Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study

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Our study aims to ascertain the risk factors that increase the propensity of perioperative blood transfusions in pediatric population. Methods A single center retrospective observational study of patients aged <18 years undergoing orthopedic surgeries at our tertiary care hospital from January 2016 to August 2024 were included and each surgery was analyzed as a discrete event. Age, type of OI, number of osteotomies, and number of bones operated simultaneously were recorded. The fall in hemoglobin, requirement for blood transfusions and associated factors were analyzed. Estimated blood loss, surgical duration, and surgical approach were not consistently available and were therefore not analyzed. Results Amongst 53 individuals who underwent surgery, 141 procedures were analyzed. A statistically significant postoperative hemoglobin decline was observed overall (mean 12.22 ± 1.06 g/dL preoperatively vs. 10.57 ± 1.48 g/dL postoperatively; p < 0.001). Procedures involving multiple osteotomies were associated with greater hemoglobin decline (p = 0.002) and higher transfusion frequency (16.3% overall; p = 0.001). Type III OI was associated with greater hemoglobin decline compared to other phenotypes (p = 0.01). Younger age showed a statistically significant but weak inverse correlation with hemoglobin decline (R2 = 0.076). Conclusion Our study inferred that the fall in hemoglobin was significant postoperatively in OI patients and was associated with younger age, type III OI, and multiple osteotomies. Before performing orthopedic surgeries on patients with OI, surgeons might consider the latter risk factors to explore therapeutic options aimed at reducing hemorrhage and improving outcomes. " } { "@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/13-1420", "name": "Assessment of perioperative bleeding in pediatric osteogenesis imperfecta..." } } ] } Home Browse Assessment of perioperative bleeding in pediatric osteogenesis imperfecta... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Kulkarni M, Shah HH, subbiah S et al. Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] . F1000Research 2026, 13 :1420 ( https://doi.org/10.12688/f1000research.158583.3 ) 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 ▬ ✚ Research Article Revised Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] Malavika Kulkarni 1 , Hitesh Hasmukhlal Shah https://orcid.org/0000-0002-2940-3108 2 , Sanjana subbiah https://orcid.org/0009-0008-5771-2953 1 , [...] Sushma Thimmaiah Kanakalakshmi https://orcid.org/0000-0002-4460-4020 1 , Laxmi Shenoy 1 , RamaRani KrishnaBhat https://orcid.org/0000-0001-6291-8544 1 , Priya Genevieve D'mello 1 Malavika Kulkarni 1 , Hitesh Hasmukhlal Shah https://orcid.org/0000-0002-2940-3108 2 , [...] Sanjana subbiah https://orcid.org/0009-0008-5771-2953 1 , Sushma Thimmaiah Kanakalakshmi https://orcid.org/0000-0002-4460-4020 1 , Laxmi Shenoy 1 , RamaRani KrishnaBhat https://orcid.org/0000-0001-6291-8544 1 , Priya Genevieve D'mello 1 PUBLISHED 28 Feb 2026 Author details Author details 1 Department of Anesthesiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India 2 Department of Pediatric Orthopedics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India Malavika Kulkarni Roles: Conceptualization, Investigation, Methodology, Project Administration, Supervision, Visualization, Writing – Review & Editing Hitesh Hasmukhlal Shah Roles: Data Curation, Investigation, Project Administration, Resources, Software, Supervision, Visualization Sanjana subbiah Roles: Data Curation, Investigation, Project Administration, Resources, Software, Writing – Review & Editing Sushma Thimmaiah Kanakalakshmi Roles: Formal Analysis, Investigation, Resources, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Laxmi Shenoy Roles: Data Curation, Project Administration, Supervision, Validation, Visualization RamaRani KrishnaBhat Roles: Investigation, Project Administration, Resources, Supervision, Visualization, Writing – Review & Editing Priya Genevieve D'mello Roles: Investigation, Project Administration, Supervision, Validation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Manipal Academy of Higher Education gateway. Abstract Background “Osteogenesis imperfecta (OI)” is a heterogeneous group of inherited disorders involving collagen type I with a 10–30% incidence of bleeding diathesis placing these individuals at an increased risk of bleeding. Our study aims to ascertain the risk factors that increase the propensity of perioperative blood transfusions in pediatric population. Methods A single center retrospective observational study of patients aged <18 years undergoing orthopedic surgeries at our tertiary care hospital from January 2016 to August 2024 were included and each surgery was analyzed as a discrete event. Age, type of OI, number of osteotomies, and number of bones operated simultaneously were recorded. The fall in hemoglobin, requirement for blood transfusions and associated factors were analyzed. Estimated blood loss, surgical duration, and surgical approach were not consistently available and were therefore not analyzed. Results Amongst 53 individuals who underwent surgery, 141 procedures were analyzed. A statistically significant postoperative hemoglobin decline was observed overall (mean 12.22 ± 1.06 g/dL preoperatively vs. 10.57 ± 1.48 g/dL postoperatively; p < 0.001). Procedures involving multiple osteotomies were associated with greater hemoglobin decline (p = 0.002) and higher transfusion frequency (16.3% overall; p = 0.001). Type III OI was associated with greater hemoglobin decline compared to other phenotypes (p = 0.01). Younger age showed a statistically significant but weak inverse correlation with hemoglobin decline (R 2 = 0.076). Conclusion Our study inferred that the fall in hemoglobin was significant postoperatively in OI patients and was associated with younger age, type III OI, and multiple osteotomies. Before performing orthopedic surgeries on patients with OI, surgeons might consider the latter risk factors to explore therapeutic options aimed at reducing hemorrhage and improving outcomes. READ ALL READ LESS Keywords Bleeding diathesis, Osteogenesis imperfecta, Osteotomies, Perioperative bleeding Corresponding Author(s) Sushma Thimmaiah Kanakalakshmi ( [email protected] ) Close Corresponding author: Sushma Thimmaiah Kanakalakshmi Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2026 Kulkarni M 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: Kulkarni M, Shah HH, subbiah S et al. Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] . F1000Research 2026, 13 :1420 ( https://doi.org/10.12688/f1000research.158583.3 ) First published: 25 Nov 2024, 13 :1420 ( https://doi.org/10.12688/f1000research.158583.1 ) Latest published: 28 Feb 2026, 13 :1420 ( https://doi.org/10.12688/f1000research.158583.3 ) Revised Amendments from Version 2 We have revised the manuscript to clarify this methodological limitation and explicitly acknowledge the absence of EBL as a constraint of our analysis. We have clarified in the revised manuscript that surgical approach was not systematically controlled for in the original analysis. We have revised the manuscript to clarify this methodological limitation and explicitly acknowledge the absence of EBL as a constraint of our analysis. We have clarified in the revised manuscript that surgical approach was not systematically controlled for in the original analysis. See the authors' detailed response to the review by Vivek Kumar Morya See the authors' detailed response to the review by Hesham Mohamed Elbaseet READ REVIEWER RESPONSES Introduction “Osteogenesis imperfecta (OI)” also known as “brittle bone disease” is a rare congenital disease resulting from a defect in the type I collagen synthesis or processing with an incidence of 1:20000. It has a wide spectrum of presentations ranging from almost asymptomatic to severe forms causing increased bone fragility, skeletal deformity, and a range of extra-skeletal manifestations. 1 Majority of the OI patients have pathogenic mutations in “COL1A1 or COL1A2” genes which code for alpha 1 and 2 chains of type I collagen which are abundant in bones, ligaments, and tendons. Collagen type 1 is produced less frequently and/or abnormally in dominant pathogenic variations. It is commonly known that the variation type, precise location, and implicated gene all affect the phenotypic presentation of these patients. 2 Numerous mutations linked to OI have been found; however, missense mutations mostly cause structural changes in the collagen protein, which results in a more severe phenotype, whereas stop mutations typically result in decreased collagen quantity and a mild phenotype. 3 OI is well known for its clinical manifestations, which include blue sclera, hearing loss, ligament laxity, increased joint mobility, small stature, easy bruising, and normal enamel with dentin abnormalities. Bony manifestations include bone abnormalities, fractures from minor trauma, and the requirement for repeated orthopedic treatments. 3 OI is also associated with easy bruising and bleeding, often attributed to the increased fragility of capillaries and perivascular connective tissue that cannot constrict adequately. The clotting abnormalities in OI patients can be explained due to reduced collagen-induced platelet aggregation response surrounding the exposed sub endothelium, reduced platelet retention, and reduced levels of factor VIII. 4 , 5 Previous research has also shown enlarged platelets, diminished retention of platelets, and decreased factor VIII (FVIII) as the possible reasons for the bleeding manifestation. 6 , 7 However, in OI patients even with normal coagulation profile, bleeding might still happen, which makes intraoperative bleeding unpredictable. 