Establishing altitude-based coagulation reference ranges in Western Sichuan

Establishing altitude-based coagulation reference ranges in Western Sichuan | 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 Article Establishing altitude-based coagulation reference ranges in Western Sichuan Qing Yuan, YanWu Liu, JiaYu Liu, MingXia Tang, Jian Yang, ShuZhi Zhou, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5500873/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 May, 2025 Read the published version in Scientific Reports → Version 1 posted 6 You are reading this latest preprint version Abstract The diagnosis and treatment of diseases in plateau regions should incorporate altitude, sex, and age in addition to hematological indicators from plain regions. This study analyzed coagulation results among individuals living at different altitudes in the Western Sichuan Plateaus and belonging to different sex and age groups to examine patterns of change and determine normal ranges. By comparing the changes in coagulation indicators among healthy male and female residents of different age groups (< 40 years, 40–59 years, ≥ 60 years) from Guza (1,400 m), Kangding (2,500 m), Luhuo (3,400 m), and Litang (4,100 m), we analyzed the association between coagulation indicators and altitude, age, and sex. Under low temperature, hypoxia, and other plateau environment factors, coagulation indicators varied among different altitudes, with some indicators showing specific trends of change with increasing altitude. Different sexes and age groups also exhibited specific patterns of change in coagulation results. This study clarified the patterns of change in coagulation results at four different altitudes in the Western Sichuan Plateau and the effects of sex and age on coagulation function. Normal ranges of coagulation values were determined for different sexes and age groups at different altitudes, providing a scientific basis for healthcare in this region. Biological sciences/Physiology/Circulation/Thrombosis Health sciences/Risk factors Health sciences/Medical research/Outcomes research Health sciences/Health care/Disease prevention/Preventive medicine plateau residents altitude sex age group coagulation reference range Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 1 Introduction The Western Sichuan Plateau, located in southwestern China, has an average altitude of more than 3,500 m and is renowned for its unique landscape. Under hypoxic, low-temperature, and other extreme conditions that characterize high-altitude regions, physiological functions can undergo a series of adaptive changes, with the most prominent being hematological changes [ 1 ] . These changes vary across altitudes, sexes, and age groups [ 2 ] . Therefore, the diagnosis and treatment of diseases in plateau regions cannot be based completely on the hematological indicators in plain regions but should incorporate altitude, sex, and age [ 3 ] . Recently, numerous scholars have explored the changes in coagulation indicators in the plateau environment [ 4 ] . However, their research focuses more on independently studying the impact of altitude on coagulation indicators, and there is relatively less research on the variation patterns of coagulation indicators under the combined influence of altitude, age, and sex. Coagulation indicators are crucial in clinical practice, particularly for preoperative preparations. Therefore, there is a need to conduct systematic and comprehensive research. This study aimed to collect blood samples from healthy individuals living at different altitudes on the Western Sichuan Plateau and test their coagulation-related indicators. Based on the analysis and comparison of these data, we aimed to elucidate the patterns of changes in coagulation findings among healthy individuals living at different altitudes. Based on these findings, coagulation reference ranges suitable for the Western Sichuan Plateau were established, which can serve as a scientific basis for local medical diagnosis and health management. 2 Materials and Methods 2.1 Participants The study was approved by the Ethics Committee of Yaan People’s Hospital (approval number: 2023 011). Before blood collection, the purpose of blood collection and the rights of the subjects were fully explained to the participants, who provided written informed consent. All experimental methods were carried out in accordance with the relevant guidelines and regulations, including but not limited to the Helsinki Declaration and its subsequent amendments, as well as any specific ethical and regulatory requirements applicable to this type of research. Healthy individuals living in Guza Town of Kangding County, Lucheng Subdistrict of Kangding County, Luhuo County, and Litang County of Ganzi Prefecture, Sichuan Province, were screened in March and August 2024. The screening criteria were as follows: 1. absence of inflammatory diseases and use of oral antibiotics, anticancer drugs, and anticoagulants within the previous month; 2. body mass index (BMI) between 18.5 and 23.9 kg/m 2 ; 3. absence of abnormalities in cardiopulmonary function; and 4. absence of abnormalities in hepatic and kidney functions; 5. no history of immunological or hematological diseases; and 6. age > 18 years. After the screening, 521 individuals (255 male and 266 female participants) from Guza Town, 980 individuals (385 male and 595 female participants) from Lucheng Subdistrict, 821 individuals (361 male and 460 female participants) from Luhuo County, and 1,135 individuals (560 male and 575 female participants) from Litang County were included in the analysis. 2.2 Methods 2.2.1 Test methods For coagulation function tests, 3 mL of venous blood was collected using a vacutainer containing 0.109 mmol/L sodium citrate as an anticoagulant, and the samples were centrifuged at 1500 × g for 15 min to separate the plasma. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT) were measured within 2 h of blood sample collection using a Sysmex CS5100 (Tokyo, Japan) Fully Automated Blood Coagulation Analyzer from Sekisui Diagnostic Japan and its supporting reagents. 2.2.2 Test parameters Test data were processed using Microsoft Excel 365, and the items included PT, TT, APTT, and FIB. 2.2.3 Statistical methods Data were analyzed using SPSS 25.0(IBM Corporation, Armonk, NY, USA). Normally distributed quantitative data are shown as mean ± standard deviation (SD) and were compared between groups using one-way analysis of variance (ANOVA). Further pairwise comparisons of between-group differences were performed using the least significant difference (LSD) method. Differences were considered statistically significant at P < 0.05. 3 Results 3.1 Comparison of coagulation indicators between different sexes at the same altitude After a meticulous analysis of the coagulation test results of the local population, we determined that the coagulation results across different altitudes, sexes, and age groups follow a normal distribution, and one-way ANOVA was employed for comparisons among various groups. Through group-by-group comparisons, we discovered that at the same altitude, male participants had significantly higher PT, APTT, TT, and FIB levels than female participants (P < 0.05) (see Tables 1 − 4). Table 1 Comparison of indicators between sexes among the residents of Guza Indicator Male ( n = 255) Female ( n = 266) T P PT (s) 14.13 ± 0.96 13.90 ± 0.82 2.927 0.004 APTT (s) 36.40 ± 1.92 35.62 ± 2.49 4.020 < 0.001 TT (s) 18.28 ± 1.43 17.87 ± 1.38 3.366 0.001 FIB (g/L) 3.17 ± 0.61 3.04 ± 0.59 3.067 0.002 PT, prothrombin time; APTT, activated partial thromboplastin time; TT, thrombin time; FIB, fibrinogen Table 2 Comparison of indicators between sexes among the residents of Kangding Indicator Male ( n = 385) Female ( n = 595) T P PT (s) 14.84 ± 1.22 14.29 ± 0.97 7.370 < 0.001 APTT (s) 38.16 ± 1.58 36.55 ± 2.48 12.424 < 0.001 TT (s) 19.72 ± 1.33 18.55 ± 1.07 14.449 < 0.001 FIB (g/L) 3.20 ± 0.06 3.13 ± 0.11 7.791 < 0.001 Table 3 Comparison of indicators between sexes among the residents of Luhuo Indicator Male ( n = 361) Female ( n = 488) t P PT (s) 15.25 ± 0.94 14.58 ± 1.03 11.733 < 0.001 APTT (s) 39.12 ± 1.86 36.97 ± 3.08 9.772 < 0.001 TT (s) 20.62 ± 1.48 17.35 ± 1.40 12.604 < 0.001 FIB (g/L) 3.47 ± 0.37 3.12 ± 0.53 2.697 0.007 Table 4 Comparison of indicators between sexes among the residents of Litang Indicator Male ( n = 560) Female ( n = 575) t P PT (s) 16.48 ± 1.37 16.06 ± 1.66 4.642 < 0.001 APTT (s) 41.91 ± 3.1 39.48 ± 5.57 9.123 < 0.001 TT (s) 21.69 ± 1.99 21.40 ± 2.11 2.311 0.021 FIB (g/L) 3.52 ± 0.69 3.28 ± 0.71 3.277 0.001 3.2 Comparison of coagulation indicators among different altitudes within the same sex Based on the analysis of coagulation indicators in male participants at different altitudes, we found the following sequences regarding PT, APTT, and TT: Litang > Luhuo and Kangding > Guza, with no difference between Luhuo and Kangding and significant differences for the remaining pairwise comparisons. For FIB, the sequence was Litang and Luhuo > Kangding and Guza, with no differences between Litang and Luhuo or between Kangding and Guza and significant differences for the remaining pairwise comparisons (Table 5 ). Table 5 Comparison of indicators among male participants in different regions Indicator Guza ( n = 255) Kangding ( n = 385) Luhuo ( n = 361) Litang ( n = 560) F P PT (s) 14.13 ± 0.96 ■▽ 14.84 ± 1.22 ▲▽ 15.25 ± 0.94 ▲▽ 16.48 ± 1.37 ▲☐■ 284.130 < 0.001 APTT (s) 36.4 ± 1.92 ☐■▽ 38.16 ± 1.58 ▲▽ 39.12 ± 1.86 ▲▽ 41.91 ± 