Thromboelastography (TEG) in patients with adenomyosis

Thromboelastography (TEG) in patients with adenomyosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Thromboelastography (TEG) in patients with adenomyosis Jilan Jiang, Jin Yu, Wenya Chen, Sen Li, Yeping Yang, Yu Lin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6220839/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Patients with adenomyosis are thought to exist in a hypercoagulable state; however, the specific alterations in thromboelastography (TEG) remain to be elucidated. This study aimed to assess changes in TEG metrics and to investigate factors influencing coagulation function in individuals diagnosed with adenomyosis. Methods This retrospective observational study included 151 patients diagnosed with adenomyosis (AM group), while the control group consisted of 187 patients without adenomyosis who underwent laparoscopic surgery for benign adnexal cysts or high-grade squamous intraepithelial lesions (HSIL) concurrently. Comprehensive analyses of clinical data, laboratory results, and ultrasound findings were conducted. Results In comparison to the control group, the adenomyosis group exhibited significantly shorter reaction time (R) and coagulation time (K) (P < 0.05). Additionally, the maximum amplitude (MA) was notably higher in the AM group than in the control group (P < 0.001). Platelet (PLT) counts were significantly elevated in the AM group, whereas the activated partial thromboplastin time (APTT) was shorter (P < 0.001). In the multivariable logistic regression analysis, significant associations were found between MA (adjusted odds ratio [aOR] 1.10, 95% confidence interval [CI] 1.06–1.15), APTT (aOR 0.871, 95% CI 0.813–0.932), and R (aOR 0.799, 95% CI 0.64–0.99) with adenomyosis. The area under the curve (AUC) for diagnosing adenomyosis based on the combination of MA, R, and APTT was calculated to be 0.74 (0.69–0.79). Conclusion The findings suggest that patients with adenomyosis are predisposed to a hypercoagulable state, which may be linked to increased serum CA125 levels, anemia and dysmenorrhea. adenomyosis hypercoagulability thromboelastography Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Adenomyosis is a prevalent benign disorder of the uterus, impacting approximately 20% of women in their reproductive years[ 1 ]. This condition, characterized by the infiltration of the endometrium into the myometrium, is also referred to as internal endometriosis[ 2 ]. The primary clinical manifestations of adenomyosis include infertility, dysmenorrhea, and menorrhagia.[ 2 , 3 ]. Additionally, this condition is known for being refractory and recurrent, significantly compromising the quality of life for affected women and imposing considerable financial strain on healthcare systems, largely due to its tumor-like characteristics and malignant behaviors such as unchecked proliferation, invasion, and migration[ 4 ]. Adenomyosis can lead to both fibrinolysis and a hypercoagulable state, which has been linked to serious complications like disseminated intravascular coagulation, thrombotic disorders, and cerebral infarction due to altered coagulation and fibrinolytic processes[ 5 ]. Contributing factors to thrombus formation may include elevated levels of tissue factor (TF), mucinous proteins, activated platelets, and estrogens[ 6 ]. In recent years, the understanding of adenomyosis has advanced, particularly regarding its pathogenesis, diagnosis, and treatment, with a focus on the observed hypercoagulable state in affected patients. This includes notable changes in platelet count (PLT), thrombin spectrum, and D-dimer (D-D) levels[ 7 , 8 ]. For instance, Liu et al. demonstrated that platelets tend to aggregate at sites of vascular injury in those with adenomyosis[ 9 ]. Moreover, studies indicate that both PLT and prothrombin time (PT) are elevated in adenomyosis patients suffering from anemia[ 10 , 11 ]. Additionally, research has shown a significant reduction in activated partial thromboplastin time (APTT) and thrombin time (TT) in adenomyosis patients exhibiting anemia[ 12 ]. Thromboelastography (TEG) serves as an effective tool for rapidly assessing clotting function in whole blood samples. It offers a more precise evaluation of the dynamics involving natural anticoagulants, coagulants, platelets, and fibrinolytic pathways compared to traditional coagulation tests. TEG is widely utilized in various clinical settings, including trauma care and intensive care, to monitor blood coagulation and inform blood transfusion protocols[ 13 – 15 ]. Key parameters measured by TEG include reaction time (R), coagulation time (K), alpha angle (α), maximum amplitude (MA), lysis at 30 minutes (LY30), and clotting index (CI). Recently, TEG has gained recognition for its role in monitoring coagulation status in patients receiving anticoagulant therapy, as well as assessing coagulation in women experiencing postpartum hemorrhage and late pregnancy bleeding[ 16 , 17 ]. It has also proven valuable in diagnosing pregnancy-related complications such as preeclampsia, threatened abortion, and fetal demise[ 18 ]. In the realm of gynecologic oncology, the TEG-CI has been identified as a potential predictor for deep vein thrombosis (VTE)[ 19 ]. Despite these advancements, no research has definitively established the relevance of TEG in diagnosing hypercoagulability in adenomyosis. Thus, the present study aims to assess the diagnostic utility of TEG parameters for adenomyosis. We hypothesize that factors such as CA125 levels, PLT, hemoglobin (HGB), uterine volume, menstrual volume, and the severity of dysmenorrhea are associated with coagulation function in patients with adenomyosis. Methods This retrospective investigation received ethical approval from the Ethics Committee of the International Peace Maternity and Child Health Hospital of the China Welfare Institute, covering the period from January 2020 to December 2023 (GKLW2022-16). The adenomyosis (AM) group consisted of patients who underwent laparoscopic resection of adenomyosis lesions or total hysterectomy at our institution, with the exclusion of those diagnosed with uterine fibroids or endometriosis. The control group included patients who had laparoscopic procedures for benign adnexal cysts or high-grade squamous intraepithelial lesions (HSIL) during the same timeframe. Patients concurrently diagnosed with endometriosis during surgery were excluded from the control group, as were those with preoperative imaging findings indicative of uterine fibroids and/or adenomyosis via ultrasound or magnetic resonance imaging. Furthermore, individuals with pathological findings of endometrial polyps, malignant tumors, autoimmune disorders, or anemia due to blood system issues or other chronic conditions were also excluded. All participants refrained from using anticoagulants and hormonal medications for three months prior to surgery. Data collected included socio-demographic information, type of adenomyosis, final pathological diagnosis, and intra- and post-operative parameters. Menstrual bleeding was evaluated using the Mansfield-Voda-Jorgensen (MVJ) menstrual bleeding scale, which rates from 1 (spotting) to 6 (gushing)[ 20 ]. A visual analog scale (VAS) measured the severity of menstrual pain on a scale from 0 to 10[ 21 ]. Uterine size was assessed via ultrasound, calculated using the formula: uterine volume = A × B × C × 0.5233, where A, B, and C represent uterine length, width, and thickness, respectively[ 22 ]. Several laboratory parameters were analyzed, including CA125 (normal range: 0–35 U/mL), CA199 (normal range: 0–27 U/mL), PLT (normal range: 125–350 × 10^9/L), and HGB (normal range: 115–150 g/L). Coagulation parameters evaluated included activated partial thromboplastin time (APTT) (normal range: 18.4–38.4 seconds), plasma prothrombin time (PT) (normal range: 8.5–14.5 seconds), D-dimer (normal range: 0–0.55 g/L), fibrinogen (FIB) (normal range: 2–4 g/L), thrombin time (TT) (normal range: 14.5–20.5 seconds), and international normalized ratio (INR) (normal range: 1.5–2.8 for anticoagulant therapy). For thromboelastography (TEG) assessments, 2.7 mL of blood was collected from each participant into citrated tubes for analysis. To prepare the sample, 1 mL of blood was transferred into a kaolin vial, inverted several times, and then 0.34 mL was extracted and placed into a cuvette. Afterward, 20 µL of calcium chloride solution (0.2 mol/L) was added for recalcification, and the assay was conducted at a controlled temperature of 37°C. Statistical analyses were performed using the SPSS version 29.0 software package, with a significance threshold set at a p-value of less than 0.05. The Shapiro-Wilk test was utilized to determine the normality of the continuous variables. For variables exhibiting non-normal distribution, the median with interquartile range (M [P25-75]) was reported. The Kruskal-Wallis test was employed to evaluate differences between groups. The Mann-Whitney U test and chi-squared tests were used to identify statistically significant differences in medians and frequencies between the AM and control groups. Univariate analysis was conducted using the chi-squared test. For multivariate analysis, logistic regression was applied, incorporating covariates identified as statistically significant in the univariate analysis. Spearman's rank correlation coefficient was employed to explore the interrelationships between TEG and coagulation parameters and the risk factors associated with adenomyosis. Results After screening, the final cohort consisted of 151 patients in the adenomyosis (AM) group and 187 patients in the control group (shown in Fig. 1 ). No significant age difference was noted between the two groups. However, the mean body mass index (BMI) of the AM group was significantly higher than that of the control group (23.25 [21.20–25.7] vs. 22.68 [20.84–24.55] kg/m², respectively). Notably, the AM group had a significantly greater number of pregnancies and deliveries compared to the control group (both P < 0.001). Additionally, the VAS scores were significantly elevated in the AM group, with a mean score of 7 (range: 4–8) compared to the control group's mean score of 0 (range: 0–1). TheMVJ index also indicated higher values in the AM group, and a larger proportion of these patients were found to have anemia compared to the control group (P < 0.001). Furthermore, the AM group presented with larger uterine sizes, as well as increased levels of CA125 and CA199 (P < 0.001). Significantly, CA125 levels were notably higher in the AM group. Detailed observations are presented in Table 1 . Table 1 Patient characteristics among AM and control group Variables AM Group(n = 151) Control Group(n = 187) P-value Age(years) 44(40–47) 43(37–47) 0.149 BMI(kg/m2) 23.25(21.20–25.7) 22.68(20.84–24.55) 0.034 Abortion 1(0–1) 0(0–1) < 0.001 Gravidity 2(1–3) 1(0–2) < 0.001 VAS 7(4–8) 0(0–1) < 0.001 MVJ 4(3–5) 2(2–3) < 0.001 Uterine size(cm3) 236.72(141.99-275.42) 72.90(53.33–85.31) < 0.001 HGB(g/L) 121.0(103.0-129.0) 125.0(117.0-133.0) < 0.001 Anaemia 61(37.7%) 38(21.1%) < 0.001 PLT(*10^9/L) 289.0(255.0-323.0) 259.0(220.0-308.0) < 0.001 WBC(*10^9/L) 6.20(6.04–6.36) 6.15(6.03–6.27) 0.780 CA125(U/mL) 66.95(40.90-132.80) 15.30(10.50-23.38) < 0.001 CA199(U/mL) 15.40(9.00-33.15) 9.70(6.50–15.00) < 0.001 Notes: Data were shown as M (P25-75) as appropriate. Abbreviations: AM, adenomyosis; BMI, body mass index; HGB, hemoglobin; MVJ, Mansfield–Voda–Jorgensen; PLT, platelet count; VAS, visual analogue scale; WBC, white blood cell. Significant differences were found in the TEG parameters including R, K, angle, MA, and CI, with p-values below 0.05. Specifically, the AM group demonstrated shorter R and K values, while the MA was significantly greater in this group. Additionally, the AM group had a substantially PLT count than the control group (P < 0.001) (illustrated in Fig. 2 ). The APTT was also shorter in the AM group compared to the control group (P < 0.001). However, no significant differences were observed between the groups regarding D-dimer, FIB, INR, PT and TT levels(shown in Fig. 3 ). Multivariable logistic regression analysis indicated that MA (adjusted odds ratio [aOR] 1.10, 95% confidence interval [CI] 1.06–1.15), APTT (aOR 0.871, 95% CI 0.813–0.932), and R (aOR 0.799, 95% CI 0.64–0.99) were significantly associated with adenomyosis (refer to Table 2 ). The receiver operating characteristic (ROC) curves illustrated the effectiveness of TEG parameters and APTT in predicting adenomyosis. These ROC curves are displayed in Fig. 4 , with areas under the curve (AUC) for R, MA, and APTT calculated as 0.645 (0.591–0.696), 0.691 (0.639–0.740), and 0.586 (0.531–0.639), respectively. The combined AUC for diagnosing adenomyosis based on MA, R, and APTT was found to be 0.74 (95% CI 0.69–0.79). Table 2 Multivariable logistic regression analysis for adenomyosis diagnosis B aOdds Ratio (95% CI) p value MA .099 1.10(1.06, 1.15) <.001 APTT − .138 .871 (.813, .932) <.001 R − .224 .799 (.639, .999) .049 Abbreviations: APTT:activated partial thromboplastin time; MA: maximum amplitude (MA); R: reaction time. Additionally, we conducted Spearman's correlation analysis to explore potential relationships among MA, R, and APTT with CA125, HGB, VAS, MVJ, and uterine volume (shown in Table S1 ). The correlation analysis revealed that MA exhibited a positive correlation with CA125 (r = 0.222, P = 0.008). R showed a positive correlation with HGB (r = 0.272, P = 0.001). Furthermore, MA had a positive correlation with VAS (r = 0.161, P = 0.048). Discussion The analysis of TEG parameters between the AM group and the control group revealed significant differences in R, K, angle, MA, and CI. Notably, the APTT was shorter in the AM group, while the PLT was higher compared to the control group. These findings suggest that patients with adenomyosis may exhibit a hypercoagulable state, as evidenced by both TEG and coagulation results. Furthermore, MA, R, and APTT emerged as valuable indicators for diagnosing adenomyosis. Spearman's analysis highlighted that variations in APTT, R, and MA were associated with elevated serum CA125 levels, anemia and dysmenorrhea. The role of platelet measurements as a supplementary diagnostic tool for adenomyosis remains uncertain. Research by Bodur et al. indicated an increase in mean platelet volume (MPV) among women with adenomyosis, although platelet count (PC) showed no significant change[ 23 ]. Conversely, Coskun et al. found no correlation between PC or MPV and either endometriosis or adenomyosis[ 24 ]. A recent investigation by Lin Q found a significant rise in PC among women with adenomyosis compared to healthy controls, reinforcing the results reported by Zhang[ 10 , 25 ]. In our study, while PLT was notably elevated in the AM group relative to the control group, multivariable logistic regression analysis did not reveal a significant correlation between platelet levels and adenomyosis. Consistent with previous findings, our study indicated that APTT was decreased in patients with adenomyosis, aligning with similar observations in endometriosis cases[ 12 ] , [ 26 ]. Research on trauma patients has shown that APTT activation is related to the pathogenesis of venous thrombosis[ 27 ]. Additionally, it has been reported that thrombin activates platelets, leading to the production of thromboxane A2 (TXA2), which further activates additional platelets and induces plasminogen activator inhibitor-1 (PAI-1) expression in ectopic endometrium[ 28 ]. This is consistent with the illustration in adenomyosis[ 29 ]. This cascade contributes to the activation of the coagulation pathway, ultimately resulting in a shorter APTT in those with adenomyosis. Numerous case reports in the literature document thromboembolic events, such as cerebral infarction and deep vein thrombosis (DVT), in patients with adenomyosis, presenting a significant clinical challenge[ 8 , 30 ]. The coexistence of heavy menstrual bleeding and thromboembolic events creates a vicious cycle, where anticoagulant therapy may exacerbate menorrhagia, and hormonal treatments for menorrhagia become contraindicated in the presence of active VTE[ 31 ]. TEG is utilized in various medical disciplines, including