Prognostic value of laboratory markers in patients with acute pulmonary embolism

Prognostic value of laboratory markers in patients with acute pulmonary embolism | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prognostic value of laboratory markers in patients with acute pulmonary embolism Yousef Ahmed Yousef Ahmed, Abd-Elazim Ahmed Abo Elfadl, Abeer Houssein, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4668387/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Acute pulmonary embolism (APE) is a serious illness. Identifying prognostic factors for APE may help in the management of those patients. This study's objective was to evaluate the prognostic value of laboratory markers in predicting right ventricular dysfunction (RVD) and 30-day mortality in pulmonary embolism patients. Methods Eighty patients with APE were enrolled and followed up for 30-day. Detailed echocardiography was done to evaluate RVD. All patients were subjected to arterial blood gas analysis, complete blood count (CBC), plasma concentration of C-reactive protein (CRP), serum D-dimer level, and serum troponin I level, and the following ratio were calculated: Neutrophil to lymphocytic ratio (NLR), Platelet to lymphocytic ratio (PLR), Red cell distribution width (RDW), Mean platelet volume (MPV) and alveolar to arterial gradient. Results Our results analysis revealed significantly elevated levels of median NLR, PLR, CRP, D-dimer, and troponin in both the RVD and non-survivor groups (P value < 0.001). The blood markers that showed the highest predictive ability for right ventricular dysfunction (RVD) and 30-day mortality, as determined by receiver operating characteristic (ROC) analysis and logistic regression, were A-a O2 gradient, serum troponin, CRP, D-dimer, NLR, and PLR (P value < 0.001). Conclusion Evaluation of different serum markers including NLR, PLR, RDW, CRP, D-dimer, troponin and A-a O 2 gradient are simple and available markers for predicting right ventricular dysfunction (RVD) and 30- day mortality in patients with APE. Trial registration: ClinicalTrials.gov ID: NCT04237974. Pulmonary embolism (PE) laboratory markers Right ventricular dysfunction Figures Figure 1 Figure 2 Introduction Acute pulmonary embolism (APE) is a life-threatening disease affecting the cardiovascular and respiratory systems, which has a high rate mortality ( 1 , 2 ). Assessing the potential adverse outcome for a patient may influence treatment choices ( 2 – 4 ). Aside from clinical assessments and imaging abnormalities, additional biomarkers and indices can be employed to forecast the severity and prognosis of patients with APE. The biomarkers initially included serum troponin and brain natriuretic peptide. These biomarkers are employed to signify right ventricular dysfunction (RVD) and injury to the myocardium. Other metrics to consider are C-reactive protein (CRP), D-dimer, arterial blood gases (ABG) values, and complete blood count (CBC) parameters. However, these biomarkers are not extensively researched or used, even though they are easily accessible and cost-effective, especially in impoverished countries ( 5 – 9 ). The use of laboratory tests for early risk stratification relies on the assumption that predictive biomarkers of disease severity might identify patients who are more likely to experience adverse consequences. This allows for timely recognition and intervention, ensuring that limited medical resources are allocated to those patients who would benefit the most. It is recommended to use echocardiography as the first imaging tool to assess RVD and rapidly initiate fibrinolytic therapy ( 10 , 11 ). Nevertheless, the challenges related to reliance on operators and technical aspects have limited the application of this imaging technique for the evaluation of the right side of the heart ( 12 ). We aimed in this study to conduct the ability of some of the laboratory biomarkers as predictors of right ventricular dysfunction and 30-day mortality in cases of acute PE. Methods We performed this study as prospective observational cross-sectional study. This study was conducted in the Department of Chest Diseases and Tuberculosis at Assuit University Hospital. The Scientific Ethics Committee of the Assuit Faculty of Medicine, Assuit University, approved the study. We included patients aged more than 18 years old who presented in either the Emergency Department, or Respiratory Intensive Care Unit (RICU) during the period from January 2021 to November 2022 with clinical manifestations suggestive of massive or sub-massive APE. The diagnosis of pulmonary embolism (PE) relies on the patient's clinical likelihood, laboratory tests, and Computed Tomography Pulmonary Angiography (CTPA), which is considered the most reliable method. ( 13 ). We excluded PE patients from the study if they had one or more of the following: hematological or coagulation disorders, active infectious disease, other cardiopulmonary disease, previous PE, taking immunosuppressive medications, taking antiplatelet and/or anticoagulant medications, blood transfusion within 3 months, chronic renal failure, advanced liver disease. Sample size was calculated using Epi-info7. According to the results of the study ( 14 ), the percentage of right ventricular dysfunction was 61%.Based on this percentage and with confidence limits of 7%, the minimum sample needed for the study was estimated to be 80 patients. All patients enrolled in the trial underwent a comprehensive assessment of their medical history, clinical examination, and standard laboratory tests. The results were determined based on the mortality rate within 30 days and categorized as either survivors or non-survivors. Upon admission, venous blood samples were promptly extracted from the patients under study and thereafter transported to the laboratory for analysis. The samples were examined to determine the CBC, CRP, serum D-dimer level, and serum troponin I level. The following ratio were calculated: Neutrophil to lymphocytic ratio (NLR) : It was calculated by dividing the absolute neutrophil count by the absolute lymphocytic count. The reference range is from 1 to 2. less than 0.7 and more than 3 is considered pathological ( 15 ). Platelet to lymphocytic ratio (PLR) : It was calculated by dividing the absolute platelet count by the absolute lymphocytic count. The reference range is from 75 to 199 ( 16 ). Red cell distribution width (RDW) : Its abnormal levels may be indicative of a range of pathological processes as inflammatory stress. Normal value is from 11.5 to 14.5%. Mean platelet volume (MPV) : MPV is a simple marker of platelet activation, which is considered the first step of thrombosis. Normal range is from 8.5 to 11 fl. Arterial blood samples were collected to determine the partial pressure of arterial oxygen (PaO 2 ), arterial carbon dioxide (PaCO 2 ), and the alveolar - arterial oxygen (A-a O 2 ) gradient equation was calculated ( 17 ). Transthoracic echocardiography was performed for all patients at presentation using a Philips HD 11 (Philips Ultrasound, Bothell, WA, USA.) for assessment of RVD. Right ventricular basal and mid diameter more than 4.2cm, 3,5cm respectively considered to be dilated. Impaired RV systolic function detected by TAPSE (Tricuspid annular plane systolic excursion) < 1.6cm, and Pulsed tissue Doppler peak velocity at the annulus (S' velocity) < 10 cm/s ( 18 ). Statistical analysis: Data analysis was conducted by SPSS version 20. Numerical data was assessed for normality by Shapiro- walk test and presented by mean and standard deviation or median and range. The independent Sample T test/Mann Whitney U test was used to compare mean/median difference between two groups. Roc curve analysis and univariate logistic regression analysis were conducted to identify potential predictors for the occurrence RVD or mortality in patients with pulmonary embolism. Significant variables were then included in a multivariate logistic regression analysis to calculate the adjusted odds ratio (AOR). The level of statistical significance was set at a P value of less than 0.05. Results The mean age of our patients was 51.43 ± 16.88, 50 (62.5%) were females and 30(37.5%) were males .The most frequent clinical presentations for pulmonary embolism among studied patients were dyspnea (95.0%) followed by chest pain (52.5%), hemodynamic instability (40.0%), hemoptysis (31.3%), lower limb swelling and pain (15.0%), cough (12.5%), and syncope (8.8%). 