3.10 ▲☐■ 393.243 < 0.001 TT (s) 18.28 ± 1.43 ☐■▽ 19.72 ± 1.33 ▲■▽ 20.62 ± 1.48 ▲☐▽ 21.69 ± 1.99 ▲☐■ 294.570 < 0.001 FIB (g/L) 3.17 ± 0.61 ■▽ 3.20 ± 0.06 ■▽ 3.47 ± 0.37 ▲☐ 3.52 ± 0.69 ▲☐ 32.160 < 0.001 “ ▲ ” indicates significant difference compared to Guza; “ ☐ ” indicates significant difference compared to Kangding; “ ■ ” indicates significant difference compared to Luhuo; “ ▽ ” indicates significant difference compared to Litang. Based on the analysis of coagulation indicators in female participants at different altitudes, we found the following sequence for PT and APTT: Litang > Luhuo and Kangding > Guza, with no difference between Luhuo and Kangding and significant differences for the remaining pairwise comparisons. For TT and FIB, the sequence was Litang > Luhuo > Kangding > Guza, with significant differences in all pairwise comparisons (Table 6 ). Table 6 Comparison of indicators among female participants in different regions Indicator Guza ( n = 266) Kangding ( n = 595) Luhuo n = 488 Litang ( n = 575) F P PT (s) 13.90 ± 0.82 ☐■▽ 14.29 ± 0.97 ▲▽ 14.58 ± 1.03 ▲▽ 16.06 ± 1.66 ▲☐■ 292.575 < 0.001 APTT (s) 35.62 ± 2.49 ☐■▽ 36.55 ± 2.48 ▲▽ 36.97 ± 3.08 ▲▽ 39.48 ± 5.57 ▲☐■ 88.905 < 0.001 TT (s) 17.87 ± 1.38 ☐■▽ 18.55 ± 1.07 ▲■▽ 19.35 ± 1.40 ▲☐▽ 21.40 ± 2.11 ▲☐■ 453.364 < 0.001 FIB (g/L) 3.04 ± 0.59 ☐■▽ 3.13 ± 0.11 ▲■▽ 3.19 ± 0.53 ▲☐▽ 3.28 ± 0.71 ▲☐■ 16.722 < 0.001 “ ▲ ” indicates significant difference compared to Guza; “ ☐ ” indicates significant difference compared to Kangding; “ ■ ” indicates significant difference compared to Luhuo; “ ▽ ” indicates significant difference compared to Litang. 4 Discussion In the human hematological system, coagulation, fibrinolysis, and anticoagulation are interconnected and mutually regulated [ 4 ] . These processes involve a series of complex biochemical reactions [ 5 ] , among which PT, TT, APTT, and FIB are key indicators. PT reflects the extrinsic pathway of coagulation and is mainly used to evaluate blood hypercoagulability and the efficacy of anticoagulant therapy [ 6 ] . TT is an indicator of the common coagulation pathway that reflects the extent of fibrinogen degradation and is used to evaluate blood hypercoagulability and the efficacy of anticoagulant therapy [ 7 ] . APTT reflects the intrinsic pathway of coagulation and is primarily used to evaluate the risk of blood hypercoagulability and thrombotic disorders [ 8 ] . FIB is a key protein in blood coagulation and a major target of the anticoagulation system [ 9 ] . It is a crucial factor that reflects blood hypercoagulability and thrombosis. Blood coagulation, fibrinolysis, and anticoagulation are the key processes in the maintenance of vascular integrity and blood fluidity [ 10 ] . Attaining a balance among these three processes is critical to human health; an imbalance may lead to the pathogenesis of various diseases, including thrombosis and bleeding disorders [ 11 , 12 ] . In high-altitude and hypoxic environments, the human body exhibits elevated red blood cell (RBC) and hemoglobin (HGB) levels [ 13 ] . The compensatory phenomenon known as high-altitude polycythemia (HAPC) [ 14 ] , which is predominantly characterized by elevated RBC, is a physiological change that occurs when the human body adapts to high-altitude environments. Higher altitudes are associated with more pronounced HAPC [ 15 ] . An increase in RBC count can lead to higher blood viscosity and increased platelet adhesion and factor VIII-related antigens [ 2 ] . Hypoxia can also damage vascular endothelial cells [ 16 ] and activate the intrinsic and extrinsic pathways of coagulation, thereby promoting blood hypercoagulability [ 17 , 18 ] . Furthermore, a hypoxic plateau environment can cause platelet activation, trigger the intrinsic coagulation system, and contribute to the consumption of coagulation factors [ 19 ] . Animal experiments [ 20 , 21 ] have also demonstrated that the expression levels of extrinsic and intrinsic coagulation factors are reduced in the hypoxic environment of plateaus. Therefore, we believe that a hypoxic plateau environment can give rise to coagulopathies [ 22 , 23 ] , resulting in the gradual increase in APTT, TT, and PT with increasing altitude [ 23 , 24 ] . In addition, the compensatory increase in RBC and blood viscosity can lead to the relative suppression of fibrinolysis [ 12 ] , which contributes to a hypercoagulable and hypofibrinolytic state [ 25 ] , thereby resulting in higher FIB values than those in the population living in plain regions [ 26 ] . Regarding the impact of high altitudes and hypoxia on individuals of different sexes, hypoxic environments stimulate the production of erythropoietin (EPO) [ 27 ] , which induces the formation of erythroid progenitors by hematopoietic stem cells, thereby promoting the increase in RBC levels [ 28 ] . As androgens can promote EPO secretion [ 29 ] , the changes in relevant indicators were more pronounced among male participants than among female participants at the same altitude. These results indicate that the existing reference ranges of coagulation indicators for adults established in plain regions are not suitable for healthcare diagnosis and treatment of populations living in plateau areas. Our findings revealed that the PT, TT, APTT, and FIB values of male participants were significantly higher than those of female participants at the same altitude. We believe that this phenomenon is related to the secretion of male androgens, which promote an increase in EPO. Analysis of the same indicators at different altitudes showed that the PT, TT, APTT, and FIB values increased gradually as altitude increased. After analyzing the ranges of the relevant indicators, we found that the upper limits of all reference ranges (except for PT, TT, APTT, and FIB values of individuals aged < 40 years in Guza; FIB values of those aged < 60 years in Guza and Kangding; and PT values of those aged < 40 years in Kangding) exceeded the existing range of normal values [ 30 ] . Based on these findings (Figs. 1 – 8 ), we can infer that PT, TT, APTT, and FIB values will increase with increasing altitude and age. Long-term exposure to the hypoxic environment of high-altitude areas can cause continuous damage to the inner wall of blood vessels [ 31 ] , and the degree of this damage is significantly positively correlated with the length of time an individual lives in this hypoxic environment [ 32 , 33 ] . Once the inner wall of the blood vessels is damaged, the intrinsic and extrinsic coagulation pathways can be rapidly activated, thereby promoting a hypercoagulable state [ 34 ] . To maintain normal blood fluidity and ensure that all organs of the body can receive sufficient blood supply, the body automatically activates regulatory mechanisms that prolong the coagulation time [ 35 ] . Therefore, when observing participants of the same altitude, the cumulative time an individual lives in the hypoxic environment increases with age, resulting in a gradual prolongation of the coagulation time parameters. This confirms that the existing reference ranges of coagulation indicators for adults established in plain regions are not suitable for healthcare diagnosis and treatment of populations living in plateau regions. This study has certain limitations. First, the effects of different races were not fully considered. Due to genetic differences and varying lifestyles, different races may have different blood indicators. For example, previous research has shown that a particular race that lives at the highest altitude and has the longest history of adaptation has developed a comprehensive oxygen supply and utilization system effective at the level of the entire body, organs, cells, and molecules. This situation has enabled them to demonstrate the most remarkable adaptability to the plateau environment. [ 36 ] . The western Sichuan plateau is also inhabited by multiple ethnic groups such as the Han, Qiang, and Yi. However, this study did not differentiate between the local population by ethnicity; therefore, the results may differ from the actual situation. Second, the study did not consider factors such as season and temperature, which are known to significantly influence both cardiovascular health and associated blood indicators [ 37 ] . Therefore, to achieve accurate results, the influence of season and temperature cannot be ignored. Third, there is a lack of continuity in the choice of altitudes. In the future, we plan to compare and classify individuals based on their ethnicity and the blood collection season, fully incorporating ethnic and seasonal factors. Additionally, we will refine the altitude points to achieve high precision and personalization. In summary, we believe that in high-altitude environments, sex, age, and altitude can alter coagulation indexes, in addition to other factors [38.39] . China has a vast territory, a complex variety of climate types, and a rich ethnic composition. Especially in high-altitude areas, the diversity of the ecological environment and lifestyle further exacerbates the complexity of physiological indexes. A single coagulation index simply cannot meet the actual needs in such complex and variable situations. Therefore, there is an urgent need for more accurate and targeted coagulation indexes to assist in the diagnosis of local patients’ diseases, the formulation of treatment plans, and the planning of public health strategies, in order to improve the quality and efficiency of medical services in plateau areas and safeguard the health and well-being of residents. For