Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease: a study protocol

Sudheeshreddy Naramreddy; Ashish Varma; Amar Taksande

doi:10.12688/f1000research.143055.1

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Study Protocol

Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease: a study protocol

[version 1; peer review: 2 approved with reservations]

Sudheeshreddy Naramreddy ¹, Ashish Varma¹, Amar Taksande¹

PUBLISHED 23 Feb 2024

Author details Author details

¹ Department of Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, 442001, India

Sudheeshreddy Naramreddy
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Ashish Varma
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Amar Taksande
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the Datta Meghe Institute of Higher Education and Research collection.

Abstract

Background

Sickle cell disease, a hereditary hemoglobinopathy, presents complex clinical challenges including increased susceptibility to iron deficiency anemia (IDA). However, the clinical profile of IDA in pediatric patients with sickle cell disease still needs to be adequately characterized. This study aims to comprehensively investigate the prevalence, severity, associated risk factors, and potential impact of IDA on morbidity and mortality in this vulnerable population.

Methods

A prospective observational study will be conducted on 303 children from January 2024 to December 2024 at the Department of Pediatrics, Jawaharlal Nehru Medical College and AVBR Hospital, Sawangi, Wardha. Participants will include pediatric patients diagnosed with sickle cell disease, with informed consent from their parents or legal guardians. Data will be collected through clinical assessments, blood sample analyses for hematological parameters, and systematic recording of relevant clinical information. Statistical analyses, including Fisher’s exact test, Chi-square test, and Student’s t-test, will be used to assess the data, with a significance level set at p < 0.05.

Expected outcomes

This study aims to provide critical insights into the prevalence and clinical profile of IDA in children with sickle cell disease, shedding light on potential risk factors and correlations with comorbid conditions. Furthermore, it seeks to explore the relationship between IDA and disease-related morbidity and mortality.

Keywords

Sickle cell disease, Iron deficiency anemia, Pediatric patients, Clinical profile, Prevalence, Morbidity

Corresponding author: Sudheeshreddy Naramreddy

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2024 Naramreddy S et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Naramreddy S, Varma A and Taksande A. Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease: a study protocol [version 1; peer review: 2 approved with reservations]. F1000Research 2024, 13:144 (https://doi.org/10.12688/f1000research.143055.1) First published: 23 Feb 2024, 13:144 (https://doi.org/10.12688/f1000research.143055.1) Latest published: 23 Feb 2024, 13:144 (https://doi.org/10.12688/f1000research.143055.1)

Introduction

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by abnormal hemoglobin levels, leading to chronic hemolytic anemia, vaso-occlusive events, and organ damage.¹ It is a significant global health concern, particularly prevalent in regions with a high malaria prevalence. While much research has been dedicated to understanding the pathophysiology and management of SCD, one aspect that continues to challenge clinicians and researchers is the co-occurrence of iron deficiency anemia (IDA) in pediatric patients with SCD.²

Iron deficiency anemia represents a distinct clinical entity marked by iron deficiency, which is necessary for red blood cell production and other critical cellular processes.³ In the context of SCD, the interplay between these two hematological conditions is complex and needs to be fully elucidated. The prevalence, severity, and clinical implications of IDA in children with SCD need to be further characterized to represent a critical gap in our understanding of the disease.⁴

Understanding the clinical profile of IDA in children with SCD is essential for several reasons. First, IDA can exacerbate the pre-existing anemia in SCD, potentially increasing the disease burden and complicating its management. Second, iron deficiency may result from SCD-related factors such as chronic hemolysis, making it a unique challenge to address. Furthermore, the presence of IDA may be associated with specific clinical outcomes, including an increased risk of infections, pain crises, and organ damage.⁵

This study adopts a prospective observational approach to address the knowledge gaps and clinical challenges. This study aims to investigate the prevalence of IDA in pediatric patients with SCD, assess the severity of anemia, identify potential risk factors contributing to IDA, explore correlations with comorbid conditions, and examine whether IDA plays a role in SCD-related morbidity and mortality. By shedding light on the intricate relationship between SCD and IDA, we hope to provide valuable insights that can inform improved clinical management and ultimately enhance the quality of life of children living with these conditions.

