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Clinical Implications of Neutrophil-to-Lymphocyte Ratio in Sickle Cell Disease

Article in Haematology International Journal · March 2024

DOI: 10.23880/hij-16000242

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Clinical Implications of Neutrophil-to-Lymphocyte Ratio in Sickle

Cell Disease

Emmanuel Ifeanyi Obeagu1* and Getrude Uzoma Obeagu2

Review Article
1
Department of Medical Laboratory Science, Kampala International University, Uganda
Volume 8 Issue 1
2
School of Nursing Science, Kampala International University, Uganda
Received Date: February 13, 2024

Published Date: March 11, 2024
*Corresponding author: Emmanuel Ifeanyi Obeagu, Department of Medical Laboratory
DOI: 10.23880/hij-16000242
Science, Kampala International University, Kampala, Uganda, Tel: +2348037369912; Email:
emmanuelobeagu@yahoo.com; obeagu.emmanuel@kiu.ac.ug

Abstract

Sickle Cell Disease (SCD) is a hereditary hemoglobinopathy characterized by chronic hemolytic anemia and vaso-occlusive
events. In recent years, the Neutrophil-to-Lymphocyte Ratio (NLR) has emerged as a potential biomarker with prognostic and
diagnostic significance in various medical conditions. This review explores the clinical implications of NLR in the context of SCD,
shedding light on its role as a valuable indicator of inflammation, disease severity, and treatment response. The inflammatory
state is a key contributor to the pathophysiology of SCD, influencing disease progression and complications. NLR, calculated
from routine complete blood counts, reflects the balance between the immune response’s cellular components and has been
implicated in assessing the inflammatory status in various diseases. In the context of SCD, elevated NLR has been associated
with increased vaso-occlusive events, suggesting its potential utility as a predictive marker for disease complications. In
conclusion, this perspective review consolidates current knowledge on the clinical implications of NLR in Sickle Cell Disease.
It highlights the potential of NLR as a readily available and cost-effective biomarker for assessing inflammation, predicting
disease severity, and monitoring treatment response in individuals with SCD. As the understanding of the immunological
aspects of SCD continues to evolve, NLR stands out as a promising parameter that may contribute to a more comprehensive
approach to managing this complex hematologic disorder.

Keywords: Sickle Cell Anemia; Neutrophil; Lymphocyte; Neutrophil to Lymphocyte Ratio; Inflammation; Biomarkers

Abbreviations: SCD: Sickle Cell Disease; NLR: Neutrophil-
to-Lymphocyte Ratio; SCA: Sickle Cell Anemia; Hbs:
Hemoglobins; ICU: Intensive Care Unit; IBD: Inflammatory
Bowel Diseases; ANC: Absolute Neutrophil Count; ALC:
Absolute Lymphocyte Count.
Introduction
Sickle cell anemia, an autosomal recessive genetic
disorder, results from a mutation in the beta-globin gene
[1-4]. This mutation leads to the production of abnormal
hemoglobin (HbS), which causes red blood cells to assume
a characteristic sickle shape [5-7]. Individuals with SCA
experience chronic anemia, vaso-occlusive crises, and are
more susceptible to infections and inflammation [8]. The
chronic inflammation observed in SCA is a critical component
of the disease, contributing to both acute and chronic
complications [9]. Therefore, the identification of biomarkers
to assess the inflammatory status in these patients is of great
importance [10]. Elevated NLR values have been associated

Clinical Implications of Neutrophil-to-Lymphocyte Ratio in Sickle Cell Disease Haematol Int J

