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BMC Women's Health
Published in: BMC Women's Health 1/2019

Open Access 01-12-2019 | Endometriosis | Research article

Is there a correlation between inflammatory markers and coagulation parameters in women with advanced ovarian endometriosis?

Authors: Shaojie Ding, Qiao Lin, Tianhong Zhu, Tiantian Li, Libo Zhu, Jianzhang Wang, Xinmei Zhang

Published in: BMC Women's Health | Issue 1/2019

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Abstract

Background

Endometriosis is defined as a chronic inflammatory disease. Recent studies have shown that increased coagulation parameters including fibrinogen and platelets are associated with endometriosis. The objective of this study was to determine the levels of inflammatory markers and coagulation parameters and their correlations in women with endometriomas compared to those with benign ovarian cysts or normal pelvic anatomy.

Methods

Between June 2015 and June 2017, a total of 548 women who underwent laparoscopic/laparotomic surgery for ovarian endometriomas (OMA group, n = 226), non-endometriosis benign ovarian cysts (Cyst group, n = 210) and tubal reanastomosis (Control group, n = 112) were recruited in this study. Inflammatory markers including c-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and coagulation parameters including platelet count, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time, and plasma fibrinogen as well as CA-125 were determined.

Results

Compared with Cyst group and Control group, TT and PT in OMA group were significantly shorter and plasma fibrinogen levels were significantly higher (P < 0.05). Moreover, the levels of plasma fibrinogen were positively correlated with CRP, NLR and PLR (P < 0.05). In addition, the confidence intervals for the area under the curve (AUC) for CA-125 × fibrinogen were significantly higher than those for CA-125 (0.904–0.952 vs. 0.899–0.949) in the diagnosis of endometrioma.

Conclusions

These results indicate that women with endometriomas demonstrate a hypercoagulable status due to the inflammatory nature of endometriosis. The combined determination for CA-125 and fibrinogen demonstrate a higher area under the curve than the single detection of CA-125 in those with endometriomas compared to these with benign ovarian cysts.