Aim

This study aims to investigate the prevalence of IDA in children diagnosed with SCD and to gain insights into the clinical profile of this patient population.

Objectives

1. To determine the prevalence of IDA among children diagnosed with SCD in the study population.
2. To assess the severity of anemia in these children by evaluating key hematological parameters, primarily focusing on hemoglobin (Hb) levels.
3. To identify and analyze potential risk factors associated with the development of IDA in pediatric patients with SCD, including factors such as age, sex, dietary habits, and disease severity.
4. To investigate the correlations between iron deficiency anemia and other comorbid conditions commonly observed in sickle cell disease, such as vaso-occlusive pain crises, infections, organ damage, and growth impairment.
5. To assess the impact of iron deficiency anemia on the overall morbidity of children with sickle cell disease, aiming to determine whether IDA exacerbates or is associated with increased disease-related complications.
6. To explore any potential relationship between iron deficiency anemia and mortality rates in the study population, focusing on understanding whether IDA contributes to a higher mortality risk in children with SCD.

Methods

Study design

The study has been structured as a prospective observational investigation, characterized by systematically gathering participant data over a specified duration from January 2024 to December 2024. Proforma for data collection can be found as Extended data.¹¹

Study population

This study will focus on pediatric patients diagnosed with SCD receiving care at the Department of Pediatrics, Jawaharlal Nehru Medical College, and AVBR Hospital, Sawangi, Wardha.

Place of study

This research will be conducted at the Department of Pediatrics, Jawaharlal Nehru Medical College, and AVBR Hospital, Sawangi, Wardha.

Inclusion criteria

1. Pediatric age group: Children within a specified age range, typically aged between 1 to 16 years diagnosed with sickle cell disease.
2. Diagnostic confirmation: Pediatric patients with a confirmed diagnosis of sickle cell disease based on High Performance Liquid Chromatography (HPLC).
3. Informed consent: Written informed consent must be obtained from parents or legal guardians for the participation of their children in the study. The consent process will involve a detailed explanation of the study’s objectives, procedures, and potential risks and benefits.

Exclusion criteria

1. Iron supplementation status: Patients currently receiving iron supplementation will be excluded from the study. This criterion aims to focus on individuals with no ongoing iron intervention, ensuring a clearer understanding of natural iron deficiency anemia in the study population.
2. Consent willingness: Patients or parents/legal guardians unwilling to provide informed consent for participation in the study will be excluded. The consent process is integral to ethical considerations and ensures voluntary participation.

Enrollment

Participants who meet the inclusion criteria and provide informed consent will be enrolled in this study. Recruitment will be conducted by the research team at the Department of Pediatrics.

Sample size

Formula

N = \frac{Z_{1 - α / 2}^{2} * p * (1 - p)}{D^{2}} .

Z_{1 - α / 2} = 1.96, at 5% level of significance

Prevalence of patients who underwent echocardiographic evaluation = 27% (As per reference article⁶)

D = estimated error (10 %) = 0.10 = ({(1.96)}^{2} * (0.27) * (1 - 0.27) / {(0.10)}^{2} = 303

Minimum sample size required = 303

Data collection

The data collection process for our prospective observational study on the clinical profile of IDA in children with SCD involves several structured steps to ensure the systematic and accurate gathering of pertinent information. First, we enroll eligible pediatric patients diagnosed with SCD under the Department of Pediatrics at Jawaharlal Nehru Medical College & AVBR Hospital, Sawangi, Wardha. During this enrollment phase, we will comprehensively explain the study’s objectives and procedures to the parents or legal guardians and obtain informed consent for their children’s participation.

