The abnormal coagulation status in endometriosis patients: a systematic review and meta-analysis

Objectives This study aimed to comprehensively examine coagulation parameters in patients with endometriosis versus those without to determine hematologic alterations associated with endometriosis.

Embase, PubMed, CINAHL, Web of Science, the Cochrane Library, CBM, CNKI, VIP, and Wanfang Database were searched through June 2024. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Statistical analyses were performed using Stata 16.0 software.

22 studies with 6,258 participants were included. The results showed significant abnormalities in coagulation parameters in patients with endometriosis compared to those without. Specifically, fibrinogen (FIB) (SMD = 0.57; 95%CI, 0.45 ~ 0.69; P < 0.001), D-dimer (D-D) (SMD = 0.62; 95%CI, 0.27 ~ 0.96; P < 0.001), and platelet count (PLT) (SMD = 0.28; 95%CI, 0.11 ~ 0.45; P = 0.001) were significantly elevated, while activated partial thromboplastin time (APTT) (SMD = -0.13; 95%CI, -0.22~-0.03; P = 0.010), prothrombin time (PT) (SMD = -0.31; 95%CI, -0.54~-0.08; P = 0.009), and thrombin time (TT) (SMD = -0.41; 95%CI, -0.63~-0.20; P < 0.001) were significantly reduced. Moreover, FIB (SMD = 0.47; 95%CI, 0.23 ~ 0.71; P < 0.001), D-D (SMD = 0.38; 95%CI, 0.10 ~ 0.66; P = 0.009), PT (SMD = -0.21; 95%CI, -0.41~-0.02; P = 0.030), and TT (SMD = -0.20; 95%CI, -0.38 ~ 0.01; P = 0.037) also vary between patients with stage I-II and stage III-IV endometriosis.

Multiple coagulation parameters were abnormal in endometriosis patients, indicating a hypercoagulable state, particularly pronounced in those with stage III-IV endometriosis. Large, globally representative prospective cohorts are needed to elucidate the causal relationship between endometriosis and hypercoagulability. Key points Women with endometriosis showed significantly elevated levels of FIB, D-D, and PLT, and significantly decreased APTT, PT, and TT than those without, indicating a hypercoagulable state. Patients with III-IV endometriosis had the most significant abnormalities in coagulation parameters, with FIB, D-D, and PLT levels much higher, and APTT, PT, and TT much shorter than those without. The levels of FIB and D-D were positively correlated with the severity of endometriosis, while PT and TT were negatively correlated with disease severity. This pattern of coagulation marker alterations is associated with more advanced stages of endometriosis. Large, globally representative prospective cohorts are needed to elucidate the causal relationship between endometriosis and hypercoagulability. Graphical Abstract Similar content being viewed by others Data availability No datasets were generated or analysed during the current study.