example, when diagnosing altitude-specific diseases closely related to coagulation function, such as high-altitude pulmonary edema and high-altitude cerebral edema, accurate coagulation indexes can help doctors judge the condition more timely and accurately and improve patient survival. When formulating public health strategies in plateau areas, these indexes can also provide a scientific basis for preventing the occurrence of thrombotic diseases and optimizing the allocation of medical resources. Declarations Acknowledgments None. Ethics approval This study was approved by the Ethics Committee of Yaan People’s Hospital [2023 011]. Written informed consent was obtained from all participants. Author contributions Qing Yuan and YanWu Liu wrote the manuscript. All authors were involved in data collection. JiaYu Liu, MingXia Tang, and Jian Yang performed the analyses and interpreted data. ShuZhi Zhou, Ling Zhang, JunWu Du, KongJie Yang, and XiaoXue Li gathered relevant information and prepared the tables in the paper. Zhenglin Huang critically revised the manuscript for important intellectual content. All authors reviewed the manuscript. All authors read and approved the final manuscript. Data availability statement The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Funding This study was funded by the transfer payment project of the Science and Technology Department of Sichuan Province. Project code: 22ZYZF0009. Competing interests The authors declare no competing interests. References Patrician, A. et al. Manipulation of iron status on cerebral blood flow at high altitude in lowlanders and adapted highlanders. J. Cereb. Blood Flow. Metab. Int. 43 , 1166–1179 (2023). Rocke, A. S. et al. Thromboelastometry and platelet function during acclimatization to high altitude. Thromb. Haemost . 118 , 63–71 (2018). Prabhakar, A. et al. Venous thrombosis at altitude presents with distinct biochemical profiles: a comparative study from the Himalayas to the plains. Blood Adv. 3 , 3713–3723 (2019). Li, M. et al. Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude. Blood 140 , 2063–2075 (2022). Wang, R., Tang, L. V. & Hu, Y. Genetic factors, risk prediction and AI application of thrombotic diseases. Exp. Hematol. Oncol. 13 , 89 (2024). Obeagu, E. I. & Obeagu, G. U. Thromboinflammation in COVID-19: Unraveling the interplay of coagulation and inflammation. Med. (Baltimore) . 103 , e38922 (2024). Heidari, Z. et al. Impact of tissue factor gene knockout on coagulation properties of umbilical cord-derived multipotent mesenchymal stromal/stem cells. Cell. Biochem. Funct. 42 , e70021 (2024). Wu, J. et al. Structure-based design and synthesis of novel FXIa inhibitors targeting the S2’ subsite for enhanced antithrombotic efficacy. Mol. Divers. 10.1007/s11030-024-11024-2 Hughes, P. R., Lewis, M. N. & Adams, S. S. Bleeding and bruising: Primary care evaluation. Am. Fam Physician . 110 , 504–514 (2024). Venancio de Lima, E. O. et al. Understanding the effects of Bothrops erythromelas and Bothrops leucurus venoms on human blood coagulation. Toxicon 255 , 108231 (2025). Campbell, J. E., Brummel-Ziedins, K. E., Butenas, S. & Mann, K. G. Cellular regulation of blood coagulation: a model for venous stasis. Blood 116 , 6082–6091 (2010). Shao, F., Liu, S., Yang, R., Zhang, X. & Zhong, Y. Predictive value of prenatal ultrasound combined with long non-coding RNA CRNDE of women for their postpartum lower extremity deep venous thrombosis. J. Matern Fetal Neonatal Med. 37 , 2352089 (2024). Cui, J. H., Zhang, X. Z., Xie, Y. Z., Zhou, X. M. & Ha, Z. D. [The changes of coagulation and fibrinolysis function on hypoxia adaptation mechanism]. Zhongguo Ying Yong Sheng Li Xue Za Zhi . 17 , 363–365 (2001). Stauffer, E. et al. Making a virtue out of an evil: Are red blood cells from chronic mountain sickness patients eligible for transfusions. Am. J. Hematol. 99 , 1407–1410 (2024). Starkey, C. R., Davies, L., Hoyer, J. D., Wilson, C. S. & Winter, S. S. Clinical manifestations of hemoglobin Chico at high altitude. J. Pediatr. Hematol. Oncol. 28 , 760–762 (2006). Ma, J. K. et al. TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia. Nat. Commun. 15 , 3976 (2024). Paz, A. A. et al. Gestational hypoxia elicits long-term cardiovascular dysfunction in female guinea pigs. Life Sci. 361 , 123282 (2025). Li, M. et al. Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude. Blood 140 , 2063–2075 (2022). DeSouza, N. M. et al. : Influence of excessive erythrocytosis on coagulation and fibrinolytic factors in Andean highlanders. Exp. Physiol. 106, 1335–1342 (2021). (2018). Garvey, M. B., Dennis, L. H., Hildebrandt, P. K. & Conrad, M. E. Hypobaric erythraemia: pathology and coagulation studies. Br. J. Haematol. 17 , 275–281 (1969). Nakanishi, K. et al. Hypercoagulable state in a hypobaric, hypoxic environment causes non-bacterial thrombotic endocarditis in rats. J. Pathol. 181 , 338–346 (1997). Akunov, A., Sydykov, A., Toktash, T., Doolotova, A. & Sarybaev, A. Hemoglobin changes after long-term intermittent work at high altitude. Front. Physiol. 9 , 1552 (2018). Treml, B., Wallner, B., Blank, C., Fries, D. & Schobersberger, W. The influence of environmental hypoxia on hemostasis-A systematic review. Front. Cardiovasc. Med. 9 , 813550 (2022). Wang, Z. et al. The quality changes in fresh frozen plasma of the blood donors at high altitude. PLoS One . 12 , e0176390 (2017). Larsen, J. B., Hvas, C. L. & Hvas, A. M. Modified rotational thromboelastometry protocol using tissue plasminogen activator for detection of hypofibrinolysis and hyperfibrinolysis. Methods Mol. Biol. 2663 , 763–773 (2023). Tan, Z. et al. Assessment of metabolomic variations among individuals returning to plain areas after exposure to high altitudes: a metabolomic analysis of human plasma samples with high-altitude de-acclimatization syndrome. Front. Mol. Biosci. 11 , 1375360 (2024). Iwamura, Y. et al. Erythropoietin production in embryonic neural cells is controlled by hypoxia signaling and histone deacetylases with an undifferentiated cellular state. Mol. Cell. Biol. 45 , 32–45 (2025). Semenza, G. L., Nejfelt, M. K., Chi, S. M. & Antonarakis, S. E. Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene. Proc. Natl. Acad. Sci. USA. 88, 5680–5684 (1991). Warren, A. M. & Grossmann, M. Haematological actions of androgens. Best Pract. Res. Clin. Endocrinol. Metab. 36 , 101653 (2022). National Health and Family Planning Commission of the People’s Republic of China. Reference intervals for blood cell analysis. (2012). http://www.nhc.gov.cn/zwgkzt/s9492/201301/d893733b674945afa63bc33f3cc7e60d.shtml Fan, N., Liu, C. & Ren, M. Effect of different high altitudes on vascular endothelial function in healthy people. Med. (Baltimore) . 99 , e19292 (2020). Bloom, S. I. et al. Reduction of double-strand DNA break repair exacerbates vascular aging. Aging (Albany NY) . 15 , 9913–9947 (2023). You, Q. et al. Loss of endothelial annexin A1 aggravates inflammation-induced vascular aging. Adv. Sci. (Weinh) . 11 , e2307040 (2024). De Pablo-Moreno, J. A., Serrano, L. J., Revuelta, L., Sánchez, M. J. & Liras, A. The vascular endothelium and coagulation: homeostasis, disease, and treatment, with a focus on the Von Willebrand factor and Factors VIII and V. Int . J. Mol. Sci. 23 , 8283 (2022). Hillary, T. M. et al. A prospective, monocentric case-control study on uncontrolled psoriasis as independent risk factor for a hypercoagulable state. Dermatol. Ther. (Heidelb) . 14 , 767–775 (2024). Shi, J. et al. Structural variants involved in high-altitude adaptation detected using single-molecule long-read sequencing. Nat. Commun. 14 , 8282 (2023). Okuno, T. et al. Association of onset-season with characteristics and long-term outcomes in acute myocardial infarction patients: results from the Japanese registry of acute myocardial infarction diagnosed by universal definition (J-MINUET) substudy. Heart Vessels . 34 , 1899–1908 (2019). [Tyravska, Y., Nadeem, T., Savchenko, O., Bondarchuk, O. & Talabko, Y. Immunohaemostasis and the significance of immune reactions in the regulation of blood coagulation. Eur. J. Microbiol. Immunol. (Bp) . 14 , 392–404 (2024). O’Connor, L. A. et al. Plasma proteomic signature of chronic psychosocial stress in mice. Physiol. Behav. 289 , 114743 (2025). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 07 May, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Accepted 29 Apr, 2025 Reviews received at journal 22 Apr, 2025 Reviewers agreed at journal 22 Apr, 2025 Reviewers invited by journal 22 Apr, 2025 Submission checks completed at journal 16 Apr, 2025 First submitted to journal 14 Apr, 2025 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-5500873","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":446499891,"identity":"84456b53-c76d-4c91-a00f-2c7cba157fd4","order_by":0,"name":"Qing Yuan","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Yuan","suffix":""},{"id":446499892,"identity":"648f967d-205e-409f-8259-60b9e786ec99","order_by":1,"name":"YanWu Liu","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"YanWu","middleName":"","lastName":"Liu","suffix":""},{"id":446499893,"identity":"ffd5d016-4b8f-4b06-b50f-636ca8abb000","order_by":2,"name":"JiaYu Liu","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"JiaYu","middleName":"","lastName":"Liu","suffix":""},{"id":446499894,"identity":"c4de95c0-252e-4eb8-ad71-17f5d993cce5","order_by":3,"name":"MingXia Tang","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"MingXia","middleName":"","lastName":"Tang","suffix":""},{"id":446499895,"identity":"cb9d6662-b552-4cbd-8b12-b2c5d621f140","order_by":4,"name":"Jian Yang","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Yang","suffix":""},{"id":446499896,"identity":"509c7b02-d0ff-4692-8ac2-270e868bf549","order_by":5,"name":"ShuZhi Zhou","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"ShuZhi","middleName":"","lastName":"Zhou","suffix":""},{"id":446499897,"identity":"0bc59c78-4593-47d6-99d5-455bbcba227f","order_by":6,"name":"Ling Zhang","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Zhang","suffix":""},{"id":446499898,"identity":"b60108e3-808d-426b-a43a-b7ef9dc69bc8","order_by":7,"name":"JunWu Du","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"JunWu","middleName":"","lastName":"Du","suffix":""},{"id":446499899,"identity":"f41cf45f-d64e-4c77-8fdf-7483317380ca","order_by":8,"name":"KongJie Yang","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"KongJie","middleName":"","lastName":"Yang","suffix":""},{"id":446499900,"identity":"1d836b7e-b626-482c-ab5c-3cdbd3089a50","order_by":9,"name":"XiaoXue Li","email":"","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"XiaoXue","middleName":"","lastName":"Li","suffix":""},{"id":446499901,"identity":"701a506c-d113-46e9-b0bb-402b474c537a","order_by":10,"name":"Zhenglin Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAu0lEQVRIiWNgGAWjYBACAwbmhgMMBjY8bOwNRGthBGqpSJPh4zlAghYGhjOHbeQkEojUYs5/sPFwYRszD5vk4403GGpsoglqsWw42HB4ZhsbD5t0WrEFw7G03AaCDjvY2HCYt40HqCXHTIKx4TARWg4zgrRIAB12hlgtx4DKeM4Y8LBJ8BCr5QxIS0UCDxsP0C8JRPnl/OHDn3kM/tvLtx/eeONDjQ1hLSjaiY4aJC2k6hgFo2AUjIKRAQCYezvoonEnlwAAAABJRU5ErkJggg==","orcid":"","institution":"Yaan People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Zhenglin","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2024-11-22 01:53:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5500873/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5500873/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-00613-2","type":"published","date":"2025-05-07T15:57:37+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81221431,"identity":"10e95d1e-4d8b-4dad-9f80-4ca4b240f028","added_by":"auto","created_at":"2025-04-23 15:11:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1655531,"visible":true,"origin":"","legend":"\u003cp\u003eAPTT reference intervals for males of different age groups. APTT, activated partial thromboplastin time\u003c/p\u003e","description":"","filename":"OnlineFig01.png","url":"https://assets-eu.researchsquare.com/files/rs-5500873/v1/581000843fd6f419f1b08307.png"},{"id":81221426,"identity":"4632473c-a3e6-4bd5-b77f-75a1949d3c62","added_by":"auto","created_at":"2025-04-23 15:11:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1652600,"visible":true,"origin":"","legend":"\u003cp\u003eAPTT reference intervals for females of different age groups. APTT, activated partial thromboplastin time\u003c/p\u003e","description":"","filename":"OnlineFig02.png","url":"https://assets-eu.researchsquare.com/files/rs-5500873/v1/d381ad8af516ba27e7db9a4b.png"},{"id":81221440,"identity":"e93f8e7f-e579-4213-871d-6fc5ea8ae479","added_by":"auto","created_at":"2025-04-23 15:11:51","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1574449,"visible":true,"origin":"","legend":"\u003cp\u003eFIB reference intervals for males of different age groups. FIB, fibrinogen\u003c/p\u003e","description":"","filename":"OnlineFig03.png","url":"https://assets-eu.researchsquare.com/files/rs-5500873/v1/ef8904d2602828e57774d60b.png"},{"id":81221439,"identity":"4e7b0a35-0802-4490-ac30-252321a683bc","added_by":"auto","created_at":"2025-04-23 15:11:51","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1553432,"visible":true,"origin":"","legend":"\u003cp\u003eFIB reference intervals for females of different age groups. FIB, fibrinogen\u003c/p\u003e","description":"","filename":"OnlineFig04.png","url":"https://assets-eu.researchsquare.com/files/rs-5500873/v1/36a32995571ed1e61fcb34d7.png"},{"id":81221700,"identity":"b3200fa4-18e7-4f58-b8be-051d307baf92","added_by":"auto","created_at":"2025-04-23 15:19:51","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1647172,"visible":true,"origin":"","legend":"\u003cp\u003ePT reference intervals for males of different age groups. PT, prothrombin time\u003c/p\u003e","description":"","filename":"OnlineFig05.png","url":"https://assets-eu.researchsquare.com/files/rs-5500873/v1/7dab32e0d9cb68d34fe82b25.png"},{"id":81221430,"identity":"c66db63a-c35c-4277-b9c5-5609ea726948","added_by":"auto","created_at":"2025-04-23 15:11:51","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1609218,"visible":true,"origin":"","legend":"\u003cp\u003ePT reference intervals for females of different age groups. PT, prothrombin time\u003c/p\u003e","description":"","filename":"OnlineFig06.png","url":"https://assets-eu.researchsquare.com/files/rs-5500873/v1/811e4555b0271147f4c83b36.png"},{"id":81221444,"identity":"a9b4f4fb-4582-4721-b302-40d6e8cc0543","added_by":"auto","created_at":"2025-04-23 15:11:51","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1687364,"visible":true,"origin":"","legend":"\u003cp\u003eTT reference intervals for males of different age groups. TT, thrombin time\u003c/p\u003e","description":"","filename":"OnlineFig07.png","url":"https://assets-eu.researchsquare.com/files/rs-5500873/v1/275a9b9f97f35e8fb2f9b068.png"},{"id":81221703,"identity":"bb8b1715-acff-4c55-9ecb-861772486724","added_by":"auto","created_at":"2025-04-23 15:19:52","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":1666220,"visible":true,"origin":"","legend":"\u003cp\u003eTT reference intervals for females of different age groups. TT, thrombin time\u003c/p\u003e","description":"","filename":"OnlineFig08.png","url":"https://assets-eu.researchsquare.com/files/rs-5500873/v1/97fe67a3cd7f343491747f3a.png"},{"id":82537532,"identity":"1f7b2f8a-ca01-4dcf-9893-310f87584c07","added_by":"auto","created_at":"2025-05-12 16:08:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4118421,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5500873/v1/a20694d1-9dd2-4c7c-b742-c13f77dd7f47.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Establishing altitude-based coagulation reference ranges in Western Sichuan","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eThe Western Sichuan Plateau, located in southwestern China, has an average altitude of more than 3,500 m and is renowned for its unique landscape. Under hypoxic, low-temperature, and other extreme conditions that characterize high-altitude regions, physiological functions can undergo a series of adaptive changes, with the most prominent being hematological changes\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. These changes vary across altitudes, sexes, and age groups\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Therefore, the diagnosis and treatment of diseases in plateau regions cannot be based completely on the hematological indicators in plain regions but should incorporate altitude, sex, and age\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Recently, numerous scholars have explored the changes in coagulation indicators in the plateau environment\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. However, their research focuses more on independently studying the impact of altitude on coagulation indicators, and there is relatively less research on the variation patterns of coagulation indicators under the combined influence of altitude, age, and sex. Coagulation indicators are crucial in clinical practice, particularly for preoperative preparations. Therefore, there is a need to conduct systematic and comprehensive research. This study aimed to collect blood samples from healthy individuals living at different altitudes on the Western Sichuan Plateau and test their coagulation-related indicators. Based on the analysis and comparison of these data, we aimed to elucidate the patterns of changes in coagulation findings among healthy individuals living at different altitudes. Based on these findings, coagulation reference ranges suitable for the Western Sichuan Plateau were established, which can serve as a scientific basis for local medical diagnosis and health management.\u003c/p\u003e"},{"header":"2 Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Participants\u003c/h2\u003e \u003cp\u003e The study was approved by the Ethics Committee of Yaan People\u0026rsquo;s Hospital (approval number: 2023 011). Before blood collection, the purpose of blood collection and the rights of the subjects were fully explained to the participants, who provided written informed consent. All experimental methods were carried out in accordance with the relevant guidelines and regulations, including but not limited to the Helsinki Declaration and its subsequent amendments, as well as any specific ethical and regulatory requirements applicable to this type of research.