Blood samples of 2 ml will be collected from the arms and drawn into plain Vacutainer tubes, ensuring the precise preservation of sample integrity. This vital procedure will be carried out by proficient healthcare professionals to maintain uniformity. Subsequently, the samples will be promptly conveyed to the laboratory within a 30-minute timeframe, thereby minimizing the risk of any potential degradation. The storage of biological samples will adhere to established guidelines to safeguard the quality of the samples. Collected blood samples will be immediately centrifuged to obtain plasma, which will then be aliquoted and stored at the recommended temperature and conditions. Detailed records of the storage process will be meticulously maintained, ensuring the traceability and reliability of the stored samples.

Once participants are enrolled, we will collect baseline data, including demographic details such as age, sex, and relevant medical history, using the proforma uploaded as Extended data. A clinical assessment involves a thorough physical examination to evaluate overall health and identify any signs or symptoms of iron deficiency anemia. A crucial aspect of our data collection process is the collection of blood samples using strict aseptic techniques. We will ensure proper labeling and documentation of each sample to maintain traceability and accuracy.

Subsequently, these blood samples will be subjected to laboratory analysis to measure key hematological parameters. This includes assessing the High Performance Liquid Chromatography⁷ to determine the presence and severity of anemia and determine serum iron levels to gauge iron status and serum ferritin levels to evaluate iron stores within the body. All collected data will be meticulously recorded in structured forms or electronic databases tailored for the study. These records will be subjected to rigorous quality control measures to ensure data accuracy and consistency.

Data validation procedures will be rigorously implemented throughout the study to ensure the completeness and accuracy of all recorded information. A systematic approach will be adopted to scrutinize data entries, promptly identifying and addressing any discrepancies or missing information. To achieve this, a dedicated data validation team will be assigned the responsibility of regularly reviewing all collected data. This team will employ a thorough process, which includes cross-checking entered information against source documents, verifying the accuracy of data points, and ensuring that all required fields are appropriately completed. Any inconsistencies or missing data will be flagged for immediate attention.

Furthermore, periodic data audits will be conducted to assess the overall quality of the dataset. This involves a comprehensive review of a random subset of collected data to validate its accuracy and consistency. Any discrepancies discovered during these audits will be thoroughly investigated, and corrective actions will be promptly taken. To maintain transparency and accountability, a detailed log of all data validation activities will be maintained. This log will document the date, nature of validation checks performed, any issues identified, and the corrective actions taken. This systematic approach to data validation aims to enhance the reliability and integrity of the dataset, ultimately ensuring the robustness of our study findings.

Throughout this process, we are committed to maintaining the utmost privacy and confidentiality of participants’ personal and medical information, adhering to ethical standards and regulations. Throughout this process, we are committed to safeguarding the privacy and confidentiality of participants’ personal and medical information, aligning with stringent ethical standards and regulations. To uphold this commitment, we will implement robust measures, including secure data storage, restricted access, and de-identification practices. Only authorized personnel directly involved in the study will have access to identifiable participant information, ensuring the utmost confidentiality. Any shared or published results will strictly maintain anonymity, protecting the privacy of the individuals who have contributed to this research. Our approach complies with the ethical guidelines set forth by the Institutional Ethics Committee of the Datta Meghe Institute of Higher Education and Research (DU) and prioritizes the well-being and privacy of our study participants. Finally, using the collected data, we will utilize appropriate statistical software, such as SPSS version 23, to perform the detailed analysis outlined in our study protocol. The results will provide valuable insights into the prevalence, risk factors, correlations, and potential associations between iron deficiency anemia and sickle cell disease outcomes. This comprehensive data collection process will ensure the reliability and robustness of our study findings, while upholding ethical considerations and participant welfare.

Ethical considerations

The Institutional Ethics Committee of the Datta Meghe Institute of Higher Education and Research (DU) has granted its approval to the study protocol (Reference number: DMIHER (DU)/IEC/2022/1074; Date: 21/07/22). Prior to commencing the study, we will obtain written informed consent from all participants, providing them with a comprehensive explanation of the study’s objectives.