50% of patients received anticoagulants, 41.2% received thrombolytics and 8.8% received catheter-directed therapy (CDT). 60 patients (75%) were survived. and the rest of them was not. Patients were classified into two groups: NO RVD group and RVD group according to Echocardiography. Table 1 shows the association between the outcome and RVD among studied patients. There was statistically significant higher percent of non -survivors among RVD group compared to no RVD group (45.2% vs 2.6% respectively), p value < 0.001. RVD patients had significantly lower PaO2, SPO2, and higher A-a O2 gradient compared to non-RVD patients (p value0.001). As regard the CBC parameters, RVD group showed significantly higher mean RDW (p = 0.008) and median NLR, PLR (p = < 0.001) compared to non-RVD group. However, median MPV did not differ significantly between both groups. In addition, RVD group had considerably higher median CRP, D dimer, and troponin levels compared to non-RVD group (p < 0.001). The most accurate serum markers able to predict RVD were A-a O 2 gradient, serum troponin, CRP, D- dimer, NLR, RDW and PLR in order as shown in table 3 and Fig. 1. Table 4 demonstrated the predictors attributed with the occurrence of RVD by univariate logistic regression analysis. These predictors included elevated A-a O2gradient, increased RDW, elevated NLR, elevated PLR, elevated CRP, increased D-dimer, and elevated troponin levels. By multivariate logistic regression analysis, the only significant predictor was an increase in the A-a O2 gradient, with an odds ratio of 1.10 and a p-value of 0.047. Patients were classified according to 30-day mortality into two groups: survivors and non-survivors. Table 5 shows the association between ABG, serum markers and mortality among studied patients. There was statistically significant lower mean PO 2, SPO 2, and higher mean A-a O 2 gradient among the non-survivors. While, there was no statistically significant difference in mean RDW and mean MPV between survivors and non-survivors (16.57 ± 5.485 vs 17.59 ± 2.48, p value = 0.425), (9.01 ± 1.32 vs 9.68 ± 2.18, p value = 0.102) respectively. On the other hand, there was statistically significant higher median NLR, PLR among non-survivors compared to survivors (9.15 vs 3.00, p value < 0.001), (270.00 vs 171.50, p value = 0.001) respectively. In addition, there was statistically significant higher median CRP, D dimer, troponin among non-survivors, p value < 0.001. Table 6 and Fig. 2 show the diagnostic ability of ABG and serum markers in prediction of 30-day mortality, the most serum markers able to predict mortality were, D- dimer, A-a gradient, serum troponin, NLR, CRP and PLR in order. The significant predictors associated with 30 day-mortality by univariate logistic regression analysis were increase A-a O 2 gradient, increase NLR, increase CRP, increase D-dimer and increase troponin level as displayed by table (7), but none of them were significant by applying multivariate regression. Discussion Acute PE is a common clinical scenario and effective risk classification and death prediction methods are necessary to cope with different ranges of clinical care strategies for patients with APE. Echocardiography and MSCT angiography may not always be accessible for assessing the prognosis of acute PE. In addition, patients may have chronic kidney disease, which is a contraindication for contrast administration This study aimed to identify the capability of particular laboratory indicators to anticipate right ventricular dysfunction and 30-day mortality in cases of APE. We displayed that the RVD group had a statistically significantly higher median NLR and PLR, and mean red cell distribution width (RDW) than the non-RVD group, but the median mean platelet volume was not significantly different. In addition, the non-survivors had a statistically significantly higher median NLR, PLR, and median MPV, but no difference in mean RDW. These findings were in consistent with the studies conducted by Phan et al. and Jia et al. who found NLR and PLR, were significantly higher in RVD patients than none RVD, and elevation of PLR and NLR suggest that acute pulmonary embolism is associated with proinflammatory state ( 21 , 22 ). In et al. found that there was higher mean RDW between both groups as in our study but differs with us in that he found that mean MPV was significantly higher in RVD group ( 21 ). Our study was not in agreement with Yardan et al. who reported that MPV was higher in RVD group and stated that platelet activation is common in patients with acute PE and correlates with RV dysfunction ( 22 ). These differences may be contributed to anticoagulant use, blood sampling timing, storage conditions, analytical techniques, calculation methods, accurate reference ranges and diagnostic cut-offs, This lack of standardization makes data from different methods and analyzers hard to compare ( 23 ). Ma et al. concurred with our study as he found statistically significant difference between survivors and non-survivors in NLR, PLR and no difference between both groups in MPV ( 24 ). The results of our study were in line with prior findings, which indicates that NLR is valuable for classifying risks in patients with venous thromboembolism ( 25 ). PLR has been recognized as a novel indicator of systemic inflammation. It was found to have superior predictive value compared to platelet count or lymphocyte count alone in forecasting specific cardiovascular conditions ( 26 ). Several studies also support our findings and found elevated NLR and PLR in non-survivors ( 27 ). Our results exhibited statistically significant higher median C-reactive protein (CRP), D-dimer and troponin in RVD and non-survivors groups. These results were in accordance with studies performed by Abul et al. and Keller et al ( 28 , 29 ). These results contradicted the findings of Ohigashi et al., who observed no statistically significant disparity in the average levels of CRP, D-dimer, and troponin between the groups with and without RVD. They also concluded that BNP was a more dependable indicator of RVD and a complex course in patients with PE compared to other factors. ( 30 ). But Ohigashi et al findings had many limitations, as they included only 50 patients retrospectively and blood samples were withdrawn within 24 hours of admission. CRP levels is raised in cases of acute PE due to inflammatory reaction with subsequent pleural effusion development and hemorrhagic necrosis of pulmonary infarction ( 31 ). In regard to the diagnostic accuracy of ABG and serum markers in prediction of RVD and 30 day mortality, the most blood markers capable of predicting RVD were A-a O 2 gradient, serum troponin, CRP, D- dimer, NLR, RDW and PLR in order. In the study conducted by Jia et al. , he found that NLR is more sensitive than troponin and D-dimer in predicting RVD with AUC = 0.803 which was not in agreement with our findings ( 20 ). Ohigashi et al. had declared that troponin, D-dimer and CRP have high accuracy in predicting RVD with area under the curve (0.703,0.562 