\u003c/p\u003e \u003cp\u003eHealthy individuals living in Guza Town of Kangding County, Lucheng Subdistrict of Kangding County, Luhuo County, and Litang County of Ganzi Prefecture, Sichuan Province, were screened in March and August 2024. The screening criteria were as follows: 1. absence of inflammatory diseases and use of oral antibiotics, anticancer drugs, and anticoagulants within the previous month; 2. body mass index (BMI) between 18.5 and 23.9 kg/m\u003csup\u003e2\u003c/sup\u003e; 3. absence of abnormalities in cardiopulmonary function; and 4. absence of abnormalities in hepatic and kidney functions; 5. no history of immunological or hematological diseases; and 6. age\u0026thinsp;\u0026gt;\u0026thinsp;18 years. After the screening, 521 individuals (255 male and 266 female participants) from Guza Town, 980 individuals (385 male and 595 female participants) from Lucheng Subdistrict, 821 individuals (361 male and 460 female participants) from Luhuo County, and 1,135 individuals (560 male and 575 female participants) from Litang County were included in the analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Methods\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1 Test methods\u003c/h2\u003e \u003cp\u003eFor coagulation function tests, 3 mL of venous blood was collected using a vacutainer containing 0.109 mmol/L sodium citrate as an anticoagulant, and the samples were centrifuged at 1500 \u0026times; \u003cem\u003eg\u003c/em\u003e for 15 min to separate the plasma. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT) were measured within 2 h of blood sample collection using a Sysmex CS5100 (Tokyo, Japan) Fully Automated Blood Coagulation Analyzer from Sekisui Diagnostic Japan and its supporting reagents.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2 Test parameters\u003c/h2\u003e \u003cp\u003eTest data were processed using Microsoft Excel 365, and the items included PT, TT, APTT, and FIB.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.2.3 Statistical methods\u003c/h2\u003e \u003cp\u003eData were analyzed using SPSS 25.0(IBM Corporation, Armonk, NY, USA). Normally distributed quantitative data are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and were compared between groups using one-way analysis of variance (ANOVA). Further pairwise comparisons of between-group differences were performed using the least significant difference (LSD) method. Differences were considered statistically significant at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Comparison of coagulation indicators between different sexes at the same altitude\u003c/h2\u003e \u003cp\u003eAfter a meticulous analysis of the coagulation test results of the local population, we determined that the coagulation results across different altitudes, sexes, and age groups follow a normal distribution, and one-way ANOVA was employed for comparisons among various groups. Through group-by-group comparisons, we discovered that at the same altitude, male participants had significantly higher PT, APTT, TT, and FIB levels than female participants (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (see Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026thinsp;\u0026minus;\u0026thinsp;4).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of indicators between sexes among the residents of Guza\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eIndicator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;255)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;266)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eT\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e13.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.927\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e36.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e35.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e18.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e17.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.366\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.067\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003ePT, prothrombin time; APTT, activated partial thromboplastin time; TT, thrombin time; FIB, fibrinogen\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of indicators between sexes among the residents of Kangding\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eIndicator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;385)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;595)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eT\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.370\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e38.16\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e36.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.424\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e19.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e18.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14.449\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.791\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of indicators between sexes among the residents of Luhuo\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eIndicator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;361)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;488)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003et\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e39.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e36.97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9.772\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e20.62\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e17.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.604\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of indicators between sexes among the residents of Litang\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eIndicator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;560)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;575)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003et\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e16.48\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e16.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.642\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e41.91\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e39.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9.123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e21.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e21.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Comparison of coagulation indicators among different altitudes within the same sex\u003c/h2\u003e \u003cp\u003eBased on the analysis of coagulation indicators in male participants at different altitudes, we found the following sequences regarding PT, APTT, and TT: Litang\u0026thinsp;\u0026gt;\u0026thinsp;Luhuo and Kangding\u0026thinsp;\u0026gt;\u0026thinsp;Guza, with no difference between Luhuo and Kangding and significant differences for the remaining pairwise comparisons. For FIB, the sequence was Litang and Luhuo\u0026thinsp;\u0026gt;\u0026thinsp;Kangding and Guza, with no differences between Litang and Luhuo or between Kangding and Guza and significant differences for the remaining pairwise comparisons (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of indicators among male participants in different regions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eIndicator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGuza\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;255)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eKangding\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;385)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLuhuo\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;361)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLitang\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;560)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003csup\u003e■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003csup\u003e▲▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003csup\u003e▲▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16.48\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003csup\u003e▲☐■\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e284.130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAPTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92\u003csup\u003e☐■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.16\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003csup\u003e▲▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.86\u003csup\u003e▲▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e41.91\u0026thinsp;\u0026plusmn;\u0026thinsp;3.10\u003csup\u003e▲☐■\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e393.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43\u003csup\u003e☐■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.33\u003csup\u003e▲■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.62\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48\u003csup\u003e▲☐▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.99\u003csup\u003e▲☐■\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e294.570\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003csup\u003e■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003e■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003csup\u003e▲☐\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003csup\u003e▲☐\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e32.160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u0026ldquo;\u003csup\u003e▲\u003c/sup\u003e\u0026rdquo; indicates significant difference compared to Guza; \u0026ldquo;\u003csup\u003e☐\u003c/sup\u003e\u0026rdquo; indicates significant difference compared to Kangding; \u0026ldquo;\u003csup\u003e■\u003c/sup\u003e\u0026rdquo; indicates significant difference compared to Luhuo; \u0026ldquo;\u003csup\u003e▽\u003c/sup\u003e\u0026rdquo; indicates significant difference compared to Litang.