Trial registration

This study was approved by the Human Ethics Committee of the Women’s Hospital, School of Medicine, Zhejiang University (No.20170174) and all women provided written informed consent.
Literature
1.
Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511–9.PubMedCrossRef
2.
Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z. Imbalance in cytokines from interleukin-1 family - role in pathogenesis of endometriosis. Am J Reprod Immunol. 2012;68(2):138–45.PubMedCrossRef
3.
Wickiewicz D, Chrobak A, Gmyrek GB, Halbersztadt A, Gabrys MS, Goluda M, et al. Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis. Arch Gynecol Obstet. 2013;288(4):805–14.PubMedCrossRef
4.
Birt JA, Nabli H, Stilley JA, Windham EA, Frazier SR, Sharpe-Timms KL. Elevated peritoneal fluid TNF-alpha incites ovarian early growth response factor 1 expression and downstream protease mediators: a correlation with ovulatory dysfunction in endometriosis. Reprod Sci. 2013;20(5):514–23.PubMedPubMedCentralCrossRef
5.
Velasco I, Acien P, Campos A, Acien MI, Ruiz-Macia E. Interleukin-6 and other soluble factors in peritoneal fluid and endometriomas and their relation to pain and aromatase expression. J Reprod Immunol. 2010;84(2):199–205.PubMedCrossRef
6.
Tokmak A, Yildirim G, Oztas E, Akar S, Erkenekli K, Gulsen P, et al. Use of neutrophil-to-lymphocyte ratio combined with CA-125 to distinguish Endometriomas from other benign ovarian cysts. Reprod Sci. 2016;23(6):795–802.PubMedCrossRef
7.
Cho S, Cho H, Nam A, Kim HY, Choi YS, Park KH, et al. Neutrophil-to-lymphocyte ratio as an adjunct to CA-125 for the diagnosis of endometriosis. Fertil Steril. 2008;90(6):2073–9.PubMedCrossRef
8.
Yang H, Zhu L, Wang S, Lang J, Xu T. Noninvasive diagnosis of moderate to severe endometriosis: the platelet-lymphocyte ratio cannot be a neoadjuvant biomarker for serum cancer antigen 125. J Minim Invasive Gynecol. 2015;22(3):373–7.PubMedCrossRef
9.
Yamaguchi K, Mandai M, Toyokuni S, Hamanishi J, Higuchi T, Takakura K, et al. Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clin Cancer Res : Official J Am Assoc Cancer Res. 2008;14(1):32–40.CrossRef
10.
Mizumoto H, Saito T, Ashihara K, Nishimura M, Takehara M, Tanaka R, et al. Expression of matrix metalloproteinases in ovarian endometriomas: immunohistochemical study and enzyme immunoassay. Life Sci. 2002;71(3):259–73.PubMedCrossRef
11.
Reis FM, Di Blasio AM, Florio P, Ambrosini G, Di Loreto C, Petraglia F. Evidence for local production of inhibin a and activin a in patients with ovarian endometriosis. Fertil Steril. 2001;75(2):367–73.PubMedCrossRef
12.
Boss EA, Massuger LF, Thomas CM, Geurts-Moespot A, van Schaik JH, Boonstra H, et al. Clinical value of components of the plasminogen activation system in ovarian cyst fluid. Anticancer Res. 2002;22(1A):275–82.PubMed
13.
Sanchez AM, Vigano P, Somigliana E, Panina-Bordignon P, Vercellini P, Candiani M. The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary. Hum Reprod Update. 2014;20(2):217–30.PubMedCrossRef
14.
Ding D, Liu X, Duan J, Guo SW. Platelets are an unindicted culprit in the development of endometriosis: clinical and experimental evidence. Hum Reprod. 2015;30(4):812–32.PubMedCrossRef
15.
Wu Q, Ding D, Liu X, Guo SW. Evidence for a Hypercoagulable state in women with ovarian Endometriomas. Reprod Sci. 2015;22(9):1107–14.PubMedCrossRef
16.
Chmaj-Wierzchowska K, Kampioni M, Wilczak M, Sajdak S, Opala T. Novel markers in the diagnostics of endometriomas: Urocortin, ghrelin, and leptin or leukocytes, fibrinogen, and CA-125? Taiwan J Obstet Gynecol. 2015;54(2):126–30.PubMedCrossRef
17.
Vigano P, Ottolina J, Sarais V, Rebonato G, Somigliana E, Candiani M. Coagulation status in women with endometriosis. Reprod Sci. 2017;1933719117718273.
18.
Lin M, Weng H, Wang X, Zhou B, Yu P, Wang Y. The role of tissue factor and protease-activated receptor 2 in endometriosis. Am J Reprod Immunol. 2012;68(3):251–7.PubMedCrossRef
19.
Bruse C, Bergqvist A, Carlstrom K, Fianu-Jonasson A, Lecander I, Astedt B. Fibrinolytic factors in endometriotic tissue, endometrium, peritoneal fluid, and plasma from women with endometriosis and in endometrium and peritoneal fluid from healthy women. Fertil Steril. 1998;70(5):821–6.PubMedCrossRef
20.
Gilabert-Estelles J, Ramon LA, Espana F, Gilabert J, Vila V, Reganon E, et al. Expression of angiogenic factors in endometriosis: relationship to fibrinolytic and metalloproteinase systems. Hum Reprod. 2007;22(8):2120–7.PubMedCrossRef
21.
22.
Hirota Y, Osuga Y, Hirata T, Harada M, Morimoto C, Yoshino O, et al. Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells. Hum Reprod. 2005;20(12):3547–53.PubMedCrossRef
23.