gynecology, obstetrics, emergency care, intensive care, and cardiovascular surgery. Its superior sensitivity and specificity for detecting thrombogenesis make it an invaluable tool across these fields[ 32 ]. Our findings illustrate a decline in R and an increase in MA among patients with adenomyosis, reinforcing the concept of a hypercoagulable state. This underscores the importance for gynecologists to monitor coagulation status, implement appropriate treatment strategies, and support long-term management of adenomyosis. There is a robust association between elevated serum CA125 levels and the presence of a hypercoagulable state[ 33 ].. Reports indicate thrombus formation in patients with adenomyosis, often accompanied by elevated CA125 levels, which may reflect hypercoagulability[ 6 , 34 ]. CA125, a tumor-associated mucin, plays a crucial role in the hypercoagulable state associated with malignant tumors, binding to P-selectin and L-selectin and facilitating interactions that lead to platelet-rich microthrombus formation[ 35 ].Furthermore, higher preoperative CA125 levels have been positively correlated with the incidence of perioperative thromboembolic events in epithelial ovarian cancer[ 36 ]. In patients presenting with cerebral venous sinus thrombosis, heightened CA125 levels have also been noted[ 37 ]. Our findings are consistent with previous studies that demonstrated a negative correlation between APTT and CA125 levels and established correlations between changes in R and MA with CA125 levels, supporting the link between increased CA125 and a hypercoagulable state in adenomyosis[ 12 ]. Furthermore, our findings revealed a correlation between the alterations in R and MA and the level of CA125, thereby substantiating the robust association between elevated CA125 levels and a hypercoagulable state in individuals with adenomyosis. Yamanaka et al. found that patients with adenomyosis whose uterine volumes exceeded 100 cm³ during menstruation were at an enhanced risk of activating the coagulation system[ 5 ]. Zhang et al. also reported a negative correlation between APTT and uterine volume[ 25 ]. However, there was no significant correlation between the coagulation function and uterine volume in our study results. Patients with adenomyosis typically experience heavier menstrual bleeding and prolonged bleeding durations, which can lead to anemia[ 38 ]. Previous research indicated that APTT during menstruation was shorter in patients with moderate anemia compared to those with milder forms. [ 25 ]. Our study confirmed that R was positively correlated with HGB, highlighting the increased risk of thrombosis as hemoglobin levels decrease. Anemia can promote a hypercoagulable state and disrupt endothelial adhesion molecule gene expression by increasing reactive platelets and red blood cells[ 39 ]. Additionally, our findings noted positive correlation between MA and VAS. However, another study found no association between APTT, TT, and the severity of dysmenorrhea in adenomyosis patients[ 12 ]. This study was the first to demonstrate the diagnostic utility of TEG in adenomyosis patients. However, due to its retrospective design, data were collected exclusively from surgical patients, and not all participants were in the uterine bleeding phase. Future studies with larger sample sizes are warranted. Conclusion Both TEG parameters and coagulation function results indicate that patients with adenomyosis tend to exhibit a hypercoagulable state, which may be correlated with elevated serum CA125 levels, anemia and dysmenorrhea. Abbreviations AM denomyosis APTT the activated partial thromboplastin time AUC the area under the curve CI coagulation index COC, combined oral contraceptive EM, endometriosis HSIL high-grade squamous intraepithelial lesions K coagulation time MA maximum amplitude PLT platelet count R reaction time TEG Thromboelastography Declarations Ethics approval and consent to participate This retrospective case-control study was approved by the Ethics Committee of the International Peace Maternity and Child Health Hospital of the China Welfare Institute (GKLW2022-16), and written informed consent was waived. And this study adhered to the Declaration of Helsinki. Consent for publication Not applicable Availability of data and materials All data generated or analyzed during this study are included in this published article. Competing Interests The authors declare that they have no conflicts of interest and nothing to disclose. F unding This work received financial support from the Shanghai Municipal Commission of Science and Technology Program [grant 22Y11906400], Fundamental Research Funds for the Central Universities [YG2023QNA47], Clinical Research Plan of IPMCH [IPMCH2022CR1-04]. All these funding bodies played role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. Authors’ contributions JLJ designed the study protocol, collected the data, performed the statistical analysis and was a major contributor in writing the manuscript. JY collected and analyzed the patient data and revised the manuscrip. WYC collected and analyzed the patient data and wrote part of the manuscript. 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Successful management of cerebral venous sinus thrombosis due to adenomyosis: Case reports and literature review. Clin Neurol Neurosurg. 2023;229:107726. Gunther R, Walker C. Adenomyosis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. Kaiafa G, Savopoulos C, Kanellos I, Mylonas KS, Tsikalakis G, Tegos T, et al. Anemia and stroke: Where do we stand? Acta Neurol Scand. 2017;135:596–602. Additional Declarations No competing interests reported. Supplementary Files TableS1Spearmancorrelation.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-6220839","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":432712400,"identity":"76f83897-101b-4fc5-bd43-be9b6e4b1239","order_by":0,"name":"Jilan Jiang","email":"","orcid":"","institution":"International Peace Maternity \u0026 Child Health Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jilan","middleName":"","lastName":"Jiang","suffix":""},{"id":432712402,"identity":"c6b57a39-e950-45b6-bf87-d31c2d323351","order_by":1,"name":"Jin Yu","email":"","orcid":"","institution":"International Peace Maternity \u0026 Child Health Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jin","middleName":"","lastName":"Yu","suffix":""},{"id":432712403,"identity":"2eb9ad6a-f795-4fb2-9db6-d9716e23e298","order_by":2,"name":"Wenya Chen","email":"","orcid":"","institution":"International Peace Maternity \u0026 Child Health Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wenya","middleName":"","lastName":"Chen","suffix":""},{"id":432712406,"identity":"0951fea0-66bd-4ed2-8e5c-8ce7e6387a77","order_by":3,"name":"Sen Li","email":"","orcid":"","institution":"International Peace Maternity \u0026 Child Health Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sen","middleName":"","lastName":"Li","suffix":""},{"id":432712408,"identity":"89c0aba0-9367-44da-9e25-1007dff494c3","order_by":4,"name":"Yeping Yang","email":"","orcid":"","institution":"International Peace Maternity \u0026 Child Health Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yeping","middleName":"","lastName":"Yang","suffix":""},{"id":432712409,"identity":"98e9c542-1c23-4db4-b077-9e980b54e92d","order_by":5,"name":"Yu Lin","email":"","orcid":"","institution":"International Peace Maternity \u0026 Child Health Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Lin","suffix":""},{"id":432712410,"identity":"93050539-b869-4713-99af-879e412cd464","order_by":6,"name":"Hong Xu","email":"","orcid":"","institution":"International Peace Maternity \u0026 Child Health Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hong","middleName":"","lastName":"Xu","suffix":""},{"id":432712411,"identity":"64972ffc-0a5b-42d8-8193-cc7ddd8df115","order_by":7,"name":"Feng Sun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYJCCD0DMY3+YsfFBQoUNUToYZwAJOYbjzM0GD86kEa/FmOE8e5vkw7ZDhNXLz8g92PBxR21iYzNjW0UC2wEG/vbuBLxaDG7kJTbOPHM8sZmZse1GAs8dBokzZzfg1yKRY/6Yt+1YYhtYi8QzoEgufi3yM3IMm/8CtfQAtRQkGBwmrIXhBlALY1uNsQRQC0NCAhFaDM68MWzsbTsgZ8DM2CyRcCCNh6Bf5NtzDBt+ttXxGPAff/jx5z8bOf72XgIOg4DDcBYPMcpBoI5YhaNgFIyCUTASAQBpVk46LV7L/wAAAABJRU5ErkJggg==","orcid":"","institution":"International Peace Maternity \u0026 Child Health Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Feng","middleName":"","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2025-03-13 14:08:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6220839/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6220839/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79342556,"identity":"066723ea-3c9c-47e9-a72c-f314ac86a789","added_by":"auto","created_at":"2025-03-27 08:55:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1801042,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of this study\u003c/p\u003e\n\u003cp\u003eAM, adenomyosis; COC, combined oral contraceptive; EM, endometriosis; GnRH, gonadotropin-releasing hormone; HSIL: high-grade squamous intraepithelial lesions; LNG-IUS, levonorgestrel-releasing intrauterine device\u003c/p\u003e","description":"","filename":"Fig1Flowchartofthisstudy.