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBased on the analysis of coagulation indicators in female participants at different altitudes, we found the following sequence for PT and APTT: Litang\u0026thinsp;\u0026gt;\u0026thinsp;Luhuo and Kangding\u0026thinsp;\u0026gt;\u0026thinsp;Guza, with no difference between Luhuo and Kangding and significant differences for the remaining pairwise comparisons. For TT and FIB, the sequence was Litang\u0026thinsp;\u0026gt;\u0026thinsp;Luhuo\u0026thinsp;\u0026gt;\u0026thinsp;Kangding\u0026thinsp;\u0026gt;\u0026thinsp;Guza, with significant differences in all pairwise comparisons (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of indicators among female participants in different regions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eIndicator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGuza\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;266)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKangding\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;595)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLuhuo\u003c/p\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;488\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLitang\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;575)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003csup\u003e☐■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003csup\u003e▲▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003csup\u003e▲▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003csup\u003e▲☐■\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e292.575\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49\u003csup\u003e☐■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48\u003csup\u003e▲▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.08\u003csup\u003e▲▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.57\u003csup\u003e▲☐■\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e88.905\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.38\u003csup\u003e☐■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003csup\u003e▲■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40\u003csup\u003e▲☐▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003csup\u003e▲☐■\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e453.364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003csup\u003e☐■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003csup\u003e▲■▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003csup\u003e▲☐▽\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003csup\u003e▲☐■\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16.722\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u0026ldquo;\u003csup\u003e▲\u003c/sup\u003e\u0026rdquo; indicates significant difference compared to Guza; \u0026ldquo;\u003csup\u003e☐\u003c/sup\u003e\u0026rdquo; indicates significant difference compared to Kangding; \u0026ldquo;\u003csup\u003e■\u003c/sup\u003e\u0026rdquo; indicates significant difference compared to Luhuo; \u0026ldquo;\u003csup\u003e▽\u003c/sup\u003e\u0026rdquo; indicates significant difference compared to Litang.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eIn the human hematological system, coagulation, fibrinolysis, and anticoagulation are interconnected and mutually regulated\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. These processes involve a series of complex biochemical reactions\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, among which PT, TT, APTT, and FIB are key indicators. PT reflects the extrinsic pathway of coagulation and is mainly used to evaluate blood hypercoagulability and the efficacy of anticoagulant therapy\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. TT is an indicator of the common coagulation pathway that reflects the extent of fibrinogen degradation and is used to evaluate blood hypercoagulability and the efficacy of anticoagulant therapy\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. APTT reflects the intrinsic pathway of coagulation and is primarily used to evaluate the risk of blood hypercoagulability and thrombotic disorders\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. FIB is a key protein in blood coagulation and a major target of the anticoagulation system\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. It is a crucial factor that reflects blood hypercoagulability and thrombosis. Blood coagulation, fibrinolysis, and anticoagulation are the key processes in the maintenance of vascular integrity and blood fluidity\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Attaining a balance among these three processes is critical to human health; an imbalance may lead to the pathogenesis of various diseases, including thrombosis and bleeding disorders \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn high-altitude and hypoxic environments, the human body exhibits elevated red blood cell (RBC) and hemoglobin (HGB) levels\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. The compensatory phenomenon known as high-altitude polycythemia (HAPC)\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e, which is predominantly characterized by elevated RBC, is a physiological change that occurs when the human body adapts to high-altitude environments. Higher altitudes are associated with more pronounced HAPC\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. An increase in RBC count can lead to higher blood viscosity and increased platelet adhesion and factor VIII-related antigens\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Hypoxia can also damage vascular endothelial cells\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e and activate the intrinsic and extrinsic pathways of coagulation, thereby promoting blood hypercoagulability\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFurthermore, a hypoxic plateau environment can cause platelet activation, trigger the intrinsic coagulation system, and contribute to the consumption of coagulation factors\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Animal experiments\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e have also demonstrated that the expression levels of extrinsic and intrinsic coagulation factors are reduced in the hypoxic environment of plateaus. Therefore, we believe that a hypoxic plateau environment can give rise to coagulopathies\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e, resulting in the gradual increase in APTT, TT, and PT with increasing altitude\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. In addition, the compensatory increase in RBC and blood viscosity can lead to the relative suppression of fibrinolysis\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e, which contributes to a hypercoagulable and hypofibrinolytic state\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e, thereby resulting in higher FIB values than those in the population living in plain regions\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Regarding the impact of high altitudes and hypoxia on individuals of different sexes, hypoxic environments stimulate the production of erythropoietin (EPO)\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e, which induces the formation of erythroid progenitors by hematopoietic stem cells, thereby promoting the increase in RBC levels\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. As androgens can promote EPO secretion\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e, the changes in relevant indicators were more pronounced among male participants than among female participants at the same altitude. These results indicate that the existing reference ranges of coagulation indicators for adults established in plain regions are not suitable for healthcare diagnosis and treatment of populations living in plateau areas.\u003c/p\u003e \u003cp\u003eOur findings revealed that the PT, TT, APTT, and FIB values of male participants were significantly higher than those of female participants at the same altitude. We believe that this phenomenon is related to the secretion of male androgens, which promote an increase in EPO. Analysis of the same indicators at different altitudes showed that the PT, TT, APTT, and FIB values increased gradually as altitude increased. After analyzing the ranges of the relevant indicators, we found that the upper limits of all reference ranges (except for PT, TT, APTT, and FIB values of individuals aged\u0026thinsp;\u0026lt;\u0026thinsp;40 years in Guza; FIB values of those aged\u0026thinsp;\u0026lt;\u0026thinsp;60 years in Guza and Kangding; and PT values of those aged\u0026thinsp;\u0026lt;\u0026thinsp;40 years in Kangding) exceeded the existing range of normal values\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. Based on these findings (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e), we can infer that PT, TT, APTT, and FIB values will increase with increasing altitude and age. Long-term exposure to the hypoxic environment of high-altitude areas can cause continuous damage to the inner wall of blood vessels\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e, and the degree of this damage is significantly positively correlated with the length of time an individual lives in this hypoxic environment\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e. Once the inner wall of the blood vessels is damaged, the intrinsic and extrinsic coagulation pathways can be rapidly activated, thereby promoting a hypercoagulable state\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e. To maintain normal blood fluidity and ensure that all organs of the body can receive sufficient blood supply, the body automatically activates regulatory mechanisms that prolong the coagulation time\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e. Therefore, when observing participants of the same altitude, the cumulative time an individual lives in the hypoxic environment increases with age, resulting in a gradual prolongation of the coagulation time parameters. This confirms that the existing reference ranges of coagulation indicators for adults established in plain regions are not suitable for healthcare diagnosis and treatment of populations living in plateau regions.