8 , 9 The literature review revealed no studies involving the pediatric population in India and a few Western studies analyzing the perioperative blood loss in pediatric OI patients undergoing orthopedic surgeries. In a retrospective analysis of 23 OI patients, aged between 6 and 13 years, who underwent osteosynthesis for femoral shaft fractures or correction of femoral deformities, Persiani et al. 10 from Italy identified predictive risk factors regarding intraoperative bleeding, revealing that patients affected by type III OI have a high risk of severe blood loss during surgery. Similarly, a study conducted in the United States by Pichard et al. 11 examined a retrospective review of 22 pediatric OI patients who had 42 surgeries involving the insertion of 52 femoral rods. The results indicated that an increase in osteotomies was associated with an increase in adjusted mean blood loss (P = 0.05). Therefore, having access to autologous blood donations or a sufficient supply of blood products will help address the potential issue of increased perioperative blood loss, a crucial component of treatment, while organizing the care of patients with OI. Therefore, the purpose of this study is to determine the variables influencing perioperative blood loss and need for blood transfusion in pediatric OI patients undergoing osteotomies. Methods This was a retrospective case-record-based study conducted in pediatric OI patients who underwent osteotomies at a tertiary care hospital. The research conducted in this study adhered to the principles outlined in the Declaration of Helsinki and was approved by the Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee (IEC 363/2024) on 18th September 2024. A waiver of consent was granted as per our institutional ethics committee due to the retrospective nature of the study. Individual patient anesthesia records, daily progress notes, initial history, physical examination, and doctor instructions from each hospital stay were obtained through electronic records and analyzed. Each surgical procedure was analyzed as a discrete event, even when multiple procedures were performed on the same patient at different time points. Variables analyzed were age, type of OI, number of osteotomies performed during the surgical session, number of bones operated on during the same anesthesia session, preoperative postoperative hemoglobin level, and requirement for perioperative blood transfusion. Single osteotomy was defined as one osteotomy performed during a surgical session whereas multiple osteotomies was defined as more than one osteotomy performed during the same anesthesia session. The anatomical site, deformity severity, and complexity grading were not systematically coded and therefore were not included in the analysis. Outcome measures As estimated blood loss (EBL) was not consistently documented in a standardized manner across all anesthesia records, it could not be reliably extracted for analysis. Therefore, the primary surrogate indicators of perioperative bleeding were postoperative decline in hemoglobin (difference between preoperative and first documented postoperative hemoglobin level) and requirement for perioperative blood transfusion. Hemoglobin measurements were those recorded as part of routine perioperative care. Timing of postoperative hemoglobin measurement varied according to clinical practice. Transfusion decisions were made based on institutional practice and clinical judgment. The following variables were not consistently retrievable in a standardized format and therefore were not included such as estimated blood loss (EBL), surgical duration, surgical approach (open vs. percutaneous) and intraoperative fluid balance. Statistical analysis Discrete variables are represented as frequencies and percentages. Continuous data are shown as mean±SD. A chi-squared test was performed to assess the association between the parameters. Differences in hemoglobin decline across OI types were assessed using Kruskal–Wallis testing with post-hoc pairwise comparisons. Correlation between age and hemoglobin decline was assessed using linear regression. Statistical significance was set at p < 0.05. The data were analyzed using SPSS version 29. Results During our study period, 53 patients who underwent a total of 141 procedures during their stay in hospital were analyzed and each surgery was analyzed as a discrete event. Their mean age was 11.07±5.29 years; 4/53 (7.8%) were phenotypically type I OI, the majority (n=33; 62.2%) were phenotypically type III OI and the remaining 16/53 (30%) were type IV OI. 61/141 (43.3%) surgeries involved a single bone, and 80/141 (56.7%) surgeries involved multiple bones. Of 53 patients requiring osteotomies, 11/53 underwent once, 9/53 underwent twice, 17/53 (majority) underwent thrice, 7/53 underwent four times, 4/53 underwent five times, 3/53 underwent six times and only 2/53 underwent osteotomies seven times ( Table 1 ). Table 1. Baseline characteristics. Characteristics n=53 (141 surgeries) Age (in years; Mean±SD) 11.07±5.29 years Type of OI (phenotype) Type I – 4 (7.8%) Type III – 33 (62.2%) Type IV – 16 (30%) Osteotomy n (%) Single – 61 (43.3%) Multiple – 80 (56.7%) Frequency of osteotomies n (%) Once – 11 2 times – 9 3 times – 17 4 times – 7 5 times – 4 6 times – 3 7 times – 2 A. Drop in hemoglobin 1. During this study, it was noted that the fall in hemoglobin was statistically significant with multiple osteotomies (p=0.002) when compared to single osteotomy (p=0.297), and the total fall in hemoglobin between the pre-operative (12.22±1.06 g/dL) and post-operative (10.57±1.48 g/dL) period was also statistically significant (p≤0.001) ( Table 2 ). 2. A statistically significant inverse relationship between age and hemoglobin decline was observed. However, linear regression demonstrated a weak association (R 2 = 0.076), indicating that age explained only 7.6% of variability in hemoglobin decline ( Figure 1 ). 3. In this study, type III OI was associated with significant hemoglobin drop (p=0.01) ( Table 3 ) and post-hoc pairwise analysis (Kruskal Wallis testing) also confirmed that the hemoglobin fall was significantly associated with type III OI (p=0.008) when compared to other types of OI ( Table 4 ). B. Requirement of blood transfusion 1. In this study, no blood transfusion was required in 58 single osteotomy and 60 multiple osteotomies (n=118; 83.7%). However, 3 single osteotomies and 20 multiple osteotomies required blood transfusions (n=23; 16.3%) which was statistically significant (p=0.001) ( Table 5 ; Figure 2 ). 2. There was no significant correlation noted between age of the patient and the need for blood transfusions. 3. In this study, we also analyzed the type of OI and requirement of transfusion, which showed that in 9 type I OI undergoing surgeries none required transfusion; in type III OI, 73 surgeries did not require transfusion and 15 surgeries required transfusion; in type IV OI, 36 surgeries did not require transfusion and 8 surgeries required transfusion, however none were significant (p=0.387) ( Table 5 ). Table 2. Surgery and fall in hemoglobin. Hb drop Pre-surgery Hb (g/dL) Post-surgery Hb (g/dL) p-value After single osteotomy 10.68±1.44 10.42±1.54 0.297 After multiple osteotomies 12.52±1.07 11.98±0.99 0.002 * Total 12.22±1.06 10.57±1.48 <0.001 * * Significant p-value. Figure 1. Hemoglobin drop vs age of the patient. Table 3. Type of OI and hemoglobin drop. Type of OI (n) Hb(g/dL) Mean ± SD p-value Type I (4) 1.12±0.57 0.01 * Type III (83) 1.82±0.86 Type IV (40) 1.19±0.58 * Significant p-value. Table 4. Post-hoc analysis (pairwise comparison). Type I- Type IV 1.000 Type I- Type III 0.250 Type IV- Type III 0.008 * * Significant p-value. Table 5. Requirement of blood transfusion. Characteristic Transfusion requirement p-value No Yes Operated on Single bone 58 3 0.001 * Multiple Bone 60 20 Type of OI I 9 0 0.387 III 73 15 IV 36 8 * Significant p-value. Figure 2. Difference in requirement of transfusion between single or multiple bone surgeries. Discussion “Osteogenesis imperfecta” is a broad category of hereditary collagen type I diseases. Bony deformities, heart valvular lesions, cognitive abnormalities, and metabolic disturbances are frequently linked to OI. In addition to defective collagen synthesis, patients with OI have increased capillary fragility, decreased platelet retention, decreased levels of factor VIII, and deficient collagen-induced platelet aggregation that causes excessive bruising and widespread oozing from wound sites, thus surgical procedures performed on these patients are more likely to result in bleeding complications despite normal coagulation parameters which makes assessment of perioperative blood loss unpredictable and is of a major concern to the surgeons. 2 , 3 , 5 In this study, 53 patients who underwent a total of 141 surgeries were analyzed (an average of 3 surgeries per patient) during their stay in hospital and each surgery was analyzed as a separate event. Their mean age was 11.07±5.29 years, the majority (n=33; 62.2%) were phenotypically type III OI, and 80/141 (56.7%) surgeries involved multiple bones. This is similar to the study by Ruck et al., 12 who conducted a retrospective analysis of 60 OI children undergoing femoral rodding, showed a mean age of 4 years which is lower when compared to our study, however, the majority (n=30/60) had type III OI which is similar to our study. The study by Persiani et al. 10 was conducted on 23 patients aged between 6 and 13 years (mean - 8.9±1.9 years) affected by type III OI, wherein 42 osteotomies were done, and the majority (n=11/23) underwent an average of 3 osteotomies which is similar to our study. Our study showed a greater fall in hemoglobin in patients with multiple osteotomies done simultaneously (p=0.002) when compared to a single osteotomy and also the total fall in hemoglobin post-operatively was statistically significant (p≤0.001) which is similar to the study done by Persiani et al. 10 that showed average effective blood loss increased significantly as the number of osteotomies increased (p=0.046). The association between multiple osteotomies and greater hemoglobin decline may reflect increased procedural invasiveness. However, surgical approach (open vs. percutaneous) and surgical duration were not systematically recorded and therefore were not included in the analysis. Both are established determinants of blood loss. Without adjustment for these variables, it is not possible to determine whether the number of osteotomies independently contributes to bleeding risk or serves as a proxy for more extensive surgical exposure. Thus, the use of a structured bleeding survey is more advantageous than laboratory measurements as there is little correlation between the severity of bleeding with the levels of a particular factor, and the standard tests do not accurately reflect in vivo hemostasis due to the unmeasurable contribution of numerous factors (such as vessel fragility or fibrinolysis). 13 – 15 This study revealed a negative correlation between the age of the patients and a fall in hemoglobin, suggesting that older children had better tolerance for blood loss when compared to a younger age group. Similar findings were reported in the study by Pichard et al., 11 which involved a retrospective review of 22 patients. The oldest patient, who underwent surgery, was 21 years and 2 months old, and the youngest, who underwent surgery, was 1 year and 7 months old. Of the 42 surgeries examined, the mean blood loss was 197 cc, with older patients generally having lower adjusted mean blood loss, though this difference was not statistically significant (p=0.07). Although younger age was statistically associated with greater hemoglobin decline, the correlation was weak (R 2 = 0.076), indicating limited predictive value. This association should therefore not be overinterpreted. The most likely explanation offered is that while a larger bone’s radius of diameter and, hence, its area of bleeding may cause more bleeding, a larger patient with a larger total blood volume may be able to withstand more bleeding. 