Marcadores do sistema hemostático e sua associação com parâmetros clínicos e laboratoriais em mulheres com síndrome dos ovários policísticos = : Markers of the hemostatic system and their association with clinical and laboratory parameters in women with polycystic ovary syndrome / Markers of the hemostatic system and their association with clinical and laboratory parameters in women with polycystic ovary syndrome

Maria Raquel Marques Furtado de Mendonça Louzeiro

Introduction: Few studies have been conducted on hemostatic disorders in polycystic ovary syndrome (PCOS). In women with PCOS, thromboembolic risk factors such as obesity, hyperandrogenism and insulin resistance are often present, indirectly suggesting a greater probability of coagulation disorders. Objective: To evaluate some markers of the hemostatic system and their association with the clinical and laboratory parameters of women with PCOS. Subjects and Methods: A cross-sectional study was conducted to evaluate 45 women with PCOS receiving care at the Gynecological Endocrinology Outpatient Clinic of the Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas (UNICAMP) and 45 women with normal ovarian function, paired for age (± 2 years) and body mass index (BMI) (± 2kg/m2). The following clinical parameters were evaluated: waist circumference (WC), hip circumference (HC), waist/hip ratio (W/H ratio) and the Ferriman-Gallwey index (FGI), as well as the following laboratory parameters: fasting glucose, fasting insulin, total testosterone (TT) and free testosterone (FT). In addition, the hemostatic markers plasminogen activator inhibitor-1 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI) and D-dimer were measured and the thrombin generation test (TGT) was performed. The groups were compared using Student s paired t-test or the Mann-Whitney test. The correlation between the hemostatic markers and some clinical and laboratory parameters of women with PCOS was evaluated using Pearson s correlation coefficient. Significance level was defined at 5%. Results: Since the women in the PCOS group were paired with those in the control group according to age and BMI, the women in both groups were young (26.13 ± 4.31 and 26.22 ± 4.28 years, respectively) and overweight (29.32 ± 6.37 and 29.25 ± 6.32kg/m2, respectively). However, the women with PCOS had a higher W/H ratio (0.79 ± 0.08 and 0.76 ± 0.05; p = 0.03), FGI (9.42 ± 5.32 and 0.62 ± 0.83; p<0.01), TT (0.53 ± 0.30 and 0.30 ± 0.29ng/ml; p<0.01) and FT levels (1.42 ± 1.00 and 0.88 ± 0.32pg/ml; p = 0.02) compared to those in the control group. There were no statistically significant differences between the two groups with respect to glucose or insulin levels or the homeostasis model of assessment - insulin resistance (HOMA-IR). With respect to the hemostatic markers, the only statistically significant difference between the PCOS and the control group was in the thrombin generation lag-time (25.65 ± 2.61 and 26.76 ± 2.11 s, respectively, p = 0.03), meaning that thrombin generation was faster in the women with PCOS, suggesting a higher risk of hypercoagulability. In the women with PCOS, serum levels of the fibrinolytic markers PAI-1 and D-dimer correlated positively with the following clinical parameters: age, BMI, WC, HC and W/H ratio, whereas TAFI correlated positively with BMI, WC and with the W/H ratio, emphasizing the role of obesity as a risk factor for thromboembolism. Of the laboratory parameters, a direct correlation was found between PAI-1 and insulin and HOMA-IR and between TAFI and glucose. In the women with PCOS, age correlated positively with PAI- 1 and D-dimer and inversely with the lag time and the time to peak thrombin generation (Tmax) of the TGT, suggesting an increase in PAI-1 and D-dimer levels with increasing age (elevating the risk of hypofibrinolysis), as well as a reduction both in the time until the initial thrombin burst and in the time to peak thrombin generation, leading to a state of hypercoagulability. In addition, BMI, WC and FT correlated positively with the maximum concentration of thrombin (Cmax) and with the area under the thrombin generation curve (AUC) or the endogenous thrombin potential (ETP) in the same test. Conclusion: Thrombin generation is faster in young women with PCOS compared to young women with the same BMI but without PCOS. Android fat distribution, increasing age, insulin resistance and free testosterone may directly affect some hemostatic markers, increasing the risk of thromboembolism.

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