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The presence of endometriosis determines an inflammatory response locally. The objective of this validation study and systematic review was to assess systemic levels of coagulation and inflammatory parameters in women with or without the disease. We conducted a retrospective analysis of a database prospectively collected from January 2017 to Februa...
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Context 1
... flow diagram of the systematic review is shown in Figure 2 (PRISMA template). The main characteristics of the included studies are summarized in Table 5. The risks of bias of the included studies are summarized in Supplementary Figure S1. ...Citations
... The SII's association with endometriosis likely stems from its reflection of the body's inflammatory-immune state, with high levels indicating increased inflammation and a weakened immune response. Ottolina J et al. [27] found higher neutrophil counts and lower lymphocyte counts in endometriosis patients, aligning with studies on neutrophils' role in early endometriosis formation [28]. Recent research has linked neutrophil infiltration in ovarian-type endometriosis lesions with disease severity and has found that these lesions induce neutrophils to express PD-L1, thereby inhibiting CD8+ T cell activity [29]. ...
Objective
The systemic immuno-inflammatory index (SII), a novel immune marker of inflammation, has not been previously associated with endometriosis. The objective of this research is to explore the link between SII and the occurrence of endometriosis.
Methods
Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2001 to 2006, we screened and extracted relevant information from the population. Participants missing data on either SII or endometriosis were excluded. We divided the remaining cohort into quartiles based on SII levels: Q1 (SII < 249, n = 848), Q2 (249 ≤ SII < 604.55, n = 847), Q3 (604.55 ≤ SII < 825.35, n = 847), and Q4 (SII ≥ 852.35, n = 848). Multiple linear regression and smooth curve fitting techniques, were to evaluate the non-linear association between SII and endometriosis.
Results
The study included 3,390 adults aged 20 to 55. Multiple linear regression analysis revealed a significant positive correlation between SII and endometriosis [3.14, 95% CI (2.22, 4.45), P < 0.01]. This correlation was consistent across subgroups defined by marital status, poverty income ratio, BMI, alcohol consumption, and age at first menstrual period. However, the relationship between SII and endometriosis was significantly modified by age, education, and history of pregnancy in the stratified analyses. The curve fitting indicated an S-shaped curve, with an inflection point at SII = 1105.76.
Conclusion
The SII may serve as a predictive marker for endometriosis risk among women in the United States, offering a potentially simple and cost-effective approach. However, given the cross-sectional design of this investigation, further validation in prospective studies is necessary.
... aPTT also measures the time required from the activation of factor 12 to the formation of fibrin [6]. Coagulation-related factors such as aPTT, PT, and other coagulator factors are associated with endometriosis [7,8], and aPTT, as well as PT, are shortened in the case of endometriosis [9]. ...
... A few blood cells and vessels are changed by inflammation, driving to a prethrombotic condition. In addition to the existence of interference between these two systems, platelet count (PLC) increases in endometriosis patients [9]. The enhancement of the coagulation process in women with endometriosis can be attributed to the idea that endometriotic lesions experience periodical bleeding, causing repetitive tissue damage and repair, which can result in platelet activation and aggregation [2]. ...
... In addition, the hypercoagulable state in endometriosis patients has been confirmed by several studies [5,11,12]. This condition of hypercoagulation may be accompanied by systemic changes in some inflammatory parameters [9]. ...
Objectives
This study evaluated the effects of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and pentoxifylline (PTX) on coagulation factors, including the amount and percentage of lymphocytes, PLC, PLR, aPTT, PT, PT.I.N. R in a model of rats with endometriosis.
Methods
Endometriosis was surgically induced in female Sprague—Dawley rats. The rats with confirmed endometrial implants were divided into control, MICT, pentoxifylline (D), HIIT+D, and MICT+D, HIIT groups. D and exercise interventions were performed for eight weeks. Then, the macroscopic size of endometriosis lesions was measured, and inflammatory factors (count and percentage of lymphocytes) and coagulation factors, including PLC, PLR, aPTT, PT, PT.I.N. R, and PLR in blood samples were evaluated.