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6220839/v1/0f84ec90ede8217b27998a54.jpg"},{"id":79343034,"identity":"df99b104-d827-4f95-be2d-86cbbbaa0ddb","added_by":"auto","created_at":"2025-03-27 09:03:40","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":205382,"visible":true,"origin":"","legend":"\u003cp\u003eComparisons of TEG and PLT between two groups\u003c/p\u003e\n\u003cp\u003eAM, adenomyosis; CI, clotting index; K, coagulation time; MA, maximum amplitude; R, reaction time; PLT, platelet count\u003c/p\u003e","description":"","filename":"Fig2ComparisonofTEGandPLTbetweentwogroups.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6220839/v1/57b7f1840fc80d5b54e95e7f.jpg"},{"id":79342555,"identity":"11570b2d-f081-4f43-97dc-e5ab58039980","added_by":"auto","created_at":"2025-03-27 08:55:40","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":216886,"visible":true,"origin":"","legend":"\u003cp\u003eComparisons of coagulation function between two groups\u003c/p\u003e\n\u003cp\u003eAM, adenomyosis; APTT, activated partial thromboplastin time; D-D, D-dimer; FIB, fibrinogen; INR, international normalized ratio; TT, thrombin time\u003c/p\u003e","description":"","filename":"Fig3Comparisonofcoagulationfunctionbetweentwogroups.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6220839/v1/c0f25a0cfbdf295722c2f87d.jpg"},{"id":79342554,"identity":"95525c8c-4d87-41a6-8870-ac357a265a7e","added_by":"auto","created_at":"2025-03-27 08:55:40","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":139759,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves of APTT and TEG in AM diagnosis\u003c/p\u003e\n\u003cp\u003eAM, adenomyosis; APTT, activated partial thromboplastin time; K, coagulation time; MA, maximum amplitude; R, reaction time; CI, clotting index\u003c/p\u003e","description":"","filename":"Fig4ROCcurvesofAPTTandTEGinAMdiagnosis.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6220839/v1/60c4a99bdaa6a5bcf16ac4e7.jpg"},{"id":104883422,"identity":"5b8470fb-ab5d-4f2d-93e7-f522f15d508e","added_by":"auto","created_at":"2026-03-18 09:41:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2901545,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6220839/v1/4c424118-25a5-4ede-a2b1-423ed3a7c9b9.pdf"},{"id":79342552,"identity":"eb6e165d-4316-438e-bee1-230ff37e1ade","added_by":"auto","created_at":"2025-03-27 08:55:40","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":14512,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1Spearmancorrelation.docx","url":"https://assets-eu.researchsquare.com/files/rs-6220839/v1/d0c28bf2ac1889259dd75589.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Thromboelastography (TEG) in patients with adenomyosis","fulltext":[{"header":"Background","content":"\u003cp\u003eAdenomyosis is a prevalent benign disorder of the uterus, impacting approximately 20% of women in their reproductive years[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This condition, characterized by the infiltration of the endometrium into the myometrium, is also referred to as internal endometriosis[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The primary clinical manifestations of adenomyosis include infertility, dysmenorrhea, and menorrhagia.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Additionally, this condition is known for being refractory and recurrent, significantly compromising the quality of life for affected women and imposing considerable financial strain on healthcare systems, largely due to its tumor-like characteristics and malignant behaviors such as unchecked proliferation, invasion, and migration[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Adenomyosis can lead to both fibrinolysis and a hypercoagulable state, which has been linked to serious complications like disseminated intravascular coagulation, thrombotic disorders, and cerebral infarction due to altered coagulation and fibrinolytic processes[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Contributing factors to thrombus formation may include elevated levels of tissue factor (TF), mucinous proteins, activated platelets, and estrogens[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn recent years, the understanding of adenomyosis has advanced, particularly regarding its pathogenesis, diagnosis, and treatment, with a focus on the observed hypercoagulable state in affected patients. This includes notable changes in platelet count (PLT), thrombin spectrum, and D-dimer (D-D) levels[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. For instance, Liu et al. demonstrated that platelets tend to aggregate at sites of vascular injury in those with adenomyosis[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Moreover, studies indicate that both PLT and prothrombin time (PT) are elevated in adenomyosis patients suffering from anemia[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additionally, research has shown a significant reduction in activated partial thromboplastin time (APTT) and thrombin time (TT) in adenomyosis patients exhibiting anemia[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThromboelastography (TEG) serves as an effective tool for rapidly assessing clotting function in whole blood samples. It offers a more precise evaluation of the dynamics involving natural anticoagulants, coagulants, platelets, and fibrinolytic pathways compared to traditional coagulation tests. TEG is widely utilized in various clinical settings, including trauma care and intensive care, to monitor blood coagulation and inform blood transfusion protocols[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Key parameters measured by TEG include reaction time (R), coagulation time (K), alpha angle (α), maximum amplitude (MA), lysis at 30 minutes (LY30), and clotting index (CI). Recently, TEG has gained recognition for its role in monitoring coagulation status in patients receiving anticoagulant therapy, as well as assessing coagulation in women experiencing postpartum hemorrhage and late pregnancy bleeding[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. It has also proven valuable in diagnosing pregnancy-related complications such as preeclampsia, threatened abortion, and fetal demise[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In the realm of gynecologic oncology, the TEG-CI has been identified as a potential predictor for deep vein thrombosis (VTE)[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite these advancements, no research has definitively established the relevance of TEG in diagnosing hypercoagulability in adenomyosis. Thus, the present study aims to assess the diagnostic utility of TEG parameters for adenomyosis. We hypothesize that factors such as CA125 levels, PLT, hemoglobin (HGB), uterine volume, menstrual volume, and the severity of dysmenorrhea are associated with coagulation function in patients with adenomyosis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This retrospective investigation received ethical approval from the Ethics Committee of the International Peace Maternity and Child Health Hospital of the China Welfare Institute, covering the period from January 2020 to December 2023 (GKLW2022-16). The adenomyosis (AM) group consisted of patients who underwent laparoscopic resection of adenomyosis lesions or total hysterectomy at our institution, with the exclusion of those diagnosed with uterine fibroids or endometriosis. The control group included patients who had laparoscopic procedures for benign adnexal cysts or high-grade squamous intraepithelial lesions (HSIL) during the same timeframe. Patients concurrently diagnosed with endometriosis during surgery were excluded from the control group, as were those with preoperative imaging findings indicative of uterine fibroids and/or adenomyosis via ultrasound or magnetic resonance imaging. Furthermore, individuals with pathological findings of endometrial polyps, malignant tumors, autoimmune disorders, or anemia due to blood system issues or other chronic conditions were also excluded. All participants refrained from using anticoagulants and hormonal medications for three months prior to surgery.