Giudice LC, Kao LC, Endometriosis Lancet 2004 Nov 13–19;364(9447):1789–99 Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98(3):511–519 Giudice LC (2010) Clinical practice. Endometriosis. N Engl J Med 362(25):2389–2398 Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS et al (2017) World endometriosis society consensus on the classification of endometriosis. Hum Reprod 32(2):315–324 Horne AW, Missmer SA (2022) Pathophysiology, diagnosis, and management of endometriosis. BMJ 379:e070750 Tchaikovski SN, Rosing J (2010) Mechanisms of estrogen-induced venous thromboembolism. Thromb Res 126(1):5–11 Schmid S, Fent K (2020) 17beta-Estradiol and the glucocorticoid Clobetasol propionate affect the blood coagulation cascade in zebrafish. Environ Pollut 259:113808 Mu F, Rich-Edwards J, Rimm EB, Spiegelman D, Missmer SA (2016) Endometriosis and risk of coronary heart disease. Circ Cardiovasc Qual Outcomes 9(3):257–264 Farland LV, Degnan WJ 3rd, Bell ML et al (2022) Laparoscopically confirmed endometriosis and risk of incident stroke: A prospective cohort study. Stroke 53(10):3116–3122 Mu F, Rich-Edwards J, Rimm EB, Spiegelman D, Forman JP, Missmer SA (2017) Association between endometriosis and hypercholesterolemia or hypertension. Hypertension 70(1):59–65 De Corte P, Milhoranca I, Mechsner S, Oberg AS, Kurth T, Heinemann K (2024) Unravelling the causal relationship between endometriosis and the risk for developing venous thromboembolism: A pooled analysis. Thromb Haemost. Sep 18 Sugiura-Ogasawara M, Ebara T, Matsuki T et al (2019) Endometriosis and recurrent pregnancy loss as new risk factors for venous thromboembolism during pregnancy and Post-Partum: the JECS birth cohort. Thromb Haemost 119(4):606–617 Ottolina J, Bartiromo L, Dolci C et al (2020) August Assessment of coagulation parameters in women affected by endometriosis: validation study and systematic review of the literature. Diagnostics (Basel).;10(8) Chen ZY, Zhang LF, Zhang YQ, Zhou Y, Li XY, Huang XF (2021) Blood tests for prediction of deep endometriosis: A case-control study. World J Clin Cases.;9(35) Vigano P, Ottolina J, Sarais V, Rebonato G, Somigliana E, Candiani M (2018) Coagulation status in women with endometriosis. Reprod Sci 01(4):559–565 Ding S, Lin Q, Zhu T et al (2019) Is there a correlation between inflammatory markers and coagulation parameters in women with advanced ovarian endometriosis? BMC Women’s Health. 30 Dec;19(1) Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71 Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283(15):2008–2012 Wells G, Shea B, O’Connell D et al The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2021 2021-05-03 [cited 2023-07-13]; Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp McGrath S, Zhao X, Steele R, Thombs BD, Benedetti A, Collaboration DESD (2020) Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis. Stat Methods Med Res 29(9):2520–2537 GRADEpro GDT [cited 2025-06-30]; Available from: https://gdt.gradepro.org/app/ Guyatt G, Oxman AD, Akl EA et al (2011) GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 64(4):383–394 Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines 6. Rating the quality of evidence–imprecision. J Clin Epidemiol 64(12):1283–1293 Schünemann H, Brożek J, Guyatt G, Oxman A, GRADE, Handbook (2013) October 2013 [cited 2025-06-30]; Available from: https://gdt.gradepro.org/app/handbook/handbook.html Cao Y, Liu P (2019) [Value of coagulation indicators, inflammatory factors and glycoantigen 125 in diagnosis and stage evaluation of endometriosis]. J Clin Med Pract 23(03):88–92 Ding M, Gu Z, Cao Y, Cui J, Sun Z (2021) [Value of serum CA125, inflammatory factors and coagulation factors in the diagnosis of endometriosis]. Mod Med J China 23(11):19–23 Dong W (2022) [Analysis of clinical diagnostic value of coagulation and inflammatory factors in moderate to severe ovarian endometriosis]. Jilin University. https://doi.org/10.27162/d.cnki.gjlin.2022.005368 Jing Y (2019) [The clinical value of detection of coagulation and inflammatory factors in endometriosis]. YANGZHOU UNIVERSITY. https://doi.org/10.27441/d.cnki.gyzdu.2019.000282 Li H (2021) [Changes of coagulation function in patients with endometriosis and its clinical significance]. Dalian Medical University. https://doi.org/10.26994/d.cnki.gdlyu.2021.000449 Lin Q, Ding SJ, Zhu TH, Li TT, Huang XF, Zhang XM (2018) [Role and clinical significance of coagulation and inflammatory factors in moderate and severe ovarian endometriosis]. Zhonghua Fu Chan Ke Za Zhi 53(03):167–171 Liu C, Li W, Wei X, Shan H (2023) [Significance of inflammation and coagulation factors in the pathogenesis and diagnosis of ovarian endometriosis]. J Nongken Med 45(04):308–312 Ren W (2020) [Role of coagulation function indexes and Th1, Th2 cytokines in endometriosis]. Clin Med 5(17):84–86 Wang H (2022) [Diagnostic value and predictive model establishment of clinical serological indexes