 2
with more severe disease manifestations in SCA, including
an increased frequency of vaso-occlusive crises, acute chest
syndrome, and other complications [11]. NLR has shown
potential in aiding risk stratification and identifying patients
who may require more intensive management [12].
SCA patients are particularly susceptible to infections,
partly due to impaired immune function [13]. High NLR
values have been linked to a higher risk of infection in
SCA. Monitoring NLR can help clinicians identify patients
at greater risk of infections and implement appropriate
preventive strategies [14]. NLR reflects the balance between
pro-inflammatory neutrophils and anti-inflammatory
lymphocytes [15]. An elevated NLR is indicative of an
enhanced inflammatory state in SCA patients [16]. Tracking
NLR over time can provide insights into the progression of
inflammation and guide treatment decisions [17]. NLR can
assist in risk stratification, allowing healthcare providers
to identify high-risk patients and tailor treatment plans
accordingly [18].
Regular monitoring of NLR can help in the early detection
of infections, enabling prompt intervention and reducing
morbidity [19]. NLR can guide treatment decisions, especially
in the context of anti-inflammatory therapies, by providing
valuable information about the patient’s inflammatory
status [20]. While the utility of NLR in SCA is promising,
more research is needed to establish standardized NLR
thresholds and validate its use as a routine clinical tool [21].
Furthermore, longitudinal studies are required to understand
the dynamic changes in NLR over time and its correlation
with clinical outcomes [22]. The neutrophil-to-lymphocyte
ratio is emerging as a valuable biomarker for assessing
disease severity, infection risk, and inflammatory status in
sickle cell anemia [23]. The integration of NLR into clinical
practice has the potential to improve risk stratification, guide
treatment decisions, and enhance patient outcomes [24].
Further research is warranted to fully elucidate its clinical
applications in the context of SCA.
Neutrophil-to-Lymphocyte Ratio (NLR)
The Neutrophil-to-Lymphocyte Ratio (NLR) is a simple
and readily available biomarker derived from complete
blood count (CBC) measurements. It has gained increasing
recognition as a valuable indicator of systemic inflammation,
immune response, and overall health. This review explores
the diverse applications of NLR across various medical
disciplines and its potential as a versatile tool in clinical
practice [25]. The NLR is calculated by dividing the absolute
neutrophil count (ANC) by the absolute lymphocyte count
(ALC). It serves as a reflection of the balance between
innate immunity (neutrophils) and adaptive immunity
(lymphocytes). Elevated NLR values are indicative of
Emmanuel Ifeanyi Obeagu and Getrude Uzoma Obeagu. Clinical Implications
of Neutrophil-to-Lymphocyte Ratio in Sickle Cell Disease. Haematol Int J 2024,
8(1): 00242.
Haematology International Journal
increased inflammation and have been associated with
various pathological conditions [26].
In cardiology, NLR has emerged as a prognostic marker
for cardiovascular diseases. Elevated NLR is linked to a
higher risk of adverse cardiac events, such as myocardial
infarction and heart failure. NLR is now being utilized to
aid risk stratification and guide treatment decisions [27-
29]. NLR has shown promise in oncology as a marker of
tumor-associated inflammation and overall survival. High
NLR values are associated with poorer outcomes in various
malignancies, making it a useful tool in cancer prognosis
and treatment planning [30,31]. In infectious diseases, NLR
can help distinguish between bacterial and viral infections.
An elevated NLR often suggests a bacterial etiology, while
a low NLR is more characteristic of viral infections. This
differentiation can guide clinicians in selecting appropriate
treatments [32,33]. NLR has relevance in rheumatological
conditions, where inflammation plays a central role. It aids
in disease activity assessment and monitoring of conditions
like rheumatoid arthritis, systemic lupus erythematosus, and
ankylosing spondylitis [34]. Inflammatory bowel diseases
(IBD) such as Crohn’s disease and ulcerative colitis are
characterized by chronic inflammation. NLR can be used to
gauge disease activity and predict the risk of flares, aiding in
the management of IBD patients [35].
In the intensive care unit (ICU), NLR has proven valuable
as a marker for disease severity and outcomes. It can assist
in predicting mortality and guiding treatment strategies
in critically ill patients [36]. NLR is being investigated in
neuroinflammatory conditions, such as multiple sclerosis and
neurodegenerative diseases. While still in the research phase,
NLR may hold promise as a complementary tool for assessing
neuroinflammation [37,38]. The Neutrophil-to-Lymphocyte
Ratio (NLR) is a versatile and easily accessible biomarker