Statistical methods

Statistical methods: Data analysis will be conducted with meticulous attention to detail, employing a combination of software tools and specific statistical tests tailored to address the study’s objectives. After the initial organization of collected data using Microsoft Excel, in-depth statistical analyses will be executed using the Statistical Package for the Social Sciences (SPSS) version 23.

Categorical variables: For categorical variables, such as those related to prevalence rates and risk factors, statistical tests including Fisher’s exact and Chi-square tests will be applied. These tests are chosen for their suitability in assessing associations and differences within qualitative data.

Quantitative variables: For quantitative variables, particularly continuous data such as hematological parameters, the analysis will involve the application of the student’s t-test. This test is chosen for its appropriateness in comparing means between two groups, providing insights into the severity of anemia in pediatric patients with sickle cell disease.

Correlation analysis: In addition to the specified tests, correlation analyses will be performed to explore relationships between variables, particularly focusing on correlations between iron deficiency anemia and comorbid conditions in sickle cell disease. The choice of correlation analysis will be based on the nature of the variables involved, with Pearson correlation for linear relationships and Spearman correlation for non-linear relationships.

Significance level: A significance level of p < 0.05 will be employed for all statistical tests, ensuring the robustness and reliability of the results. This stringent threshold is set to ascertain the validity of observed associations and differences in the study population.

Dissemination

After completion of the study, we will publish it in an indexed journal or conference.

Study status

This study is yet to be conducted. After publication of the protocol, we will begin recruitment for the study.

Discussion

In a study conducted by Anwesha Singh,⁸ a cohort of 100 children who have SCD exhibiting the SS hemoglobin pattern, aged between six months and 12 years, were enrolled. Among these participants, sex distribution revealed that 52% were male and 48% were female, portraying a nearly balanced male-to-female ratio of 1.08:1.

Moreover, a study by Salman⁹ demonstrated a similar pattern, in which 91 individuals (56.88%) were male and 69 (43.12%) were female, with ages ranging from 0 to 14 years. Notably, these sex distributions echo the findings of other studies conducted.¹⁰

These findings have a substantial clinical significance. They underscore the importance of routine monitoring of iron status in pediatric patients with SCD, particularly emphasizing the early detection and effective management of IDA. Tailored interventions, including judicious iron supplementation and targeted dietary counseling, may prove essential in addressing IDA in this vulnerable patient population.¹⁰

Additionally, these observations emphasize the indispensability of adopting a multidisciplinary approach to patient care and fostering collaboration between hematologists, nutritionists, and other specialized healthcare professionals. Such an integrated approach can potentially optimize the overall well-being and health outcomes of pediatric individuals grappling with the complexities of SCD.

Data availability

Underlying data

No data are associated with this article.

Extended data

Zenodo: Proforma for the data collections ‘Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease’. https://zenodo.org/doi/10.5281/zenodo.10360381.¹¹