and 0.536 respectively)( 30 ). Roc curve of troponin in predicting RVD and 30 day mortality (at cut of point > 0.07 ng/ml). This was in consistent with Henzler et al. that found cutoff point of troponin 0.07ng/ml with area under the curve 0.70( 32 ). Other studies had found that cutoff value of troponin in predicting RVD were 0.01ng/ml which was different from our findings but agreed with us in that it has higher accuracy in predicting RVD (29,33,) . Limitations There are some discrepancies between our findings and those from previous studies, and because of the different cut-off points, we suggest carrying out more research using a larger sample size of patients. Also, this will allow for a more thorough investigation into the causal relationship between various blood markers and the adverse outcomes caused by pulmonary embolism. Detection of RVD was assessed using TAPSE and pulsed tissue Doppler peak velocity at the TV annulus (S' velocity), and there are some other novel methods such as fractional area change and RV strain that have higher sensitivity in detecting RV dysfunction. Conclusion Evaluation of different serum markers including NLR, PLR, RDW, CRP, D-dimer, troponin and A-a O 2 gradient are simple and available markers for predicting right ventricular dysfunction (RVD) and 30- day mortality in patients with APE. Abbreviations A-a O 2: Alveolar - arterial oxygen APE: Acute pulmonary embolism AOR: Adjusted odds ratio ABG: Arterial blood gas analysis CBC: Complete blood count Computed Tomography Pulmonary Angiography (CTPA) CRP: C-reactive protein MPV: Mean platelet volume NLR: Neutrophil to lymphocytic ratio PaO 2: Partial pressure of arterial oxygen PaCo2: Partial arterial carbon dioxide PLR: Platelet to lymphocytic ratio PE: Pulmonary embolism RICU : Respiratory Intensive Care Unit RDW: Red cell distribution width RVD: Right ventricular dysfunction ROC: Roc curve analysis S' velocity: Pulsed tissue Doppler peak velocity at the annulus TAPSE: Tricuspid annular plane systolic excursion Declarations We wish to submit an original article entitled (Prognostic value of laboratory markers in patients with acute pulmonary embolism) for consideration by Expert Review of Pulmonology. We confirm that this work is original and has not been published elsewhere, nor it is currently under consideration for publication elsewhere. We had full access to all the data in this study and accept responsibility to submit this publication. We have no conflicts of interest to disclose. Acknowledgements: Not applicable. Funding: Not applicable. Authors’ contributions All the authors participated in conception and design. AA collected the data and samples. AO, AF and YA were responsible for analysis and interpretation of data. KM and AH were responsible for drafting the article. AO and AF revised it critically for final approval of the version to be published. All authors have read and approved the manuscript. Ethical approval Ethics approval and consent to participate the study was approved by the Local Ethics Committee of the Assiut University Hospital, the committee’s reference number IRB no: 17200409. Informed consent was obtained from all the participants before enrollment . Consent for publication All the authors approved the manuscript for publication. Identifying images or other personal or clinical details of participants is “Not Applicable.” Consent for publication from the participants is “Not Applicable.” Availability of data: Data available on request Competing of interests The authors declare that they have no competing interests. References Elias A, Mallett S, Daoud-Elias M, Poggi JN, Clarke M. Prognostic models in acute pulmonary embolism: A systematic review and meta-analysis. BMJ Open. 2016;6(4). de-Miguel-Diez J, López-de-Andrés A, Hernandez-Barrera V, Jimenez D, Monreal M, López-Herranz M, et al. The significance of heart failure in hospitalised patients with pulmonary embolism. A gender-specific analysis. Int J Clin Pract. 2021;75(10):1–9. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: A scientific statement from the american heart association. Circulation. 2011;123(16):1788–830. Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, et al. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism. N Engl J Med. 2014;370(15):1402–11. Lega JC, Lacasse Y, Lakhal L, Provencher S. Natriuretic peptides and troponins in pulmonary embolism: a meta-analysis. Thorax. 2009;64(10):869–75. Soomro AY, Guerchicoff A, Nichols DJ, Suleman J, Dangas GD. The current role and future prospects of D-dimer Biomarker. Eur Hear J - Cardiovasc Pharmacother. 2016;2(3):175–84. Abul Y, Karakurt S, Ozben B, Toprak A, Celikel T. C-Reactive Protein in Acute Pulmonary Embolism. 2023;59(1):8–14. Liu J, Liu Y, Zhang F, Fu C, Ling Y, Fang P, et al. Short-term prognostic value of clinical data in hospitalized patients with intermediate-risk acute pulmonary embolism. BMC Cardiovasc Disord. 2022;22(1):1–14. Faghihi Langhroudi T, Borji Esfahani M, Khaheshi I, Naderian M, Zahedi Tajrishi F, Namazi MJ. Correlation of Hematologic Indices with CT-pulmonary Arterial Obstruction Index in Patients with Acute Pulmonary Emboli. Int J Cardiovasc Pract. 2019;4(3):89–93. Dabbouseh NM, Patel JJ, Bergl PA. Role of echocardiography in managing acute pulmonary embolism. Heart. 2019;105(23):1785–92. Bikdeli B, Lobo JL, Jiménez D, Green P, Fernández-Capitán C, Bura-Riviere A, et al. Early use of echocardiography in patients with acute pulmonary embolism: Findings from the RIETE registry. J Am Heart Assoc. 2018;7(17):1–7. Bing R, Chow V, Lau JK, Thomas L, Kritharides L, Ng ACC. Prevalence of echocardiography use in patients hospitalized with confirmed acute pulmonary embolism: A Real-World observational multicenter study. PLoS One. 2016;11(12):1–13. Konstantinides, S. V., Meyer, G., Becattini, C., Bueno, H., Geersing, G. J., Harjola, V. P., … Zamorano, J. L. (2019). The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC) Eur Respir J, 54 (3), 1901647. Subramanian M, Ramadurai S, Arthur P, Gopalan S. Hypoxia as an independent predictor of adverse outcomes in pulmonary embolism. Asian Cardiovasc Thorac Ann. 2018;26(1):38–43. Sarejloo S, Khanzadeh S, Hosseini S, Gargari MK, Lucke-Wold B, Mosalamiaghili S, et al. Role of the Neutrophil to Lymphocyte Ratio in Guillain Barré Syndrome: A Systematic Review and Meta-Analysis. Mediators Inflamm. 2022;2022. NI A. Reference Values of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio and Mean Platelet Volume in Healthy Adults in North Central Nigeria. J Blood Lymph. 2016;6(1):1–4. Abdelghany EA, Othman AM, Abdelfatah RA, Magdy M-E, Abd Elghany HS, Higazi MM. Can alveolar—arterial oxygen gradient predict severity of pulmonary embolism? Egypt J Bronchol. 2019;13(2):273–9. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the Echocardiographic Assessment of the Right Heart in Adults: A Report from the American Society of Echocardiography. Endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and. J Am Soc Echocardiogr. 2010;23(7):685–713. Phan T, Brailovsky Y, Fareed J, Hoppensteadt D, Iqbal O, Darki A. Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios Predict All-Cause Mortality in Acute Pulmonary Embolism. 2020; Jia D, Liu F, Zhang Q, Zeng GQ, Li XL, Hou G. Rapid on-site evaluation of routine biochemical parameters to predict right ventricular dysfunction in and the prognosis of patients with acute pulmonary embolism upon admission to the emergency room. J Clin Lab Anal. 2018;32(4):1–8. In E, Deveci F, Kaman D, Özdemir C, Sökücü SN, Kuluöztürk M, et al. The importance of mean platelet volume and red cell distribution width in acute pulmonary embolism. Acta Medica Mediterr. 