with wide-ranging applications in the field of medicine. Its
utility spans across multiple specialties, from cardiology
and oncology to infectious diseases and rheumatology.
NLR provides valuable insights into inflammation, immune
response, and disease prognosis, enhancing clinical decision-
making and patient care [39,40]. As research continues to
uncover the significance of NLR in various medical contexts,
its incorporation into routine clinical practice is poised to
grow. The NLR represents a simple yet powerful tool that can
aid healthcare professionals in diagnosing and managing of
sickle cell anaemia patients [41].
The Utility of Neutrophil-to-Lymphocyte
Ratio (NLR) in Sickle Cell Anemia (SCA)
Sickle Cell Anemia (SCA) is a hereditary blood disorder
characterized by chronic inflammation and an increased risk
of infections [42]. This review examines the emerging role
Copyright© Emmanuel Ifeanyi Obeagu and Getrude Uzoma Obeagu.
 3
of the Neutrophil-to-Lymphocyte Ratio (NLR) as a valuable
biomarker in assessing disease severity and predicting
clinical outcomes in individuals with SCA. Sickle Cell Anemia
is a genetic disorder caused by a mutation in the beta-globin
gene, leading to the production of abnormal hemoglobin
(HbS). This results in the deformation of red blood cells into
a characteristic sickle shape, causing chronic anemia, vaso-
occlusive crises, and susceptibility to infections. Chronic
inflammation is a hallmark of SCA, and NLR, as a marker of
systemic inflammation, has recently gained attention in the
context of this disease [43,44].
NLR is calculated by dividing the absolute neutrophil
count (ANC) by the absolute lymphocyte count (ALC) from a
complete blood count (CBC). Neutrophils are key players in
innate immunity, while lymphocytes are central to adaptive
immunity. An elevated NLR indicates an imbalance between
these two immune cell types and is recognized as a sign
of systemic inflammation [45]. Elevated NLR values have
been associated with more severe clinical manifestations
in SCA, including increased frequency and severity of
vaso-occlusive crises, acute chest syndrome, and other
complications. NLR can serve as a valuable indicator for
assessing the overall disease severity in SCA patients, aiding
in risk stratification and treatment planning [46]. Individuals
with SCA are particularly vulnerable to infections due to
their compromised immune function. High NLR values
have been linked to a greater susceptibility to infections
in these patients. Monitoring NLR can help healthcare
providers identify individuals at higher risk of infections and
implement proactive preventive measures [47]. NLR serves
as a dynamic marker reflecting the inflammatory status in
SCA patients. Elevations in NLR may indicate an increase in
systemic inflammation, which is a common feature of the
disease. Regular NLR monitoring can provide insights into
the progression of inflammation over time, helping clinicians
make informed treatment decisions [48,49].
Clinical Implications
NLR can aid in risk stratification, enabling healthcare
providers to identify high-risk SCA patients and tailor their
treatment plans accordingly [50]. Routine monitoring of NLR
can assist in the early detection of infections, allowing for
prompt intervention and reducing morbidity and mortality
[51]. NLR can guide treatment decisions, especially in the
context of anti-inflammatory therapies, by providing valuable
information about the patient’s inflammatory status [52].
The Neutrophil-to-Lymphocyte Ratio (NLR) is emerging as
a valuable and readily accessible biomarker for assessing
disease severity, infection risk, and inflammatory status
in Sickle Cell Anemia. Its integration into clinical practice
has the potential to improve risk stratification, inform
treatment decisions, and enhance the overall management
Emmanuel Ifeanyi Obeagu and Getrude Uzoma Obeagu. Clinical Implications
of Neutrophil-to-Lymphocyte Ratio in Sickle Cell Disease. Haematol Int J 2024,
8(1): 00242.
Haematology International Journal
of SCA patients. Further research is needed to establish
standardized NLR thresholds and validate its role as a
routine clinical tool in the management of SCA [53]. As our
understanding of NLR in SCA continues to evolve, it offers
a simple yet effective tool to help healthcare professionals
address the unique challenges presented by this complex
hematological disorder.
The dynamic nature of NLR allows for the monitoring
of disease progression in SCA. Changes in NLR values over
time can provide insights into the course of inflammation
and its response to treatment. Serial measurements of
NLR offer a non-invasive and cost-effective way to assess
the effectiveness of therapeutic interventions and adjust
treatment plans accordingly [54]. NLR has shown promise
as a prognostic marker in SCA. Patients with persistently
elevated NLR values may be at higher risk for adverse