Results
D significantly decreased the volume of lesions and significantly increased PT and PT.I.N. R in blood. HIIT decreased the volume of lesions and significantly increased PT. MICT did not cause significant effects on the target variables. MICT+D decreased the volume of lesions. HIIT+D significantly decreased the volume of lesions and PLC and increased aPTT as well as the count and percentage of lymphocytes, PT, and PT.I.N. R, and decreased PLR.
Conclusions
All interventions(except for MICT) especially HIIT+D and D by priority, induced a significant effect on reducing some indices of inflammation and coagulation.
... In contrast, neutrophil populations in the tumor microenvironment are essentially determined by their functional phenotype, with neutrophils performing proinflammatory/anti-inflammatory and protumor/antitumor roles [20,22]. Neutrophils and their released cytokines have been demonstrated to be higher in the circulatory system and peritoneal fluid of endometriosis patients, promoting endometriotic cell proliferation, invasion, and angiogenesis [11,[23][24][25]. In this review, we focus on the involvement of neutrophils in endometriosis pathophysiology, including the abundance, function, and activation status of the neutrophil population, as well as the role of neutrophil heterogeneity and plasticity in endometriosis lesion formation and angiogenesis. ...
Endometriosis is a common inflammatory illness in which endometrial tissue grows outside the uterine cavity. Immune dysfunction is now widely acknowledged as the primary cause of endometriosis. The immune cell population represented by neutrophils is thought to play an essential role in the etiology, pathophysiology, and associated clinical outcome. There is growing evidence that neutrophils have a role in chronic and aseptic inflammatory diseases, and endometriosis patients have increased levels of neutrophils in plasma, peritoneal fluid, and ectopic endometrium. Here, we sought to review the function of neutrophils in the pathogenesis of endometriosis, with an emphasis on the role of neutrophils in regulating endometrial angiogenesis and the local inflammatory microenvironment.
... Numerous inflammatory indicators, such as interleukins, neutrophils, and neutrophil to lymphocyte ratio (NLR), are raised in severe endometriosis because of the chronic inflammatory course of the disease [19][20][21]. In particular, the NLR has been suggested as a straightforward and practical prognostic and diagnostic biomarker for several illnesses [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. Without early management and a precise diagnosis, endometriosis may become an emerging gynecological problem and cause infertility and dysmenorrhea. ...
... In the initial search, we found a total of 272 results, and among them, 18 papers were included after multiple stags of screening [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39], shown in Fig. 1. ...
... In total, 18 articles were included in the analysis [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39], including 2507 patients with endometriosis and 2179 healthy controls. Seventeen of the included studies compared patients with endometriosis with healthy controls [22-36, 38, 39], five of them compared patients with endometriosis and those with other benign tumors [25,26,29,34,38], three of them compared endometriosis patients with and without deep lesions [30,31,37], two of them compared endometriosis patients with and without peritoneal lesions [31,37], four study compared endometriosis patients with and without endometrioma [30,31,37,39], and four studies compared patients with stage III and IV endometriosis with those with stage I and II endometrioma [31,32,36,37]. ...
Background
The purpose of this systematic review and meta-analysis was to compile existing evidence on the significance of the NLR in predicting endometriosis in order to aid clinical decision-making and outcomes.
Methods
We searched ProQuest, Web of Science, and PubMed for related studies published before January 2, 2023. Standardized mean difference (SMD) with a 95% confidence interval (CI) was reported for each outcome. Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used Newcastle-Ottawa Scale (NOS) for quality assessment.
Results
Overall, 18 article with were included in the analysis. A random-effect model revealed that patients with endometriosis had elevated levels of NLR compared to healthy controls (SMD = 0.79, 95% CI = 0.33 to 1.25, P < 0.001). Patients with endometriosis had elevated levels of NLR compared to those with other benign tumors (SMD = 0.85, 95% CI = 0.17 to 1.53, P = 0.014). In addition, NLR level of patients with stage III and IV endometriosis was not different from that of patients with stage I and II endometrioma (SMD = 0.30, 95% CI = -0.14 to 0.74, P = 0.18). However, NLR level was not different between endometriosis patients with and without peritoneal lesions (SMD = -0.12, 95% CI = -0.34to 0.10, P = 0.28), between patients with and without endometrioma (SMD = 0.20, 95% CI = -0.15 to 0.55, P = 0.26) and between endometriosis patients with and without deep lesions (SMD = 0.04, 95% CI = -0.20 to 0.28, P = 0.72). The pooled sensitivity of NLR was 0.67 (95% CI = 0.60–0.73), and the pooled specificity was 0.68 (95% CI, 0.62–0.73).