\u003c/p\u003e\u003cp\u003eThis study has certain limitations. First, the effects of different races were not fully considered. Due to genetic differences and varying lifestyles, different races may have different blood indicators. For example, previous research has shown that a particular race that lives at the highest altitude and has the longest history of adaptation has developed a comprehensive oxygen supply and utilization system effective at the level of the entire body, organs, cells, and molecules. This situation has enabled them to demonstrate the most remarkable adaptability to the plateau environment.\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e. The western Sichuan plateau is also inhabited by multiple ethnic groups such as the Han, Qiang, and Yi. However, this study did not differentiate between the local population by ethnicity; therefore, the results may differ from the actual situation. Second, the study did not consider factors such as season and temperature, which are known to significantly influence both cardiovascular health and associated blood indicators\u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e. Therefore, to achieve accurate results, the influence of season and temperature cannot be ignored. Third, there is a lack of continuity in the choice of altitudes. In the future, we plan to compare and classify individuals based on their ethnicity and the blood collection season, fully incorporating ethnic and seasonal factors. Additionally, we will refine the altitude points to achieve high precision and personalization.\u003c/p\u003e \u003cp\u003eIn summary, we believe that in high-altitude environments, sex, age, and altitude can alter coagulation indexes, in addition to other factors\u003csup\u003e[38.39]\u003c/sup\u003e. China has a vast territory, a complex variety of climate types, and a rich ethnic composition. Especially in high-altitude areas, the diversity of the ecological environment and lifestyle further exacerbates the complexity of physiological indexes. A single coagulation index simply cannot meet the actual needs in such complex and variable situations. Therefore, there is an urgent need for more accurate and targeted coagulation indexes to assist in the diagnosis of local patients\u0026rsquo; diseases, the formulation of treatment plans, and the planning of public health strategies, in order to improve the quality and efficiency of medical services in plateau areas and safeguard the health and well-being of residents. For example, when diagnosing altitude-specific diseases closely related to coagulation function, such as high-altitude pulmonary edema and high-altitude cerebral edema, accurate coagulation indexes can help doctors judge the condition more timely and accurately and improve patient survival. When formulating public health strategies in plateau areas, these indexes can also provide a scientific basis for preventing the occurrence of thrombotic diseases and optimizing the allocation of medical resources.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Yaan People\u0026rsquo;s Hospital [2023 011].\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eWritten informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQing Yuan and YanWu Liu wrote the manuscript. All authors were involved in data collection. JiaYu Liu, MingXia Tang, and Jian Yang performed the analyses and interpreted data. ShuZhi Zhou, Ling Zhang, JunWu Du, KongJie Yang, and XiaoXue Li gathered relevant information and prepared the tables in the paper. Zhenglin Huang critically revised the manuscript for important intellectual content. All authors reviewed the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the transfer payment project of the Science and Technology Department of Sichuan Province. Project code: 22ZYZF0009.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePatrician, A. et al. Manipulation of iron status on cerebral blood flow at high altitude in lowlanders and adapted highlanders. \u003cem\u003eJ. Cereb. Blood Flow. Metab. Int.\u003c/em\u003e \u003cb\u003e43\u003c/b\u003e, 1166\u0026ndash;1179 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRocke, A. S. et al. Thromboelastometry and platelet function during acclimatization to high altitude. \u003cem\u003eThromb. Haemost\u003c/em\u003e. \u003cb\u003e118\u003c/b\u003e, 63\u0026ndash;71 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrabhakar, A. et al. Venous thrombosis at altitude presents with distinct biochemical profiles: a comparative study from the Himalayas to the plains. \u003cem\u003eBlood Adv.\u003c/em\u003e \u003cb\u003e3\u003c/b\u003e, 3713\u0026ndash;3723 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi, M. et al. Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude. \u003cem\u003eBlood\u003c/em\u003e \u003cb\u003e140\u003c/b\u003e, 2063\u0026ndash;2075 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, R., Tang, L. V. \u0026amp; Hu, Y. Genetic factors, risk prediction and AI application of thrombotic diseases. \u003cem\u003eExp. Hematol. Oncol.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e, 89 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eObeagu, E. I. \u0026amp; Obeagu, G. U. Thromboinflammation in COVID-19: Unraveling the interplay of coagulation and inflammation. \u003cem\u003eMed. (Baltimore)\u003c/em\u003e. \u003cb\u003e103\u003c/b\u003e, e38922 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeidari, Z. et al. Impact of tissue factor gene knockout on coagulation properties of umbilical cord-derived multipotent mesenchymal stromal/stem cells. \u003cem\u003eCell. Biochem. Funct.\u003c/em\u003e \u003cb\u003e42\u003c/b\u003e, e70021 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu, J. et al. Structure-based design and synthesis of novel FXIa inhibitors targeting the S2\u0026rsquo; subsite for enhanced antithrombotic efficacy. \u003cem\u003eMol. Divers.\u003c/em\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11030-024-11024-2\u003c/span\u003e\u003cspan address=\"10.1007/s11030-024-11024-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHughes, P. R., Lewis, M. N. \u0026amp; Adams, S. S. Bleeding and bruising: Primary care evaluation. \u003cem\u003eAm. Fam Physician\u003c/em\u003e. \u003cb\u003e110\u003c/b\u003e, 504\u0026ndash;514 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVenancio de Lima, E. O. et al. Understanding the effects of Bothrops erythromelas and Bothrops leucurus venoms on human blood coagulation. \u003cem\u003eToxicon\u003c/em\u003e \u003cb\u003e255\u003c/b\u003e, 108231 (2025).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCampbell, J. E., Brummel-Ziedins, K. E., Butenas, S. \u0026amp; Mann, K. G. Cellular regulation of blood coagulation: a model for venous stasis. \u003cem\u003eBlood\u003c/em\u003e \u003cb\u003e116\u003c/b\u003e, 6082\u0026ndash;6091 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShao, F., Liu, S., Yang, R., Zhang, X. \u0026amp; Zhong, Y. Predictive value of prenatal ultrasound combined with long non-coding RNA CRNDE of women for their postpartum lower extremity deep venous thrombosis. \u003cem\u003eJ. Matern Fetal Neonatal Med.\u003c/em\u003e \u003cb\u003e37\u003c/b\u003e, 2352089 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCui, J. H., Zhang, X. Z., Xie, Y. Z., Zhou, X. M. \u0026amp; Ha, Z. D. [The changes of coagulation and fibrinolysis function on hypoxia adaptation mechanism]. \u003cem\u003eZhongguo Ying Yong Sheng Li Xue Za Zhi\u003c/em\u003e. \u003cb\u003e17\u003c/b\u003e, 363\u0026ndash;365 (2001).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStauffer, E. et al. Making a virtue out of an evil: Are red blood cells from chronic mountain sickness patients eligible for transfusions. \u003cem\u003eAm. J. Hematol.\u003c/em\u003e \u003cb\u003e99\u003c/b\u003e, 1407\u0026ndash;1410 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStarkey, C. R., Davies, L., Hoyer, J. D., Wilson, C. S. \u0026amp; Winter, S. S. Clinical manifestations of hemoglobin Chico at high altitude. \u003cem\u003eJ. Pediatr. Hematol. Oncol.\u003c/em\u003e \u003cb\u003e28\u003c/b\u003e, 760\u0026ndash;762 (2006).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa, J. K. et al. TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia. \u003cem\u003eNat. Commun.\u003c/em\u003e \u003cb\u003e15\u003c/b\u003e, 3976 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaz, A. A. et al. Gestational hypoxia elicits long-term cardiovascular dysfunction in female guinea pigs. \u003cem\u003eLife Sci.\u003c/em\u003e \u003cb\u003e361\u003c/b\u003e, 123282 (2025).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi, M. et al. Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude. \u003cem\u003eBlood\u003c/em\u003e \u003cb\u003e140\u003c/b\u003e, 2063\u0026ndash;2075 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeSouza, N. M. et al. : Influence of excessive erythrocytosis on coagulation and fibrinolytic factors in Andean highlanders. \u003cem\u003eExp. Physiol.