC. Conclusion: The findings of this study revealed marked changes in the biochemical parameters of the liver in VOC than in steady state. It will be recommended that routine evaluation and proper interpretation of liver enzymes is paramount in early detection of liver pathology in SCD.

scholarly journals Is there a role for selective vasodilation in the management of sickle cell disease?

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602 ◽  
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Microvascular Obstruction ◽  
Controlled Study ◽  
Control Group ◽  
Cell Disease ◽  
Retinal Arteriolar

Abstract To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.

scholarly journals Association between Endothelial Dysfunction, Biomarkers of Renal Function, and Disease Severity in Sickle Cell Disease

Kidney360 ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 79-85
Author(s):  
Oluwagbemiga Oluwole Ayoola ◽  
Rahman Ayodele Bolarinwa ◽  
Chidiogo Chukwunweike Onwuka ◽  
Bukunmi Michael Idowu ◽  
Adeniyi Sunday Aderibigbe
Keyword(s):  
Renal Function ◽  
Steady State ◽  
Endothelial Dysfunction ◽  
Sickle Cell Disease ◽  
Disease Severity ◽  
Sickle Cell ◽  
Negative Correlation ◽  
Brachial Artery ◽  
Control Group ◽  
Cell Disease

BackgroundEndothelial dysfunction (ED), as ascertained by brachial artery flow-mediated dilation (FMD), is a known feature of sickle cell disease (SCD), which is present both in crisis and in steady state. The assessment of FMD was introduced to examine the vasodilator function. Our objective was to establish the relationship between ED determined by FMD, biomarkers of renal dysfunction, and biomarkers of disease severity in SCD subjects asymptomatic of renal disease.MethodsWe enrolled 44 patients with homozygous SCD in steady state and 33 age- and sex-matched controls between 2013 and 2014 in a tropical tertiary hospital. Ultrasonographic FMD of the right brachial artery, renal arterial Doppler, complete blood count, creatinine, fetal hemoglobin, soluble P-selectin, and cystatin C (Cys-C) levels were determined. Using the median FMD value of the control group, the SCD subjects were further classified into two groups for comparison.ResultsThe median FMD in SCD subjects of 3.44 (IQR, 0.00–7.08) was significantly lower than that of controls, which was 5.35 (IQR, 3.60–6.78; P=0.04). There was negative correlation between FMD and Cys-C levels (r=−0.372; P=0.01) along with renal artery resistivity index (RARI; r=−0.307; P=0.04) in SCD subjects. Additionally, Cys-C level was significantly higher in SCD subjects with FMD<5.35.ConclusionsBrachial artery FMD was significantly lower in SCD subjects compared with a control group. Cys-C and RARI show a negative correlation with FMD, indicating that renal function is related to ED in SCD.

scholarly journals Alpha-1 Antitrypsin and SERPINA1 gene Mutation As New Biomarker in Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4918-4918
Author(s):  
Magda Oliveira Seixas Carvalho ◽  
Carvalho Luís André ◽  
Mauri­cio Batista Carvalho ◽  
Larissa Carneiro Rocha ◽  
Valma Maria Lopes Nascimento ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Cells ◽  
Gene Polymorphisms ◽  
Clinical History ◽  
Control Group ◽  
Cell Disease ◽  
Serpina1 Gene ◽  
Alpha 1 Antitrypsin