\u003c/p\u003e \u003cp\u003eData collected included socio-demographic information, type of adenomyosis, final pathological diagnosis, and intra- and post-operative parameters. Menstrual bleeding was evaluated using the Mansfield-Voda-Jorgensen (MVJ) menstrual bleeding scale, which rates from 1 (spotting) to 6 (gushing)[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. A visual analog scale (VAS) measured the severity of menstrual pain on a scale from 0 to 10[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Uterine size was assessed via ultrasound, calculated using the formula: uterine volume\u0026thinsp;=\u0026thinsp;A \u0026times; B \u0026times; C \u0026times; 0.5233, where A, B, and C represent uterine length, width, and thickness, respectively[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Several laboratory parameters were analyzed, including CA125 (normal range: 0\u0026ndash;35 U/mL), CA199 (normal range: 0\u0026ndash;27 U/mL), PLT (normal range: 125\u0026ndash;350 \u0026times; 10^9/L), and HGB (normal range: 115\u0026ndash;150 g/L). Coagulation parameters evaluated included activated partial thromboplastin time (APTT) (normal range: 18.4\u0026ndash;38.4 seconds), plasma prothrombin time (PT) (normal range: 8.5\u0026ndash;14.5 seconds), D-dimer (normal range: 0\u0026ndash;0.55 g/L), fibrinogen (FIB) (normal range: 2\u0026ndash;4 g/L), thrombin time (TT) (normal range: 14.5\u0026ndash;20.5 seconds), and international normalized ratio (INR) (normal range: 1.5\u0026ndash;2.8 for anticoagulant therapy). For thromboelastography (TEG) assessments, 2.7 mL of blood was collected from each participant into citrated tubes for analysis. To prepare the sample, 1 mL of blood was transferred into a kaolin vial, inverted several times, and then 0.34 mL was extracted and placed into a cuvette. Afterward, 20 \u0026micro;L of calcium chloride solution (0.2 mol/L) was added for recalcification, and the assay was conducted at a controlled temperature of 37\u0026deg;C.\u003c/p\u003e \u003cp\u003eStatistical analyses were performed using the SPSS version 29.0 software package, with a significance threshold set at a p-value of less than 0.05. The Shapiro-Wilk test was utilized to determine the normality of the continuous variables. For variables exhibiting non-normal distribution, the median with interquartile range (M [P25-75]) was reported. The Kruskal-Wallis test was employed to evaluate differences between groups. The Mann-Whitney U test and chi-squared tests were used to identify statistically significant differences in medians and frequencies between the AM and control groups. Univariate analysis was conducted using the chi-squared test. For multivariate analysis, logistic regression was applied, incorporating covariates identified as statistically significant in the univariate analysis. Spearman's rank correlation coefficient was employed to explore the interrelationships between TEG and coagulation parameters and the risk factors associated with adenomyosis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAfter screening, the final cohort consisted of 151 patients in the adenomyosis (AM) group and 187 patients in the control group (shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). No significant age difference was noted between the two groups. However, the mean body mass index (BMI) of the AM group was significantly higher than that of the control group (23.25 [21.20\u0026ndash;25.7] vs. 22.68 [20.84\u0026ndash;24.55] kg/m\u0026sup2;, respectively). Notably, the AM group had a significantly greater number of pregnancies and deliveries compared to the control group (both P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, the VAS scores were significantly elevated in the AM group, with a mean score of 7 (range: 4\u0026ndash;8) compared to the control group's mean score of 0 (range: 0\u0026ndash;1). TheMVJ index also indicated higher values in the AM group, and a larger proportion of these patients were found to have anemia compared to the control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Furthermore, the AM group presented with larger uterine sizes, as well as increased levels of CA125 and CA199 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Significantly, CA125 levels were notably higher in the AM group. Detailed observations are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \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\u003ePatient characteristics among AM and control group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAM Group(n\u0026thinsp;=\u0026thinsp;151)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group(n\u0026thinsp;=\u0026thinsp;187)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(40\u0026ndash;47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43(37\u0026ndash;47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.149\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI(kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.25(21.20\u0026ndash;25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.68(20.84\u0026ndash;24.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbortion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eGravidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(4\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eMVJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(3\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eUterine size(cm3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e236.72(141.99-275.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.90(53.33\u0026ndash;85.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eHGB(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e121.0(103.0-129.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e125.0(117.0-133.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eAnaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61(37.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38(21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003ePLT(*10^9/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e289.0(255.0-323.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e259.0(220.0-308.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eWBC(*10^9/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.20(6.04\u0026ndash;6.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.15(6.03\u0026ndash;6.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.780\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA125(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.95(40.90-132.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.30(10.50-23.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003eCA199(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.40(9.00-33.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.70(6.50\u0026ndash;15.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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=\"4\"\u003eNotes: Data were shown as M (P25-75) as appropriate.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: AM, adenomyosis; BMI, body mass index; HGB, hemoglobin; MVJ, Mansfield\u0026ndash;Voda\u0026ndash;Jorgensen; PLT, platelet count; VAS, visual analogue scale; WBC, white blood cell.