open access

Vol 94, No 4 (2023)
Research paper
Published online: 2021-08-06
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Endometriosis is associated with an increased whole-blood thrombogenicity detected by a novel automated microchip flow-chamber system (T-TAS®)

Malgorzata Kedzia1, Maciej Osinski1, Urszula Mantaj1, Ewa Wender-Ozegowska1
·
Pubmed: 34541639
·
Ginekol Pol 2023;94(4):291-297.
Affiliations
  1. Division of Reproduction, Poznan University of Medical Sciences, Poland

open access

Vol 94, No 4 (2023)
ORIGINAL PAPERS Gynecology
Published online: 2021-08-06

Abstract

Objectives: Potential thrombotic and antifibrinolytic influence of endometriosis on haemostasis has been recently reported in the literature, as well as increased cardiovascular morbidity in women suffering from the disease. We performed a pilot study to assess the influence of endometriosis on the thrombus formation process under in vitro flow conditions.
Material and methods: This study compared women with confirmed endometriosis (n = 23) surgically and control healthy subjects (n = 10). In both groups, the same exclusion criteria were used: a prior episode of thrombosis diagnosed as acquired or inherited thrombophilia, neoplasm, and an uncertain family history of thrombosis. We evaluated the whole blood thrombogenicity using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan).
Results: The blood clot formation initiation time (T10) and occlusion time (OT) were significantly shortened in the endometriosis group (p < 0.05). The area under the curve (AUC30) of blood clot time formation values (BCTF) was substantially higher in the patients suffering from a disease (p = 0.03). An increase in AUC (TTAS) values by 100 increases the risk of developing endometriosis by 1.56-fold [adjusted OR = 1.56 (p = 0.01); (95% CI: 1.10–2.18)]. Inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), and the leucocyte, neutrophil, basophil, and neutrophil concentrations) were also substantially higher in the endometriosis group (p < 0.05).
Conclusions: The alteration of the T-TAS® and NLR values supports the thesis of a shift of the equilibrium towards thrombosis in women who have endometriosis. This phenomenon links to a state of chronic inflammation. It is detectable using a novel system for the quantitative assessment of the platelet thrombus formation process under flow conditions in vitro.

Abstract

Objectives: Potential thrombotic and antifibrinolytic influence of endometriosis on haemostasis has been recently reported in the literature, as well as increased cardiovascular morbidity in women suffering from the disease. We performed a pilot study to assess the influence of endometriosis on the thrombus formation process under in vitro flow conditions.
Material and methods: This study compared women with confirmed endometriosis (n = 23) surgically and control healthy subjects (n = 10). In both groups, the same exclusion criteria were used: a prior episode of thrombosis diagnosed as acquired or inherited thrombophilia, neoplasm, and an uncertain family history of thrombosis. We evaluated the whole blood thrombogenicity using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan).
Results: The blood clot formation initiation time (T10) and occlusion time (OT) were significantly shortened in the endometriosis group (p < 0.05). The area under the curve (AUC30) of blood clot time formation values (BCTF) was substantially higher in the patients suffering from a disease (p = 0.03). An increase in AUC (TTAS) values by 100 increases the risk of developing endometriosis by 1.56-fold [adjusted OR = 1.56 (p = 0.01); (95% CI: 1.10–2.18)]. Inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), and the leucocyte, neutrophil, basophil, and neutrophil concentrations) were also substantially higher in the endometriosis group (p < 0.05).
Conclusions: The alteration of the T-TAS® and NLR values supports the thesis of a shift of the equilibrium towards thrombosis in women who have endometriosis. This phenomenon links to a state of chronic inflammation. It is detectable using a novel system for the quantitative assessment of the platelet thrombus formation process under flow conditions in vitro.

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Keywords

endometriosis; thrombosis; prothrombotic state

About this article
Title

Endometriosis is associated with an increased whole-blood thrombogenicity detected by a novel automated microchip flow-chamber system (T-TAS®)

Journal

Ginekologia Polska

Issue

Vol 94, No 4 (2023)

Article type

Research paper

Pages

291-297

Published online

2021-08-06

Page views

3295

Article views/downloads

2500

DOI

10.5603/GP.a2021.0153

Pubmed

34541639

Bibliographic record

Ginekol Pol 2023;94(4):291-297.

