Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol

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The objectives of this study include estimation of platelet indices and neutrophil:lymphocyte ratio in sickle cell disease (SCD) patients with and without vaso-occlusive crisis. This cross-sectional study will be conducted in the Department of Medicine at a tertiary care teaching hospital situated in the rural area of Wardha district. The participants will include patients of SCD older than 18 years of age attending the sickle cell clinic. We hypothesize the use of neutrophil:lymphocyte ratio (NLR) and platelet indices as clinically significant predictive markers in acute sickle cell vaso-occlusive crisis." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/12-1111", "name": "Platelet indices and neutrophil:lymphocyte ratio as a predictive tool..." } } ] } Home Browse Platelet indices and neutrophil:lymphocyte ratio as a predictive tool... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Khurana K and Mahajan S. Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.12688/f1000research.136668.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol Revised Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] Kashish Khurana https://orcid.org/0000-0002-6672-3784 1 , Satish Mahajan 1 Kashish Khurana https://orcid.org/0000-0002-6672-3784 1 , Satish Mahajan 1 PUBLISHED 23 Apr 2024 Author details Author details 1 Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India Kashish Khurana Roles: Conceptualization, Writing – Original Draft Preparation Satish Mahajan Roles: Supervision, Validation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Datta Meghe Institute of Higher Education and Research collection. Abstract Platelet indices and the neutrophil:lymphocyte ratio are newly emerging indicators of systemic inflammation in chronic diseases, such as hemoglobinopathies. The objectives of this study include estimation of platelet indices and neutrophil:lymphocyte ratio in sickle cell disease (SCD) patients with and without vaso-occlusive crisis. This cross-sectional study will be conducted in the Department of Medicine at a tertiary care teaching hospital situated in the rural area of Wardha district. The participants will include patients of SCD older than 18 years of age attending the sickle cell clinic. We hypothesize the use of neutrophil:lymphocyte ratio (NLR) and platelet indices as clinically significant predictive markers in acute sickle cell vaso-occlusive crisis. READ ALL READ LESS Keywords Neutrophil:lymphocyte ratio, Platelet Indices, Sickle cell disease, vaso occlusive crisis Corresponding Author(s) Kashish Khurana ( [email protected] ) Close Corresponding author: Kashish Khurana Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2024 Khurana K and Mahajan S. 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: Khurana K and Mahajan S. Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.12688/f1000research.136668.3 ) First published: 06 Sep 2023, 12 :1111 ( https://doi.org/10.12688/f1000research.136668.1 ) Latest published: 23 Apr 2024, 12 :1111 ( https://doi.org/10.12688/f1000research.136668.3 ) Revised Amendments from Version 2 The reviewer's comments has been addressed thoroughly and vital changes has been made to the article including grammatical corrections. The reviewer's comments has been addressed thoroughly and vital changes has been made to the article including grammatical corrections. See the authors' detailed response to the review by Ashwin P. Patel READ REVIEWER RESPONSES Introduction The sickle cell disease (SCD)-causing globin gene mutation can be inherited homozygously or compound heterozygously. The hydrophobic amino acid valine replaces the hydrophilic amino acid glutamic acid in the sixth position to produce haemoglobin S (HbS). HbS polymerizes as a result of deoxygenation, and this polymerization is associated with both increased red cell density and cell dehydration. The disease’s acute (painful episodes, acute chest syndrome) and chronic (avascular necrosis, renal insufficiency) consequences are considered to be caused by the thick, rigid, and sickling red cells, which cause vaso-occlusion and reduced blood flow and are associated with these symptoms. 1 In SCD, the complicated interactions between sickled erythrocytes, endothelial cells, leukocytes, platelets, and plasma proteins lead to the vaso-occlusive crisis (VOC). It is generally known that platelets play a part in these interactions. While platelet levels typically rise and are functionally hyperactive in the “steady-state” of sickle cell illness, during a sickle cell crisis, platelet count falls first and then increases, later on, during recovery. Although it is uncommon, acute splenic sequestration, aplastic crisis brought on by parvovirus B19 infection, and fat embolism can all cause thrombocytopenia. 2 Vaso-occlusive crises are associated with enhanced platelet reactivity and activation, which raises platelet volume and widens platelet distribution. Moreover, patients with sickle cell anaemia who experienced more crises had higher platelet concentrations than other patients. In contrast to wealthy nations, patients in central India, also referred to as the sickle cell belt, sadly experience more severe symptoms, with vaso-occlusive crisis and stroke being the two main clinical manifestations. 3 A number of studies done in this region reflect on the severity of SCD related complications. 4 – 6 In addition to the pain associated with VOC, there are a number of clinical consequences. Acute chest syndrome, acute bone pain, hepatic and renal involvement, cerebrovascular accident, and multi-organ failure resulting in death can develop in association with SCD which comprises of VOC. All these presentations of SCD will be included in this study. 5 , 6 In several inflammatory and hemolytic illnesses, mean platelet volume serves as a prognostic indicator. Moreover, higher platelet production will result in larger, more reactive platelets with a larger mean platelet size, hence the MPV readings can be utilised to draw conclusions about disorders causing platelet destruction. 3 The high cost of hydroxyurea therapy for sickle cell anaemia challenges the significant population that hail from tribal and socioeconomically disadvantaged backgrounds. Also, there hasn’t been much research done on the use of platelet counts as prognostic indicators, which might be very helpful, particularly for a nation like India with a significant population of sickle cell sufferers. As a result, the goal of this study is to evaluate the role of platelet indices in the early identification of patients at a higher risk of crisis. If a positive correlation is found, platelet indices may be used as a required investigation in the evaluation of sickle cell patients to predict the possibility of vaso-occlusive crisis and to start hydroxyurea therapy early for better patient outcomes. 