2015;31(6):1209–16. Yardan T, Meric M, Kati C, Celenk Y, Atici AG. Mean platelet volume and mean platelet volume/platelet count ratio in risk stratification of pulmonary embolism. Med. 2016;52(2):110–5. Lippi, G., Sanchis-Gomar, F., & Favaloro, E. J. (2020). Mean platelet volume in arterial and venous thrombotic disorders. Journal of Laboratory Medicine, 44 (5), 305–312. Ma Y, Mao Y, He X, Sun Y, Huang S, Qiu J. The values of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in predicting 30 day mortality in patients with acute pulmonary embolism. BMC Cardiovasc Disord. 2016;16(1):1–6. Bakirci EM, Topcu S, Kalkan K, Tanboga IH, Borekci A, Sevimli S, et al. The role of the nonspecific inflammatory markers in determining the anatomic extent of venous thromboembolism. Clin Appl Thromb. 2015;21(2):181–5. Wang D, Yang JX, Cao DY, Wan XR, Feng FZ, Huang HF, et al. Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma. Onco Targets Ther. 2013;6:211–6. Karataş MB, İpek G, Onuk T, Güngör B, Durmuş G, Çanga Y, et al. Assessment of prognostic value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patients with pulmonary embolism. Acta Cardiol Sin. 2016;32(3):313–20. Abul Y, Karakurt S, Ozben B, Toprak A, Celikel T. C-Reactive Protein in Acute Pulmonary Embolism. 2023;59(1):8–14. Keller K, Beule J, Schulz A, Coldewey M, Dippold W, Balzer JO. Cardiac troponin I for predicting right ventricular dysfunction and intermediate risk in patients with normotensive pulmonary embolism. Netherlands Hear J. 2015;23(1):55–61. Ohigashi H, Haraguchi G, Yoshikawa S, Sasaki T, Kimura S, Inagaki H, et al. Comparison of biomarkers for predicting disease severity and long-term respiratory prognosis in patients with acute pulmonary embolism. Int Heart J. 2010;51(6):416–20. Büyükşirin, M., Anar, C., Polat, G., & Karadeniz, G. (2021). Can the level of crp in acute pulmonary embolism determine early mortality?. Turkish Thoracic Journal, 22 (1), 4. Henzler T, Roeger S, Meyer M, Schoepf UJ, Jr JWN, Haghi D, et al. Pulmonary embolism: CT signs and cardiac biomarkers for predicting right ventricular dysfunction. 2012;39(4):919–26. Kucher N, Wallmann D, Carone A, Windecker S, Meier B, Hess OM. Incremental prognostic value of troponin I and echocardiography in patients with acute pulmonary embolism. Eur Heart J. 2003;24(18):1651–6. Tables Table 1 to 7 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table17.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4668387","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":329827798,"identity":"b1902f4b-c935-498e-864c-aab461553820","order_by":0,"name":"Yousef Ahmed Yousef Ahmed","email":"","orcid":"","institution":"Assuit University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yousef","middleName":"Ahmed Yousef","lastName":"Ahmed","suffix":""},{"id":329827799,"identity":"c51f9c5c-1734-47b8-9d8f-f54e7dfb575f","order_by":1,"name":"Abd-Elazim Ahmed Abo Elfadl","email":"","orcid":"","institution":"Assuit University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Abd-Elazim","middleName":"Ahmed Abo","lastName":"Elfadl","suffix":""},{"id":329827800,"identity":"167e3317-a682-4bc2-a1ed-d6b5adc52a9a","order_by":2,"name":"Abeer Houssein","email":"","orcid":"","institution":"Assuit University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Abeer","middleName":"","lastName":"Houssein","suffix":""},{"id":329827801,"identity":"ba0c9c9f-2450-408c-aec6-916d9b7dc27e","order_by":3,"name":"Amal Abdallah Abdelrahman","email":"","orcid":"","institution":"Assuit University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Amal","middleName":"Abdallah","lastName":"Abdelrahman","suffix":""},{"id":329827802,"identity":"31f1417a-43c9-404a-a7d8-ea517dc7d957","order_by":4,"name":"Khaled Mohamed Ali Shehata","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIie3PsYrCMBjA8S8UnE5cIz3aV4j7vYlLp3Mx0Kl0UCkc1MUHyKF4r2AROicE6hLqenBLH6FuXYSLBcGlDW4Hl/+Q7xu+3xAAm+0PhjEgDoN2JxxiPRwnMRF4IOpG0BMEUHqbBjLeflS8jsAfbWXGL/vldLTWpInzTuK+FkSwEiasfA/FZ36iTKIEbdRPJ/FwQOQwhQDUi17ygiaaOCjtI7NaXjXxW7Ir6JeJuHhOpP51QFqSLOjBRMZsHopNiSeZGoSCFZxmmoi+v+DvWVY10ZvvKedY14sV3Z+lqJq4m9zlfZHty033j62eObbZbLZ/0i8u42AN2WJmVAAAAABJRU5ErkJggg==","orcid":"","institution":"Assuit University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Khaled","middleName":"Mohamed Ali","lastName":"Shehata","suffix":""},{"id":329827803,"identity":"8ed3bbbb-9f25-481c-a7c9-42a12ec1938c","order_by":5,"name":"Amany Omar Mohamed Omar","email":"","orcid":"","institution":"Assuit University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Amany","middleName":"Omar Mohamed","lastName":"Omar","suffix":""}],"badges":[],"createdAt":"2024-07-01 13:29:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4668387/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4668387/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62123586,"identity":"5687e0fc-0fc0-4b02-aeeb-56ec5814d347","added_by":"auto","created_at":"2024-08-09 14:23:52","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":271326,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for ability of A-a O\u003csub\u003e2\u003c/sub\u003e gradient and serum markers to predict RVD among studied patients.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4668387/v1/945cca324c7e678c15ec6ae2.jpeg"},{"id":62124801,"identity":"c889b1f8-cc37-4c69-9d15-f91f3cd9cc2e","added_by":"auto","created_at":"2024-08-09 14:31:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":56191,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for ability of A-a O\u003csub\u003e2 \u003c/sub\u003egradient and serum markers to predict mortality among studied patients.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4668387/v1/9a9dfd6191d4dc63a2702c43.png"},{"id":70616853,"identity":"23192e30-d83d-42f8-9e5f-ff973facba80","added_by":"auto","created_at":"2024-12-05 02:17:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":713695,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4668387/v1/e7b0610c-da0a-4850-b05e-4b1af6d50e31.pdf"},{"id":62123584,"identity":"4f3ebb33-92be-430f-aacf-16a1452e4585","added_by":"auto","created_at":"2024-08-09 14:23:52","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":32129,"visible":true,"origin":"","legend":"","description":"","filename":"Table17.docx","url":"https://assets-eu.researchsquare.com/files/rs-4668387/v1/fa675d0010096068a9e7a427.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic value of laboratory markers in patients with acute pulmonary embolism","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute pulmonary embolism (APE) is a life-threatening disease affecting the cardiovascular and respiratory systems, which has a high rate mortality (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Assessing the potential adverse outcome for a patient may influence treatment choices (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAside from clinical assessments and imaging abnormalities, additional biomarkers and indices can be employed to forecast the severity and prognosis of patients with APE. The biomarkers initially included serum troponin and brain natriuretic peptide. These biomarkers are employed to signify right ventricular dysfunction (RVD) and injury to the myocardium. Other metrics to consider are C-reactive protein (CRP), D-dimer, arterial blood gases (ABG) values, and complete blood count (CBC) parameters. However, these biomarkers are not extensively researched or used, even though they are easily accessible and cost-effective, especially in impoverished countries (\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The use of laboratory tests for early risk stratification relies on the assumption that predictive biomarkers of disease severity might identify patients who are more likely to experience adverse consequences. This allows for timely recognition and intervention, ensuring that limited medical resources are allocated to those patients who would benefit the most.