Keywords

endometriosis
thrombosis
prothrombotic state

Authors

Malgorzata Kedzia
Maciej Osinski
Urszula Mantaj
Ewa Wender-Ozegowska

References (49)
  1. Szczepańska M, Wirstlein P, Skrzypczak J, et al. Expression of HOXA11 in the mid-luteal endometrium from women with endometriosis-associated infertility. Reprod Biol Endocrinol. 2012; 10: 1.
  2. Cramer DW, Missmer SA. The epidemiology of endometriosis. Ann N Y Acad Sci. 2002; 955: 11–22; discussion 34.
  3. Szczepańska M, Wirstlein P, Zawadzka M, et al. Alternation of ten-eleven translocation 1, 2, and 3 expression in eutopic endometrium of women with endometriosis-associated infertility. Gynecol Endocrinol. 2018; 34(12): 1084–1090.
  4. Andrisani A, Donà G, Brunati AM, et al. Increased oxidation-related glutathionylation and carbonic anhydrase activity in endometriosis. Reprod Biomed Online. 2014; 28(6): 773–779.
  5. Agic A, Xu H, Finas D, et al. Is endometriosis associated with systemic subclinical inflammation? Gynecol Obstet Invest. 2006; 62(3): 139–147.
  6. Kvaskoff M, Mu F, Terry KL, et al. Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update. 2015; 21(4): 500–516.
  7. Teng SW, Horng HC, Ho CH, et al. Taiwan Association of Gynecology Systematic Review Group. Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan. J Chin Med Assoc. 2016; 79(11): 577–582.
  8. Gemmill JA, Stratton P, Cleary SD, et al. Cancers, infections, and endocrine diseases in women with endometriosis. Fertil Steril. 2010; 94(5): 1627–1631.
  9. Mu F, Rich-Edwards J, Rimm EB, et al. Endometriosis and Risk of Coronary Heart Disease. Circ Cardiovasc Qual Outcomes. 2016; 9(3): 257–264.
  10. Alhurani RE, Chahal CA, Ahmed AT, et al. Sex hormone therapy and progression of cardiovascular disease in menopausal women. Clin Sci (Lond). 2016; 130(13): 1065–1074.
  11. Lobo RA. Surgical menopause and cardiovascular risks. Menopause. 2007; 14(3 Pt 2): 562–566.
  12. Koumantakis E, Matalliotakis I, Neonaki M, et al. Soluble serum interleukin-2 receptor, interleukin-6 and interleukin-1a in patients with endometriosis and in controls. Arch Gynecol Obstet. 1994; 255(3): 107–112.
  13. Pizzo A, Salmeri FM, Ardita FV, et al. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest. 2002; 54(2): 82–87.
  14. Agic A, Xu H, Altgassen C, et al. Relative expression of 1,25-dihydroxyvitamin D3 receptor, vitamin D 1 alpha-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers. Reprod Sci. 2007; 14(5): 486–497.
  15. Bedaiwy MA, Falcone T, Mascha EJ, et al. Genetic polymorphism in the fibrinolytic system and endometriosis. Obstet Gynecol. 2006; 108(1): 162–168.
  16. Szczepańska M, Mostowska A, Wirstlein P, et al. Polymorphic variants in vitamin D signaling pathway genes and the risk of endometriosis-associated infertility. Mol Med Rep. 2015; 12(5): 7109–7115.
  17. Dionigi R. Effects of surgical trauma of laparoscopic vs. open cholecystectomy. Hepatogastroenterology. 1994; 41(5): 471–476.
  18. Jilma B, Blann A, Pernerstorfer T, et al. Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin. Am J Respir Crit Care Med. 1999; 159(3): 857–863.
  19. Ding S, Lin Q, Zhu T, et al. Is there a correlation between inflammatory markers and coagulation parameters in women with advanced ovarian endometriosis? BMC Womens Health. 2019; 19(1): 169.
  20. Velasco I, Acién P, Campos A, et al. 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.
  21. Wu Q, Ding D, Liu X, et al. Evidence for a Hypercoagulable State in Women With Ovarian Endometriomas. Reprod Sci. 2015; 22(9): 1107–1114.
  22. Lipinski S, Bremer L, Lammers T, et al. Coagulation and inflammation. Molecular insights and diagnostic implications. Hamostaseologie. 2011; 31(2): 94–102, 104.
  23. Petäjä J. Inflammation and coagulation. An overview. Thrombosis Research. 2011; 127: S34–S37.
  24. Hirota Y, Osuga Y, Hirata T, et al. Possible involvement of thrombin/protease-activated receptor 1 system in the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2005; 90(6): 3673–3679.
  25. Hirota Y, Osuga Y, Hirata T, 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): 3547–3553.