3 Objectives • To estimate platelet indices in sickle cell disease patients with and without crisis. • To estimate neutrophil:lymphocyte ratio in SCD patients with and without crisis. Protocol Setting The study will be conducted in the Department of Medicine, at a tertiary care teaching hospital Acharya Vinoba Bhave Rural hospital situated in the rural area of Wardha district. The overview of the study has been shown in Figure 1 . Figure 1. Study flow chart showing the overview of the study. Study design This will be a cross-sectional study. Participants Cases of sickle cell disease more than 18 years attending Sickle cell clinic at a tertiary care teaching hospital Acharya Vinoba Bhave Rural hospital situated in the rural area of Wardha district. Inclusion criteria • Known patients of SCD older than 18 years of age • Newly detected cases of SCD older than 18 years of age Exclusion criteria • Age - less than 18 years • Patients with other causes of thrombocytopenia • Chronic liver disease and chronic kidney disease • Patients with hereditary disorders of large platelets • Patients on anticoagulants • Patients on antiplatelet agents Sample size Daniel et al. formula for sample size: n = Z ∝ 2 2 X P X 1 − P d 2 where, Z ∝ 2 2 is the level of significance at 5% i.e. 95% confidence interval = 1.96 P = prevalence of sickle cell anemia = 4.6 % = 0.046 D = Desired error of margin = 5 % = 0.05 n = 1.96 2 × 0.046 × 1 − 0.046 0.05 2 = 67.43 n = 70 patients needed in each group Statistical methods: Chi Square test Student t-test Software used: SPSS 27.0 Version Methods The following data will be collected for all patients with SCD older than 18 years of age. 1. Age of the patient 2. Thorough history – including family history and previous history of crisis, history of chest pain, medication history 3. Assessing pre-existing comorbidities in patient if any: • H/O Cancer • H/O Chronic Kidney disease • H/O Chronic Liver Disease 4. Complete blood count-platelet count and Platelet indices – MPV (mean platelet volume), PDW (platelet distribution width) & PCT (plateletocrit) (blood sample to be collected on day of admission) and differential leucocyte count (neutrophil, lymphocyte, basophils, monocytes and eosinophils) Lab investigations Complete blood count with hemoglobin and differential leucocyte count (neutrophil, lymphocytes, eosinophils, basophils and monocytes), platelet count. Mean platelet volume (fl), Platelet distribution width (%), plateletcrit (%). Statistical analysis Data collection will be done on demography, comorbidities, platelet count, MPV, PDW and PCT. The data will be examined using IBM and SPSS (IBM Corp., Statistics for Windows, version 27.0, Armonk, NY). Continuous variables with a normal distribution are expressed as mean and standard deviation while continuous variables with a non-normal distribution are expressed as median and inter-quartile range. If there is a statistically significant difference between the bivariate samples in independent groups, it will be determined using the unpaired sample t-test and the Chi-square test. For all of the aforementioned statistical techniques, a p-value ≤ 0.05 will be considered as statistically significant. Dissemination The report will be published in an indexed journal. Study status The study has not yet started. Discussion The most often performed laboratory test in patients with sickle cell disease is the complete blood counts. Little is known, however, about the frequency of platelet-count abnormalities, clinical correlation of various forms of sickle cell crises, and the prognostic importance of platelet indices in these critically ill patients in the ICU. This is the main reason behind designing this protocol. 3 Common complications include vaso-occlusive crisis and stroke. The main event in pathophysiology of sickle cell crisis is vaso-occlusion with ischemia-reperfusion damage, although the pathophysiology at play is complicated. 3 Deoxyhemoglobin S polymerization causes tissue ischemia, which causes both acute and chronic pain. It can also cause damage to any organ in the body including the bones, joints, brain, eyes, liver, kidneys and lungs. SCD activates all cellular components in the blood system. 4 Additionally, aberrant red cells and activated platelets may interact, resulting in vaso-occlusion and aggregation. MPV is a simple way to measure platelet activation and function. 3 , 7 In illnesses like idiopathic thrombocytopenic purpura, platelet production and/or destruction are accelerated and MPV, a measure of platelet size, is increased. In individuals with coronary heart disease, higher MPV levels have been found to be an independent risk factor for myocardial infarction, as well as for death or recurrent vascular events following myocardial infarction. 4 Studies have linked high NLR with clinical outcomes in cardiovascular disease, malignancies, as well as renal disease in SCD NLR has been proposed as marker of inflammation. The transition from steady state to vaso- occlusive crisis (VOC) is facilitated by leukocytes, which are both elevated and active in SCD. By secreting pro-inflammatory mediators and expressing related adhesion molecules, leukocytes increase the adhesiveness of the endothelial cells in the presence of the proper VOC-producing substances, hence intensifying vaso-occlusion and the pain process. 5 Just prior to or during VOC, there is a surge in hematopoietic activity in addition to the shift of the marginating leukocytes to the circulation pool. The significant leukocytosis seen in the VOC group as opposed to the steady state non vaso occlusive SCD patients may be caused by this. The tendency of leukocytes to stick to the postcapillary venular endothelium is increased during leukocytosis, which reduces the vessel lumen. Sickled and unsickled RBCs, platelets and leukocytes all have a greater propensity to cling to the arterial wall and to other cells in these patients, which exacerbates this blockage. Contrarily, in these individuals, leukocytosis might be a type of defence against overwhelming infectious pathogens to which SCD patients are sensitive as a result of functional asplenia brought on by repeated splenic infarction. Patients with functional asplenia are more susceptible to severe infections, especially those caused by encapsulated pathogens such as Streptococcus pneumoniae and Hemophilus influenzae. 8 In SCD patients, a high NLR increases the chance of developing VOC and other end-organ damage. In line with John et al. , this study aims to discover the relation of NLRs in SCD patients as compared to HbA controls. 8 Another study, on the other hand, was unable to show a connection between increased NLR and sickle cell nephropathy, perhaps as a result of the cohort being made up of SCD patients in the steady state. 8 In line with earlier studies, a rebound thrombocytosis may have been the cause of the dramatically higher platelet count in the VOC and steady state group. Due to the compensating feedback impact that anaemia has on the synthesis of erythropoietin, rebound thrombocytosis may coexist with hemolytic anemias and the anaemia caused by chronic diseases. The structural similarity between erythropoietin and thrombopoietin is to blame for this. Additionally, hyposplenism in SCD excludes the spleen’s pooling impact on platelets, which greatly contributes to the high platelet count seen in voc state. 