outcomes. Identifying individuals at greater risk allows
healthcare providers to implement more aggressive
management strategies and enhance patient outcomes [55].
Future Directions
The Neutrophil-to-Lymphocyte Ratio (NLR) has shown
promise as a valuable biomarker in the management of
Sickle Cell Anemia (SCA). However, there is still much to
explore and uncover about its full potential and applications
in this complex hematological disorder. This article discusses
the future directions and potential research avenues for
NLR in the context of SCA, including standardization, novel
applications, and precision medicine [56]. One of the critical
challenges in utilizing NLR in SCA is the lack of standardized
NLR thresholds specific to this patient population. Future
research should focus on establishing these thresholds to
aid in consistent risk stratification and treatment decisions.
Defining clinically relevant NLR values for various SCA
subgroups (e.g., pediatric vs. adult patients, genotypic
variations) could enhance its clinical utility [57].
More comprehensive longitudinal studies are needed
to better understand the dynamic changes in NLR over time
and their correlation with disease progression and clinical
outcomes. These studies can help identify trends in NLR
values in individual patients and offer insights into the long-
term implications of inflammation in SCA. Longitudinal data
can also aid in tracking the effectiveness of interventions
and therapies aimed at reducing inflammation [58]. Future
research should explore potential molecular and genetic
associations with NLR in SCA. Investigating whether specific
genetic markers or gene expression profiles are linked to
variations in NLR could provide a deeper understanding
of the underlying mechanisms of inflammation in SCA.
Identifying genetic factors that influence NLR may open
doors for targeted therapies [59].
Copyright© Emmanuel Ifeanyi Obeagu and Getrude Uzoma Obeagu.
 4
NLR has the potential to guide personalized treatment
strategies in SCA. Future research should delve into how NLR
can be integrated into precision medicine approaches. This
involves tailoring treatments based on an individual’s unique
characteristics, including their NLR profile. Developing
personalized treatment algorithms using NLR as a component
could significantly improve the management of SCA [60]. The
development of predictive models that incorporate NLR as
a variable is a promising avenue for future research. These
models could be used to forecast disease exacerbations,
identify patients at high risk of complications, and guide
clinical decision-making. By utilizing artificial intelligence
and machine learning techniques, researchers can develop
sophisticated predictive models that harness the power of
NLR alongside other clinical and genetic data [61-64].
Investigations into the impact of therapeutic
interventions on NLR in SCA are warranted. Understanding
how treatments, such as hydroxyurea, transfusion therapy,
or anti-inflammatory agents, influence NLR can help refine
treatment strategies and assess the efficacy of interventions
designed to mitigate inflammation and its associated
complications [65-75]. Future studies should focus on how
NLR relates to patient-reported outcomes and quality of
life in SCA. Exploring the connection between NLR and
the burden of symptoms, pain, and overall well-being can
provide a more holistic view of the patient experience and
guide interventions aimed at improving their quality of life
[76]. Neutrophil-to-Lymphocyte Ratio (NLR) holds promise
as a valuable biomarker in SCA, but its full potential is yet
to be realized [77-87]. Future research should concentrate
on standardization, molecular and genetic associations,
personalized treatment strategies, predictive modeling,
therapeutic interventions, and patient-centered outcomes.
A deeper understanding of NLR in SCA has the potential
to transform the management of this challenging disease,
improving the quality of care and outcomes for affected
individuals [88-90].
Conclusion
The neutrophil-to-lymphocyte ratio is emerging as a
valuable biomarker for assessing disease severity, infection
risk, and inflammatory status in sickle cell anemia. The
integration of NLR into clinical practice has the potential to
improve risk stratification, guide treatment decisions, and
enhance patient outcomes. Further research is warranted to
fully elucidate its clinical applications in the context of SCA.
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8(1): 00242.
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outcomes. Int J Adv Res Biol Sci 10(3): 134-143.
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Anaemia With Falciparum Malaria Infection in University
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Cell Trait Conferring Selective Protective Advantage to
Malaria. J Clin Med Res 2(2): 1-4.
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