  26. Ding D, Liu X, Duan J, et al. Platelets are an unindicted culprit in the development of endometriosis: clinical and experimental evidence. Hum Reprod. 2015; 30(4): 812–832.
  27. Liu J, Liu X, Li Y, et al. The association of neutrophil to lymphocyte ratio, mean platelet volume, and platelet distribution width with diabetic retinopathy and nephropathy: a meta-analysis. Biosci Rep. 2018; 38(3).
  28. Lipets EN, Ataullakhanov FI. Global assays of hemostasis in the diagnostics of hypercoagulation and evaluation of thrombosis risk. Thromb J. 2015; 13(1): 4.
  29. Hosokawa K, Ohnishi T, Kondo T, et al. A novel automated microchip flow-chamber system to quantitatively evaluate thrombus formation and antithrombotic agents under blood flow conditions. J Thromb Haemost. 2011; 9(10): 2029–2037.
  30. Ogawa S, Szlam F, Dunn AL, et al. Evaluation of a novel flow chamber system to assess clot formation in factor VIII-deficient mouse and anti-factor IXa-treated human blood. Haemophilia. 2012; 18(6): 926–932.
  31. Hosokawa K, Ohnishi T, Fukasawa M, et al. A microchip flow-chamber system for quantitative assessment of the platelet thrombus formation process. Microvasc Res. 2012; 83(2): 154–161.
  32. Viganò P, Ottolina J, Sarais V, et al. Coagulation Status in Women With Endometriosis. Reprod Sci. 2018; 25(4): 559–565.
  33. Ding D, Liu X, Guo SW. Further Evidence for Hypercoagulability in Women With Ovarian Endometriomas. Reprod Sci. 2018; 25(11): 1540–1548.
  34. Krikun G, Schatz F, Taylor H, et al. Endometriosis and tissue factor. Ann N Y Acad Sci. 2008; 1127: 101–105.
  35. Zorio E, Gilabert-Estellés J, España F, et al. Fibrinolysis: the key to new pathogenetic mechanisms. Curr Med Chem. 2008; 15(9): 923–929.
  36. Hellgren M. Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003; 29(2): 125–130.
  37. Ye Y, Vattai A, Zhang Xi, et al. Role of Plasminogen Activator Inhibitor Type 1 in Pathologies of Female Reproductive Diseases. Int J Mol Sci. 2017; 18(8).
  38. Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br J Haematol. 2005; 129(3): 307–321.
  39. Duffy MJ, McGowan PM, Harbeck N, et al. uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Res. 2014; 16(4): 428.
  40. Lyon CJ, Hsueh WA. Effect of plasminogen activator inhibitor-1 in diabetes mellitus and cardiovascular disease. Am J Med. 2003; 115 Suppl 8A: 62S–68S.
  41. Gentilini D, Vigano P, Castaldi D, et al. Plasminogen activator inhibitor-1 4G/5G polymorphism and susceptibility to endometriosis in the Italian population. Eur J Obstet Gynecol Reprod Biol. 2009; 146(2): 219–221.
  42. Ramón LA, Gilabert-Estellés J, Cosín R, et al. Plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and endometriosis. Influence of PAI-1 polymorphism on PAI-1 antigen and mRNA expression. Thromb Res. 2008; 122(6): 854–860.
  43. Bruse C, Guan Y, Carlberg M, et al. Basal release of urokinase plasminogen activator, plasminogen activator inhibitor-1, and soluble plasminogen activator receptor from separated and cultured endometriotic and endometrial stromal and epithelial cells. Fertil Steril. 2005; 83 Suppl 1: 1155–1160.
  44. Greene AD, Lang SA, Kendziorski JA, et al. Endometriosis: where are we and where are we going? Reproduction. 2016; 152(3): R63–R78.
  45. Gonçalves-Filho RP, Brandes A, Christofolini DM, et al. Plasminogen activator inhibitor-1 4G/5G polymorphism in infertile women with and without endometriosis. Acta Obstet Gynecol Scand. 2011; 90(5): 473–477.
  46. Gilabert-Estellés J, Estellés A, Gilabert J, et al. Expression of several components of the plasminogen activator and matrix metalloproteinase systems in endometriosis. Hum Reprod. 2003; 18(7): 1516–1522.
  47. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012; 98(3): 511–519.
  48. Tokmak A, Yildirim G, Öztaş E, 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.
  49. Cho S, Cho H, Nam A, et al. Neutrophil-to-lymphocyte ratio as an adjunct to CA-125 for the diagnosis of endometriosis. Fertil Steril. 2008; 90(6): 2073–2079.

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