Oxidative stress markers and disease severity among children with Sickle Cell Anaemia
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Oxidative Stress in Sickle Cell Anaemia
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PUBLISHED BY THE MEDICAL
AND DENTAL CONSULTANTS ASSOCIATION
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Annals of Health Research
Volume 5, Issue No 2: 193-202
July-December 2019
doi:10.30442/ahr.0502-21-51
CC BY-NC
ORIGINAL RESEARCH
Oxidative stress markers and disease severity among children
with Sickle Cell Anaemia
Smith OS*1, Adegoke SA2, Akinlosotu MA3, Ajose OA4
1Department
of Chemical Pathology, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
of Paediatrics and Child Health, Obafemi Awolowo University, Ile-Ife, Nigeria
3Department of Paediatrics, University of Medical Sciences, Ondo, Nigeria
4Department of Chemical Pathology, Obafemi Awolowo University, Ile-Ife, Nigeria
2Department
*Correspondence: Dr. OS Smith, Department of Chemical Pathology, Obafemi Awolowo University Teaching
Hospitals Complex, P. M. B 5538, Ile-Ife, Nigeria; Email: ;
ORCID – https://orcid.org/0000-0002-9293-8885
Abstract
Background: Sickle cell anaemia has been associated with oxidative stress. Total Antioxidant Capacity (TAC), Total
Oxidant Status (TOS) and Oxidative Stress Index (OSI) are cumulative markers of oxidative stress.
Objective: To evaluate the serum levels of oxidative stress markers in children with sickle cell anaemia (SCA) and
determine the relationship between these markers and disease severity.
Method: One hundred and fifty-six children, comprising 78 with SCA, aged 1 - 15 years and 78 age- and sex-matched
Haemoglobin AA controls were studied. Serum TOS, OSI, and TAC were determined using ELISA kits. The severity
of the SCA was determined using clinical and laboratory parameters.
Result: Children with SCA had lower mean serum TAC (0.83±0.31UAE) than controls (1.19±0.24UAE) with p<0.001.
However, the mean serum TOS and OSI of children with SCA was higher than among the controls (13.33±4.64U/ml
vs. 9.70±2.72U/ml and 20.95±16.75 vs. 8.68±3.76 respectively) with p<0.001. SCA subjects with mild disease had
higher mean serum TAC (0.91 ± 0.27UAE) than those with moderate disease (0.54±0.27UAE) (p<0.001). On the other
hand, the mean TOS and OSI were lower in children with mild disease compared to those with moderate disease
(12.64±4.32U/ml vs. 15.63±5.07U/ml, p = 0.016 and 16.26±10.25 vs. 36.61±23.89 p<0.001 respectively). Sickle cell
disease severity score had negative correlation with TAC (r = -0.60, p < 0.001) but positive correlation with TOS (r =
0.3, p = 0.008) and OSI (r = 0.6, p < 0.001).
Conclusion: Children with SCA had lower TAC but higher TOS and OSI than matched controls. Oxidative stress
markers had a significant relationship with SCD severity.
Keywords: Children, Oxidative Stress Index, Severity Score, Sickle Cell Anaemia, Total Antioxidant Capacity, Total
Oxidant Status.
Introduction
Sickle cell anaemia (SCA) is the most common
haematological disorder globally and it is found
more frequently in sub-Saharan Africa. [1] It is a
homozygous
genetic
disorder
with
approximately 150,000 to 300,000 individuals
born with the disease every year in Africa and
Annals of Health Research. Volume 5, Issue No 2, 2019________________________________193
Oxidative stress markers in Sickle Cell Anaemia_________________________________________
Nigeria has one of the highest burdens of SCA
with a prevalence of 2-3%. [2] Vaso-occlusive
crisis is the commonest clinical phenotypic
expression in children with SCA in Nigeria and
its frequency has been used as a marker of
disease severity.[3] However, other devastating
clinical manifestations such as acute chest
syndrome, stroke, priapism, osteomyelitis,
cholecystitis, leg ulcer, and socio-demographic
factors have cumulative lifetime effects that
determine the severity of disease in these
patients. [4]
crises and rate of haemolysis, [16] no report has
examined the relationship of the oxidative stress
markers with the overall sickle cell disease
severity. In addition to evaluating the serum
levels of oxidative stress markers (TOS, TAC,
and OSI), this study determined the relationship
between them and steady-state sickle cell
disease severity using a validated scoring
system. [4]
Individuals with SCA are prone to oxidative
damage as a result of excessive generation of
reactive oxygen species such as hydrogen
peroxide, superoxide, hydroxyl radicals, and
malondialdehyde. This is associated with lower
levels of human antioxidant vitamins and
enzyme activities leading to chronic redox
imbalance in their red blood cell metabolic
activities. [5-9] The resultant oxidative stress has
been implicated in the pathophysiologic
mechanism of SCA. [10] Individual oxidants and
antioxidants usually interact in cells and body
fluids of humans, leading to cumulative effects
that can be measured directly in plasma, with
the use of serum Total Oxidative Status (TOS)
and Total Antioxidant Capacity (TAC)
respectively. [11-13] These parameters measure all
the biological components of plasma with
oxidant and antioxidant activity at once and
represent a dynamic equilibrium that occurs as a
result of various synergistic interactions
between individual oxidants and antioxidants,
giving an insight into the delicate balance
between them. [14,15] Previous workers on
oxidative stress used the ratio of total oxidative
status to total antioxidant capacity (oxidative
stress index, OSI) as another measure of
oxidative stress in their various studies. [11,12]
Study design and location
This study was a descriptive, cross-sectional
comparative study conducted at the Children
Sickle cell Disease Clinic of the Wesley Guild
Hospital Ilesa, one of the two tertiary units of
Obafemi
Awolowo
University
Teaching
Hospitals Complex, Ile-Ife, Nigeria.
Although some studies have assessed the effect
of oxidative stress markers on individual clinical
manifestations of SCA such as vaso-occlusive
Methods
Study Population
The haemoglobin genotype of each participant
was confirmed using alkaline hemoglobin
electrophoresis on cellulose acetate, before
recruitment into the study. Steady-state in SCA
was defined as a period without acute illness,
pain, and infection for at least four weeks and
no blood transfusion in the preceding three
months. [17] Children whose parents failed to
give consent, those on antioxidants and
hydroxyurea were excluded from the study
since these agents could modify the severity of
sickle cell anaemia. [1]
Data collection
Socio-demographic and clinical information
such as age, gender, frequency of v (...truncated)