11 In this study, type III OI showed a significant hemoglobin drop (1.82±0.86 g/dL; p=0.01) and post hoc analysis also confirmed that the hemoglobin fall was significantly associated with type III OI (p=0.008) when compared to the other types of OI which are similar to the study by Persiani et al. 10 wherein patients affected by type III OI had a high risk of severe blood loss during surgery. The probable explanation is that type III OI is characterized by increased capillary fragility and an altered platelet function caused by platelet dysfunction due to alteration in collagen when compared to other types of OI. However, these findings must be interpreted with caution. Hemoglobin decline was used as a surrogate marker for perioperative blood loss because standardized documentation of estimated blood loss was not available. Hemoglobin levels may be influenced by hemodilution, intraoperative fluid administration, timing of measurement, and transfusion practices. Therefore, the observed changes reflect perioperative hematologic alterations rather than directly measured blood loss. The perioperative transfusion requirement in surgeries for OI patients was found to be 23/141 surgeries (16.3%) in this study. Our study is similar to the study by Pichard et al. 11 wherein six blood transfusions were given with a transfusion rate of 14%. The study under reference revealed that the average blood loss among transfused patients was 279 cc. Additionally, patients who underwent transfusion had an adjusted blood loss of 0.330 as opposed to those who did not get blood transfusion, who had an adjusted blood loss of only 0.003. Our findings are in line with studies by Gooijer et al. 16 and Oakley et al., 17 which found that 17% of OI patients needed blood transfusions following surgery. For this reason, it is crucial to be aware of the bleeding risk. Despite a normal pre-operative hematological assessment, several studies 18 – 21 describe severe bleeding in OI patients as a result of surgery, thus in patients with OI, “American Society of Anesthesiologists transfusion guidelines” state, “platelet transfusion may be indicated despite an adequate platelet count if there are known platelet dysfunction and microvascular bleeding.” “Bleeding time and platelet aggregation tests are not useful in the operating room”, and “there is an urgent need for the development of clinically relevant measures of in vivo platelet function and bleeding risk to guide the rational use of platelet transfusion”. Our study showed incidence of transfusion was higher in those who underwent multiple osteotomies simultaneously (p=0.001) which is similar to the study by Persiani et al. 10 wherein the perioperative transfusion requirement was more in type III OI but not statistically significant (p=0.387). These results were comparable to those of research by Hathaway et al. 22 and others, 23 , 24 which discovered aberrant platelet adhesion, poor platelet factor 3 (PF3) release, aberrant platelet aggregation to ADP, and commonly faulty platelet aggregation in type III OI patients, thus corroborating with our finding of increased transfusion requirement in type III OI patients. Since the relationship between genotype and phenotype is frequently less strict than previously believed due to variability in penetrance and expressivity, coinheritance of hemostatic defects, or superimposed genetic modifiers, a genomic search for the molecular basis of inherited clotting and platelet defects may not be as beneficial. 15 When regular hemostasis testing revealed no repeatable anomaly in a group of individuals with a significant history of bleeding, Obaji et al. 25 administered tranexamic acid or desmopressin, and they observed no bleeding in 90% of the patients at high risk of bleeding receiving an intervention which can be used in OI patients as well before surgery to reduce the bleeding incidence post operatively. Yet another prospective randomized controlled study by Elbaseet HM et al. 26 wherein patients with osteogenesis imperfecta undergoing femoral telescoping nail the use of tranexamic acid (local or intravenous) intraoperatively revealed a significant decrease in blood loss, thus supporting the use of antifibrinolytic agents in these patients. Limitations 1. Single-center study and retrospective design. 2. Surgical duration and approach (open vs. percutaneous) were not systematically stratified. 3. Estimated blood loss (EBL) was not available. 4. Transfusion decisions were based on clinical judgment. Conclusion The most reliable indicators of perioperative bleeding and the need for transfusion in procedures involving OI patients were the patient’s age, the type of OI, and the number of osteotomies. These results imply that higher perioperative hematologic changes in children with OI may be linked to specific patient and procedural characteristics; however, to determine clear risk factors and direct perioperative management strategies, prospective studies involving standardized blood loss measurement, comprehensive surgical variables, and multivariable analysis are needed. Ethics and consent statement The research followed the tenets of the Declaration of Helsinki. The institutional ethical committee namely Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee (IEC 542/2019) approved all study protocols (IEC 363-2024) on 18th September 2024. A waiver of consent was granted as per our institutional ethics committee due to the retrospective nature of the study. Data availability Underlying data Figshare: This study contains the underlying data for ‘Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study”. ( https://figshare.com/s/5feb7e72a5648bf4263b ) DOI: ( https://doi.org/10.6084/m9.figshare.27292956.v4 ) 27 • Data OI. xlsx Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Extended data Figshare: Extended data for ‘Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study’. ( https://figshare.com/s/5feb7e72a5648bf4263b ) This project contains the following extended data: • Strobe checklist • Proforma • Protocol DOI : ( https://doi.org/10.6084/m9.figshare.27292956.v4 ) 27 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgements Nil References 1. 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Publisher Full Text Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 25 Nov 2024 ADD YOUR COMMENT Comment Author details Author details 1 Department of Anesthesiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India 2 Department of Pediatric Orthopedics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India Malavika Kulkarni Roles: Conceptualization, Investigation, Methodology, Project Administration, Supervision, Visualization, Writing – Review & Editing Hitesh Hasmukhlal Shah Roles: Data Curation, Investigation, Project Administration, Resources, Software, Supervision, Visualization Sanjana subbiah Roles: Data Curation, Investigation, Project Administration, Resources, Software, Writing – Review & Editing Sushma Thimmaiah Kanakalakshmi Roles: Formal Analysis, Investigation, Resources, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Laxmi Shenoy Roles: Data Curation, Project Administration, Supervision, Validation, Visualization RamaRani KrishnaBhat Roles: Investigation, Project Administration, Resources, Supervision, Visualization, Writing – Review & Editing Priya Genevieve D'mello Roles: Investigation, Project Administration, 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: 28 Feb 2026, 13:1420 https://doi.org/10.12688/f1000research.158583.3 version 2 Revised Published: 17 Feb 2025, 13:1420 https://doi.org/10.12688/f1000research.158583.2 version 1 Published: 25 Nov 2024, 13:1420 https://doi.org/10.12688/f1000research.158583.1 Copyright © 2026 Kulkarni M 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. 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 Kulkarni M, Shah HH, subbiah S et al. Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] . F1000Research 2026, 13 :1420 ( https://doi.org/10.12688/f1000research.158583.3 ) 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 2 VERSION 2 PUBLISHED 17 Feb 2025 Revised Views 0 Cite How to cite this report: Morya VK. Reviewer Report For: Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] . F1000Research 2026, 13 :1420 ( https://doi.org/10.5256/f1000research.178083.r383091 ) The direct URL for this report is: https://f1000research.com/articles/13-1420/v2#referee-response-383091 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 02 Jun 2025 Vivek Kumar Morya , Hallym University Dongtan Sacred Heart Hospital, Dongtan, South Korea Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.178083.r383091 This single-center retrospective observational study investigates perioperative bleeding and the need for blood transfusions in pediatric osteogenesis imperfecta (OI) patients undergoing orthopedic surgeries. The study analyzed 141 procedures in 53 patients (mean age 11.07±5.29 years) from January 2016 to ... Continue reading READ ALL This single-center retrospective observational study investigates perioperative bleeding and the need for blood transfusions in pediatric osteogenesis imperfecta (OI) patients undergoing orthopedic surgeries. The study analyzed 141 procedures in 53 patients (mean age 11.07±5.29 years) from January 2016 to August 2024. The majority of patients were phenotypically type III OI (62.2%), and many underwent multiple osteotomies. The study reports a significant postoperative fall in hemoglobin, particularly in patients undergoing multiple osteotomies (p=0.002), younger children, and those with type III OI (1.82±0.86 g/dL fall, p=0.01). Blood transfusions were required in 16.3% of surgeries, with a significant association with multiple osteotomies (p=0.001). The authors conclude that younger age, type III OI, and multiple osteotomies are key factors associated with increased perioperative bleeding and transfusion needs in this cohort. The revised version also highlights the potential utility of antifibrinolytic agents. The article presents its findings but lacks clarity and accuracy in critical areas due to methodological deficiencies outlined below. For instance, while claiming to assess "perioperative bleeding," it doesn't quantify estimated blood loss (EBL), a key metric. The presentation of risk factors is potentially misleading because significant confounders, such as the surgical approach (open vs. percutaneous), were not systematically analyzed or accounted for. The authors admit that most single osteotomies requiring transfusion were open procedures, which clouds the interpretation that the number of osteotomies alone is the primary driver. The literature cited for background on OI and its bleeding manifestations is generally adequate, though the authors defend the use of older references for foundational concepts. However, the recommendation for antifibrinolytics based on external literature feels somewhat disconnected given none were used in their study cohort. The retrospective observational design is acceptable in principle for identifying associations. However, the technical execution of the study is unsound due to several critical flaws: The primary aim is to assess perioperative bleeding, yet the study fails to quantify estimated blood loss (EBL). Hemoglobin drop is an indirect and less precise measure, influenced by fluid management and other factors. This is a fundamental flaw for a study focused on bleeding. Failure to Control for Major Confounding Variables: The authors acknowledge that osteotomies could be "percutaneous as well as open" and that "Most of the single osteotomy [cases requiring transfusion] were open procedure". The study does not stratify or adjust its analysis based on whether procedures were open or percutaneous. Open procedures are inherently associated with greater blood loss. This unaddressed confounder severely undermines the conclusions drawn about the number of osteotomies or bones operated on as independent risk factors. The study acknowledges that "Surgical time...not recorded.". Surgical duration is a well-established factor influencing blood loss. Its absence further weakens the analysis. The definition of "single" versus "multiple" osteotomies is not sufficiently detailed in terms of complexity or specific anatomical sites, making comparisons difficult. These technical deficiencies mean the study cannot reliably determine the true risk factors for bleeding in this population. 