\u003c/p\u003e \u003cp\u003eIt is recommended to use echocardiography as the first imaging tool to assess RVD and rapidly initiate fibrinolytic therapy (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Nevertheless, the challenges related to reliance on operators and technical aspects have limited the application of this imaging technique for the evaluation of the right side of the heart (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWe aimed in this study to conduct the ability of some of the laboratory biomarkers as predictors of right ventricular dysfunction and 30-day mortality in cases of acute PE.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe performed this study as prospective observational cross-sectional study. This study was conducted in the Department of Chest Diseases and Tuberculosis at Assuit University Hospital. The Scientific Ethics Committee of the Assuit Faculty of Medicine, Assuit University, approved the study.\u003c/p\u003e \u003cp\u003eWe included patients aged more than 18 years old who presented in either the Emergency Department, or Respiratory Intensive Care Unit (RICU) during the period from January 2021 to November 2022 with clinical manifestations suggestive of massive or sub-massive APE. The diagnosis of pulmonary embolism (PE) relies on the patient's clinical likelihood, laboratory tests, and Computed Tomography Pulmonary Angiography (CTPA), which is considered the most reliable method. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). We excluded PE patients from the study if they had one or more of the following: hematological or coagulation disorders, active infectious disease, other cardiopulmonary disease, previous PE, taking immunosuppressive medications, taking antiplatelet and/or anticoagulant medications, blood transfusion within 3 months, chronic renal failure, advanced liver disease.\u003c/p\u003e \u003cp\u003eSample size was calculated using Epi-info7. According to the results of the study (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), the percentage of right ventricular dysfunction was 61%.Based on this percentage and with confidence limits of 7%, the minimum sample needed for the study was estimated to be 80 patients.\u003c/p\u003e \u003cp\u003eAll patients enrolled in the trial underwent a comprehensive assessment of their medical history, clinical examination, and standard laboratory tests. The results were determined based on the mortality rate within 30 days and categorized as either survivors or non-survivors. Upon admission, venous blood samples were promptly extracted from the patients under study and thereafter transported to the laboratory for analysis. The samples were examined to determine the CBC, CRP, serum D-dimer level, and serum troponin I level. The following ratio were calculated:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eNeutrophil to lymphocytic ratio (NLR)\u003c/b\u003e: It was calculated by dividing the absolute neutrophil count by the absolute lymphocytic count. The reference range is from 1 to 2. less than 0.7 and more than 3 is considered pathological (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePlatelet to lymphocytic ratio (PLR)\u003c/b\u003e: It was calculated by dividing the absolute platelet count by the absolute lymphocytic count. The reference range is from 75 to 199 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eRed cell distribution width (RDW)\u003c/b\u003e: Its abnormal levels may be indicative of a range of pathological processes as inflammatory stress. Normal value is from 11.5 to 14.5%.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eMean platelet volume (MPV)\u003c/b\u003e: MPV is a simple marker of platelet activation, which is considered the first step of thrombosis. Normal range is from 8.5 to 11 fl.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eArterial blood samples were collected to determine the partial pressure of arterial oxygen (PaO\u003csub\u003e2\u003c/sub\u003e), arterial carbon dioxide (PaCO\u003csub\u003e2\u003c/sub\u003e), and the alveolar - arterial oxygen (A-a O\u003csub\u003e2\u003c/sub\u003e) gradient equation was calculated (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTransthoracic echocardiography was performed for all patients at presentation using a Philips HD 11 (Philips Ultrasound, Bothell, WA, USA.) for assessment of RVD. Right ventricular basal and mid diameter more than 4.2cm, 3,5cm respectively considered to be dilated. Impaired RV systolic function detected by TAPSE (Tricuspid annular plane systolic excursion)\u0026thinsp;\u0026lt;\u0026thinsp;1.6cm, and Pulsed tissue Doppler peak velocity at the annulus (S' velocity)\u0026thinsp;\u0026lt;\u0026thinsp;10 cm/s (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eData analysis was conducted by SPSS version 20. Numerical data was assessed for normality by Shapiro- walk test and presented by mean and standard deviation or median and range. The independent Sample T test/Mann Whitney U test was used to compare mean/median difference between two groups. Roc curve analysis and univariate logistic regression analysis were conducted to identify potential predictors for the occurrence RVD or mortality in patients with pulmonary embolism. Significant variables were then included in a multivariate logistic regression analysis to calculate the adjusted odds ratio (AOR). The level of statistical significance was set at a P value of less than 0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean age of our patients was 51.43\u0026thinsp;\u0026plusmn;\u0026thinsp;16.88, 50 (62.5%) were females and 30(37.5%) were males .The most frequent clinical presentations for pulmonary embolism among studied patients were dyspnea (95.0%) followed by chest pain (52.5%), hemodynamic instability (40.0%), hemoptysis (31.3%), lower limb swelling and pain (15.0%), cough (12.5%), and syncope (8.8%). 50% of patients received anticoagulants, 41.2% received thrombolytics and 8.8% received catheter-directed therapy (CDT). 60 patients (75%) were survived. and the rest of them was not.\u003c/p\u003e \u003cp\u003ePatients were classified into two groups: \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNO RVD\u003c/span\u003e group and \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRVD\u003c/span\u003e group according to Echocardiography. Table\u0026nbsp;1 shows the association between the outcome and RVD among studied patients. There was statistically significant higher percent of non -survivors among RVD group compared to no RVD group (45.2% vs 2.6% respectively), p value\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e \u003cp\u003eRVD patients had significantly lower PaO2, SPO2, and higher A-a O2 gradient compared to non-RVD patients (p value0.001).\u003c/p\u003e \u003cp\u003eAs regard the CBC parameters, RVD group showed significantly higher mean RDW (p\u0026thinsp;=\u0026thinsp;0.008) and median NLR, PLR (p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to non-RVD group. However, median MPV did not differ significantly between both groups.\u003c/p\u003e \u003cp\u003eIn addition, RVD group had considerably higher median CRP, D dimer, and troponin levels compared to non-RVD group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eThe most accurate serum markers able to predict RVD were A-a O\u003csub\u003e2\u003c/sub\u003e gradient, serum troponin, CRP, D- dimer, NLR, RDW and PLR in order as shown in table 3 and Fig.\u0026nbsp;1.