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

References

1. Mangla A, Ehsan M, Agarwal N, et al.: Sickle Cell Anemia. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.
2. Chao DL, Oron AP, Chabot-Couture G, et al.: Contribution of malaria and sickle cell disease to anaemia among children aged 6–59 months in Nigeria: a cross-sectional study using data from the 2018 Demographic and Health Survey. BMJ Open. 2022; 12: e063369. Publisher Full Text
3. Bermejo F, García-López S: A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J. Gastroenterol. 2009; 15: 4638–4643. Publisher Full Text
4. Mohanty D, Mukherjee MB, Colah RB, et al.: Iron deficiency anaemia in sickle cell disorders in India. Indian J. Med. Res. 2008; 127: 366–369.
5. Odunlade O, Adeodu O, Owa J, et al.: Iron deficiency, still a rarity in children with sickle cell anemia in Ile-Ife, Nigeria. Hematol. Transfus. Cell Ther. 2019; 41: 216–221. Publisher Full Text
6. Madoori S, Ramya C, Valugula S, et al.: Clinico hematological profile and outcome of anemia in children at tertiary care hospital, Karimnagar, Telangana, India. Int. J. Res. Med. Sci. 2015; 3: 3567–3571. Publisher Full Text
7. High Performance Liquid Chromatography (HPLC)|ELGA LabWater. Accessed: December 12, 2023. Reference Source
8. Singh A, Bokade C, Tirpude B, et al.: Clinical Profiles of Children With Sickle Cell Anaemia Presenting With Acute Clinical Events: A Single-Center Study. Cureus. 15: e39008. Publisher Full Text
9. Salman ZA, Hassan MK: Hospitalization Events among Children and Adolescents with Sickle Cell Disease in Basra, Iraq. Anemia. 2015; 2015: 195469. Publisher Full Text
10. Özdemir N: Iron deficiency anemia from diagnosis to treatment in children. Turk. Pediatri. Ars. 2015; 50: 11–19. Publisher Full Text
11. Sudheeshreddy N: Proforma for the data collections ‘Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease’. [Dataset]. Zenodo. 2023. Publisher Full Text

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Version 1

VERSION 1 PUBLISHED 23 Feb 2024

Author details Author details

¹ Department of Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, 442001, India

Sudheeshreddy Naramreddy
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Ashish Varma
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Amar Taksande
Roles: Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Article Versions (1)

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Published: 23 Feb 2024, 13:144

https://doi.org/10.12688/f1000research.143055.1

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© 2024 Naramreddy S et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Naramreddy S, Varma A and Taksande A. Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease: a study protocol [version 1; peer review: 2 approved with reservations]. F1000Research 2024, 13:144 (https://doi.org/10.12688/f1000research.143055.1)

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Reviewer Report 03 Jul 2024

Berengere Koehl, Paris University, Paris, France; Blood Group Antigen, Hematopoiesis and Sickle cell disease, INSERM UMR_S1134, BIGR, Paris, France; Hematology unit, HÃ´pital Robert DebrÃ©, Paris, France

Approved with Reservations

https://doi.org/10.5256/f1000research.156673.r287988

The study protocol of Naramreddy aim to explore the interesting question of iron deficiency in children with SCD. The challenge is both to describe the prevalence of iron deficiency in this population, and to investigate the impact of IDA on ... Continue reading

The study protocol of Naramreddy aim to explore the interesting question of iron deficiency in children with SCD. The challenge is both to describe the prevalence of iron deficiency in this population, and to investigate the impact of IDA on the severity of SCD.
To answer these questions, the authors propose to collect biological and clinical data from patients with SCD, age 1 to 16 yo.
1/Concerning the evaluation of iron deficiency, the authors propose to measure serum iron levels and serum ferritin levels. Since these parameters could be impacted by the chronic inflammation status in patients with SCD, the mesure of transferrin and the transferrin saturation levels should probably be added to fully explore the iron status.
2/The second objective of the study is to correlate the iron deficiency with the severity of the disease, and to look for risk factors associated with IDA. Nevertheless, the detail of the clinical /biological parameters that will be recorder remains elusive and should definitely be precised.
For exemple, the authors propose to include “factors of disease severity”. Which parameters will precisely be assessed? History of acute chest syndrome? Number of vaso-occlusive event? Same question about several items:
“dietary habits”: what will precisely be evaluated?
“Organ damage”= which organ? With which criteria?
“growth impairment” = BMI? or a inflection/ break in the growth curve
3/ No mention is made about the transfusion history for the patients. However, since red blood cell transfusion has a strong impact on iron status, these information seem important to collect in order to interpret the results (for exemple the volume/kg of packed red blood cells transfused in the past 12 months before the inclusion?)
4/ One of the objective is to “determine whether IDA exacerbates or is associated with increased disease-related complications”. Which clinical/biological criteria will be used to evaluate this correlation?
5/ Idem for the objective “explore any potential relationship between iron deficiency anemia and mortality rates in the study population, focusing on understanding whether IDA contributes to a higher mortality risk in children with SCD”. How will the authors answer this question? How will be explored the relationship between IDA and mortality rate?