1. While the study outlines the data sources (electronic records) and variables collected (age, OI type, number of osteotomies, hemoglobin levels, transfusion), crucial methodological details are missing: Precise definitions and criteria for classifying "single" versus "multiple" osteotomies are lacking. As mentioned, details distinguishing open versus percutaneous approaches for all procedures are not integrated into the analysis, nor is surgical time. Timing of pre- and post-operative hemoglobin measurements is not specified, which can affect comparability. While transfusion requirement was an outcome, the specific clinical or laboratory triggers for transfusion in this cohort are not detailed. 2. The study lists the statistical tests used (chi-squared, Kruskal-Wallis for post-hoc) and states that SPSS version 29 was used. However, the appropriateness of the interpretation is questionable due to: The statistical significance attributed to factors like "multiple osteotomies" may be erroneous if, for example, multiple osteotomies were also predominantly open procedures or longer in duration—factors not included in the model. For the relationship between age and hemoglobin drop, Figure 1 shows an "R2 Linear=0.076", indicating that age explains only 7.6% of the variability in hemoglobin drop. While a p-value might indicate statistical significance, the clinical relevance of such a weak correlation is not adequately discussed and may be overemphasized. The paper reports a "significant hemoglobin fall" (p<0.001) with a mean drop from 12.22 g/dL to 10.57 g/dL overall. While statistically significant, the clinical implications and relation to actual measured blood loss are not thoroughly explored. 3. authors state that underlying and extended data are available via Figshare, under a CC-BY 4.0 license. This is commendable. However, the utility of this data for full reproducibility of valid conclusions is limited if the crucial variables (EBL, specific surgical approach for each case, surgical time) were not recorded in the first place within that dataset. 4. The primary conclusion that "fall in hemoglobin was significant postoperatively in OI patients and was associated with younger age, type III OI, and multiple osteotomies" [page 2 conclusion section] and that these are "reliable indicators of perioperative bleeding and the need for transfusion" is not adequately supported by the presented results due to the major methodological flaws: The impact of "multiple osteotomies" cannot be reliably determined without accounting for whether these were predominantly open procedures or longer in duration compared to single osteotomies. The absence of EBL data means that conclusions about "perioperative bleeding" are based on an indirect measure (hemoglobin drop), which is less precise. The reported association between age and hemoglobin drop is statistically weak (R2=0.076), suggesting its limited predictive power despite statistical significance. To make this article scientifically sound, the authors must address the following: If possible, from anesthesia records, retrospectively collect EBL for each procedure. This is the most critical piece of missing information for a study on "perioperative bleeding." Re-analyze all data using EBL as a primary outcome, in addition to Hb drop and transfusion rates. For every osteotomy procedure, meticulously determine and record whether it was performed via an open or percutaneous approach. Stratify the analysis by surgical approach. Use multivariate regression models to assess the independent effects of the number of osteotomies, OI type, age, etc., while controlling for the surgical approach (and ideally, surgical duration). This is essential to determine if "multiple osteotomies" is an independent risk factor or merely a proxy for more invasive (open) surgery. If possible, retrieve surgical duration for each procedure from the records. Include surgical duration as a variable in the multivariate analysis to assess its contribution to blood loss and transfusion risk. When interpreting statistical significance, also thoroughly discuss the magnitude of the effect and its clinical relevance (e.g., effect sizes, R2 values for correlations). Acknowledge weak correlations even if statistically significant. Based on the re-analysis incorporating EBL, surgical approach, and surgical duration, the conclusions must be revised. It is possible that the currently identified risk factors will change in significance or that new, more critical factors (like open approach) will emerge. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: regenerative orthopedics 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 Morya VK. Reviewer Report For: Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] . F1000Research 2026, 13 :1420 ( https://doi.org/10.5256/f1000research.178083.r383091 ) The direct URL for this report is: https://f1000research.com/articles/13-1420/v2#referee-response-383091 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 28 Feb 2026 Sushma Thimmaiah Kanakalakshmi , Department of Anesthesiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, India 28 Feb 2026 Author Response Dear Reviewer, We sincerely thank the reviewer for the detailed comments, which have helped us improve the manuscript. Comment 1: Lack of Estimated Blood Loss (EBL): The primary aim is ... Continue reading Dear Reviewer, We sincerely thank the reviewer for the detailed comments, which have helped us improve the manuscript. Comment 1: Lack of Estimated Blood Loss (EBL): The primary aim is to assess perioperative bleeding; however, estimated blood loss (EBL) was not quantified. Hemoglobin drop is an indirect and less precise measure. Response: Many thanks for your response. We agree that direct quantification of EBL would provide a more accurate and objective assessment of intraoperative bleeding. Due to the retrospective design of our study, standardized documentation of EBL was inconsistent across anesthesia records, limiting reliable data extraction. Therefore, postoperative hemoglobin decline and transfusion requirement were used as surrogate indicators of perioperative bleeding. We acknowledge that hemoglobin levels may be influenced by intraoperative fluid administration and hemodilution. Revision: The manuscript now clearly states that hemoglobin drop is a surrogate marker of perioperative blood loss; The limitations section has been expanded to emphasize the absence of recorded EBL as a major limitation; The conclusions have been modified to avoid implying direct measurement of blood loss. Comment 2: Failure to Control for Major Confounding Variables A. Surgical Approach (Open vs. Percutaneous): Surgical approach was not stratified or adjusted for, despite acknowledgment that most single osteotomies requiring transfusion were open procedures. Response: We agree that surgical approach is a significant potential confounder. In our cohort osteotomies were performed either percutaneously or via open technique based on surgeon discretion, surgical approach was not consistently coded in the electronic records in a standardized manner. As a result, stratified or multivariate adjustment by surgical approach could not be performed reliably. Revision: We have explicitly acknowledged surgical approach as an uncontrolled confounder; The discussion now clarifies that the association between multiple osteotomies and hemoglobin decline may partly reflect procedural invasiveness; The conclusions have been revised to reflect associative findings rather than independent risk factors. B. Surgical Duration : Surgical duration was not recorded, despite being a known determinant of blood loss. Response: We agree. Surgical time was not consistently retrievable in a standardized format from retrospective electronic records. This variable was therefore not included in the analysis. Revisions made: The absence of surgical duration has been clearly stated as a limitation; We acknowledge potential omitted-variable bias resulting from this omission. Reviewer Comment 3: Definition of Single vs. Multiple Osteotomies: The definitions lack sufficient detail regarding anatomical complexity or specific sites. Response: In our study, “Single osteotomy” refers to one osteotomy performed during a surgical session and “Multiple osteotomies” refers to more than one osteotomy during the same anesthesia session. We acknowledge that complexity grading, anatomical location, and deformity severity were not standardized variables in the dataset. Revision: Operational definitions have been clarified in the Methods section. We have noted heterogeneity of surgical complexity as a limitation. Reviewer Comment 4: Interpretation of Statistical Significance A. Weak Correlation Between Age and Hemoglobin Drop (R² = 0.076): The association between age and hemoglobin drop is statistically weak. Response: We agree that R² = 0.076 indicates that age explains only 7.6% of variability in hemoglobin decline, reflecting limited predictive power. Revision: The Results and Discussion describe this correlation as weak. We have tempered the interpretation to avoid overstating clinical significance. B. Clinical Relevance of Overall Hemoglobin Drop: Statistical significance does not necessarily equate to clinical significance. Response: Although the mean hemoglobin decline was statistically significant, the clinical impact depends on baseline hemoglobin, transfusion thresholds, and patient condition. Revision: The discussion now contextualizes the magnitude of hemoglobin decline. We clarify that transfusion requirement represents a more clinically meaningful endpoint. Reviewer Comment 5: Transfusion Triggers Not Defined: Transfusion criteria were not specified. Response: Transfusion decisions were based on institutional practice and clinical judgment, including hemodynamic instability, ongoing bleeding, hemoglobin levels (generally <8 g/dL, or <10 g/dL in symptomatic patients) and overall clinical assessment. Revision: Institutional transfusion practices are now described in the methods section, and the lack of standardized transfusion thresholds is acknowledged as a limitation. Reviewer Comment 6: Data Availability and Reproducibility: We appreciate the recognition of open data availability. However, we agree that reproducibility is limited by the absence of certain procedural variables (EBL, surgical