in endometriosis]. Zhengzhou University. https://doi.org/10.27466/d.cnki.gzzdu.2022.005609 Wang H, guo Z, Liu X (2023) [Value of fib, NLR and IL-6 in peripheral blood in diagnosing patients with moderate to severe ovarian endometriosis]. Jiangsu Med J 49(03):272–275 Wang Y, Song D, Zhang W (2021) [The diagnostic value of platelet and coagulation indexes in ovarian endometriosis cysts ]. Int J Gynecol Obstet 48(05):597–600 Wang Z, Zhou Y, Ding Y, Dang J, Hu D, Jin Z (2021) [Roles of peripheral blood inflammatory factors and coagulation indicators in endometriosis patients with pelvic adhesion]. Lab Med 36:1050–1054 Wu Z (2022) [Correlation between the expression of NLR, FIB, HMGB1 and endometriosis]. Dalian Medical University. https://doi.org/10.26994/d.cnki.gdlyu.2022.000407 Yin Y (2021) [Clinial predictive significance of NLR, Coagulation-related factors and CA125 in endometriosis]. Southern Medical University. https://doi.org/10.27003/d.cnki.gojyu.2021.000417 Zhang Y (2021) [Correlation between the level of coagulation index and inflammatory factors of the women with endometriosis and their degree of pelvic adhesion]. Chin J Fam Plann 29(05):971–975 Zhu J, Zhang Y, Wang L, Lu Y, Wang X (2022) [Changes of coagulation function in patients with endometriosis and its clinical significance]. Electron J Pract Gynecol Endocrinol 9(11):35–38 Chmaj-Wierzchowska K, Kampioni M, Wilczak M, Sajdak S, Opala T (2015) Novel markers in the diagnostics of endometriomas: urocortin, ghrelin, and leptin or leukocytes, fibrinogen, and CA-125? Taiwan J obstet gynecol. 01(2):126–130 Zhao K, Qu P (2021) Noninvasive evaluation of ovarian endometriosis: a single-center experience. Ann Palliat Med 01(4):4728–4735 Moore HB, Moore EE, Huebner BR et al (2017) Fibrinolysis shutdown is associated with a fivefold increase in mortality in trauma patients lacking hypersensitivity to tissue plasminogen activator. J Trauma Acute Care Surg 83(6):1014–1022 Bronic A, Coen Herak D, Margetic S, Milic M (2019) Croatian society of medical biochemistry and laboratory medicine: National recommendations for blood collection, processing, performance and reporting of results for coagulation screening assays prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen and D-dimer. Biochem Med (Zagreb) 29(2):020503 Maresca G, Di Blasio A, Marchioli R, Di Minno G (1999) Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol 19(6):1368–1377 Franchini M, Focosi D, Pezzo MP, Mannucci PM (2024) How we manage a high D-dimer. Haematologica 109(4):1035–1045 Zhang M, Xu T, Tong D et al (2023) Research advances in endometriosis-related signaling pathways: A review. Biomed Pharmacother 164:114909 Marquardt RM, Tran DN, Lessey BA, Rahman MS, Jeong JW (2023) Epigenetic dysregulation in endometriosis: implications for pathophysiology and therapeutics. Endocr Rev 44(6):1074–1095 Riemma G, Lagana AS, Schiattarella A et al (2020) Ion channels in the pathogenesis of endometriosis: A Cutting-Edge point of view. Int J Mol Sci.;21(3) Vercellini P, Vigano P, Somigliana E, Fedele L (2014) Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 10(5):261–275 Liu M, Wu K, Wu Y (2023) The emerging role of ferroptosis in female reproductive disorders. Biomed Pharmacother 166:115415 Li G, Lin Y, Zhang Y et al (2022) Endometrial stromal cell ferroptosis promotes angiogenesis in endometriosis. Cell Death Discov 8(1):29 Korosec S, Riemma G, Salamun V et al (2024) Coexistence of endometriosis and thyroid autoimmunity in infertile women: impact on in vitro fertilization and reproductive outcomes. Gynecol Obstet Invest 89(5):413–423 Revised American Society for Reproductive Medicine classification of endometriosis (1996) Fertil Steril. 1997;67(5):817– 21 Munro MG, Critchley HOD, Fraser IS, Committee FMD (2018) The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet 143(3):393–408 Pfeifer SM, Attaran M, Goldstein J et al (2021) ASRM mullerian anomalies classification 2021. Fertil Steril 116(5):1238–1252 Urman B, Yakin K, Ertas S et al (2024) Fertility and anatomical outcomes following hysteroscopic adhesiolysis: an 11-year retrospective cohort study to validate a new classification system for intrauterine adhesions (Urman-Vitale classification System). Int J Gynaecol Obstet 165(2):644–654

None. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author information Authors and Affiliations Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by X.Z., J.Z., Y.P., K.Z. and Y.H. The first draft of the manuscript was written byX.Z. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Corresponding author Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Zeng, X., Zhang, J., Peng, Y. et al. The abnormal coagulation status in endometriosis patients: a systematic review and meta-analysis. J Thromb Thrombolysis 59, 167–178 (2026). https://doi.org/10.1007/s11239-025-03157-4 Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11239-025-03157-4