Vol 94, No 4 (2023)
Research paper
Published online: 2021-08-06

open access

Page views 3535
Article views/downloads 2940
Get Citation

Connect on Social Media

Connect on Social Media

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.

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.

Article available in PDF format

View PDF Download PDF file

References

  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.