Metabolic consequences of obesity on the hypercoagulable state of polycystic ovary syndrome

Abu Saleh Md Moin,Mohamed A Elrayess,Alexandra E Butler,Stephen L Atkin,Ilhame Diboun,Thozhukat Sathyapalan

doi:10.1038/s41598-021-84586-y

Abstract

Polycystic ovary syndrome (PCOS) women have a hypercoagulable state; however, whether this is intrinsically due to PCOS or, alternatively, a consequence of its metabolic complications is unclear. We determined plasma coagulation pathway protein levels in PCOS (n = 146) and control (n = 97) women recruited to a PCOS biobank. Circulating levels of a panel of 18 clotting pathway proteins were determined by Slow Off-rate Modified Aptamer-scan plasma protein measurement. Cohorts were age matched, though PCOS had elevated body mass index (p < 0.001), insulin (p < 0.001) and C-reactive protein (CRP) (p < 0.0001). Eight pro-coagulation proteins were elevated in PCOS: plasminogen activator inhibitor-1 (p < 0.0001), fibrinogen (p < 0.01), fibrinogen gamma chain (p < 0.0001), fibronectin (p < 0.01), von Willebrand factor (p < 0.05), D-dimer (p < 0.0001), P-selectin (p < 0.05), and plasma kallikrein (p < 0.001). However, two anticoagulant proteins, vitamin K-dependent protein-S (p < 0.0001) and heparin cofactor-II (p < 0.001) were elevated and prothrombin was decreased (p < 0.05). CRP, as a marker of inflammation, and insulin resistance (HOMA-IR) correlated with 11 and 6 of the clotting proteins, respectively (p < 0.05). When matched for BMI < 25 (16 PCOS, 53 controls) HOMA-IR remained elevated (p < 0.05) and heparin cofactor-II was increased (p < 0.05). In a multivariate analysis accounting for inflammation, insulin resistance and BMI, there was no correlation of PCOS with any of the coagulation proteins. The hypercoagulable state in PCOS is not intrinsic to the disease as it can be fully accounted for by BMI, inflammation and insulin resistance.

Highlights

Polycystic ovary syndrome (PCOS) women have a hypercoagulable state; whether this is intrinsically due to PCOS or, alternatively, a consequence of its metabolic complications is unclear
It has been reported that coagulation proteins such as thrombin-activatable fibrinolysis inhibitor, plasminogen activator inhibitor-1 (PAI-1), D-dimer, Antithrombin III and thrombomodulin are significantly increased in women with PCOS compared with age- and BMI-matched controls[4]
Pro-coagulation proteins elevated in PCOS are shown in Fig. 1 and include plasminogen activator inhibitor-1 (PAI-1) (2259 ± 137 vs 1457 ± 107 RFU, PCOS vs control, p < 0.0001), fibrinogen (177,423 ± 2108 vs 169,230 ± 2425 RFU, PCOS vs control, p < 0.01), fibrinogen gamma chain (63,118 ± 946 vs 57,328 ± 830 RFU, p < 0.0001), fibronectin (24,594 ± 2627 vs 16,041 ± 698 RFU, p < 0.01), von Willebrand factor (19,849 ± 3038 vs 13,159 ± 595 RFU, p < 0.05), D-dimer (13,860 ± 185 vs 12,708 ± 172 RFU, p < 0.0001), P-selectin (13,843 ± 317 vs 12,660 ± 412 RFU, p < 0.05), and plasma kallikrein (24,868 ± 376 vs 22,981 ± 447 RFU, p < 0.001)

Summary

Introduction

Polycystic ovary syndrome (PCOS) women have a hypercoagulable state; whether this is intrinsically due to PCOS or, alternatively, a consequence of its metabolic complications is unclear. When matched for BMI < 25 (16 PCOS, 53 controls) HOMA-IR remained elevated (p < 0.05) and heparin cofactor-II was increased (p < 0.05). The hypercoagulable state in PCOS is not intrinsic to the disease as it can be fully accounted for by BMI, inflammation and insulin resistance. It has been reported that coagulation proteins such as thrombin-activatable fibrinolysis inhibitor, PAI-1, D-dimer, Antithrombin III and thrombomodulin are significantly increased in women with PCOS compared with age- and BMI-matched controls[4]. This suggests that PCOS, independent of its metabolic features, may be a risk factor for a hypercoagulable state. This study was undertaken to determine the parameters contributing to the hypercoagulable state reported for PCOS

Methods

Results

Conclusion