Hirota Y, Osuga Y, Hirata T, Yoshino O, Koga K, Harada M, et al. Possible involvement of thrombin/protease-activated receptor 1 system in the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2005;90(6):3673–9.PubMedCrossRef
24.
Szaba FM, Smiley ST. Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood. 2002;99(3):1053–9.PubMedCrossRef
25.
Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertility and sterility. 1997;67(5):817–21.
26.
Levi M, Keller TT, van Gorp E, ten Cate H. Infection and inflammation and the coagulation system. Cardiovasc Res. 2003;60(1):26–39.PubMedCrossRef
27.
Parry GC, Mackman N. Transcriptional regulation of tissue factor expression in human endothelial cells. Arterioscler Thromb Vasc Biol. 1995;15(5):612–21.PubMedCrossRef
28.
Syrovets T, Jendrach M, Rohwedder A, Schule A, Simmet T. Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKKbeta-mediated NF-kappaB activation. Blood. 2001;97(12):3941–50.PubMedCrossRef
29.
Rauch U, Bonderman D, Bohrmann B, Badimon JJ, Himber J, Riederer MA, et al. Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood. 2000;96(1):170–5.PubMedCrossRef
30.
Eilertsen KE, Osterud B. Tissue factor: (patho)physiology and cellular biology. Blood Coagul Fibrinolysis : Int J Haemost Thromb. 2004;15(7):521–38.
31.
Murphy G, Knauper V, Atkinson S, Gavrilovic J, Edwards D. Cellular mechanisms for focal proteolysis and the regulation of the microenvironment. Fibrinolysis Proteol. 2000;14(2–3):165–74.CrossRef
32.
Ugwu F, Lemmens G, Collen D, Lijnen HR. Modulation of cell-associated plasminogen activation by stromelysin-1 (MMP-3). Thromb Haemost. 1999;82(3):1127–31.PubMedCrossRef
33.
Gilabert-Estelles J, Estelles A, Gilabert J, Castello R, Espana F, Falco C, et al. Expression of several components of the plasminogen activator and matrix metalloproteinase systems in endometriosis. Hum Reprod. 2003;18(7):1516–22.PubMedCrossRef
34.
Ramon L, Gilabert-Estelles J, Castello R, Gilabert J, Espana F, Romeu A, et al. mRNA analysis of several components of the plasminogen activator and matrix metalloproteinase systems in endometriosis using a real-time quantitative RT-PCR assay. Hum Reprod. 2005;20(1):272–8.PubMedCrossRef
35.
Zhao Y, Zhang J, Zhang J, Wu J. Diabetes mellitus is associated with shortened activated partial thromboplastin time and increased fibrinogen values. PLoS One. 2011;6(1):e16470.PubMedPubMedCentralCrossRef
36.
Zwaginga JJ, Koomans HA, Sixma JJ, Rabelink TJ. Thrombus formation and platelet-vessel wall interaction in the nephrotic syndrome under flow conditions. J Clin Invest. 1994;93(1):204–11.PubMedPubMedCentralCrossRef
37.
Kurata M, Sasayama Y, Yamasaki N, Kitazawa I, Hamada Y, Horii I. Mechanism for shortening PT and APTT in dogs and rats--effect of fibrinogen on PT and APTT. J Toxicol Sci. 2003;28(5):439–43.PubMedCrossRef
38.
Ng VL. Prothrombin time and partial thromboplastin time assay considerations. Clin Lab Med. 2009;29(2):253–63.PubMedCrossRef
39.
Yavuzcan A, Caglar M, Ustun Y, Dilbaz S, Ozdemir I, Yildiz E, et al. Evaluation of mean platelet volume, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in advanced stage endometriosis with endometrioma. J Turk Ger Gynecol Association. 2013;14(4):210–5.CrossRef
40.
Kim SK, Park JY, Jee BC, Suh CS, Kim SH. Association of the neutrophil-to-lymphocyte ratio and CA-125 with the endometriosis score. Clin Exp Repro Med. 2014;41(4):151–7.CrossRef
41.
Tchaikovski SN, Thomassen MC, Costa SD, Bremme K, Rosing J. Changes in haemostatic parameters during the menstrual cycle and subsequent use of drospirenone-containing oral contraceptives. Thromb Res. 2014;134(5):1032–7.PubMedCrossRef
42.
Ahamed J, Versteeg HH, Kerver M, Chen VM, Mueller BM, Hogg PJ, et al. Disulfide isomerization switches tissue factor from coagulation to cell signaling. Proc Natl Acad Sci U S A. 2006;103(38):13932–7.PubMedPubMedCentralCrossRef
43.
Krikun G, Hu Z, Osteen K, Bruner-Tran KL, Schatz F, Taylor HS, et al. The immunoconjugate "icon" targets aberrantly expressed endothelial tissue factor causing regression of endometriosis. Am J Pathol. 2010;176(2):1050–6.PubMedPubMedCentralCrossRef
44.
Guo SW, Ding D, Geng JG, Wang L, Liu X. P-selectin as a potential therapeutic target for endometriosis. Fertil Steril. 2015;103(4):990–1000 e8.PubMedCrossRef
Metadata
Title
Is there a correlation between inflammatory markers and coagulation parameters in women with advanced ovarian endometriosis?
Authors
Shaojie Ding
Qiao Lin
Tianhong Zhu
Tiantian Li
Libo Zhu
Jianzhang Wang
Xinmei Zhang
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Endometriosis
Published in
BMC Women's Health / Issue 1/2019
Electronic ISSN: 1472-6874
DOI
https://doi.org/10.1186/s12905-019-0860-9

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