Abstract Sickle cell disease (SCD) has heterogeneous clinical picture and there are several pathway involved in SCD pathogenesis, and chronic inflammation and hemolysis are important hallmarks of the disease. Based on such points, there is a search for prognostic markers to establish possible sub-genotypes of the disease. The present study investigated the alpha-1 antitrypsin (AAT) levels, a serum glycoprotein inhibitor of proteases responsible for trigger inflammatory reactions, describing its associations with SERPINA1 gene polymorphisms, hematological and chemistry biomarkers, and clinical history in a group of SCD children in steady-state. The study was approved at FIOCRUZ research board and followed the principle of Declaration of Helsinki. A total of 356 steady state unrelated SCD patients were included at the present study and a control group (CG) compound by 100 unrelated healthy individuals sex and age matched with the patients group, which were from the same geographical origin. Patients age ranging 13.96+9.91 years of age, the AAT levels higher than the 50th percentile (158.0 mg/mL) had significantly lower red blood cells (RBC) count (p=0.003), hemoglobin (Hb) (p=0.0002) and hematocrit (Hct) (0.0002) concentration, and higher white blood cells (WBC) (p=0.004) and neutrophils (p=0.0001) counts, and higher C-reactive protein (CRP) levels (p<0.0001), and lower urea levels (p=0.0003). AAT had significant negative correlation with RBC (r=-0.205, p=0.0001), Hb (r=-0.203, p=0.0001), Hct (r=-0.256, p<0.0001), high density lipoprotein cholesterol (HDL-C) (r=-0.205, p=0.0001), urea (r=-0.184, p=0.0005), creatinine (r=-134, p=0.012), and albumin (r=-0.135, p=0.011), and significant positive correlation with WBC (r=0.18, 0.0007), neutrophils (r=0.2297, p<0.0001), HbS (r=0.2874), total bilirubin (r=0.137, p=0.01), direct bilirubin (r=0.136, p=0.001), indirect bilirubin (r=0.115, p=0.032), lactate dehydrogenase (r=0.159, p=0.003), ferritin (r=0.1353, 9=0.011), CRP (r=0.355, p<0.0001). Patients with higher levels of AAT had clinical history of more than three infection episodes (OR=1.71, CI:1.05-2.65, p=0.02), gallstones presence (OR=1.75, CI:1.03-2.97, p=0.02), and received more blood therapy (OR=2.35, CI:1.51-3.65, p=0.0001).The SERPINA1 gene polymorphisms were analyzed in 126 SCD patients and 100 CG individuals, the protease inhibitor (Pi)*MM or wide type genotype was find in 115 (91.3%) of SCD patients and 92 (92%) of CG; the PI*SS genotype was find in 2 (1.6%) SCD patients and in none individual of the CG; the PI*MS genotype was find in 9 (7.1%) SCD patients and in 6 (6%) CG individuals; and the PI*MZ genotype was find in 2 (2%) CG individuals. Ours results suggest that the AAT may be considerer as a marker of SCD patients’ outcome, once increased levels is related to stress situation, anti-inflammatory and inhibitory proteases properties and may act as a physiological and cytoprotective regulator influencing the severity of SCD. Our results related to SERPINA1 genotypes emphasize the role of the mutant allele in decrease the AAT production what may represent a risk factor. Additional studies should be carried out in order to investigate mechanisms throughout the AAT can induce several important events in the SCD pathogenesis. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1608
Author(s):  
Qinhong Wang ◽  
Rahima Zennadi
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Redox State ◽  
Continuous Production ◽  
Globin Gene ◽  
Critical Role ◽  
Cell Disease ◽  
Membrane Structure And Function

Sickle cell disease (SCD) is an inherited monogenic disorder and the most common severe hemoglobinopathy in the world. SCD is characterized by a point mutation in the β-globin gene, which results in hemoglobin (Hb) S production, leading to a variety of mechanistic and phenotypic changes within the sickle red blood cell (RBC). In SCD, the sickle RBCs are the root cause of the disease and they are a primary source of oxidative stress since sickle RBC redox state is compromised due to an imbalance between prooxidants and antioxidants. This imbalance in redox state is a result of a continuous production of reactive oxygen species (ROS) within the sickle RBC caused by the constant endogenous Hb autoxidation and NADPH oxidase activation, as well as by a deficiency in the antioxidant defense system. Accumulation of non-neutralized ROS within the sickle RBCs affects RBC membrane structure and function, leading to membrane integrity deficiency, low deformability, phosphatidylserine exposure, and release of micro-vesicles. These oxidative stress-associated RBC phenotypic modifications consequently evoke a myriad of physiological changes involved in multi-system manifestations. Thus, RBC oxidative stress in SCD can ultimately instigate major processes involved in organ damage. The critical role of the sickle RBC ROS production and its regulation in SCD pathophysiology are discussed here.

scholarly journals Is there a role for selective vasodilation in the management of sickle cell disease?

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Microvascular Obstruction ◽  
Controlled Study ◽  
Control Group ◽  
Cell Disease ◽  
Retinal Arteriolar

To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.

scholarly journals Impact of arginine therapy on mitochondrial function in children with sickle cell disease during vaso-occlusive pain

Blood ◽  
2020 ◽  
Vol 136 (12) ◽  
pp. 1402-1406 ◽  
Author(s):  
Claudia R. Morris ◽  
Lou Ann S. Brown ◽  
Michael Reynolds ◽  
Carlton D. Dampier ◽  
Peter A. Lane ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mitochondrial Function ◽  
Protein Carbonyls ◽  
Mitochondrial Activity ◽  
No Production ◽  
Loading Dose ◽  
Cell Disease

Abstract Altered mitochondrial function occurs in sickle cell disease (SCD), due in part to low nitric oxide (NO) bioavailability. Arginine, the substrate for NO production, becomes acutely deficient in SCD patients with vaso-occlusive pain episodes (VOE). To determine if arginine improves mitochondrial function, 12 children with SCD-VOE (13.6 ± 3 years; 67% male; 75% hemoglobin-SS) were randomized to 1 of 3 arginine doses: (1) 100 mg/kg IV 3 times/day (TID); (2) loading dose (200 mg/kg) then 100 mg/kg TID; or (3) loading dose (200 mg/kg) followed by continuous infusion (300 mg/kg per day) until discharge. Platelet-rich plasma mitochondrial activity, protein expression, and protein-carbonyls were measured from emergency department (ED) presentation vs discharge. All VOE subjects at ED presentation had significantly decreased complex-V activity compared to a steady-state cohort. Notably, complex-V activity was increased at discharge in subjects from all 3 arginine-dosing schemes; greatest increase occurred with a loading dose (P &lt; .001). Although complex-IV and citrate synthase activities were similar in VOE platelets vs steady state, enzyme activities were significantly increased in VOE subjects after arginine-loading dose treatment. Arginine also decreased protein-carbonyl levels across all treatment doses (P &lt; .01), suggesting a decrease in oxidative stress. Arginine therapy increases mitochondrial activity and reduces oxidative stress in children with SCD/VOE. This trial was registered at www.clinicaltrials.gov as #NCT02536170.