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

No
Are the datasets clearly presented in a useable and accessible format?

Not applicable

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: red cells disorders, haemoglobinopathy, transfusion, pediatrics

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Reviewer Report 28 Jun 2024

Yaddanapudi Ravindranath, Wayne State University School of Medicine, Detroit, Michigan, USA

Approved with Reservations

https://doi.org/10.5256/f1000research.156673.r262395

This is research proposal and therefore no data available for review.
The proposal aims to assess the frequency of concurrent iron deficiency in children with Sickle cell anemia- the authors wish to focus on cases with homozygous Sickle cell ... Continue reading

This is research proposal and therefore no data available for review.
The proposal aims to assess the frequency of concurrent iron deficiency in children with Sickle cell anemia- the authors wish to focus on cases with homozygous Sickle cell disease. The disease status will be established by HPLC and iron status will be assessed by iron profile including serum ferritin.Â
I recommend adding soluble transferrin receptor measurement as well as serum ferritin levels are influenced by concurrent infections - serum ferritin is an acute phase reactant. Also standard blood counts should be done in real time on EDTA containing vaccutainer tubes.
In general the incidence of Iron Deficiency in SCD is low in the US given the high meat containing diets. The situation could be vastly different in India considering the varied dietary habits and as well the risk for hookworm infestation.

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

Yes
Are the datasets clearly presented in a useable and accessible format?

Not applicable

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Red cell disorders

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

CITE

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VERSION 1 PUBLISHED 23 Feb 2024

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Yaddanapudi Ravindranath, Wayne State University School of Medicine, Detroit, USA
Berengere Koehl, Paris University, Paris, France; INSERM UMR_S1134, BIGR, Paris, France; HÃ´pital Robert DebrÃ©, Paris, France

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03 Jul 2024 | for Version 1

Berengere Koehl, Paris University, Paris, France; Blood Group Antigen, Hematopoiesis and Sickle cell disease, INSERM UMR_S1134, BIGR, Paris, France; Hematology unit, HÃ´pital Robert DebrÃ©, Paris, France

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Approved With Reservations

The study protocol of Naramreddy aim to explore the interesting question of iron deficiency in children with SCD. The challenge is both to describe the prevalence of iron deficiency in this population, and to investigate the impact of IDA on the severity of SCD.
To answer these questions, the authors propose to collect biological and clinical data from patients with SCD, age 1 to 16 yo.
1/Concerning the evaluation of iron deficiency, the authors propose to measure serum iron levels and serum ferritin levels. Since these parameters could be impacted by the chronic inflammation status in patients with SCD, the mesure of transferrin and the transferrin saturation levels should probably be added to fully explore the iron status.
2/The second objective of the study is to correlate the iron deficiency with the severity of the disease, and to look for risk factors associated with IDA. Nevertheless, the detail of the clinical /biological parameters that will be recorder remains elusive and should definitely be precised.
For exemple, the authors propose to include “factors of disease severity”. Which parameters will precisely be assessed? History of acute chest syndrome? Number of vaso-occlusive event? Same question about several items:
“dietary habits”: what will precisely be evaluated?
“Organ damage”= which organ? With which criteria?
“growth impairment” = BMI? or a inflection/ break in the growth curve
3/ No mention is made about the transfusion history for the patients. However, since red blood cell transfusion has a strong impact on iron status, these information seem important to collect in order to interpret the results (for exemple the volume/kg of packed red blood cells transfused in the past 12 months before the inclusion?)
4/ One of the objective is to “determine whether IDA exacerbates or is associated with increased disease-related complications”. Which clinical/biological criteria will be used to evaluate this correlation?
5/ Idem for the objective “explore any potential relationship between iron deficiency anemia and mortality rates in the study population, focusing on understanding whether IDA contributes to a higher mortality risk in children with SCD”. How will the authors answer this question? How will be explored the relationship between IDA and mortality rate?

