An investigation of the pathophysiology underlying the prothrombotic effect of obesity during pregnancy

McNeill, Susan Heather (2026) An investigation of the pathophysiology underlying the prothrombotic effect of obesity during pregnancy. MD thesis, University of Glasgow.

Abstract

Obesity has been over-represented in the UK-MBRRACE maternal mortality reports, with 73% of VTE-related deaths in between 2019-2021 occurring in women who were either overweight or obese. The pathophysiology underlying the increased thrombotic risk in overweight and obese pregnant women is poorly understood. In the non-pregnant obese population, a chronic inflammatory state, dysfunctional adipocytes and adipose tissue distribution are thought to contribute to the prothrombotic state. Whether these elements also contribute to increased thrombotic risk in the obese pregnant population is yet to be determined.

This thesis aimed to investigate, in a prospective observational study, the pathophysiology underlying the prothrombotic state in obese pregnant women. Blood samples and anthropomorphic measurements (BMI, waist and hip circumference, SAT and VAT thickness) were obtained from 262 pregnant women (lean n=109, overweight/obese class I n=115, obese class II n=24, obese class III n=14) at the booking appointment (means 10.2 weeks' gestation). Adipokines (leptin, adiponectin, IL-6, TNF-α and IL-1β) and adipose tissue distribution were correlated with thrombin generation and other laboratory measures of the prothrombotic state (FVIII, fibrinogen Clauss, D-dimer, PAI-1, protein S and TFPI).

BMI at the booking appointment had a significant positive association with thrombin generation, as assessed by ETP (p=0.0058). BMI was also positively associated with fibrinogen (p<0.0001), TFPI (p=0.002) and PAI-1 (p=0.039). There a significant interaction between time x BMI with ETP (p=0.0498), TFPI (p-0.047) and PAI-1 (p<0.0001) which, together with the data from the booking appointment, reflected that obese pregnant women have a more prolonged prothrombotic state compared to their lean counterparts. Waist circumference, SAT and IL-6 were able to explain 32.01% of variance in fibrinogen at booking (p<0.0001) whilst BMI, SAT and leptin were able to predict 13.62% of variance in ETP at booking (p<0.0001).

The increased risk of VTE for obese pregnant women may relate to the more prolonged prothrombotic state, with greater loss of naturally occurring anticoagulants. Central obesity, as measured by waist circumference, and SAT, may be driving the procoagulant state via leptin and IL-6.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Supported by a Clinical Research Training Fellowship, funded by the British Heart Foundation.
• Subjects: R Medicine > R Medicine (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Funder's Name: British Heart Foundation
• Supervisor's Name: Freeman, Dr. Dilys and Bagot, Dr. Catherine
• Date of Award: 2026
• Depositing User: Theses Team
• Unique ID: glathesis:2026-86270
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 23 Oct 2026 10:43
• Last Modified: 23 Oct 2026 14:01
• Thesis DOI: 10.5525/gla.thesis.86270
• URI: https://theses.gla.ac.uk/id/eprint/86270