8 Although there is no statistically significant difference between the steady state and VOC groups in the percentage of haemoglobin S in each red blood cell, it is inversely correlated with HbF levels and inversely proportionate to the degree of polymerization of deoxygenated sickle haemoglobin. However, in all previous studies conducted, NLR was not correlated with HbF. 8 The neutrophil and platelet contributions to the chronic inflammatory state in SCD patients are supported by the positive connection between neutrophil to lymphocyte ratio in these individuals. These ratios may serve as reliable, inexpensive and stable indicators of inflammation. When determining the level of inflammation in SCD patients, the use of these simple indicators may be beneficial and superior to using absolute neutrophil count or platelet count alone. 8 This is due to the fact that these ratios are a little bit more stable and are less susceptible to the physiological, pathological or stressful circumstances that are known to affect platelet and neutrophil counts. 8 Ethical considerations IEC approval was obtained from Datta Meghe Institute of Medical Sciences and research (Reference number: DMIMS (DU)/IEC/2022/1084). Written informed consent will be obtained from the patients and their relatives/parents in case of minor patients. Data availability No data are associated with this article. References 1. Pakbaz Z, Wun T: Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics. Hematol. Oncol. Clin. North Am. 2014 Apr; 28 (2): 355–374. PubMed Abstract | Publisher Full Text | Free Full Text 2. Shome DK, Jaradat A, Mahozi AI, et al. : The platelet count and its implications in sickle cell disease patients admitted for intensive care. Indian J. Crit. Care Med. 2018 Aug; 22 (8): 585–590. PubMed Abstract | Publisher Full Text | Free Full Text 3. Student AK: Mean Platelet Volume as a Prognostic Indicator in Sickle Cell Anemia. Int. J. Recent Surg. Med. Sci. 2018 Jan; 04 (01): 005–009. Publisher Full Text 4. Serum Lactate to Albumin Ratio as a Prognostic Marker of Sepsis Syndrome|Annals of the Romanian Society for Cell Biology. [cited 2023 May 30].. http 5. Jadhav U, Babu R, Ghewade B, et al. : Acute chest syndrome, a distinctive manifestation in sickle cell disease – A case study. J. Datta Meghe Inst. Med. Sci. Univ. 2020 Jul 1; 15 (3): 492. Publisher Full Text 6. Taksande A, Jameel PZ, Pujari D, et al. : Variation in pulmonary function tests among children with sickle cell anemia: a systematic review and meta-analysis. Pan. Afr. Med. J. 2021; 39 : 140. 7. Celik T, Unal S, Ekinci O, et al. : Mean Platelet Volume can Predict Cerebrovascular Events in Patients with Sickle Cell Anemia. Pak. J. Med. Sci. 2015; 31 (1): 203–208. PubMed Abstract | Publisher Full Text 8. Alagbe: Pattern of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in sickle cell anemia patients at steady state and vaso-occlusive crisis.[cited 2023 May 30]. Reference Source Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 06 Sep 2023 ADD YOUR COMMENT Comment Author details Author details 1 Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India Kashish Khurana Roles: Conceptualization, Writing – Original Draft Preparation Satish Mahajan Roles: Supervision, Validation, 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 (3) version 3 Revised Published: 23 Apr 2024, 12:1111 https://doi.org/10.12688/f1000research.136668.3 version 2 Revised Published: 05 Mar 2024, 12:1111 https://doi.org/10.12688/f1000research.136668.2 version 1 Published: 06 Sep 2023, 12:1111 https://doi.org/10.12688/f1000research.136668.1 Copyright © 2024 Khurana K and Mahajan S. 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. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Khurana K and Mahajan S. Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.12688/f1000research.136668.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 3 VERSION 3 PUBLISHED 23 Apr 2024 Revised Views 0 Cite How to cite this report: Nri-ezedi CA. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.165308.r360270 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v3#referee-response-360270 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 20 Jan 2025 Chisom Adaobi Nri-ezedi , Nnamdi Azikiwe University, Awka, Anambra, Nigeria Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.165308.r360270 Question 1: Is the rationale for, and objectives of, the study clearly described? Answer: Partly Comments: The rationale for the study is vaguely described and does not align well with the research title. While the study aims ... Continue reading READ ALL Question 1: Is the rationale for, and objectives of, the study clearly described? Answer: Partly Comments: The rationale for the study is vaguely described and does not align well with the research title. While the study aims to evaluate platelet indices and the neutrophil: lymphocyte ratio (NLR) as predictive markers in sickle cell disease (SCD) patients experiencing vaso-occlusive crisis (VOC), the introduction lacks clarity in establishing why these specific markers are significant. Additionally, the study objectives could be stated more precisely to reflect the novelty and clinical utility of the findings. For example, details about how these markers compare to existing prognostic tools should be included. Question 2: Is the study design appropriate for the research question? Answer: No Comments: The authors describe this as a cross-sectional study, but the design seems misaligned with the stated objectives. Cross-sectional studies are typically descriptive and not suited for evaluating predictive relationships as implied by the study's hypotheses. If the authors intend to evaluate predictors of VOC, a longitudinal or case-control study design may be more appropriate. Additionally, the exclusion criteria fail to address whether the patients are in a VOC or stable state, making it unclear how control and case groups are defined. Question 3: Are sufficient details of the methods provided to allow replication by others? Answer: No Comments: The methods section lacks sufficient details to ensure replicability: Hydroxyurea Usage: It is unclear whether patients are on hydroxyurea therapy, which could significantly influence platelet indices and NLR. This must be explicitly stated. Patient Selection: The inclusion and exclusion criteria do not clarify how patients in VOC and those in steady-state SCD are identified or separated. Platelet Indices: While platelet indices are mentioned, they are not clearly defined. For instance, which specific platelet indices (e.g., MPV, PDW) are included, and how they are measured? Statistical Methods: Although chi-square and t-tests are mentioned, a multivariate regression analysis is necessary to account for potential confounders and to identify independent predictors of VOC. Question 4: Are the datasets clearly presented in a useable and accessible format? Answer: Not applicable Comments: No datasets are associated with this article as the study has not yet started. However, the authors should outline a plan for data sharing and ensure the dataset will be anonymized and accessible for replication purposes in future publications. Summary of the Article This study protocol aims to evaluate platelet indices and the neutrophil:lymphocyte ratio as predictive markers in sickle cell disease patients experiencing vaso-occlusive crises. It proposes a cross-sectional study conducted in a tertiary care hospital in Wardha district, India, with the objective of comparing these markers between SCD patients in VOC and those in a steady state. The authors hypothesize that platelet indices and NLR are significant predictors of VOC and can aid in early intervention and improved outcomes. Strengths of the Article The study addresses a clinically relevant question in a population heavily burdened by SCD. The use of platelet indices and NLR as prognostic markers is novel and has potential clinical utility, especially in resource-limited settings. Areas for Improvement 1. Introduction: The introduction lacks clarity and fails to align with the research objectives. It should establish a stronger rationale for studying platelet indices and NLR in SCD and VOC. For example, the authors could highlight gaps in existing literature and discuss the potential advantages of using these markers over current prognostic tools. Several statements lack appropriate references to support their claims. 