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

No
Are the datasets clearly presented in a useable and accessible format?

Not applicable

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

red cells disorders, haemoglobinopathy, transfusion, pediatrics

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Respond to this report

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Reviewer Report

1 Views

28 Jun 2024 | for Version 1

Yaddanapudi Ravindranath, Wayne State University School of Medicine, Detroit, Michigan, USA

1 Views Cite this report Responses(0)

Approved With Reservations

This is research proposal and therefore no data available for review.
The proposal aims to assess the frequency of concurrent iron deficiency in children with Sickle cell anemia- the authors wish to focus on cases with homozygous Sickle cell disease. The disease status will be established by HPLC and iron status will be assessed by iron profile including serum ferritin.Â
I recommend adding soluble transferrin receptor measurement as well as serum ferritin levels are influenced by concurrent infections - serum ferritin is an acute phase reactant. Also standard blood counts should be done in real time on EDTA containing vaccutainer tubes.
In general the incidence of Iron Deficiency in SCD is low in the US given the high meat containing diets. The situation could be vastly different in India considering the varied dietary habits and as well the risk for hookworm infestation.

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

Yes
Are the datasets clearly presented in a useable and accessible format?

Not applicable

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Red cell disorders

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Respond to this report

Responses (0)

[1] 1. Mangla A, Ehsan M, Agarwal N, et al.: Sickle Cell Anemia. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.

[2] 2. Chao DL, Oron AP, Chabot-Couture G, et al.: Contribution of malaria and sickle cell disease to anaemia among children aged 6–59 months in Nigeria: a cross-sectional study using data from the 2018 Demographic and Health Survey. BMJ Open. 2022; 12: e063369. Publisher Full Text

[3] 3. Bermejo F, García-López S: A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J. Gastroenterol. 2009; 15: 4638–4643. Publisher Full Text

[4] 4. Mohanty D, Mukherjee MB, Colah RB, et al.: Iron deficiency anaemia in sickle cell disorders in India. Indian J. Med. Res. 2008; 127: 366–369.

[5] 5. Odunlade O, Adeodu O, Owa J, et al.: Iron deficiency, still a rarity in children with sickle cell anemia in Ile-Ife, Nigeria. Hematol. Transfus. Cell Ther. 2019; 41: 216–221. Publisher Full Text

[6] 6. Madoori S, Ramya C, Valugula S, et al.: Clinico hematological profile and outcome of anemia in children at tertiary care hospital, Karimnagar, Telangana, India. Int. J. Res. Med. Sci. 2015; 3: 3567–3571. Publisher Full Text

[7] 7. High Performance Liquid Chromatography (HPLC)|ELGA LabWater. Accessed: December 12, 2023. Reference Source

[8] 8. Singh A, Bokade C, Tirpude B, et al.: Clinical Profiles of Children With Sickle Cell Anaemia Presenting With Acute Clinical Events: A Single-Center Study. Cureus. 15: e39008. Publisher Full Text

[9] 9. Salman ZA, Hassan MK: Hospitalization Events among Children and Adolescents with Sickle Cell Disease in Basra, Iraq. Anemia. 2015; 2015: 195469. Publisher Full Text

[10] 10. Özdemir N: Iron deficiency anemia from diagnosis to treatment in children. Turk. Pediatri. Ars. 2015; 50: 11–19. Publisher Full Text

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Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease: a study protocol

Abstract

Background

Methods

Expected outcomes

Keywords

Introduction

Aim

Objectives

Methods

Study design

Study population

Place of study

Inclusion criteria

Exclusion criteria

Enrollment

Sample size

Data collection

Ethical considerations

Statistical methods

Dissemination

Study status

Discussion

Data availability

Underlying data

Extended data

References

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