OC 51.3 - Leptin and IL-6 are linked to the mechanism underlying the prothrombotic state in obese pregnant women

Background: Venous thromboembolism (VTE) is the leading direct cause of maternal death, with obese women over-represented in the mortality data. Obesity is associated with hyperleptinaemia and low-grade chronic inflammation, and both are associated with a prothrombotic state. A similar pathophysiology may underly the prothrombotic state in obese pregnant women and understanding this mechanism may assist in the development of more effective VTE prevention strategies.

Aims: To investigate the role of adipokines in the pathophysiology underlying the prothrombotic state in obese pregnant women.

Methods: 262 women, grouped by BMI class, were recruited to a British Heart Foundation funded prospective longitudinal study, approved by the West of Scotland Research Ethics Committee. Following written informed consent, blood samples were obtained at the antenatal booking appointment and repeated at 28 weeks’ gestation. Thrombin generation was performed using the Calibrated Automated Thrombogram method. Protein S (PS) and fibrinogen were assayed by the ACL TOP analyser. Leptin, IL-6, Tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1(PAI-1) were quantified by ELISA.

Results: Leptin (Fig.1) and IL-6 (Fig.2) were significantly higher in obese compared to lean women at booking and 28 weeks’ gestation (all p< 0.001). At booking, multiple regression analysis, adjusted for BMI, age and parity, demonstrated leptin to be independently associated with fibrinogen (adjusted R2=20.16%, p< 0.0001) and ETP (adjusted R2=15.08%, p< 0.0001), and IL-6 to be independently associated with fibrinogen (adjusted R2=26.86%, p< 0.0001). At 28 weeks’, fibrinogen remained independently associated with leptin (adjusted R2=15.33%, p< 0.0001) and IL-6 (adjusted R2=22.37%, p< 0.0001)

Conclusion(s): We have previously demonstrated obese women to have higher thrombin generation and fibrinogen in early pregnancy. We are the first to demonstrate, in pregnancy, that leptin and IL-6 correlate with thrombin generation and fibrinogen, suggesting that the pathophysiology underlying the prothrombotic state in obese pregnant women is linked to leptin and IL-6.