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;4 demonstrated the predictors attributed with the occurrence of RVD by univariate logistic regression analysis. These predictors included elevated A-a O2gradient, increased RDW, elevated NLR, elevated PLR, elevated CRP, increased D-dimer, and elevated troponin levels. By multivariate logistic regression analysis, the only significant predictor was an increase in the A-a O2 gradient, with an odds ratio of 1.10 and a p-value of 0.047.\u003c/p\u003e \u003cp\u003ePatients were classified according to 30-day mortality into two groups: survivors and non-survivors. Table\u0026nbsp;5 shows the association between ABG, serum markers and mortality among studied patients. There was statistically significant lower mean PO\u003csub\u003e2,\u003c/sub\u003e SPO\u003csub\u003e2,\u003c/sub\u003e and higher mean A-a O\u003csub\u003e2\u003c/sub\u003e gradient among the non-survivors. While, there was no statistically significant difference in mean RDW and mean MPV between survivors and non-survivors (16.57\u0026thinsp;\u0026plusmn;\u0026thinsp;5.485 vs 17.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48, p value\u0026thinsp;=\u0026thinsp;0.425), (9.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32 vs 9.68\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18, p value\u0026thinsp;=\u0026thinsp;0.102) respectively. On the other hand, there was statistically significant higher median NLR, PLR among non-survivors compared to survivors (9.15 vs 3.00, p value\u0026thinsp;\u0026lt;\u0026thinsp;0.001), (270.00 vs 171.50, p value\u0026thinsp;=\u0026thinsp;0.001) respectively. In addition, there was statistically significant higher median CRP, D dimer, troponin among non-survivors, p value\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;6 and Fig.\u0026nbsp;2 show the diagnostic ability of ABG and serum markers in prediction of 30-day mortality, the most serum markers able to predict mortality were, D- dimer, A-a gradient, serum troponin, NLR, CRP and PLR in order.\u003c/p\u003e \u003cp\u003eThe significant predictors associated with 30 day-mortality by univariate logistic regression analysis were increase A-a O\u003csub\u003e2\u003c/sub\u003e gradient, increase NLR, increase CRP, increase D-dimer and increase troponin level as displayed by table (7), but none of them were significant by applying multivariate regression.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAcute PE is a common clinical scenario and effective risk classification and death prediction methods are necessary to cope with different ranges of clinical care strategies for patients with APE.\u003c/p\u003e \u003cp\u003eEchocardiography and MSCT angiography may not always be accessible for assessing the prognosis of acute PE. In addition, patients may have chronic kidney disease, which is a contraindication for contrast administration\u003c/p\u003e \u003cp\u003eThis study aimed to identify the capability of particular laboratory indicators to anticipate right ventricular dysfunction and 30-day mortality in cases of APE.\u003c/p\u003e \u003cp\u003eWe displayed that the RVD group had a statistically significantly higher median NLR and PLR, and mean red cell distribution width (RDW) than the non-RVD group, but the median mean platelet volume was not significantly different. In addition, the non-survivors had a statistically significantly higher median NLR, PLR, and median MPV, but no difference in mean RDW.\u003c/p\u003e \u003cp\u003eThese findings were in consistent with the studies conducted by \u003cb\u003ePhan et al.\u003c/b\u003e and \u003cb\u003eJia et al.\u003c/b\u003e who found NLR and PLR, were significantly higher in RVD patients than none RVD, and elevation of PLR and NLR suggest that acute pulmonary embolism is associated with proinflammatory state (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). \u003cb\u003eIn et al.\u003c/b\u003e found that there was higher mean RDW between both groups as in our study but differs with us in that he found that mean MPV was significantly higher in RVD group (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Our study was not in agreement with \u003cb\u003eYardan et al.\u003c/b\u003e who reported that MPV was higher in RVD group and stated that platelet activation is common in patients with acute PE and correlates with RV dysfunction (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). These differences may be contributed to anticoagulant use, blood sampling timing, storage conditions, analytical techniques, calculation methods, accurate reference ranges and diagnostic cut-offs, This lack of standardization makes data from different methods and analyzers hard to compare (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). \u003cb\u003eMa et al.\u003c/b\u003e concurred with our study as he found statistically significant difference between survivors and non-survivors in NLR, PLR and no difference between both groups in MPV (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe results of our study were in line with prior findings, which indicates that NLR is valuable for classifying risks in patients with venous thromboembolism (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). PLR has been recognized as a novel indicator of systemic inflammation. It was found to have superior predictive value compared to platelet count or lymphocyte count alone in forecasting specific cardiovascular conditions (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Several studies also support our findings and found elevated NLR and PLR in non-survivors (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur results exhibited statistically significant higher median C-reactive protein (CRP), D-dimer and troponin in RVD and non-survivors groups. These results were in accordance with studies performed by \u003cb\u003eAbul et al.\u003c/b\u003e and \u003cb\u003eKeller et al\u003c/b\u003e (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). These results contradicted the findings of Ohigashi et al., who observed no statistically significant disparity in the average levels of CRP, D-dimer, and troponin between the groups with and without RVD. They also concluded that BNP was a more dependable indicator of RVD and a complex course in patients with PE compared to other factors. (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). But Ohigashi et al findings had many limitations, as they included only 50 patients retrospectively and blood samples were withdrawn within 24 hours of admission.\u003c/p\u003e \u003cp\u003eCRP levels is raised in cases of acute PE due to inflammatory reaction with subsequent pleural effusion development and hemorrhagic necrosis of pulmonary infarction (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn regard to the diagnostic accuracy of ABG and serum markers in prediction of RVD and 30 day mortality, the most blood markers capable of predicting RVD were A-a O\u003csub\u003e2\u003c/sub\u003e gradient, serum troponin, CRP, D- dimer, NLR, RDW and PLR in order. In the study conducted by \u003cb\u003eJia et al.\u003c/b\u003e, he found that NLR is more sensitive than troponin and D-dimer in predicting RVD with AUC\u0026thinsp;=\u0026thinsp;0.803 which was not in agreement with our findings (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). \u003cb\u003eOhigashi et al.\u003c/b\u003e had declared that troponin, D-dimer and CRP have high accuracy in predicting RVD with area under the curve (0.703,0.562 and 0.536 respectively)(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRoc curve of troponin in predicting RVD and 30 day mortality (at cut of point\u0026thinsp;\u0026gt;\u0026thinsp;0.07 ng/ml). This was in consistent with \u003cb\u003eHenzler et al.\u003c/b\u003e that found cutoff point of troponin 0.07ng/ml with area under the curve 0.70(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Other studies had found that cutoff value of troponin in predicting RVD were 0.01ng/ml which was different from our findings but agreed with us in that it has higher accuracy in predicting RVD \u003cb\u003e(29,33,)\u003c/b\u003e.