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5.2 The effect of morbid obesity on thrombin generation and sensitivity to the anticoagulant activated protein C in pregnant women
  1. HD O’Connor1,
  2. B Kevane2,
  3. S Cooley1,
  4. K Egan3,
  5. K Flood1,
  6. F Ni Ainle2
  1. 1Department of Obstetrics, Rotunda Hospital, Dublin 1, Ireland
  2. 2Department of Haematology, Rotunda Hospital, Dublin 1, Ireland
  3. 3School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland

Abstract

Introduction Obese pregnant women have greatly increased risk of venous thromboembolism (VTE). However, underlying mechanisms are poorly understood. To address this, plasma samples were obtained with consent from pregnant women of varying body mass index (BMI) and analysed using an assay that characterises pro-and anticoagulant pathways.

Methods Blood samples were collected in citrated tubes with contact pathway inhibitor and platelet poor plasma prepared. Tissue factor (TF)-stimulated thrombin generation was determined by measuring cleavage of a thrombin-specific fluorogenic substrate using Thrombinoscope™ software.

Results 13 otherwise healthy women of similar third trimester gestation (BMI 20–29 kg/m2, n = 6; 30–39 kg/m2, n = 4; >40 kg/m2, n = 3) and 2 non-pregnant volunteers were recruited. Mean endogenous thrombin potential (area under the thrombin generation curve; 0.5 pM TF stimulus) was significantly higher in BMI > 40kg/m2 (2056 +/- 88 nm*min) compared with 20–29 kg/m2 (1350+/-97 nm*min; p = 0.003), 30–39 kg/m2 (1259+/-253.4 nm*min; p = 0.049) and non-pregnant volunteers (1084+/-264.8 nm*min; p = 0.0235). Characterisation of the anticoagulant protein C pathway was performed by incubation with activated protein C (APC; 5nM; 1pM TF trigger). Remarkably, while APC resistance was observed in all pregnant plasma samples, those of BMI >40 kg/m2 were most resistant to APC-induced attenuation of thrombin generation compared with patients of BMI 30–40 and 20–30 kg/m2. In these three groups, preincubation with APC attenuated ETP by 20%, 57% and 70% respectively.

Conclusion VTE is a potentially life-threatening complication of pregnancy. Morbidly obese pregnant women have pro-and anticoagulant pathways variations that may represent potential mechanisms underlying the observed high VTE risk in these patients.

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