Conclusions
NLR might be utilized in clinics as a possible predictor to help clinicians diagnose endometriosis in affected women.
... Alterations in platelet levels, fluxes, activation and interactions are relevant to a host of diverse medical conditions, including endometriosis [91], glioblastoma [92], mood disorders [93], cancer [94], viral infection [95] and 'autoimmune' disorders [96]. Alzheimer's disease/dementia is strongly linked to aging, mitochondrial dysfunction, circadian dysregulation, gut dysbiosis and 'immune-mediated' processes that underpin many other medical conditions. ...
Platelets have traditionally been investigated for their role in clot formation in the course of cardiovascular diseases and strokes. However, recent work indicates platelets to be an integral aspect of wider systemic processes, with relevance to the pathophysiology of a host of diverse medical conditions, including neurodegenerative disorders and cancer. This article reviews platelet function and interactions with the gut microbiome and circadian systems, highlighting the role of the platelet mitochondrial melatonergic pathway in determining platelet activation, fluxes and plasticity. This provides a number of novel conceptualizations of platelet function and mode of interaction with other cell types, including the pathoetiology and pathophysiology of diverse medical conditions, such as cancer, Alzheimer's disease, and amyotrophic lateral sclerosis. It is proposed that a platelet-gut axis allows platelets to contribute to many of the pathophysiological processes linked to gut dysbiosis and gut permeability. This is at least partly via platelet sphin-gosine-1-phosphate release, which regulates enteric glial cells and lymphocyte chemotaxis, indicating an etiological role for platelets in a wide array of medical conditions linked to alterations in the gut microbiome. Platelets are also an important regulator of the various microenvironments that underpin most human medical conditions, including the tumor microenvironment, neurodegenerative diseases, and autoimmune disorders. Platelet serotonin release regulates the availability of the mitochondrial melatonergic pathway systemically, thereby being an important determinant of the dynamic metabolic interactions occurring across cell types that underpin the pathoetiology of many medical conditions. In addition, a number of novel and diverse future research directions and treatment implications are proposed.
... This does not seem to occur in women with endometriosis where peritoneal macrophages are increased in number [6] but, most importantly, exhibit a dysfunctional phenotype consistent with a reduced phagocytic capacity. The consequence is that endometrial cells in the pelvic cavity may evade immune response, survive, adhere and spread, leading to a local production of proinflammatory cytokines and chemokines -such as interleukin (IL)-1, IL-8, Tumor Necrosis Factor-a (TNF-a), Monocyte Chemoattractant Protein-1 (MCP-1), RANTES [3,[7][8][9][10][11]. The inability of the immune system to eliminate endometrial cells in the pelvic cavity could represent a critical factor in the establishment of endometriosis. ...
... In addition, endometriotic lesions might unbalance the homeostasis system by inhibiting the fibrinolysis pathways [39] and by the proteinase-activated receptors [40]. Also, it has been reported that women with endometrioma have plasmatic alterations in coagulation and fibrinolysis parameters, such as for TT [41], platelet count [42], fibrinogen [41,43,44], platelet-tolymphocyte ratio [45], D-dimer [41,43] and aPTT [11,34,41], although most of these parameters were within the normal range. More than that, it has been described that women with endometrioma who undergo endometriotic cyst rupture presented with high levels of coagulation factors in the peripheral blood [43,[45][46][47][48]. ...
... All in all, the above studies are in favor of a local perturbation of the axis VWF-ADAMTS-13, but documented evidence for this perturbation in peripheral blood is lacking. Figure 1 describes some of the alterations in cytokines, endotoxins, and coagulation factors in endometriosis patients compared to control patients; however, it is important to bear in mind that, despite some observational studies have been conducted trying to explore the relationship between primary hemostasis/coagulation and endometriosis, this possible link remains under-investigated and results (especially for coagulation) are contrasting [11,31,34]. This is in part due to the lack of appropriate methods to study the function of primary hemostasis or coagulation in peripheral blood [52] and also because the above functions were investigated mostly in the milieu located within or close to endometrial lesions and not in the peripheral blood. ...