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSignificant differences were found in the TEG parameters including R, K, angle, MA, and CI, with p-values below 0.05. Specifically, the AM group demonstrated shorter R and K values, while the MA was significantly greater in this group. Additionally, the AM group had a substantially PLT count than the control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The APTT was also shorter in the AM group compared to the control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, no significant differences were observed between the groups regarding D-dimer, FIB, INR, PT and TT levels(shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMultivariable logistic regression analysis indicated that MA (adjusted odds ratio [aOR] 1.10, 95% confidence interval [CI] 1.06\u0026ndash;1.15), APTT (aOR 0.871, 95% CI 0.813\u0026ndash;0.932), and R (aOR 0.799, 95% CI 0.64\u0026ndash;0.99) were significantly associated with adenomyosis (refer to Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The receiver operating characteristic (ROC) curves illustrated the effectiveness of TEG parameters and APTT in predicting adenomyosis. These ROC curves are displayed in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, with areas under the curve (AUC) for R, MA, and APTT calculated as 0.645 (0.591\u0026ndash;0.696), 0.691 (0.639\u0026ndash;0.740), and 0.586 (0.531\u0026ndash;0.639), respectively. The combined AUC for diagnosing adenomyosis based on MA, R, and APTT was found to be 0.74 (95% CI 0.69\u0026ndash;0.79).\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\u003e\u003cb\u003eMultivariable logistic regression analysis for adenomyosis diagnosis\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eaOdds Ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.099\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.10(1.06, 1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;.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\u0026minus;\u0026thinsp;.138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e.871 (.813, .932)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.224\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e.799 (.639, .999)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.049\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: APTT:activated partial thromboplastin time; MA: maximum amplitude (MA); R: reaction time.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAdditionally, we conducted Spearman's correlation analysis to explore potential relationships among MA, R, and APTT with CA125, HGB, VAS, MVJ, and uterine volume (shown in Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). The correlation analysis revealed that MA exhibited a positive correlation with CA125 (r\u0026thinsp;=\u0026thinsp;0.222, P\u0026thinsp;=\u0026thinsp;0.008). R showed a positive correlation with HGB (r\u0026thinsp;=\u0026thinsp;0.272, P\u0026thinsp;=\u0026thinsp;0.001). Furthermore, MA had a positive correlation with VAS (r\u0026thinsp;=\u0026thinsp;0.161, P\u0026thinsp;=\u0026thinsp;0.048).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe analysis of TEG parameters between the AM group and the control group revealed significant differences in R, K, angle, MA, and CI. Notably, the APTT was shorter in the AM group, while the PLT was higher compared to the control group. These findings suggest that patients with adenomyosis may exhibit a hypercoagulable state, as evidenced by both TEG and coagulation results. Furthermore, MA, R, and APTT emerged as valuable indicators for diagnosing adenomyosis. Spearman's analysis highlighted that variations in APTT, R, and MA were associated with elevated serum CA125 levels, anemia and dysmenorrhea.\u003c/p\u003e \u003cp\u003eThe role of platelet measurements as a supplementary diagnostic tool for adenomyosis remains uncertain. Research by Bodur et al. indicated an increase in mean platelet volume (MPV) among women with adenomyosis, although platelet count (PC) showed no significant change[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Conversely, Coskun et al. found no correlation between PC or MPV and either endometriosis or adenomyosis[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. A recent investigation by Lin Q found a significant rise in PC among women with adenomyosis compared to healthy controls, reinforcing the results reported by Zhang[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In our study, while PLT was notably elevated in the AM group relative to the control group, multivariable logistic regression analysis did not reveal a significant correlation between platelet levels and adenomyosis.\u003c/p\u003e \u003cp\u003eConsistent with previous findings, our study indicated that APTT was decreased in patients with adenomyosis, aligning with similar observations in endometriosis cases[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003csup\u003e,\u003c/sup\u003e [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Research on trauma patients has shown that APTT activation is related to the pathogenesis of venous thrombosis[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Additionally, it has been reported that thrombin activates platelets, leading to the production of thromboxane A2 (TXA2), which further activates additional platelets and induces plasminogen activator inhibitor-1 (PAI-1) expression in ectopic endometrium[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. This is consistent with the illustration in adenomyosis[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. This cascade contributes to the activation of the coagulation pathway, ultimately resulting in a shorter APTT in those with adenomyosis.\u003c/p\u003e \u003cp\u003eNumerous case reports in the literature document thromboembolic events, such as cerebral infarction and deep vein thrombosis (DVT), in patients with adenomyosis, presenting a significant clinical challenge[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The coexistence of heavy menstrual bleeding and thromboembolic events creates a vicious cycle, where anticoagulant therapy may exacerbate menorrhagia, and hormonal treatments for menorrhagia become contraindicated in the presence of active VTE[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. TEG is utilized in various medical disciplines, including gynecology, obstetrics, emergency care, intensive care, and cardiovascular surgery. Its superior sensitivity and specificity for detecting thrombogenesis make it an invaluable tool across these fields[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Our findings illustrate a decline in R and an increase in MA among patients with adenomyosis, reinforcing the concept of a hypercoagulable state. This underscores the importance for gynecologists to monitor coagulation status, implement appropriate treatment strategies, and support long-term management of adenomyosis.\u003c/p\u003e \u003cp\u003eThere is a robust association between elevated serum CA125 levels and the presence of a hypercoagulable state[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].. Reports indicate thrombus formation in patients with adenomyosis, often accompanied by elevated CA125 levels, which may reflect hypercoagulability[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. CA125, a tumor-associated mucin, plays a crucial role in the hypercoagulable state associated with malignant tumors, binding to P-selectin and L-selectin and facilitating interactions that lead to platelet-rich microthrombus formation[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].Furthermore, higher preoperative CA125 levels have been positively correlated with the incidence of perioperative thromboembolic events in epithelial ovarian cancer[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In patients presenting with cerebral venous sinus thrombosis, heightened CA125 levels have also been noted[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Our findings are consistent with previous studies that demonstrated a negative correlation between APTT and CA125 levels and established correlations between changes in R and MA with CA125 levels, supporting the link between increased CA125 and a hypercoagulable state in adenomyosis[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Furthermore, our findings revealed a correlation between the alterations in R and MA and the level of CA125, thereby substantiating the robust association between elevated CA125 levels and a hypercoagulable state in individuals with adenomyosis.