2. Study Design: The described cross-sectional design is not suitable for studying predictive relationships. The authors should reconsider using a longitudinal or case-control design to better address their research question. The inclusion and exclusion criteria need to specify whether patients in VOC or steady states will be included. A clear definition of control groups is necessary. The authors should specify whether patients are on hydroxyurea or other medications that could affect platelet indices and NLR. 3. Methods: The term platelet is not explicitly defined. The authors should list the specific indices (e.g., MPV, PDW) and describe how they will be measured. The methodology for measuring NLR is unclear. Will it be derived from standard complete blood counts, or are additional tests required? Statistical analyses need improvement. Multivariate regression analysis should be included to adjust for confounding variables such as age, sex, medication use, and comorbidities. 4. Ethical Considerations: Ethical approval is mentioned, but the consent process for adults requires clarification. For example, how will informed consent be obtained in cases where patients are unable to provide it themselves (e.g., during VOC)? Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? No 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: Pediatric Hematology-Oncology, Sickle Cell Disease, Data Analytics in Healthcare, Platelet-Neutrophil Ratios as Monitoring Tools in Sickle Cell Diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Nri-ezedi CA. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.165308.r360270 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v3#referee-response-360270 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Hsu L. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.165308.r337142 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v3#referee-response-337142 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 21 Nov 2024 Lewis Hsu , University of Illinois at Chicago, Chicago, Illinois, USA Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.165308.r337142 Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol Khurana K and Mahajan S This study protocol has the admirable goal of finding information in the ordinary ... Continue reading READ ALL Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol Khurana K and Mahajan S This study protocol has the admirable goal of finding information in the ordinary Complete Blood Count and leukocyte differential to predict sickle cell pain vs steady state, and perhaps use this information to decide which patients should start hydroxyurea. Published data show statistical correlations with neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) that appear to support their hypotheses, and some of these data are in the same population of sickle cell disease in central India. A power analysis estimates that the study should have 70 patients per arm. Moderate critique of the study The study design has no control group without sickle cell disease. Descriptions of the eligibility criteria are different in the text and in Figure 1. The Figure shows sickle cell trait (HbAS), which should be excluded from this study. There is no stratification by malnutrition, which can be a very significant risk factor for sickle cell crises in central India (Patel AB, et.al Ref 1.) Will compound heterozygotes such as sickle cell disease S-beta-thalassemia or S-D-Punjab be excluded or stratified? Adults with sickle cell disease often develop organ damage as they age. Thresholds are needed for the exclusion criteria for chronic liver disease and chronic kidney disease. The study would be more powerful if it could include comparison between established predictors of sickle cell complications (Hemoglobin level, Hemoglobin F level, reticulocytes, Lactate dehydrogenase) and these proposed new predictors (platelet parameters and NLR) Minor: Multiple citations to reference #8 as preliminary data, but this reference link is incomplete. An internet search found the complete citation. Please supplement the current reference #8 with this information: Alagbe, Adekunle Emmanuel and John Ayodele Olaniyi. “Pattern of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in sickle cell anemia patients at steady state and vaso-occlusive crisis.” Journal of Applied Hematology 10 (2019): 45 - 50. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? No 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 References 1. Patel AB, Athavale AM: Sickle cell disease in central India. Indian J Pediatr . 2004; 71 (9): 789-93 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: sickle cell disease I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Hsu L. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.165308.r337142 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v3#referee-response-337142 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Patel AP. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.165308.r268986 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v3#referee-response-268986 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 Jun 2024 Ashwin P. Patel , Emory University, Atlanta, USA Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.165308.r268986 I thank authors for editing their protocol. However, some of the previous concerns are not addressed and the protocol contains some ambiguous or contradictory statements. Overall, the protocol fails to convey the clear picture about the proposed research. ... Continue reading READ ALL I thank authors for editing their protocol. However, some of the previous concerns are not addressed and the protocol contains some ambiguous or contradictory statements. Overall, the protocol fails to convey the clear picture about the proposed research. Authors have not clearly defined “acute vaso-occlusive crisis” for the purpose of this research. Figure 1 mentions that HbSS and HbAS subjects will be enrolled. If that is correct, SCA (sickle cell anemia) may be a better terminology instead of SCD. Authors have not discussed rationality of enrolling HbAS genotype. The protocol still contains contradictory statements. For example, the figure 1 mentions “Patients on anticoagulants previously” while the text mentions “Patients on anticoagulants” as an exclusion criteria. Statistical analysis plan is not clear. Authors mention “If there is a statistically significant difference between the bivariate samples in independent groups, it will be determined using the unpaired sample t-test and the Chi-square test.” This sentence is difficult to interpret. Authors mentioned “In line with John et al. , this study aims to discover the relation of NLRs in SCD patients as compared to HbA controls”. However, they have not included HbAA in the inclusion criteria. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Hematology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Patel AP. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.165308.r268986 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v3#referee-response-268986 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 2 VERSION 2 PUBLISHED 05 Mar 2024 Revised Views 0 Cite How to cite this report: Patel AP. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.163296.r252862 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v2#referee-response-252862 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 28 Mar 2024 Ashwin P. Patel , Emory University, Atlanta, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.163296.r252862 I thank the authors for editing their protocol as per my suggestions. Clarification of some aspects of the revised version will be helpful: (1) How is acute sickle cell vaso-occlusive crisis defined? Patients usually receive treatment from a local ... Continue reading READ ALL I thank the authors for editing their protocol as per my suggestions. Clarification of some aspects of the revised version will be helpful: (1) How is acute sickle cell vaso-occlusive crisis defined? Patients usually receive treatment from a local physician before they get admitted. Higher than baseline steady-state pain score at the admission? Admission within a pre-defined period of a new onset of pain? (2) Inclusion and exclusion criteria should be well defined. For example, one of the exclusion criteria is "Patients with liver and renal disease". The criterion is too broad and ambiguous. Authors should clearly define this and all other criteria. (3) Data extraction, statistical analysis plan, and objectives do not align well. E.g. (1) The authors propose to collect information on serum electrolytes but do not discuss how this information will be used. Please describe how each extracted variable will be analyzed and how it will be helpful for the evaluation of the project's aims/objectives. (4) Each of the two objectives involves a continuous variable and a grouping variable. This will require a t-test or a non-parametric test. A non-parametric test is not included in the statistical analysis plan. Similarly, it is not clear when a Chi2 test will be used. Please mention all the statistical tests you plan to use to analyze aims/objectives. (5) Please check if SCA and SCD words are not used interchangeably. (6) Some of the sentences create an impression that the project is completed or an interim analysis has been performed. For example, the discussion section mentions "In line with John et al., this study discovered that SCA patients had greater NLRs than HbA controls." If this is not the case, please edit this and similar other sentences. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Hematology 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. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Patel AP. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.163296.r252862 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v2#referee-response-252862 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 04 Jun 2024 Kashish Khurana , Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 04 Jun 2024 Author Response The reviewer's comments has been addressed thoroughly and vital changes has been made to the article including grammatical corrections. 1.) Definition of vaso occlusive crisis has been added to the ... Continue reading The reviewer's comments has been addressed thoroughly and vital changes has been made to the article including grammatical corrections. 1.) Definition of vaso occlusive crisis has been added to the manuscript. However Pain score was not added as this study is not using this particular criteria. 2.) Inclusion and exclusion criteria has been revised 3.) The variables which were not utilized in the study has been removed from the manuscript. 4.) Statistical analysis methods to be used has been included in the manuscript. 5.) Similar abbreviations for Sickle cell disease, i.e., SCD has now been included throughout the manuscript. 6.) Minor grammatical has been rectified . The reviewer's comments has been addressed thoroughly and vital changes has been made to the article including grammatical corrections. 1.) Definition of vaso occlusive crisis has been added to the manuscript. However Pain score was not added as this study is not using this particular criteria. 2.) Inclusion and exclusion criteria has been revised 3.) The variables which were not utilized in the study has been removed from the manuscript. 4.) Statistical analysis methods to be used has been included in the manuscript. 5.) Similar abbreviations for Sickle cell disease, i.e., SCD has now been included throughout the manuscript. 6.) Minor grammatical has been rectified . Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 04 Jun 2024 Kashish Khurana , Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 04 Jun 2024 Author Response The reviewer's comments has been addressed thoroughly and vital changes has been made to the article including grammatical corrections. 1.) Definition of vaso occlusive crisis has been added to the ... Continue reading The reviewer's comments has been addressed thoroughly and vital changes has been made to the article including grammatical corrections. 1.) Definition of vaso occlusive crisis has been added to the manuscript. However Pain score was not added as this study is not using this particular criteria. 2.) Inclusion and exclusion criteria has been revised 3.) The variables which were not utilized in the study has been removed from the manuscript. 4.) Statistical analysis methods to be used has been included in the manuscript. 5.) Similar abbreviations for Sickle cell disease, i.e., SCD has now been included throughout the manuscript. 6.) Minor grammatical has been rectified . The reviewer's comments has been addressed thoroughly and vital changes has been made to the article including grammatical corrections. 1.) Definition of vaso occlusive crisis has been added to the manuscript. However Pain score was not added as this study is not using this particular criteria. 2.) Inclusion and exclusion criteria has been revised 3.) The variables which were not utilized in the study has been removed from the manuscript. 4.) Statistical analysis methods to be used has been included in the manuscript. 5.) Similar abbreviations for Sickle cell disease, i.e., SCD has now been included throughout the manuscript. 6.) Minor grammatical has been rectified . Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 06 Sep 2023 Views 0 Cite How to cite this report: Patel AP. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.149812.r232202 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v1#referee-response-232202 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 24 Jan 2024 Ashwin P. Patel , Emory University, Atlanta, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.149812.r232202 The authors should address the following queries to increase the clarity of the proposed research. (1) The inclusion and exclusion criteria mentioned in the draft and Figure 1 are different. For example, the figure mentions age < 18 years ... Continue reading READ ALL The authors should address the following queries to increase the clarity of the proposed research. (1) The inclusion and exclusion criteria mentioned in the draft and Figure 1 are different. For example, the figure mentions age < 18 years as an exclusion criterion while the text mentioned < 14 years. (2) Two different versions of SPSS are mentioned in the manuscript. (3) The statistical analysis section needs clarity. The authors mentioned, " Continuous variables will be expressed as mean standard deviation". Continuous variables with a normal distribution are expressed as mean and standard deviation while continuous variables with a non-normal distribution are expressed as median and inter-quartile range. (4) The language used the the manuscript creates confusion. Is this project completed or is it to be carried out? Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Hematology 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. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Patel AP. Reviewer Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.149812.r232202 ) The direct URL for this report is: https://f1000research.com/articles/12-1111/v1#referee-response-232202 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 13 Apr 2024 Kashish Khurana , Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 13 Apr 2024 Author Response 1) In the age criteria mentioned in the article, there is a typing mistake and the age criteria in exclusion criteria should be <18 years and not <14 years. It ... Continue reading 1) In the age criteria mentioned in the article, there is a typing mistake and the age criteria in exclusion criteria should be <18 years and not <14 years. It has been rectified in the article. 2) SPSS software version used in the manuscript was version 27.0 and not version 23. That was a typing error. 3) I will rectify the statistical analysis section and will write the following: Continuous variables with a normal distribution are expressed as mean and standard deviation while continuous variables with a non-normal distribution are expressed as median and inter-quartile range. 4) This project is currently in process and is likely to be completed in June 2024. 1) In the age criteria mentioned in the article, there is a typing mistake and the age criteria in exclusion criteria should be <18 years and not <14 years. It has been rectified in the article. 2) SPSS software version used in the manuscript was version 27.0 and not version 23. That was a typing error. 3) I will rectify the statistical analysis section and will write the following: Continuous variables with a normal distribution are expressed as mean and standard deviation while continuous variables with a non-normal distribution are expressed as median and inter-quartile range. 4) This project is currently in process and is likely to be completed in June 2024. Competing Interests: none Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 13 Apr 2024 Kashish Khurana , Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 13 Apr 2024 Author Response 1) In the age criteria mentioned in the article, there is a typing mistake and the age criteria in exclusion criteria should be <18 years and not <14 years. It ... Continue reading 1) In the age criteria mentioned in the article, there is a typing mistake and the age criteria in exclusion criteria should be <18 years and not <14 years. It has been rectified in the article. 2) SPSS software version used in the manuscript was version 27.0 and not version 23. That was a typing error. 3) I will rectify the statistical analysis section and will write the following: Continuous variables with a normal distribution are expressed as mean and standard deviation while continuous variables with a non-normal distribution are expressed as median and inter-quartile range. 4) This project is currently in process and is likely to be completed in June 2024. 1) In the age criteria mentioned in the article, there is a typing mistake and the age criteria in exclusion criteria should be <18 years and not <14 years. It has been rectified in the article. 2) SPSS software version used in the manuscript was version 27.0 and not version 23. That was a typing error. 3) I will rectify the statistical analysis section and will write the following: Continuous variables with a normal distribution are expressed as mean and standard deviation while continuous variables with a non-normal distribution are expressed as median and inter-quartile range. 4) This project is currently in process and is likely to be completed in June 2024. Competing Interests: none Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 06 Sep 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 3 (revision) 23 Apr 24 read read read Version 2 (revision) 05 Mar 24 read Version 1 06 Sep 23 read Ashwin P. Patel , Emory University, Atlanta, USA Lewis Hsu , University of Illinois at Chicago, Chicago, USA Chisom Adaobi Nri-ezedi , Nnamdi Azikiwe University, Awka, Nigeria Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Nri-ezedi C. This is an open access peer review report 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. 20 Jan 2025 | for Version 3 Chisom Adaobi Nri-ezedi , Nnamdi Azikiwe University, Awka, Anambra, Nigeria 0 Views copyright © 2025 Nri-ezedi C. This is an open access peer review report 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. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Question 1: Is the rationale for, and objectives of, the study clearly described? Answer: Partly Comments: The rationale for the study is vaguely described and does not align well with the research title. While the study aims to evaluate platelet indices and the neutrophil: lymphocyte ratio (NLR) as predictive markers in sickle cell disease (SCD) patients experiencing vaso-occlusive crisis (VOC), the introduction lacks clarity in establishing why these specific markers are significant. Additionally, the study objectives could be stated more precisely to reflect the novelty and clinical utility of the findings. For example, details about how these markers compare to existing prognostic tools should be included. Question 2: Is the study design appropriate for the research question? Answer: No Comments: The authors describe this as a cross-sectional study, but the design seems misaligned with the stated objectives. Cross-sectional studies are typically descriptive and not suited for evaluating predictive relationships as implied by the study's hypotheses. If the authors intend to evaluate predictors of VOC, a longitudinal or case-control study design may be more appropriate. Additionally, the exclusion criteria fail to address whether the patients are in a VOC or stable state, making it unclear how control and case groups are defined. Question 3: Are sufficient details of the methods provided to allow replication by others? Answer: No Comments: The methods section lacks sufficient details to ensure replicability: Hydroxyurea Usage: It is unclear whether patients are on hydroxyurea therapy, which could significantly influence platelet indices and NLR. This must be explicitly stated. Patient Selection: The inclusion and exclusion criteria do not clarify how patients in VOC and those in steady-state SCD are identified or