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eThere are some discrepancies between our findings and those from previous studies, and because of the different cut-off points, we suggest carrying out more research using a larger sample size of patients. Also, this will allow for a more thorough investigation into the causal relationship between various blood markers and the adverse outcomes caused by pulmonary embolism. Detection of RVD was assessed using TAPSE and pulsed tissue Doppler peak velocity at the TV annulus (S' velocity), and there are some other novel methods such as fractional area change and RV strain that have higher sensitivity in detecting RV dysfunction.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eEvaluation of different serum markers including NLR, PLR, RDW, CRP, D-dimer, troponin and A-a O\u003csub\u003e2\u003c/sub\u003e gradient are simple and available markers for predicting right ventricular dysfunction (RVD) and 30- day mortality in patients with APE.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eA-a O\u003csub\u003e2: \u0026nbsp;\u003c/sub\u003eAlveolar - arterial oxygen\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAPE: Acute pulmonary embolism\u003c/p\u003e\n\u003cp\u003eAOR: Adjusted odds ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eABG: Arterial blood gas analysis\u003c/p\u003e\n\u003cp\u003eCBC: Complete blood count\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eComputed Tomography Pulmonary Angiography (CTPA)\u003c/p\u003e\n\u003cp\u003eCRP: C-reactive protein\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMPV: Mean platelet volume\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNLR: Neutrophil to lymphocytic ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePaO\u003csub\u003e2:\u0026nbsp;\u003c/sub\u003ePartial pressure of arterial oxygen\u003c/p\u003e\n\u003cp\u003ePaCo2: Partial arterial carbon dioxide\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePLR: Platelet to lymphocytic ratio \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePE: Pulmonary embolism\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRICU\u0026nbsp;:\u0026nbsp;Respiratory Intensive Care Unit \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRDW: Red cell distribution width \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRVD: Right ventricular dysfunction\u003c/p\u003e\n\u003cp\u003eROC: Roc curve analysis\u003c/p\u003e\n\u003cp\u003eS\u0026apos; velocity: Pulsed tissue Doppler peak velocity at the annulus\u003c/p\u003e\n\u003cp\u003eTAPSE: Tricuspid annular plane systolic excursion\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eWe wish to submit an original article entitled (Prognostic value of laboratory markers in patients with acute pulmonary embolism) for consideration by Expert Review of Pulmonology.\u003c/p\u003e\n\u003cp\u003eWe confirm that this work is original and has not been published elsewhere, nor it is currently under consideration for publication elsewhere.\u003c/p\u003e\n\u003cp\u003eWe had full access to all the data in this study and accept responsibility to submit this publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe have no conflicts of interest to disclose.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors participated in conception and design. AA collected the data and samples. AO, AF and YA were responsible for analysis and interpretation of data. KM and AH were responsible for drafting the article. AO and AF revised it critically for final approval of the version to be published. All authors have read and approved the manuscript.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate the study was approved by the Local Ethics Committee of the Assiut University Hospital, the committee\u0026rsquo;s reference number IRB no:\u0026nbsp;17200409. Informed consent was obtained from all the participants before enrollment\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors approved the manuscript for publication. Identifying images or other personal or clinical details of participants is \u0026ldquo;Not Applicable.\u0026rdquo; Consent for publication from the participants is \u0026ldquo;Not Applicable.\u0026rdquo;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData available on request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eElias A, Mallett S, Daoud-Elias M, Poggi JN, Clarke M. Prognostic models in acute pulmonary embolism: A systematic review and meta-analysis. BMJ Open. 2016;6(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede-Miguel-Diez J, L\u0026oacute;pez-de-Andr\u0026eacute;s A, Hernandez-Barrera V, Jimenez D, Monreal M, L\u0026oacute;pez-Herranz M, et al. The significance of heart failure in hospitalised patients with pulmonary embolism. A gender-specific analysis. Int J Clin Pract. 2021;75(10):1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: A scientific statement from the american heart association. Circulation. 2011;123(16):1788\u0026ndash;830.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, et al. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism. N Engl J Med. 2014;370(15):1402\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLega JC, Lacasse Y, Lakhal L, Provencher S. Natriuretic peptides and troponins in pulmonary embolism: a meta-analysis. Thorax. 2009;64(10):869\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoomro AY, Guerchicoff A, Nichols DJ, Suleman J, Dangas GD. The current role and future prospects of D-dimer Biomarker. Eur Hear J - Cardiovasc Pharmacother. 2016;2(3):175\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbul Y, Karakurt S, Ozben B, Toprak A, Celikel T. C-Reactive Protein in Acute Pulmonary Embolism. 2023;59(1):8\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu J, Liu Y, Zhang F, Fu C, Ling Y, Fang P, et al. Short-term prognostic value of clinical data in hospitalized patients with intermediate-risk acute pulmonary embolism. BMC Cardiovasc Disord. 2022;22(1):1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaghihi Langhroudi T, Borji Esfahani M, Khaheshi I, Naderian M, Zahedi Tajrishi F, Namazi MJ. Correlation of Hematologic Indices with CT-pulmonary Arterial Obstruction Index in Patients with Acute Pulmonary Emboli. Int J Cardiovasc Pract. 2019;4(3):89\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDabbouseh NM, Patel JJ, Bergl PA. Role of echocardiography in managing acute pulmonary embolism. Heart. 2019;105(23):1785\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBikdeli B, Lobo JL, Jim\u0026eacute;nez D, Green P, Fern\u0026aacute;ndez-Capit\u0026aacute;n C, Bura-Riviere A, et al. Early use of echocardiography in patients with acute pulmonary embolism: Findings from the RIETE registry. J Am Heart Assoc. 2018;7(17):1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBing R, Chow V, Lau JK, Thomas L, Kritharides L, Ng ACC. Prevalence of echocardiography use in patients hospitalized with confirmed acute pulmonary embolism: A Real-World observational multicenter study. PLoS One. 2016;11(12):1\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKonstantinides, S. V., Meyer, G., Becattini, C., Bueno, H., Geersing, G. J., Harjola, V. P., \u0026hellip; Zamorano, J. L. (2019). The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC) Eur Respir J, \u003cem\u003e54\u003c/em\u003e(3), 1901647.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSubramanian M, Ramadurai S, Arthur P, Gopalan S. Hypoxia as an independent predictor of adverse outcomes in pulmonary embolism. Asian Cardiovasc Thorac Ann. 2018;26(1):38\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarejloo S, Khanzadeh S, Hosseini S, Gargari MK, Lucke-Wold B, Mosalamiaghili S, et al. Role of the Neutrophil to Lymphocyte Ratio in Guillain Barr\u0026eacute; Syndrome: A Systematic Review and Meta-Analysis. Mediators Inflamm. 