duration, surgical approach). This limitation is now clearly stated. Revision of Conclusion: In response to the reviewer’s concern that our conclusions may overstate the findings, we have revised the conclusion section. Dear Reviewer, We sincerely thank the reviewer for the detailed comments, which have helped us improve the manuscript. Comment 1: Lack of Estimated Blood Loss (EBL): The primary aim is to assess perioperative bleeding; however, estimated blood loss (EBL) was not quantified. Hemoglobin drop is an indirect and less precise measure. Response: Many thanks for your response. We agree that direct quantification of EBL would provide a more accurate and objective assessment of intraoperative bleeding. Due to the retrospective design of our study, standardized documentation of EBL was inconsistent across anesthesia records, limiting reliable data extraction. Therefore, postoperative hemoglobin decline and transfusion requirement were used as surrogate indicators of perioperative bleeding. We acknowledge that hemoglobin levels may be influenced by intraoperative fluid administration and hemodilution. Revision: The manuscript now clearly states that hemoglobin drop is a surrogate marker of perioperative blood loss; The limitations section has been expanded to emphasize the absence of recorded EBL as a major limitation; The conclusions have been modified to avoid implying direct measurement of blood loss. Comment 2: Failure to Control for Major Confounding Variables A. Surgical Approach (Open vs. Percutaneous): Surgical approach was not stratified or adjusted for, despite acknowledgment that most single osteotomies requiring transfusion were open procedures. Response: We agree that surgical approach is a significant potential confounder. In our cohort osteotomies were performed either percutaneously or via open technique based on surgeon discretion, surgical approach was not consistently coded in the electronic records in a standardized manner. As a result, stratified or multivariate adjustment by surgical approach could not be performed reliably. Revision: We have explicitly acknowledged surgical approach as an uncontrolled confounder; The discussion now clarifies that the association between multiple osteotomies and hemoglobin decline may partly reflect procedural invasiveness; The conclusions have been revised to reflect associative findings rather than independent risk factors. B. Surgical Duration : Surgical duration was not recorded, despite being a known determinant of blood loss. Response: We agree. Surgical time was not consistently retrievable in a standardized format from retrospective electronic records. This variable was therefore not included in the analysis. Revisions made: The absence of surgical duration has been clearly stated as a limitation; We acknowledge potential omitted-variable bias resulting from this omission. Reviewer Comment 3: Definition of Single vs. Multiple Osteotomies: The definitions lack sufficient detail regarding anatomical complexity or specific sites. Response: In our study, “Single osteotomy” refers to one osteotomy performed during a surgical session and “Multiple osteotomies” refers to more than one osteotomy during the same anesthesia session. We acknowledge that complexity grading, anatomical location, and deformity severity were not standardized variables in the dataset. Revision: Operational definitions have been clarified in the Methods section. We have noted heterogeneity of surgical complexity as a limitation. Reviewer Comment 4: Interpretation of Statistical Significance A. Weak Correlation Between Age and Hemoglobin Drop (R² = 0.076): The association between age and hemoglobin drop is statistically weak. Response: We agree that R² = 0.076 indicates that age explains only 7.6% of variability in hemoglobin decline, reflecting limited predictive power. Revision: The Results and Discussion describe this correlation as weak. We have tempered the interpretation to avoid overstating clinical significance. B. Clinical Relevance of Overall Hemoglobin Drop: Statistical significance does not necessarily equate to clinical significance. Response: Although the mean hemoglobin decline was statistically significant, the clinical impact depends on baseline hemoglobin, transfusion thresholds, and patient condition. Revision: The discussion now contextualizes the magnitude of hemoglobin decline. We clarify that transfusion requirement represents a more clinically meaningful endpoint. Reviewer Comment 5: Transfusion Triggers Not Defined: Transfusion criteria were not specified. Response: Transfusion decisions were based on institutional practice and clinical judgment, including hemodynamic instability, ongoing bleeding, hemoglobin levels (generally <8 g/dL, or <10 g/dL in symptomatic patients) and overall clinical assessment. Revision: Institutional transfusion practices are now described in the methods section, and the lack of standardized transfusion thresholds is acknowledged as a limitation. Reviewer Comment 6: Data Availability and Reproducibility: We appreciate the recognition of open data availability. However, we agree that reproducibility is limited by the absence of certain procedural variables (EBL, surgical duration, surgical approach). This limitation is now clearly stated. Revision of Conclusion: In response to the reviewer’s concern that our conclusions may overstate the findings, we have revised the conclusion section. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 28 Feb 2026 Sushma Thimmaiah Kanakalakshmi , Department of Anesthesiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, India 28 Feb 2026 Author Response Dear Reviewer, We sincerely thank the reviewer for the detailed comments, which have helped us improve the manuscript. Comment 1: Lack of Estimated Blood Loss (EBL): The primary aim is ... Continue reading Dear Reviewer, We sincerely thank the reviewer for the detailed comments, which have helped us improve the manuscript. Comment 1: Lack of Estimated Blood Loss (EBL): The primary aim is to assess perioperative bleeding; however, estimated blood loss (EBL) was not quantified. Hemoglobin drop is an indirect and less precise measure. Response: Many thanks for your response. We agree that direct quantification of EBL would provide a more accurate and objective assessment of intraoperative bleeding. Due to the retrospective design of our study, standardized documentation of EBL was inconsistent across anesthesia records, limiting reliable data extraction. Therefore, postoperative hemoglobin decline and transfusion requirement were used as surrogate indicators of perioperative bleeding. We acknowledge that hemoglobin levels may be influenced by intraoperative fluid administration and hemodilution. Revision: The manuscript now clearly states that hemoglobin drop is a surrogate marker of perioperative blood loss; The limitations section has been expanded to emphasize the absence of recorded EBL as a major limitation; The conclusions have been modified to avoid implying direct measurement of blood loss. Comment 2: Failure to Control for Major Confounding Variables A. Surgical Approach (Open vs. Percutaneous): Surgical approach was not stratified or adjusted for, despite acknowledgment that most single osteotomies requiring transfusion were open procedures. Response: We agree that surgical approach is a significant potential confounder. In our cohort osteotomies were performed either percutaneously or via open technique based on surgeon discretion, surgical approach was not consistently coded in the electronic records in a standardized manner. As a result, stratified or multivariate adjustment by surgical approach could not be performed reliably. Revision: We have explicitly acknowledged surgical approach as an uncontrolled confounder; The discussion now clarifies that the association between multiple osteotomies and hemoglobin decline may partly reflect procedural invasiveness; The conclusions have been revised to reflect associative findings rather than independent risk factors. B. Surgical Duration : Surgical duration was not recorded, despite being a known determinant of blood loss. Response: We agree. Surgical time was not consistently retrievable in a standardized format from retrospective electronic records. This variable was therefore not included in the analysis. Revisions made: The absence of surgical duration has been clearly stated as a limitation; We acknowledge potential omitted-variable bias resulting from this omission. Reviewer Comment 3: Definition of Single vs. Multiple Osteotomies: The definitions lack sufficient detail regarding anatomical complexity or specific sites. Response: In our study, “Single osteotomy” refers to one osteotomy performed during a surgical session and “Multiple osteotomies” refers to more than one osteotomy during the same anesthesia session. We acknowledge that complexity grading, anatomical location, and deformity severity were not standardized variables in the dataset. Revision: Operational definitions have been clarified in the Methods section. We have noted heterogeneity of surgical complexity as a limitation. Reviewer Comment 4: Interpretation of Statistical Significance A. Weak Correlation Between Age and Hemoglobin Drop (R² = 0.076): The association between age and hemoglobin drop is statistically weak. Response: We agree that R² = 0.076 indicates that age explains only 7.6% of variability in hemoglobin decline, reflecting limited predictive power. Revision: The Results and Discussion describe this correlation as weak. We have tempered the interpretation to avoid overstating clinical significance. B. Clinical Relevance of Overall Hemoglobin Drop: Statistical significance does not necessarily equate to clinical significance. Response: Although the mean hemoglobin decline was statistically significant, the clinical impact depends on baseline hemoglobin, transfusion thresholds, and patient condition. Revision: The discussion now contextualizes the magnitude of hemoglobin decline. We clarify that transfusion requirement represents a more clinically meaningful endpoint. Reviewer Comment 5: Transfusion Triggers Not Defined: Transfusion criteria were not specified. Response: Transfusion decisions were based on institutional practice and clinical judgment, including hemodynamic instability, ongoing bleeding, hemoglobin levels (generally <8 g/dL, or <10 g/dL in symptomatic patients) and overall clinical assessment. Revision: Institutional transfusion practices are now described in the methods section, and the lack of standardized transfusion thresholds is acknowledged as a limitation. Reviewer Comment 6: Data Availability and Reproducibility: We appreciate the recognition of open data availability. However, we agree that reproducibility is limited by the absence of certain procedural variables (EBL, surgical duration, surgical approach). This limitation is now clearly stated. Revision of Conclusion: In response to the reviewer’s concern that our conclusions may overstate the findings, we have revised the conclusion section. Dear Reviewer, We sincerely thank the reviewer for the detailed comments, which have helped us improve the manuscript. Comment 1: Lack