separated. Platelet Indices: While platelet indices are mentioned, they are not clearly defined. For instance, which specific platelet indices (e.g., MPV, PDW) are included, and how they are measured? Statistical Methods: Although chi-square and t-tests are mentioned, a multivariate regression analysis is necessary to account for potential confounders and to identify independent predictors of VOC. Question 4: Are the datasets clearly presented in a useable and accessible format? Answer: Not applicable Comments: No datasets are associated with this article as the study has not yet started. However, the authors should outline a plan for data sharing and ensure the dataset will be anonymized and accessible for replication purposes in future publications. Summary of the Article This study protocol aims to evaluate platelet indices and the neutrophil:lymphocyte ratio as predictive markers in sickle cell disease patients experiencing vaso-occlusive crises. It proposes a cross-sectional study conducted in a tertiary care hospital in Wardha district, India, with the objective of comparing these markers between SCD patients in VOC and those in a steady state. The authors hypothesize that platelet indices and NLR are significant predictors of VOC and can aid in early intervention and improved outcomes. Strengths of the Article The study addresses a clinically relevant question in a population heavily burdened by SCD. The use of platelet indices and NLR as prognostic markers is novel and has potential clinical utility, especially in resource-limited settings. Areas for Improvement 1. Introduction: The introduction lacks clarity and fails to align with the research objectives. It should establish a stronger rationale for studying platelet indices and NLR in SCD and VOC. For example, the authors could highlight gaps in existing literature and discuss the potential advantages of using these markers over current prognostic tools. Several statements lack appropriate references to support their claims. 2. Study Design: The described cross-sectional design is not suitable for studying predictive relationships. The authors should reconsider using a longitudinal or case-control design to better address their research question. The inclusion and exclusion criteria need to specify whether patients in VOC or steady states will be included. A clear definition of control groups is necessary. The authors should specify whether patients are on hydroxyurea or other medications that could affect platelet indices and NLR. 3. Methods: The term platelet is not explicitly defined. The authors should list the specific indices (e.g., MPV, PDW) and describe how they will be measured. The methodology for measuring NLR is unclear. Will it be derived from standard complete blood counts, or are additional tests required? Statistical analyses need improvement. Multivariate regression analysis should be included to adjust for confounding variables such as age, sex, medication use, and comorbidities. 4. Ethical Considerations: Ethical approval is mentioned, but the consent process for adults requires clarification. For example, how will informed consent be obtained in cases where patients are unable to provide it themselves (e.g., during VOC)? Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? No 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 Pediatric Hematology-Oncology, Sickle Cell Disease, Data Analytics in Healthcare, Platelet-Neutrophil Ratios as Monitoring Tools in Sickle Cell Diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Nri-ezedi CA. Peer Review Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.165308.r360270) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1111/v3#referee-response-360270 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Hsu L. This is an open access peer review report 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. 21 Nov 2024 | for Version 3 Lewis Hsu , University of Illinois at Chicago, Chicago, Illinois, USA 0 Views copyright © 2024 Hsu L. This is an open access peer review report 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. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol Khurana K and Mahajan S This study protocol has the admirable goal of finding information in the ordinary Complete Blood Count and leukocyte differential to predict sickle cell pain vs steady state, and perhaps use this information to decide which patients should start hydroxyurea. Published data show statistical correlations with neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) that appear to support their hypotheses, and some of these data are in the same population of sickle cell disease in central India. A power analysis estimates that the study should have 70 patients per arm. Moderate critique of the study The study design has no control group without sickle cell disease. Descriptions of the eligibility criteria are different in the text and in Figure 1. The Figure shows sickle cell trait (HbAS), which should be excluded from this study. There is no stratification by malnutrition, which can be a very significant risk factor for sickle cell crises in central India (Patel AB, et.al Ref 1.) Will compound heterozygotes such as sickle cell disease S-beta-thalassemia or S-D-Punjab be excluded or stratified? Adults with sickle cell disease often develop organ damage as they age. Thresholds are needed for the exclusion criteria for chronic liver disease and chronic kidney disease. The study would be more powerful if it could include comparison between established predictors of sickle cell complications (Hemoglobin level, Hemoglobin F level, reticulocytes, Lactate dehydrogenase) and these proposed new predictors (platelet parameters and NLR) Minor: Multiple citations to reference #8 as preliminary data, but this reference link is incomplete. An internet search found the complete citation. Please supplement the current reference #8 with this information: Alagbe, Adekunle Emmanuel and John Ayodele Olaniyi. “Pattern of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in sickle cell anemia patients at steady state and vaso-occlusive crisis.” Journal of Applied Hematology 10 (2019): 45 - 50. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? No 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 References 1. Patel AB, Athavale AM: Sickle cell disease in central India. Indian J Pediatr . 2004; 71 (9): 789-93 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise sickle cell disease I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Hsu L. Peer Review Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.165308.r337142) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1111/v3#referee-response-337142 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Patel A. This is an open access peer review report 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. 12 Jun 2024 | for Version 3 Ashwin P. Patel , Emory University, Atlanta, USA 0 Views copyright © 2024 Patel A. This is an open access peer review report 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. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I thank authors for editing their protocol. However, some of the previous concerns are not addressed and the protocol contains some ambiguous or contradictory statements. Overall, the protocol fails to convey the clear picture about the proposed research. Authors have not clearly defined “acute vaso-occlusive crisis” for the purpose of this research. Figure 1 mentions that HbSS and HbAS subjects will be enrolled. If that is correct, SCA (sickle cell anemia) may be a better terminology instead of SCD. Authors have not discussed rationality of enrolling HbAS genotype. The protocol still contains contradictory statements. For example, the figure 1 mentions “Patients on anticoagulants previously” while the text mentions “Patients on anticoagulants” as an exclusion criteria. Statistical analysis plan is not clear. Authors mention “If there is a statistically significant difference between the bivariate samples in independent groups, it will be determined using the unpaired sample t-test and the Chi-square test.” This sentence is difficult to interpret. Authors mentioned “In line with John et al. , this study aims to discover the relation of NLRs in SCD patients as compared to HbA controls”. However, they have not included HbAA in the inclusion criteria. Competing Interests No competing interests were disclosed. Reviewer Expertise Hematology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Patel AP. Peer Review Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.165308.r268986) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1111/v3#referee-response-268986 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Patel A. This is an open access peer review report 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. 28 Mar 2024 | for Version 2 Ashwin P. Patel , Emory University, Atlanta, USA 0 Views copyright © 2024 Patel A. This is an open access peer review report 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. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I thank the authors for editing their protocol as per my suggestions. Clarification of some aspects of the revised version will be helpful: (1) How is acute sickle cell vaso-occlusive crisis defined? Patients usually receive treatment from a local physician before they get admitted. Higher than baseline steady-state pain score at the admission? Admission within a pre-defined period of a new onset of pain? (2) Inclusion and exclusion criteria should be well defined. For example, one of the exclusion criteria is "Patients with liver and renal disease". The criterion is too broad and ambiguous. Authors should clearly define this and all other criteria. (3) Data extraction, statistical analysis plan, and objectives do not align well. E.g. (1) The authors propose to collect information on serum electrolytes but do not discuss how this information will be used. Please describe how each extracted variable will be analyzed and how it will be helpful for the evaluation of the project's aims/objectives. (4) Each of the two objectives involves a continuous variable and a grouping variable. This will require a t-test or a non-parametric test. A non-parametric test is not included in the statistical analysis plan. Similarly, it is not clear when a Chi2 test will be used. Please mention all the statistical tests you plan to use to analyze aims/objectives. (5) Please check if SCA and SCD words are not used interchangeably. (6) Some of the sentences create an impression that the project is completed or an interim analysis has been performed. For example, the discussion section mentions "In line with John et al., this study discovered that SCA patients had greater NLRs than HbA controls." If this is not the case, please edit this and similar other sentences. Competing Interests No competing interests were disclosed. Reviewer Expertise Hematology 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. reply Respond to this report Responses (1) Author Response 04 Jun 2024 Kashish Khurana, Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India The reviewer's comments has been addressed thoroughly and vital changes has been made to the article including grammatical corrections. 1.) Definition of vaso occlusive crisis has been added to the manuscript. However Pain score was not added as this study is not using this particular criteria. 2.) Inclusion and exclusion criteria has been revised 3.) The variables which were not utilized in the study has been removed from the manuscript. 4.) Statistical analysis methods to be used has been included in the manuscript. 5.) Similar abbreviations for Sickle cell disease, i.e., SCD has now been included throughout the manuscript. 6.) Minor grammatical has been rectified . View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Patel AP. Peer Review Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.163296.r252862) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1111/v2#referee-response-252862 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Patel A. This is an open access peer review report 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. 24 Jan 2024 | for Version 1 Ashwin P. Patel , Emory University, Atlanta, USA 0 Views copyright © 2024 Patel A. This is an open access peer review report 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. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors should address the following queries to increase the clarity of the proposed research. (1) The inclusion and exclusion criteria mentioned in the draft and Figure 1 are different. For example, the figure mentions age < 18 years as an exclusion criterion while the text mentioned < 14 years. (2) Two different versions of SPSS are mentioned in the manuscript. (3) The statistical analysis section needs clarity. The authors mentioned, " Continuous variables will be expressed as mean standard deviation". Continuous variables with a normal distribution are expressed as mean and standard deviation while continuous variables with a non-normal distribution are expressed as median and inter-quartile range. (4) The language used the the manuscript creates confusion. Is this project completed or is it to be carried out? Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Hematology 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. reply Respond to this report Responses (1) Author Response 13 Apr 2024 Kashish Khurana, Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, 442001, India 1) In the age criteria mentioned in the article, there is a typing mistake and the age criteria in exclusion criteria should be <18 years and not <14 years. It has been rectified in the article. 2) SPSS software version used in the manuscript was version 27.0 and not version 23. That was a typing error. 3) I will rectify the statistical analysis section and will write the following: Continuous variables with a normal distribution are expressed as mean and standard deviation while continuous variables with a non-normal distribution are expressed as median and inter-quartile range. 4) This project is currently in process and is likely to be completed in June 2024. View more View less Competing Interests none reply Respond Report a concern Patel AP. Peer Review Report For: Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol [version 3; peer review: 3 not approved] . F1000Research 2024, 12 :1111 ( https://doi.org/10.5256/f1000research.149812.r232202) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1111/v1#referee-response-232202 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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