... Coagulation cascades have been implicated in both inflammatory responses and angiogenesis [12,[14][15][16]. Several epidemiological observational studies have found that patients with endometriosis are hypercoagulable and hyperfibrinolytic [17,18]. Plasma fibrinogen, d-dimer, and plasminogen activator inhibitor levels are higher in women with endometriosis when compared to healthy controls while thrombin time and activated partial thromboplastin time decrease [19]. ...
Background
Endometriosis is recognized as a complex gynecological disorder that can cause severe pain and infertility, affecting 6–10% of all reproductive-aged women. Endometriosis is a condition in which endometrial tissue, which normally lines the inside of the uterus, deposits in other tissues. The etiology and pathogenesis of endometriosis remain ambiguous. Despite debates, it is generally agreed that endometriosis is a chronic inflammatory disease, and patients with endometriosis appear to be in a hypercoagulable state. The coagulation system plays important roles in hemostasis and inflammatory responses. Therefore, the purpose of this study is to use publicly available GWAS summary statistics to examine the causal relationship between coagulation factors and the risk of endometriosis.
Methods
To investigate the causal relationship between coagulation factors and the risk of endometriosis, a two-sample Mendelian randomization (MR) analytic framework was used. A series of quality control procedures were followed in order to select eligible instrumental variables that were strongly associated with the exposures (vWF, ADAMTS13, aPTT, FVIII, FXI, FVII, FX, ETP, PAI-1, protein C, and plasmin). Two independent cohorts of European ancestry with endometriosis GWAS summary statistics were used: UK Biobank (4354 cases and 217,500 controls) and FinnGen (8288 cases and 68,969 controls). We conducted MR analyses separately in the UK Biobank and FinnGen, followed by a meta-analysis. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out sensitivity analyses were used to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis.
Results
Our two-sample MR analysis of 11 coagulation factors in the UK Biobank suggested a reliable causal effect of genetically predicted plasma ADAMTS13 level on decreased endometriosis risk. A negative causal effect of ADAMTS13 and a positive causal effect of vWF on endometriosis were observed in the FinnGen. In the meta-analysis, the causal associations remained significant with a strong effect size. The MR analyses also identified potential causal effects of ADAMTS13 and vWF on different sub-phenotypes of endometrioses.
Conclusions
Our MR analysis based on GWAS data from large-scale population studies demonstrated the causal associations between ADAMTS13/vWF and the risk of endometriosis. These findings suggest that these coagulation factors are involved in the development of endometriosis and may represent potential therapeutic targets for the management of this complex disease.
... In contrast, neutrophil populations in the tumor microenvironment are essentially determined by their functional phenotype, with neutrophils performing proinflammatory/anti-inflammatory and protumor/antitumor roles [20,22]. Neutrophils and their released cytokines have been demonstrated to be higher in the circulatory system and peritoneal fluid of endometriosis patients, promoting endometriotic cell proliferation, invasion, and angiogenesis [11,[23][24][25]. In this review, we focus on the involvement of neutrophils in endometriosis pathophysiology, including the abundance, function, and activation status of the neutrophil population, as well as the role of neutrophil heterogeneity and plasticity in endometriosis lesion formation and angiogenesis. ...
Endometriosis is a common inflammatory illness in which endometrial tissue grows outside the uterine cavity. Immune dysfunction is now widely acknowledged as the primary cause of endometriosis. The immune cell population represented by neutrophils is thought to play an essential role in the etiology, pathophysiology, and associated clinical outcome. There is growing evidence that neutrophils have a role in chronic and aseptic inflammatory diseases, and endometriosis patients have increased levels of neutrophils in plasma, peritoneal fluid, and ectopic endometrium. Here, we sought to review the function of neutrophils in the pathogenesis of endometriosis, with an emphasis on the role of neutrophils in regulating endometrial angiogenesis and the local inflammatory microenvironment.