of Estimated Blood Loss (EBL): The primary aim is to assess perioperative bleeding; however, estimated blood loss (EBL) was not quantified. Hemoglobin drop is an indirect and less precise measure. Response: Many thanks for your response. We agree that direct quantification of EBL would provide a more accurate and objective assessment of intraoperative bleeding. Due to the retrospective design of our study, standardized documentation of EBL was inconsistent across anesthesia records, limiting reliable data extraction. Therefore, postoperative hemoglobin decline and transfusion requirement were used as surrogate indicators of perioperative bleeding. We acknowledge that hemoglobin levels may be influenced by intraoperative fluid administration and hemodilution. Revision: The manuscript now clearly states that hemoglobin drop is a surrogate marker of perioperative blood loss; The limitations section has been expanded to emphasize the absence of recorded EBL as a major limitation; The conclusions have been modified to avoid implying direct measurement of blood loss. Comment 2: Failure to Control for Major Confounding Variables A. Surgical Approach (Open vs. Percutaneous): Surgical approach was not stratified or adjusted for, despite acknowledgment that most single osteotomies requiring transfusion were open procedures. Response: We agree that surgical approach is a significant potential confounder. In our cohort osteotomies were performed either percutaneously or via open technique based on surgeon discretion, surgical approach was not consistently coded in the electronic records in a standardized manner. As a result, stratified or multivariate adjustment by surgical approach could not be performed reliably. Revision: We have explicitly acknowledged surgical approach as an uncontrolled confounder; The discussion now clarifies that the association between multiple osteotomies and hemoglobin decline may partly reflect procedural invasiveness; The conclusions have been revised to reflect associative findings rather than independent risk factors. B. Surgical Duration : Surgical duration was not recorded, despite being a known determinant of blood loss. Response: We agree. Surgical time was not consistently retrievable in a standardized format from retrospective electronic records. This variable was therefore not included in the analysis. Revisions made: The absence of surgical duration has been clearly stated as a limitation; We acknowledge potential omitted-variable bias resulting from this omission. Reviewer Comment 3: Definition of Single vs. Multiple Osteotomies: The definitions lack sufficient detail regarding anatomical complexity or specific sites. Response: In our study, “Single osteotomy” refers to one osteotomy performed during a surgical session and “Multiple osteotomies” refers to more than one osteotomy during the same anesthesia session. We acknowledge that complexity grading, anatomical location, and deformity severity were not standardized variables in the dataset. Revision: Operational definitions have been clarified in the Methods section. We have noted heterogeneity of surgical complexity as a limitation. Reviewer Comment 4: Interpretation of Statistical Significance A. Weak Correlation Between Age and Hemoglobin Drop (R² = 0.076): The association between age and hemoglobin drop is statistically weak. Response: We agree that R² = 0.076 indicates that age explains only 7.6% of variability in hemoglobin decline, reflecting limited predictive power. Revision: The Results and Discussion describe this correlation as weak. We have tempered the interpretation to avoid overstating clinical significance. B. Clinical Relevance of Overall Hemoglobin Drop: Statistical significance does not necessarily equate to clinical significance. Response: Although the mean hemoglobin decline was statistically significant, the clinical impact depends on baseline hemoglobin, transfusion thresholds, and patient condition. Revision: The discussion now contextualizes the magnitude of hemoglobin decline. We clarify that transfusion requirement represents a more clinically meaningful endpoint. Reviewer Comment 5: Transfusion Triggers Not Defined: Transfusion criteria were not specified. Response: Transfusion decisions were based on institutional practice and clinical judgment, including hemodynamic instability, ongoing bleeding, hemoglobin levels (generally <8 g/dL, or <10 g/dL in symptomatic patients) and overall clinical assessment. Revision: Institutional transfusion practices are now described in the methods section, and the lack of standardized transfusion thresholds is acknowledged as a limitation. Reviewer Comment 6: Data Availability and Reproducibility: We appreciate the recognition of open data availability. However, we agree that reproducibility is limited by the absence of certain procedural variables (EBL, surgical duration, surgical approach). This limitation is now clearly stated. Revision of Conclusion: In response to the reviewer’s concern that our conclusions may overstate the findings, we have revised the conclusion section. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 25 Nov 2024 Views 0 Cite How to cite this report: Elbaseet HM. Reviewer Report For: Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] . F1000Research 2026, 13 :1420 ( https://doi.org/10.5256/f1000research.174199.r363165 ) The direct URL for this report is: https://f1000research.com/articles/13-1420/v1#referee-response-363165 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 05 Feb 2025 Hesham Mohamed Elbaseet , Assiut University, Asyut, Assiut Governorate, Egypt Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.174199.r363165 Thanks for your effort in writing the manuscript. Please add and / or modify the following: 1- A lot of cited references are out of date (one of them was 1971) please use recent references. 2- ... Continue reading READ ALL Thanks for your effort in writing the manuscript. Please add and / or modify the following: 1- A lot of cited references are out of date (one of them was 1971) please use recent references. 2- Mention whether osteotomies were done per cutaneous or open and explain why single osteotomy cases required blood transfusion. 3- Mention whether antifibrinolytic drugs were administrated or not? 4- Cite the following References in discussion part: [ref1]. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Elbaseet HM, Aldeen AJ, Irahim AKH: Efficacy of intraoperative use of tranexamic acid in reducing blood loss from telescoping nail application in osteogenesis imperfecta. A randomized controlled trial. Orthop Traumatol Surg Res . 2024. 103927 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pediatric orthopedic surgeon specialized inosteogenesis imperfecta surgical treatment 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 Elbaseet HM. Reviewer Report For: Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] . F1000Research 2026, 13 :1420 ( https://doi.org/10.5256/f1000research.174199.r363165 ) The direct URL for this report is: https://f1000research.com/articles/13-1420/v1#referee-response-363165 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 17 Feb 2025 Sushma Thimmaiah Kanakalakshmi , Department of Anesthesiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, India 17 Feb 2025 Author Response Response to comments: Many thanks for reviewing our manuscript. We have made the suggested changes and resubmitted a revised version for your reference. Comment: 1- A lot of cited references ... Continue reading Response to comments: Many thanks for reviewing our manuscript. We have made the suggested changes and resubmitted a revised version for your reference. Comment: 1- A lot of cited references are out of date (one of them was 1971) please use recent references. Response: Many thanks for your comment. The references have been used for supporting the platelet dysfunction in patients with osteogenesis imperfecta and they have been explained in very early research articles involving osteogenesis imperfecta as well as are used as reference by other recent articles (Léguillier T, Favier R, Harroche A et al. Assessing bleeding risk in 18 children with Osteogenesis imperfecta. Br J Haematol. 2021 Feb;192(4):785-788. doi: 10.1111/bjh.17303) explaining bleeding risk in those with osteogenesis imperfecta, hence we have used the original reference articles to explain the mechanism of platelet dysfunction. Also, majority of the older references used in this study are to explain the pathophysiology which have been proven in early original research articles. Comment: 2- Mention whether osteotomies were done per cutaneous or open and explain why single osteotomy cases required blood transfusion. Response: Many thanks for your comment. The osteotomies involved both percutaneous as well as open based on operating surgeon's discretion. Most of the single osteotomy were open procedure, hence these cases required blood transfusion. Comment: 3- Mention whether antifibrinolytic drugs were administrated or not? Response: Many thanks for your comment. None of the patients received any intraoperative (local or intravenous) antifibrinolytic agent in our study. Comment: 4- Cite the following References in discussion part: [ref1]. Response: Many thanks for your comment. We have cited this reference in our discussion and the revised manuscript is added as suggested. Response to comments: Many thanks for reviewing our manuscript. We have made the suggested changes and resubmitted a revised version for your reference. Comment: 1- A lot of cited references are out of date (one of them was 1971) please use recent references. Response: Many thanks for your comment. The references have been used for supporting the platelet dysfunction in patients with osteogenesis imperfecta and they have been explained in very early research articles involving osteogenesis imperfecta as well as are used as reference by other recent articles (Léguillier T, Favier R, Harroche A et al. Assessing bleeding risk in 18 children with Osteogenesis imperfecta. Br J Haematol. 2021 Feb;192(4):785-788. doi: 10.1111/bjh.17303) explaining bleeding risk in those with osteogenesis imperfecta, hence we have used the original reference articles to explain the mechanism of platelet dysfunction. Also, majority of the older references used in this study are to explain the pathophysiology which have been proven in early original research articles. Comment: 2- Mention whether osteotomies were done per cutaneous or open and explain why single osteotomy cases required blood transfusion. Response: Many thanks for your comment. The osteotomies involved both percutaneous as well as open based on operating surgeon's discretion. Most of the single osteotomy were open procedure, hence these cases required blood transfusion. Comment: 3- Mention whether antifibrinolytic drugs were administrated or not? Response: Many thanks for your comment. None of the patients received any intraoperative (local or intravenous) antifibrinolytic agent in our study. Comment: 4- Cite the following References in discussion part: [ref1]. Response: Many thanks for your comment. We have cited this reference in our discussion and the revised manuscript is added as suggested. Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 17 Feb 2025 Sushma Thimmaiah Kanakalakshmi , Department of Anesthesiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, India 17 Feb 2025 Author Response Response to comments: Many thanks for reviewing our manuscript. We have made the suggested changes and resubmitted a revised version for your reference. Comment: 1- A lot of cited references ... Continue reading Response to comments: Many thanks for reviewing our manuscript. We have made the suggested changes and resubmitted a revised version for your reference. Comment: 1- A lot of cited references are out of date (one of them was 1971) please use recent references. Response: Many thanks for your comment. The references have been used for supporting the platelet dysfunction in patients with osteogenesis imperfecta and they have been explained in very early research articles involving osteogenesis imperfecta as well as are used as reference by other recent articles (Léguillier T, Favier R, Harroche A et al. Assessing bleeding risk in 18 children with Osteogenesis imperfecta. Br J Haematol. 2021 Feb;192(4):785-788. doi: 10.1111/bjh.17303) explaining bleeding risk in those with osteogenesis imperfecta, hence we have used the original reference articles to explain the mechanism of platelet dysfunction. Also, majority of the older references used in this study are to explain the pathophysiology which have been proven in early original research articles. Comment: 2- Mention whether osteotomies were done per cutaneous or open and explain why single osteotomy cases required blood transfusion. Response: Many thanks for your comment. The osteotomies involved both percutaneous as well as open based on operating surgeon's discretion. Most of the single osteotomy were open procedure, hence these cases required blood transfusion. Comment: 3- Mention whether antifibrinolytic drugs were administrated or not? Response: Many thanks for your comment. None of the patients received any intraoperative (local or intravenous) antifibrinolytic agent in our study. Comment: 4- Cite the following References in discussion part: [ref1]. Response: Many thanks for your comment. We have cited this reference in our discussion and the revised manuscript is added as suggested. Response to comments: Many thanks for reviewing our manuscript. We have made the suggested changes and resubmitted a revised version for your reference. Comment: 1- A lot of cited references are out of date (one of them was 1971) please use recent references. Response: Many thanks for your comment. The references have been used for supporting the platelet dysfunction in patients with osteogenesis imperfecta and they have been explained in very early research articles involving osteogenesis imperfecta as well as are used as reference by other recent articles (Léguillier T, Favier R, Harroche A et al. Assessing bleeding risk in 18 children with Osteogenesis imperfecta. Br J Haematol. 2021 Feb;192(4):785-788. doi: 10.1111/bjh.17303) explaining bleeding risk in those with osteogenesis imperfecta, hence we have used the original reference articles to explain the mechanism of platelet dysfunction. Also, majority of the older references used in this study are to explain the pathophysiology which have been proven in early original research articles. Comment: 2- Mention whether osteotomies were done per cutaneous or open and explain why single osteotomy cases required blood transfusion. Response: Many thanks for your comment. The osteotomies involved both percutaneous as well as open based on operating surgeon's discretion. Most of the single osteotomy were open procedure, hence these cases required blood transfusion. Comment: 3- Mention whether antifibrinolytic drugs were administrated or not? Response: Many thanks for your comment. None of the patients received any intraoperative (local or intravenous) antifibrinolytic agent in our study. Comment: 4- Cite the following References in discussion part: [ref1]. Response: Many thanks for your comment. We have cited this reference in our discussion and the revised manuscript is added as suggested. Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 25 Nov 2024 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 Version 3 (revision) 28 Feb 26 Version 2 (revision) 17 Feb 25 read Version 1 25 Nov 24 read Hesham Mohamed Elbaseet , Assiut University, Asyut, Egypt Vivek Kumar Morya , Hallym University Dongtan Sacred Heart Hospital, Dongtan, South Korea 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 Morya V. 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. 02 Jun 2025 | for Version 2 Vivek Kumar Morya , Hallym University Dongtan Sacred Heart Hospital, Dongtan, South Korea 0 Views copyright © 2025 Morya V. 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 This single-center retrospective observational study investigates perioperative bleeding and the need for blood transfusions in pediatric osteogenesis imperfecta (OI) patients undergoing orthopedic surgeries. The study analyzed 141 procedures in 53 patients (mean age 11.07±5.29 years) from January 2016 to August 2024. The majority of patients were phenotypically type III OI (62.2%), and many underwent multiple osteotomies. The study reports a significant postoperative fall in hemoglobin, particularly in patients undergoing multiple osteotomies (p=0.002), younger children, and those with type III OI (1.82±0.86 g/dL fall, p=0.01). Blood transfusions were required in 16.3% of surgeries, with a significant association with multiple osteotomies (p=0.001). The authors conclude that younger age, type III OI, and multiple osteotomies are key factors associated with increased perioperative bleeding and transfusion needs in this cohort. The revised version also highlights the potential utility of antifibrinolytic agents. The article presents its findings but lacks clarity and accuracy in critical areas due to methodological deficiencies outlined below. For instance, while claiming to assess "perioperative bleeding," it doesn't quantify estimated blood loss (EBL), a key metric. The presentation of risk factors is potentially misleading because significant confounders, such as the surgical approach (open vs. percutaneous), were not systematically analyzed or accounted for. The authors admit that most single osteotomies requiring transfusion were open procedures, which clouds the interpretation that the number of osteotomies alone is the primary driver. The literature cited for background on OI and its bleeding manifestations is generally adequate, though the authors defend the use of older references for foundational concepts. However, the recommendation for antifibrinolytics based on external literature feels somewhat disconnected given none were used in their study cohort. The retrospective observational design is acceptable in principle for identifying associations. However, the technical execution of the study is unsound due to several critical flaws: The primary aim is to assess perioperative bleeding, yet the study fails to quantify estimated blood loss (EBL). Hemoglobin drop is an indirect and less precise measure, influenced by fluid management and other factors. This is a fundamental flaw for a study focused on bleeding. Failure to Control for Major Confounding Variables: The authors acknowledge that osteotomies could be "percutaneous as well as open" and that "Most of the single osteotomy [cases requiring transfusion] were open procedure". The study does not stratify or adjust its analysis based on whether procedures were open or percutaneous. Open procedures are inherently associated with greater blood loss. This unaddressed confounder severely undermines the conclusions drawn about the number of osteotomies or bones operated on as independent risk factors. The study acknowledges that "Surgical time...not recorded.". Surgical duration is a well-established factor influencing blood loss. Its absence further weakens the analysis. The definition of "single" versus "multiple" osteotomies is not sufficiently detailed in terms of complexity or specific anatomical sites, making comparisons difficult. These technical deficiencies mean the study cannot reliably determine the true risk factors for bleeding in this population. 1. While the study outlines the data sources (electronic records) and variables collected (age, OI type, number of osteotomies, hemoglobin levels, transfusion), crucial methodological details are missing: Precise definitions and criteria for classifying "single" versus "multiple" osteotomies are lacking. As mentioned, details distinguishing open versus percutaneous approaches for all procedures are not integrated into the analysis, nor is surgical time. Timing of pre- and post-operative hemoglobin measurements is not specified, which can affect comparability. While transfusion requirement was an outcome, the specific clinical or laboratory triggers for transfusion in this cohort are not detailed. 2. The study lists the statistical tests used (chi-squared, Kruskal-Wallis for post-hoc) and states that SPSS version 29 was used. However, the appropriateness of the interpretation is questionable due to: The statistical significance attributed to factors like "multiple osteotomies" may be erroneous if, for example, multiple osteotomies were also predominantly open procedures or longer in duration—factors not included in the model. For the relationship between age and hemoglobin drop, Figure 1 shows an "R2 Linear=0.076", indicating that age explains only 7.6% of the variability in hemoglobin drop. While a p-value might indicate statistical significance, the clinical relevance of such a weak correlation is not adequately discussed and may be overemphasized. The paper reports a "significant hemoglobin fall" (p<0.001) with a mean drop from 12.22 g/dL to 10.57 g/dL overall. While statistically significant, the clinical implications and relation to actual measured blood loss are not thoroughly explored. 3. authors state that underlying and extended data are available via Figshare, under a CC-BY 4.0 license. This is commendable. However, the utility of this data for full reproducibility of valid conclusions is limited if the crucial variables (EBL, specific surgical approach for each case, surgical time) were not recorded in the first place within that dataset. 