\u003c/p\u003e \u003cp\u003eYamanaka et al. found that patients with adenomyosis whose uterine volumes exceeded 100 cm\u0026sup3; during menstruation were at an enhanced risk of activating the coagulation system[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Zhang et al. also reported a negative correlation between APTT and uterine volume[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. However, there was no significant correlation between the coagulation function and uterine volume in our study results.\u003c/p\u003e \u003cp\u003ePatients with adenomyosis typically experience heavier menstrual bleeding and prolonged bleeding durations, which can lead to anemia[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Previous research indicated that APTT during menstruation was shorter in patients with moderate anemia compared to those with milder forms. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Our study confirmed that R was positively correlated with HGB, highlighting the increased risk of thrombosis as hemoglobin levels decrease. Anemia can promote a hypercoagulable state and disrupt endothelial adhesion molecule gene expression by increasing reactive platelets and red blood cells[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Additionally, our findings noted positive correlation between MA and VAS. However, another study found no association between APTT, TT, and the severity of dysmenorrhea in adenomyosis patients[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study was the first to demonstrate the diagnostic utility of TEG in adenomyosis patients. However, due to its retrospective design, data were collected exclusively from surgical patients, and not all participants were in the uterine bleeding phase. Future studies with larger sample sizes are warranted.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBoth TEG parameters and coagulation function results indicate that patients with adenomyosis tend to exhibit a hypercoagulable state, which may be correlated with elevated serum CA125 levels, anemia and dysmenorrhea.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edenomyosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethe activated partial thromboplastin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAUC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethe area under the curve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecoagulation index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOC, combined oral contraceptive\u003c/div\u003e \u003cdiv class=\"Description\"\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEM, endometriosis\u003c/div\u003e \u003cdiv class=\"Description\"\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHSIL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehigh-grade squamous intraepithelial lesions\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eK\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecoagulation time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emaximum amplitude\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePLT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eplatelet count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ereaction time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTEG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThromboelastography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective case-control study was approved by the Ethics Committee of the International Peace Maternity and Child Health Hospital of the China Welfare Institute (GKLW2022-16), and written informed consent was waived. And this study adhered to the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest and nothing to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eF\u003c/strong\u003e\u003cstrong\u003eunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work received financial support from the Shanghai Municipal Commission of Science and Technology Program [grant 22Y11906400], Fundamental Research Funds for the Central Universities [YG2023QNA47], Clinical Research Plan of IPMCH [IPMCH2022CR1-04]. All these funding bodies played role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJLJ designed the study protocol, collected the data, performed the statistical analysis and was a major contributor in writing the manuscript. JY collected and analyzed the patient data and \u0026nbsp; revised the manuscrip. WYC collected and analyzed the patient data and wrote part of the manuscript. SL and YPY collected the data and performed the statistical. FS concepted and design of the study and revised the manuscript. HX conceived the study concept and co-ordinate the whole research procedure. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGarc\u0026iacute;a-Solares J, Donnez J, Donnez O, Dolmans M-M. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018;109:371\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eBulun SE, Yildiz S, Adli M, Wei J-J. Adenomyosis pathogenesis: insights from next-generation sequencing. Hum Reprod Update. 2021;27:1086\u0026ndash;97.\u003c/li\u003e\n\u003cli\u003eKho KA, Chen JS, Halvorson LM. Diagnosis, Evaluation, and Treatment of Adenomyosis. JAMA. 2021;326:177\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eVannuccini S, Tosti C, Carmona F, Huang SJ, Chapron C, Guo S-W, et al. Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod Biomed Online. 2017;35:592\u0026ndash;601.\u003c/li\u003e\n\u003cli\u003eYamanaka A, Kimura F, Yoshida T, Kita N, Takahashi K, Kushima R, et al. Dysfunctional coagulation and fibrinolysis systems due to adenomyosis is a possible cause of thrombosis and menorrhagia. Eur J Obstet Gynecol Reprod Biol. 2016;204:99\u0026ndash;103.\u003c/li\u003e\n\u003cli\u003eYan Y, Zhang X, Zhong D, Wang A, Wu S, Wu B. Adenomyosis-Associated Ischemic Stroke: Pathophysiology, Detection and Management. Brain Sciences. 2022;12:1410.\u003c/li\u003e\n\u003cli\u003eKuriakose D, Xiao Z. Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives. International Journal of Molecular Sciences. 2020;21:7609.\u003c/li\u003e\n\u003cli\u003eKim B, Kim S-H, Kim T. Cerebral Infarcts by Nonbacterial Thrombotic Endocarditis Associated with Adenomyosis: A Case Report. J Stroke Cerebrovasc Dis. 2018;27:e50\u0026ndash;3.\u003c/li\u003e\n\u003cli\u003eLiu X, Shen M, Qi Q, Zhang H, Guo S-W. Corroborating evidence for platelet-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis. Hum Reprod. 2016;31:734\u0026ndash;49.\u003c/li\u003e\n\u003cli\u003eLin Q, Li T, Ding S, Yu Q, Zhang X. Anemia-Associated Platelets and Plasma Prothrombin Time Increase in Patients with Adenomyosis. J Clin Med. 2022;11:4382.\u003c/li\u003e\n\u003cli\u003eGuo S-W. The Role of Platelets in the Pathogenesis and Pathophysiology of Adenomyosis. J Clin Med. 2023;12:842.\u003c/li\u003e\n\u003cli\u003eYang F, Wang Q, Ma R, Deng F, Liu J. CA125-Associated Activated Partial Thromboplastin Time and Thrombin Time Decrease in Patients with Adenomyosis. J Multidiscip Healthc. 2024;17:251\u0026ndash;61.\u003c/li\u003e\n\u003cli\u003eHartmann J, Walsh M, Grisoli A, Thomas AV, Shariff F, McCauley R, et al. Diagnosis and Treatment of Trauma-Induced Coagulopathy by Viscoelastography. Semin Thromb Hemost. 2020;46:134\u0026ndash;46.\u003c/li\u003e\n\u003cli\u003eHarahsheh Y, Ho KM. Use of viscoelastic tests to predict clinical thromboembolic events: A systematic review and meta-analysis. Eur J Haematol. 2018;100:113\u0026ndash;23.\u003c/li\u003e\n\u003cli\u003eLarsen J, Hvas A. Predictive Value of Whole Blood and Plasma Coagulation Tests for Intra- and Postoperative Bleeding Risk: A Systematic Review. Seminars in Thrombosis and Hemostasis. 