... [11] The endometriosis tumor microenvironment is characterized by chronic inflammation and hypoxic conditions, and previous studies have shown that endometriosis patients are in a hypercoagulable state like OCCC. [9,12] Otherwise, angiogenesis, immune escape and metastasis facilitate tumor development, and all these processes involve activation of the coagulation system. Coagulation factors can participate in tumor progression through coagulation-dependent pathways (including fibrin formation, platelet recruitment, immunomodulatory responses, and tissue factor particle secretion) and non-dependent pathways (intracellular signaling). ...
Rationale:
Trousseau syndrome is known as patients with tumors have a combination of multiple thrombi with systemic organ infarction. The incidence of ovarian clear cell cancer associated with Trousseau syndrome is relatively low. We report the case of a 41-year-old woman diagnosed with ovarian clear cell cancer with deep vein thrombosis and cerebral infarction who had a poor prognosis.
Patient concerns:
A 41-year-old woman was brought to our hospital with abdominal pain. Abdominal computerized tomography scan suggested large mass of ovarian origin which was considered an ovarian tumor with pelvic metastasis and peritoneal metastasis. Laboratory analyses indicated an elevated levels of serum tumor marker carbohydrate antigen 125 was 321.9 U/mL and the level of D-dimer was 16.71 mg/L.
Diagnosis:
The patient underwent pelvic mass aspiration was diagnosed with ovarian clear cell cancer. B-ultrasound revealed thrombosis of the lower limbs.
Interventions:
She underwent 2 neoadjuvant chemotherapies, along with anticoagulation therapy. However, it had a poor therapeutic effect, and the patient suffered from acute cerebral infarction that worsened.
Outcomes:
Chemotherapy and anticoagulation failed to stop the tumor and blood clot progression. The patient died 2 months after cerebral infarction without surgical treatment.
Lessons:
Gynecologists should be aware of the need for clinical suspicion of the risk of thrombosis during the treatment period of ovarian cancer and make careful decisions.
... Hence, the coagulation parameters of adenomyosis, such as endometriosis, including platelet count (PC), APTT, PT, TT, and FB, are also helpful for its clinical diagnosis, although the exact mechanism of the hypercoagulable state of adenomyosis remains unclear [6][7][8][9]. Recently, a recent systematic review by Ottolina et al. did not find any significant difference in PC between patients with and without endometriosis, regardless of the disease stage and type [18]. In comparison to women without endometriosis, women with ovarian endometriosis have lower PC values but higher mean platelet volume (MPV) [19]. ...
Patients with adenomyosis are hypercoagulable and often accompanied by anemia, but the specific changes in anemia-related coagulation parameters are still unclear. This study investigated the changes in and influencing factors of coagulation parameters related to anemia in patients with adenomyosis (AM). The coagulation parameters, including platelet count (PC), plasma prothrombin time (PT), activated partial prothrombin time (APTT), thrombin time (TT) and fibrinogen (FB), and hemoglobin (Hb), were measured in patients with adenomyosis (229 cases in AM group), uterine leiomyoma (265 cases in LM group), and undergoing tubal anastomosis (142 cases in the control group). The age of the control group was younger than that of the AM group and the LM group. Compared with the AM and LM groups, the uterus size of the control group was smaller; the AM group was larger than the LM group. The Hb concentration of the AM group was lower than that of the LM and control groups. Compared with the LM and control groups, PC increased and TT shortened in the AM group. APTT in the AM group was shorter than in the control group, and PT was longer than in the LM group. After adjustment using multiple logistic regression analysis, adenomyosis was correlated with Hb concentration (or = 0.971, 95% CI 0.954–0.988, p < 0.001), PC (or = 1.006, 95% CI 1.002–1.011, p = 0.004), PT (or = 3.878, 95% CI 2.347–6.409, p < 0.001), age (or = 1.062, 95% CI 1.013–1.114, p = 0.013), and uterine size (or = 1.103, 95% CI 1.011–1.203, p = 0.028). Correlation analysis showed that PC (r = −0.309) and PT (r = −0.252) were negatively correlated with anemia. The increase in Hb-related PC and PT in patients with adenomyosis indicates that the timely and early detection of coagulation parameters is needed for patients with severe anemia, older age, and larger uterine volume.