2022;2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNI A. Reference Values of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio and Mean Platelet Volume in Healthy Adults in North Central Nigeria. J Blood Lymph. 2016;6(1):1\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdelghany EA, Othman AM, Abdelfatah RA, Magdy M-E, Abd Elghany HS, Higazi MM. Can alveolar\u0026mdash;arterial oxygen gradient predict severity of pulmonary embolism? Egypt J Bronchol. 2019;13(2):273\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the Echocardiographic Assessment of the Right Heart in Adults: A Report from the American Society of Echocardiography. Endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and. J Am Soc Echocardiogr. 2010;23(7):685\u0026ndash;713.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhan T, Brailovsky Y, Fareed J, Hoppensteadt D, Iqbal O, Darki A. Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios Predict All-Cause Mortality in Acute Pulmonary Embolism. 2020;\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJia D, Liu F, Zhang Q, Zeng GQ, Li XL, Hou G. Rapid on-site evaluation of routine biochemical parameters to predict right ventricular dysfunction in and the prognosis of patients with acute pulmonary embolism upon admission to the emergency room. J Clin Lab Anal. 2018;32(4):1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIn E, Deveci F, Kaman D, \u0026Ouml;zdemir C, S\u0026ouml;k\u0026uuml;c\u0026uuml; SN, Kulu\u0026ouml;zt\u0026uuml;rk M, et al. The importance of mean platelet volume and red cell distribution width in acute pulmonary embolism. Acta Medica Mediterr. 2015;31(6):1209\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYardan T, Meric M, Kati C, Celenk Y, Atici AG. Mean platelet volume and mean platelet volume/platelet count ratio in risk stratification of pulmonary embolism. Med. 2016;52(2):110\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLippi, G., Sanchis-Gomar, F., \u0026amp; Favaloro, E. J. (2020). Mean platelet volume in arterial and venous thrombotic disorders. Journal of Laboratory Medicine, \u003cem\u003e44\u003c/em\u003e(5), 305\u0026ndash;312.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa Y, Mao Y, He X, Sun Y, Huang S, Qiu J. The values of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in predicting 30 day mortality in patients with acute pulmonary embolism. BMC Cardiovasc Disord. 2016;16(1):1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBakirci EM, Topcu S, Kalkan K, Tanboga IH, Borekci A, Sevimli S, et al. The role of the nonspecific inflammatory markers in determining the anatomic extent of venous thromboembolism. Clin Appl Thromb. 2015;21(2):181\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang D, Yang JX, Cao DY, Wan XR, Feng FZ, Huang HF, et al. Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma. Onco Targets Ther. 2013;6:211\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarataş MB, İpek G, Onuk T, G\u0026uuml;ng\u0026ouml;r B, Durmuş G, \u0026Ccedil;anga Y, et al. Assessment of prognostic value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patients with pulmonary embolism. Acta Cardiol Sin. 2016;32(3):313\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbul Y, Karakurt S, Ozben B, Toprak A, Celikel T. C-Reactive Protein in Acute Pulmonary Embolism. 2023;59(1):8\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeller K, Beule J, Schulz A, Coldewey M, Dippold W, Balzer JO. Cardiac troponin I for predicting right ventricular dysfunction and intermediate risk in patients with normotensive pulmonary embolism. Netherlands Hear J. 2015;23(1):55\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhigashi H, Haraguchi G, Yoshikawa S, Sasaki T, Kimura S, Inagaki H, et al. Comparison of biomarkers for predicting disease severity and long-term respiratory prognosis in patients with acute pulmonary embolism. Int Heart J. 2010;51(6):416\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026uuml;y\u0026uuml;kşirin, M., Anar, C., Polat, G., \u0026amp; Karadeniz, G. (2021). Can the level of crp in acute pulmonary embolism determine early mortality?. Turkish Thoracic Journal, \u003cem\u003e22\u003c/em\u003e(1), 4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHenzler T, Roeger S, Meyer M, Schoepf UJ, Jr JWN, Haghi D, et al. Pulmonary embolism: CT signs and cardiac biomarkers for predicting right ventricular dysfunction. 2012;39(4):919\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKucher N, Wallmann D, Carone A, Windecker S, Meier B, Hess OM. Incremental prognostic value of troponin I and echocardiography in patients with acute pulmonary embolism. Eur Heart J. 2003;24(18):1651\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 7 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pulmonary embolism (PE), laboratory markers, Right ventricular dysfunction","lastPublishedDoi":"10.21203/rs.3.rs-4668387/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4668387/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAcute pulmonary embolism (APE) is a serious illness. Identifying prognostic factors for APE may help in the management of those patients. This study's objective was to evaluate the prognostic value of laboratory markers in predicting right ventricular dysfunction (RVD) and 30-day mortality in pulmonary embolism patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eEighty patients with APE were enrolled and followed up for 30-day. Detailed echocardiography was done to evaluate RVD. All patients were subjected to arterial blood gas analysis, complete blood count (CBC), plasma concentration of C-reactive protein (CRP), serum D-dimer level, and serum troponin I level, and the following ratio were calculated: Neutrophil to lymphocytic ratio (NLR), Platelet to lymphocytic ratio (PLR), Red cell distribution width (RDW), Mean platelet volume (MPV) and alveolar to arterial gradient.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOur results analysis revealed significantly elevated levels of median NLR, PLR, CRP, D-dimer, and troponin in both the RVD and non-survivor groups (P value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The blood markers that showed the highest predictive ability for right ventricular dysfunction (RVD) and 30-day mortality, as determined by receiver operating characteristic (ROC) analysis and logistic regression, were A-a O2 gradient, serum troponin, CRP, D-dimer, NLR, and PLR (P value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eEvaluation of different serum markers including NLR, PLR, RDW, CRP, D-dimer, troponin and A-a O\u003csub\u003e2\u003c/sub\u003e gradient are simple and available markers for predicting right ventricular dysfunction (RVD) and 30- day mortality in patients with APE.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003eClinicalTrials.gov ID: NCT04237974.\u003c/p\u003e","manuscriptTitle":"Prognostic value of laboratory markers in patients with acute pulmonary embolism","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-09 14:23:48","doi":"10.21203/rs.3.rs-4668387/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"efd3560d-7494-47db-8b60-ed11c36b0c94","owner":[],"postedDate":"August 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-05T02:08:55+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-09 14:23:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4668387","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4668387","identity":"rs-4668387","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}