2017;43:772\u0026ndash;805.\u003c/li\u003e\n\u003cli\u003eJackson DL, DeLoughery TG. Postpartum Hemorrhage: Management of Massive Transfusion. Obstet Gynecol Surv. 2018;73:418\u0026ndash;22.\u003c/li\u003e\n\u003cli\u003eYoung JS, White LM. Vaginal Bleeding in Late Pregnancy. Emerg Med Clin North Am. 2019;37:251\u0026ndash;64.\u003c/li\u003e\n\u003cli\u003eZhao H, Cheng H, Huang M, Mei F. Application of thromboelastography in diagnosing normal pregnancies and pregnancies with complications. J Clin Lab Anal. 2022;36:e24446.\u003c/li\u003e\n\u003cli\u003eLiu J, Wang N, Chen Y, Lu R, Ye X. Thrombelastography coagulation index may be a predictor of venous thromboembolism in gynecological oncology patients. J Obstet Gynaecol Res. 2017;43:202\u0026ndash;10.\u003c/li\u003e\n\u003cli\u003eMansfield PK, Voda A, Allison G. Validating a pencil-and-paper measure of perimenopausal menstrual blood loss. Womens Health Issues. 2004;14:242\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eGerlinger C, Schumacher U, Wentzeck R, Uhl-Hochgraeber K, Solomayer E, Schmitz H, et al. How can we measure endometriosis-associated pelvic pain? Journal of Endometriosis and Pelvic Pain Disorders. 2012.\u003c/li\u003e\n\u003cli\u003ePark DS, Kim M-L, Song T, Yun BS, Kim MK, Jun HS, et al. Clinical experiences of the levonorgestrel-releasing intrauterine system in patients with large symptomatic adenomyosis. Taiwan J Obstet Gynecol. 2015;54:412\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eBodur S, G\u0026uuml;n I, Alpaslan Babayigit M. The significance of mean platelet volume on diagnosis and management of adenomyosis. Med Glas (Zenica). 2013;10:59\u0026ndash;62.\u003c/li\u003e\n\u003cli\u003eStephanou A, Jessop DS, Knight RA, Lightman SL. Corticotrophin-releasing factor-like immunoreactivity and mRNA in human leukocytes. Brain Behav Immun. 1990;4:67\u0026ndash;73.\u003c/li\u003e\n\u003cli\u003eZhang HY, Wang AQ, Zhu S, Yu L, Sun JF, Xu W, et al. [Changes of coagulation function in patients with adenomyosis]. Zhonghua Fu Chan Ke Za Zhi. 2022;57:179\u0026ndash;89.\u003c/li\u003e\n\u003cli\u003eLing X, Wang T. Diagnostic and prognostic value of coagulation-related factors in endometriosis. Am J Transl Res. 2022;14:7924\u0026ndash;31.\u003c/li\u003e\n\u003cli\u003eTanaka KA, Terada R, Butt AL, Mazzeffi MA, McNeil JS. Factor VIII: A Dynamic Modulator of Hemostasis and Thrombosis in Trauma. Anesth Analg. 2023;136:894\u0026ndash;904.\u003c/li\u003e\n\u003cli\u003eZhang Q, Duan J, Liu X, Guo S-W. Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation. Mol Cell Endocrinol. 2016;428:1\u0026ndash;16.\u003c/li\u003e\n\u003cli\u003eYang B, Gu N, Shi S, Zhang C, Chen L, Ouyang J, et al. Immunoreactivity of Plasminogen Activator Inhibitor 1 and Its Correlation with Dysmenorrhea and Lesional Fibrosis in Adenomyosis. Reprod Sci. 2021;28:2378\u0026ndash;86.\u003c/li\u003e\n\u003cli\u003eYin X, Wu J, Song S, Zhang B, Chen Y. Cerebral infarcts associated with adenomyosis: a rare risk factor for stroke in middle-aged women: a case series. BMC Neurol. 2018;18:213.\u003c/li\u003e\n\u003cli\u003eHong EY, Lin HZ, Fong YF. Venous Thromboembolism and Adenomyosis: A Retrospective Review. Gynecol Minim Invasive Ther. 2020;9:64\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eSpiezia L, Vasques F, Behr A, Campello E, Maggiolo S, Berizzi A, et al. Perioperative coagulation assessment of patients undergoing major elective orthopedic surgery. Intern Emerg Med. 2016;11:793\u0026ndash;801.\u003c/li\u003e\n\u003cli\u003eShao B, Wahrenbrock MG, Yao L, David T, Coughlin SR, Xia L, et al. Carcinoma mucins trigger reciprocal activation of platelets and neutrophils in a murine model of Trousseau syndrome. Blood. 2011;118:4015\u0026ndash;23.\u003c/li\u003e\n\u003cli\u003eAiura R, Nakayama S, Yamaga H, Kato Y, Fujishima H. Systemic thromboembolism including multiple cerebral infarctions with middle cerebral artery occlusion caused by the progression of adenomyosis with benign gynecological tumor: a case report. BMC Neurol. 2021;21:14.\u003c/li\u003e\n\u003cli\u003eMosevoll KA, Johansen S, Wendelbo \u0026Oslash;, Nepstad I, Bruserud \u0026Oslash;, Reikvam H. Cytokines, Adhesion Molecules, and Matrix Metalloproteases as Predisposing, Diagnostic, and Prognostic Factors in Venous Thrombosis. Front Med (Lausanne). 2018;5:147.\u003c/li\u003e\n\u003cli\u003eZhou Q, Zhu C, Shen Z, Zhang T, Li M, Zhu J, et al. Incidence and potential predictors of thromboembolic events in epithelial ovarian carcinoma patients during perioperative period. Eur J Surg Oncol. 2020;46:855\u0026ndash;61.\u003c/li\u003e\n\u003cli\u003eLi B, Shi K, Jing C, Xu L, Kong M, Ba M. Successful management of cerebral venous sinus thrombosis due to adenomyosis: Case reports and literature review. Clin Neurol Neurosurg. 2023;229:107726.\u003c/li\u003e\n\u003cli\u003eGunther R, Walker C. Adenomyosis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.\u003c/li\u003e\n\u003cli\u003eKaiafa G, Savopoulos C, Kanellos I, Mylonas KS, Tsikalakis G, Tegos T, et al. Anemia and stroke: Where do we stand? Acta Neurol Scand. 2017;135:596\u0026ndash;602.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"adenomyosis, hypercoagulability, thromboelastography","lastPublishedDoi":"10.21203/rs.3.rs-6220839/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6220839/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePatients with adenomyosis are thought to exist in a hypercoagulable state; however, the specific alterations in thromboelastography (TEG) remain to be elucidated. This study aimed to assess changes in TEG metrics and to investigate factors influencing coagulation function in individuals diagnosed with adenomyosis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective observational study included 151 patients diagnosed with adenomyosis (AM group), while the control group consisted of 187 patients without adenomyosis who underwent laparoscopic surgery for benign adnexal cysts or high-grade squamous intraepithelial lesions (HSIL) concurrently. Comprehensive analyses of clinical data, laboratory results, and ultrasound findings were conducted.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn comparison to the control group, the adenomyosis group exhibited significantly shorter reaction time (R) and coagulation time (K) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Additionally, the maximum amplitude (MA) was notably higher in the AM group than in the control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Platelet (PLT) counts were significantly elevated in the AM group, whereas the activated partial thromboplastin time (APTT) was shorter (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In the multivariable logistic regression analysis, significant associations were found between MA (adjusted odds ratio [aOR] 1.10, 95% confidence interval [CI] 1.06\u0026ndash;1.15), APTT (aOR 0.871, 95% CI 0.813\u0026ndash;0.932), and R (aOR 0.799, 95% CI 0.64\u0026ndash;0.99) with adenomyosis. The area under the curve (AUC) for diagnosing adenomyosis based on the combination of MA, R, and APTT was calculated to be 0.74 (0.69\u0026ndash;0.79).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe findings suggest that patients with adenomyosis are predisposed to a hypercoagulable state, which may be linked to increased serum CA125 levels, anemia and dysmenorrhea.\u003c/p\u003e","manuscriptTitle":"Thromboelastography (TEG) in patients with adenomyosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-27 08:55:36","doi":"10.21203/rs.3.rs-6220839/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"54f04a5e-8f25-45a7-b795-b1398be50133","owner":[],"postedDate":"March 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-18T09:38:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-27 08:55:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6220839","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6220839","identity":"rs-6220839","version":["v1"]},"buildId":"B-jG_2CBjPDmsCi4Wdhf-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}