\u003c/em\u003e 106, 1335\u0026ndash;1342 (2021). (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarvey, M. B., Dennis, L. H., Hildebrandt, P. K. \u0026amp; Conrad, M. E. Hypobaric erythraemia: pathology and coagulation studies. \u003cem\u003eBr. J. Haematol.\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e, 275\u0026ndash;281 (1969).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakanishi, K. et al. Hypercoagulable state in a hypobaric, hypoxic environment causes non-bacterial thrombotic endocarditis in rats. \u003cem\u003eJ. Pathol.\u003c/em\u003e \u003cb\u003e181\u003c/b\u003e, 338\u0026ndash;346 (1997).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkunov, A., Sydykov, A., Toktash, T., Doolotova, A. \u0026amp; Sarybaev, A. Hemoglobin changes after long-term intermittent work at high altitude. \u003cem\u003eFront. Physiol.\u003c/em\u003e \u003cb\u003e9\u003c/b\u003e, 1552 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTreml, B., Wallner, B., Blank, C., Fries, D. \u0026amp; Schobersberger, W. The influence of environmental hypoxia on hemostasis-A systematic review. \u003cem\u003eFront. Cardiovasc. Med.\u003c/em\u003e \u003cb\u003e9\u003c/b\u003e, 813550 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, Z. et al. The quality changes in fresh frozen plasma of the blood donors at high altitude. \u003cem\u003ePLoS One\u003c/em\u003e. \u003cb\u003e12\u003c/b\u003e, e0176390 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLarsen, J. B., Hvas, C. L. \u0026amp; Hvas, A. M. Modified rotational thromboelastometry protocol using tissue plasminogen activator for detection of hypofibrinolysis and hyperfibrinolysis. \u003cem\u003eMethods Mol. Biol.\u003c/em\u003e \u003cb\u003e2663\u003c/b\u003e, 763\u0026ndash;773 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTan, Z. et al. Assessment of metabolomic variations among individuals returning to plain areas after exposure to high altitudes: a metabolomic analysis of human plasma samples with high-altitude de-acclimatization syndrome. \u003cem\u003eFront. Mol. Biosci.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e, 1375360 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIwamura, Y. et al. Erythropoietin production in embryonic neural cells is controlled by hypoxia signaling and histone deacetylases with an undifferentiated cellular state. \u003cem\u003eMol. Cell. Biol.\u003c/em\u003e \u003cb\u003e45\u003c/b\u003e, 32\u0026ndash;45 (2025).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSemenza, G. L., Nejfelt, M. K., Chi, S. M. \u0026amp; Antonarakis, S. E. Hypoxia-inducible nuclear factors bind to an enhancer element located 3\u0026rsquo; to the human erythropoietin gene. \u003cem\u003eProc. Natl. Acad. Sci. USA.\u003c/em\u003e 88, 5680\u0026ndash;5684 (1991).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWarren, A. M. \u0026amp; Grossmann, M. Haematological actions of androgens. \u003cem\u003eBest Pract. Res. Clin. Endocrinol. Metab.\u003c/em\u003e \u003cb\u003e36\u003c/b\u003e, 101653 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNational Health and Family Planning Commission of the People\u0026rsquo;s Republic of China. Reference intervals for blood cell analysis. (2012). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.nhc.gov.cn/zwgkzt/s9492/201301/d893733b674945afa63bc33f3cc7e60d.shtml\u003c/span\u003e\u003cspan address=\"http://www.nhc.gov.cn/zwgkzt/s9492/201301/d893733b674945afa63bc33f3cc7e60d.shtml\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFan, N., Liu, C. \u0026amp; Ren, M. Effect of different high altitudes on vascular endothelial function in healthy people. \u003cem\u003eMed. (Baltimore)\u003c/em\u003e. \u003cb\u003e99\u003c/b\u003e, e19292 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBloom, S. I. et al. Reduction of double-strand DNA break repair exacerbates vascular aging. \u003cem\u003eAging (Albany NY)\u003c/em\u003e. \u003cb\u003e15\u003c/b\u003e, 9913\u0026ndash;9947 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYou, Q. et al. Loss of endothelial annexin A1 aggravates inflammation-induced vascular aging. \u003cem\u003eAdv. Sci. (Weinh)\u003c/em\u003e. \u003cb\u003e11\u003c/b\u003e, e2307040 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Pablo-Moreno, J. A., Serrano, L. J., Revuelta, L., S\u0026aacute;nchez, M. J. \u0026amp; Liras, A. The vascular endothelium and coagulation: homeostasis, disease, and treatment, with a focus on the Von Willebrand factor and Factors VIII and V. \u003cem\u003eInt\u003c/em\u003e. \u003cem\u003eJ. Mol. Sci.\u003c/em\u003e \u003cb\u003e23\u003c/b\u003e, 8283 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHillary, T. M. et al. A prospective, monocentric case-control study on uncontrolled psoriasis as independent risk factor for a hypercoagulable state. \u003cem\u003eDermatol. Ther. (Heidelb)\u003c/em\u003e. \u003cb\u003e14\u003c/b\u003e, 767\u0026ndash;775 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi, J. et al. Structural variants involved in high-altitude adaptation detected using single-molecule long-read sequencing. \u003cem\u003eNat. Commun.\u003c/em\u003e \u003cb\u003e14\u003c/b\u003e, 8282 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkuno, T. et al. Association of onset-season with characteristics and long-term outcomes in acute myocardial infarction patients: results from the Japanese registry of acute myocardial infarction diagnosed by universal definition (J-MINUET) substudy. \u003cem\u003eHeart Vessels\u003c/em\u003e. \u003cb\u003e34\u003c/b\u003e, 1899\u0026ndash;1908 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e[Tyravska, Y., Nadeem, T., Savchenko, O., Bondarchuk, O. \u0026amp; Talabko, Y. Immunohaemostasis and the significance of immune reactions in the regulation of blood coagulation. \u003cem\u003eEur. J. Microbiol. Immunol. (Bp)\u003c/em\u003e. \u003cb\u003e14\u003c/b\u003e, 392\u0026ndash;404 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO\u0026rsquo;Connor, L. A. et al. Plasma proteomic signature of chronic psychosocial stress in mice. \u003cem\u003ePhysiol. Behav.\u003c/em\u003e \u003cb\u003e289\u003c/b\u003e, 114743 (2025).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"plateau residents, altitude, sex, age group, coagulation, reference range","lastPublishedDoi":"10.21203/rs.3.rs-5500873/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5500873/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe diagnosis and treatment of diseases in plateau regions should incorporate altitude, sex, and age in addition to hematological indicators from plain regions. This study analyzed coagulation results among individuals living at different altitudes in the Western Sichuan Plateaus and belonging to different sex and age groups to examine patterns of change and determine normal ranges. By comparing the changes in coagulation indicators among healthy male and female residents of different age groups (\u0026lt;\u0026thinsp;40 years, 40\u0026ndash;59 years, \u0026ge;\u0026thinsp;60 years) from Guza (1,400 m), Kangding (2,500 m), Luhuo (3,400 m), and Litang (4,100 m), we analyzed the association between coagulation indicators and altitude, age, and sex. Under low temperature, hypoxia, and other plateau environment factors, coagulation indicators varied among different altitudes, with some indicators showing specific trends of change with increasing altitude. Different sexes and age groups also exhibited specific patterns of change in coagulation results. This study clarified the patterns of change in coagulation results at four different altitudes in the Western Sichuan Plateau and the effects of sex and age on coagulation function. Normal ranges of coagulation values were determined for different sexes and age groups at different altitudes, providing a scientific basis for healthcare in this region.\u003c/p\u003e","manuscriptTitle":"Establishing altitude-based coagulation reference ranges in Western Sichuan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-23 15:11:45","doi":"10.21203/rs.3.rs-5500873/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-04-29T08:26:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-22T17:07:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"218697458490164421694783845320977490573","date":"2025-04-22T17:05:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-22T09:43:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-16T09:49:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-04-14T07:49:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b692e1ed-693d-4be9-9917-a659c9756686","owner":[],"postedDate":"April 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":47527569,"name":"Biological sciences/Physiology/Circulation/Thrombosis"},{"id":47527570,"name":"Health sciences/Risk factors"},{"id":47527571,"name":"Health sciences/Medical research/Outcomes research"},{"id":47527572,"name":"Health sciences/Health care/Disease prevention/Preventive medicine"}],"tags":[],"updatedAt":"2025-05-12T16:02:27+00:00","versionOfRecord":{"articleIdentity":"rs-5500873","link":"https://doi.org/10.1038/s41598-025-00613-2","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-05-07 15:57:37","publishedOnDateReadable":"May 7th, 2025"},"versionCreatedAt":"2025-04-23 15:11:45","video":"","vorDoi":"10.1038/s41598-025-00613-2","vorDoiUrl":"https://doi.org/10.1038/s41598-025-00613-2","workflowStages":[]},"version":"v1","identity":"rs-5500873","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5500873","identity":"rs-5500873","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}