Abstract

Abstract Study question Are women with endometriosis in a state of systemic imbalance between pro- and anti-coagulants? Summary answer Women with endometriosis do not seem to exhibit a coagulation imbalance, at least at a systemic level. What is known already A state of platelet hyperactivation potentially leading to a hypercoagulation status has been described in women with endometriosis. This phenomenon could induce an altered local environment, promoting platelet-mediated paracrine changes in endometrial tissue and also increasing cardiovascular risk, which could be worsened by the use of estrogen dependent hormonal treatments. However, despite a slight difference in some coagulation parameters has been observed between women affected and controls, their levels remain, generally, within the normal reference range. Study design, size, duration This prospective case-control study including 101 women seeking infertility consultation at the Infertility Unit of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano between January and July 2023 aimed to assess hemostasis function beyond traditional coagulation parameters. Participants/materials, setting, methods Blood of women with endometriosis (n = 51) or tubal or male factor infertility (controls; n = 50) was obtained before any ART treatment, and a complete panel of coagulation tests were performed, including basic parameters (aPTT, PT, FVIII, FII, PC, AT, FIV-C, DD, vWF, ADMT) as well as more sophisticated ones, such as Thrombin Generation Assay and Thromboelastometry, providing data on endogenous thrombin potential (ETP), clot formation time (CFT) and maximal clot firmness (MCF). Main results and the role of chance There were no significant differences between cases and controls in terms of age (37 [34-39] vs 36 [33-39]; p = 0.53, respectively) and smoking habits (14% vs 28%; p = 0.14, respectively). Women affected had a lower BMI compared to controls (22.7 [20.9-24.9] vs 21.4 [19.6-23.8]; p = 0.03), as it is usually expected. Results from TGA were expressed as ETP ratio (with-/without- thrombomodulin), and high ones were indicative of thrombomodulin resistance, taken as indexes of procoagulant imbalance; however, it was not different between women with and without the disease (0.75 [0.65-0.82] vs 0.75 [0.66-0.82]; p = 0.82, respectively). Other markers of procoagulant imbalance evaluated by thromboelastometry were also similar between cases and controls, including CFT (66 sec [58-78] vs 65 sec [59-79]; p = 0.69, respectively) and MCF (65 mm [62-68] vs 66mm [63-68]; p = 0.95, respectively). Considering the vWF/ADAMTS13 ratio, recently proposed to be altered in endometriosis, no difference was seen between affected and no-affected women (0.95 [0.76-1.14] vs 0.91 [0.68-1.15]; p = 0.41, respectively). Finally, all the basic coagulation parameters were also similar between groups. Limitations, reasons for caution Our sample size does not allow us to perform sub-analyses regarding the type of endometriosis, although we cannot exclude differences according to the various manifestations of the disease. Also, not having a systemic haemostasis imbalance does not exclude the possibility of local coagulation imbalances. Wider implications of the findings An altered systemic haemostasis could be worsened by the use of hormonal treatments. Our result indicating that there is no coagulation imbalance at a systemic level reassures about the absence of further contraindications to hormonal drugs as a treatment for endometriosis. Trial registration number not applicable

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