4. The primary conclusion that "fall in hemoglobin was significant postoperatively in OI patients and was associated with younger age, type III OI, and multiple osteotomies" [page 2 conclusion section] and that these are "reliable indicators of perioperative bleeding and the need for transfusion" is not adequately supported by the presented results due to the major methodological flaws: The impact of "multiple osteotomies" cannot be reliably determined without accounting for whether these were predominantly open procedures or longer in duration compared to single osteotomies. The absence of EBL data means that conclusions about "perioperative bleeding" are based on an indirect measure (hemoglobin drop), which is less precise. The reported association between age and hemoglobin drop is statistically weak (R2=0.076), suggesting its limited predictive power despite statistical significance. To make this article scientifically sound, the authors must address the following: If possible, from anesthesia records, retrospectively collect EBL for each procedure. This is the most critical piece of missing information for a study on "perioperative bleeding." Re-analyze all data using EBL as a primary outcome, in addition to Hb drop and transfusion rates. For every osteotomy procedure, meticulously determine and record whether it was performed via an open or percutaneous approach. Stratify the analysis by surgical approach. Use multivariate regression models to assess the independent effects of the number of osteotomies, OI type, age, etc., while controlling for the surgical approach (and ideally, surgical duration). This is essential to determine if "multiple osteotomies" is an independent risk factor or merely a proxy for more invasive (open) surgery. If possible, retrieve surgical duration for each procedure from the records. Include surgical duration as a variable in the multivariate analysis to assess its contribution to blood loss and transfusion risk. When interpreting statistical significance, also thoroughly discuss the magnitude of the effect and its clinical relevance (e.g., effect sizes, R2 values for correlations). Acknowledge weak correlations even if statistically significant. Based on the re-analysis incorporating EBL, surgical approach, and surgical duration, the conclusions must be revised. It is possible that the currently identified risk factors will change in significance or that new, more critical factors (like open approach) will emerge. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise regenerative orthopedics 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 28 Feb 2026 Sushma Thimmaiah Kanakalakshmi, Department of Anesthesiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, India Dear Reviewer, We sincerely thank the reviewer for the detailed comments, which have helped us improve the manuscript. Comment 1: Lack of Estimated Blood Loss (EBL): The primary aim is to assess perioperative bleeding; however, estimated blood loss (EBL) was not quantified. Hemoglobin drop is an indirect and less precise measure. Response: Many thanks for your response. We agree that direct quantification of EBL would provide a more accurate and objective assessment of intraoperative bleeding. Due to the retrospective design of our study, standardized documentation of EBL was inconsistent across anesthesia records, limiting reliable data extraction. Therefore, postoperative hemoglobin decline and transfusion requirement were used as surrogate indicators of perioperative bleeding. We acknowledge that hemoglobin levels may be influenced by intraoperative fluid administration and hemodilution. Revision: The manuscript now clearly states that hemoglobin drop is a surrogate marker of perioperative blood loss; The limitations section has been expanded to emphasize the absence of recorded EBL as a major limitation; The conclusions have been modified to avoid implying direct measurement of blood loss. Comment 2: Failure to Control for Major Confounding Variables A. Surgical Approach (Open vs. Percutaneous): Surgical approach was not stratified or adjusted for, despite acknowledgment that most single osteotomies requiring transfusion were open procedures. Response: We agree that surgical approach is a significant potential confounder. In our cohort osteotomies were performed either percutaneously or via open technique based on surgeon discretion, surgical approach was not consistently coded in the electronic records in a standardized manner. As a result, stratified or multivariate adjustment by surgical approach could not be performed reliably. Revision: We have explicitly acknowledged surgical approach as an uncontrolled confounder; The discussion now clarifies that the association between multiple osteotomies and hemoglobin decline may partly reflect procedural invasiveness; The conclusions have been revised to reflect associative findings rather than independent risk factors. B. Surgical Duration : Surgical duration was not recorded, despite being a known determinant of blood loss. Response: We agree. Surgical time was not consistently retrievable in a standardized format from retrospective electronic records. This variable was therefore not included in the analysis. Revisions made: The absence of surgical duration has been clearly stated as a limitation; We acknowledge potential omitted-variable bias resulting from this omission. Reviewer Comment 3: Definition of Single vs. Multiple Osteotomies: The definitions lack sufficient detail regarding anatomical complexity or specific sites. Response: In our study, “Single osteotomy” refers to one osteotomy performed during a surgical session and “Multiple osteotomies” refers to more than one osteotomy during the same anesthesia session. We acknowledge that complexity grading, anatomical location, and deformity severity were not standardized variables in the dataset. Revision: Operational definitions have been clarified in the Methods section. We have noted heterogeneity of surgical complexity as a limitation. Reviewer Comment 4: Interpretation of Statistical Significance A. Weak Correlation Between Age and Hemoglobin Drop (R² = 0.076): The association between age and hemoglobin drop is statistically weak. Response: We agree that R² = 0.076 indicates that age explains only 7.6% of variability in hemoglobin decline, reflecting limited predictive power. Revision: The Results and Discussion describe this correlation as weak. We have tempered the interpretation to avoid overstating clinical significance. B. Clinical Relevance of Overall Hemoglobin Drop: Statistical significance does not necessarily equate to clinical significance. Response: Although the mean hemoglobin decline was statistically significant, the clinical impact depends on baseline hemoglobin, transfusion thresholds, and patient condition. Revision: The discussion now contextualizes the magnitude of hemoglobin decline. We clarify that transfusion requirement represents a more clinically meaningful endpoint. Reviewer Comment 5: Transfusion Triggers Not Defined: Transfusion criteria were not specified. Response: Transfusion decisions were based on institutional practice and clinical judgment, including hemodynamic instability, ongoing bleeding, hemoglobin levels (generally <8 g/dL, or <10 g/dL in symptomatic patients) and overall clinical assessment. Revision: Institutional transfusion practices are now described in the methods section, and the lack of standardized transfusion thresholds is acknowledged as a limitation. Reviewer Comment 6: Data Availability and Reproducibility: We appreciate the recognition of open data availability. However, we agree that reproducibility is limited by the absence of certain procedural variables (EBL, surgical duration, surgical approach). This limitation is now clearly stated. Revision of Conclusion: In response to the reviewer’s concern that our conclusions may overstate the findings, we have revised the conclusion section. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Morya VK. Peer Review Report For: Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] . F1000Research 2026, 13 :1420 ( https://doi.org/10.5256/f1000research.178083.r383091) 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/13-1420/v2#referee-response-383091 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Elbaseet H. 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. 05 Feb 2025 | for Version 1 Hesham Mohamed Elbaseet , Assiut University, Asyut, Assiut Governorate, Egypt 0 Views copyright © 2025 Elbaseet H. 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 Thanks for your effort in writing the manuscript. Please add and / or modify the following: 1- A lot of cited references are out of date (one of them was 1971) please use recent references. 2- Mention whether osteotomies were done per cutaneous or open and explain why single osteotomy cases required blood transfusion. 3- Mention whether antifibrinolytic drugs were administrated or not? 4- Cite the following References in discussion part: [ref1]. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Elbaseet HM, Aldeen AJ, Irahim AKH: Efficacy of intraoperative use of tranexamic acid in reducing blood loss from telescoping nail application in osteogenesis imperfecta. A randomized controlled trial. Orthop Traumatol Surg Res . 2024. 103927 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Pediatric orthopedic surgeon specialized inosteogenesis imperfecta surgical treatment 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 17 Feb 2025 Sushma Thimmaiah Kanakalakshmi, Department of Anesthesiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, India Response to comments: Many thanks for reviewing our manuscript. We have made the suggested changes and resubmitted a revised version for your reference. Comment: 1- A lot of cited references are out of date (one of them was 1971) please use recent references. Response: Many thanks for your comment. The references have been used for supporting the platelet dysfunction in patients with osteogenesis imperfecta and they have been explained in very early research articles involving osteogenesis imperfecta as well as are used as reference by other recent articles (Léguillier T, Favier R, Harroche A et al. Assessing bleeding risk in 18 children with Osteogenesis imperfecta. Br J Haematol. 2021 Feb;192(4):785-788. doi: 10.1111/bjh.17303) explaining bleeding risk in those with osteogenesis imperfecta, hence we have used the original reference articles to explain the mechanism of platelet dysfunction. Also, majority of the older references used in this study are to explain the pathophysiology which have been proven in early original research articles. Comment: 2- Mention whether osteotomies were done per cutaneous or open and explain why single osteotomy cases required blood transfusion. Response: Many thanks for your comment. The osteotomies involved both percutaneous as well as open based on operating surgeon's discretion. Most of the single osteotomy were open procedure, hence these cases required blood transfusion. Comment: 3- Mention whether antifibrinolytic drugs were administrated or not? Response: Many thanks for your comment. None of the patients received any intraoperative (local or intravenous) antifibrinolytic agent in our study. Comment: 4- Cite the following References in discussion part: [ref1]. Response: Many thanks for your comment. We have cited this reference in our discussion and the revised manuscript is added as suggested. View more View less Competing Interests None reply Respond Report a concern Elbaseet HM. Peer Review Report For: Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study [version 3; peer review: 2 approved with reservations] . F1000Research 2026, 13 :1420 ( https://doi.org/10.5256/f1000research.174199.r363165) 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/13-1420/v1#referee-response-363165 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. 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