Increased Pre-Transfusion Reticulocytosis Among Chronically Transfused Sickle Cell Disease Patients Is Associated With More Severe Cerebral Vasculopathy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1163-1163
Author(s):  
Megha Kaushal ◽  
Ross M. Fasano ◽  
Colleen Byrnes ◽  
Naomi L.C. Luban ◽  
Emily Riehm Meier ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Sickle Cell Disease ◽  
Magnetic Resonance Angiography ◽  
Sickle Cell ◽  
Control Group ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Blood Samples ◽  
History Of ◽  
The Mean

Abstract Chronic red blood cell transfusion therapy is indicated for primary and secondary stroke prevention in children with sickle cell disease (SCD). The main transfusion goal is achievement of pre-transfusion sickle hemoglobin (HbS) levels of 30%. Unfortunately, there continues to be a population of patients with a history of stroke who have progressive vasculopathy and/or secondary stroke, despite chronic transfusion therapy. Predictive markers for vasculopathy and cerebral events are needed to identify patients at risk for disease progression. Increased reticulocytosis was previously associated with other sickle cell disease complications, and adherent reticulocytes may contribute to the vascular pathology. The objective of this study was to explore the hypothesis that pre-transfusion reticulocytosis may serve as a disease severity marker for cerebral vasculopathy among chronically transfused children with sickle cell disease. After obtaining consent and assent, reticulocytosis was studied in a cohort of pediatric sickle cell patients treated with chronic transfusions (n=33, ages 2-17 years). The group was stratified into three groups: group 1 with an abnormal transcranial doppler (TCD) study in the absence of magnetic resonance angiography (MRA) detected vasculopathy [TCD(+), MRA(-), n=14], group 2 with a history of a stroke in the absence of MRA-detected vasculopathy [Stroke(+), MRA(-), n=5], and group 3 with a history of abnormal TCD or stroke and more severe vasculopathy detected by magnetic resonance angiography [MRA(+), n=14]. Pre-transfusion blood samples were analyzed within 72 hours of collection. Steady-state blood samples were also examined from a control group of pediatric SCD patients (>6 years of age) with normal TCD studies who were receiving supportive care in the absence of chronic transfusions or hydroxyurea (n=7). Hematologic data, including automated complete blood counts, absolute reticulocyte counts (ARC) with reticulocyte maturity were obtained. In addition, a flow cytometric approach was developed to further examine and quantitate reticulocyte subsets based upon staining with thiazole orange combined with CD36, CD45, CD49d, CD71, and CD235. The pre-transfusion HbS levels were not statistically different among the three transfused groups ([TCD(+), MRA(-)]: 30.2 ± 11.8%; [Stroke(+), MRA(-)]: 28.4 ± 3.3%; [MRA(+)]: 33.3 ± 9%, p>0.3). The high levels of reticulocytosis in the pre-transfusion samples were similar to those measured in the control group (ARC: 451 ± 126 K/uL in the chronically transfused cohort; ARC: 369 ± 94 K/uL in the control group, p=0.11). Pre-transfusion reticulocytosis was detected in every chronically transfused subject (ARC range 151-701 K/ul). The mean ARC in the [TCD(+), MRA(-)] group was not significantly different from the [Stroke(+), MRA(-)] group (411 ± 135 K/uL and 396 ± 97 K/uL respectively, p=0.82). However, the mean ARC in the [MRA(+)] group (512 ± 107 K/uL) was significantly higher than the control group, the [TCD(+), MRA(-)] group and the [Stroke(+), MRA(-)] group (p<0.05). The increased ARC in the MRA(+) group included higher absolute numbers of circulating reticulocytes at all stages of maturation including the immature reticulocyte subset [CD36(+), CD71(+)] that was detected in every sample. These data suggest that reticulocytosis with the release of immature CD36(+), CD71(+) cells into the peripheral blood remains as a characteristic feature of pediatric SCD even among chronically transfused patients. More severe vasculopathy, detected by MRA, was associated with significantly higher levels of pre-transfusion reticulocytosis. As such, reticulocytosis should be explored further as a marker or a potential contributor to more severe vasculopathy among chronically transfused children with SCD. Disclosures: No relevant conflicts of interest to declare.

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