An observational study of haemostatic changes, leptin and soluble endoglin during pregnancy in women with different BMIs

Abstract

Obesity increases the risk of venous thromboembolism (VTE) in pregnancy. The pathogenesis is hypothesized to be because of multiple factors including prothrombotic changes, but there has been minimal haemostatic research looking at the combined state of obesity and pregnancy. We aimed to determine whether variation in BMI in the third trimester of pregnancy was associated with prothrombotic changes. We recruited 110 women into four groups depending on their BMI at first antenatal appointment: normal, overweight, obese and morbidly obese. Women with increased risk of VTE, and/or receiving thromboprophylaxis, and/or more than 35 years and those in labour were excluded. Thromboelastography, platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, prothrombin fragment 1 + 2, free and total protein S, plasminogen activator inhibitor type 1, tissue plasminogen activator antigen, D-dimers, soluble endoglin and leptin levels were measured. There were no significant differences in haemostatic measures with changing BMI. There was a positive correlation between BMI and both platelet count (correlation coefficient r = 0.214, P = 0.036) and leptin (r = 0.435, P < 0.001), but only leptin had a significant association with BMI once adjusted for age, gestation and parity. Despite recruitment into the morbidly obese group being suboptimal, these findings suggest that in pregnancy, the increased risk of VTE seen in obese mothers is not mediated through increased prothrombotic changes, and thus the increased risk of VTE in obese pregnant women may be because of other mechanisms, for example endothelial dysfunction, inflammation and venous stasis.

Hemostasis at Extremes of Body Weight

“…PAI-1 values in the obese group increased from a median of 15.9 ng/mL (interquartile [IQ] range: 13.1-17.3 ng/mL) in the first trimester to 72.5 ng/mL (IQ range: 51.3-123.6) in the third trimester. In our study, 78 we also found no association between PAI-1 and BMI in pregnancy, once adjusted for age, gestation, and parity. The strong suggestion from the studies of prothrombotic states in pregnancy is that biomarkers of hemostasis in pregnancy are not significantly affected by BMI.…”

“…We conducted a study where we aimed to determine whether variation in BMI in the third trimester of pregnancy was associated with prothrombotic changes. 78 We recruited 110 women into four groups depending on their BMI at first antenatal appointment: normal, overweight, obese, and morbidly obese. Women with increased risk of VTE due to other reasons, and/or receiving thromboprophylaxis, and/or older than 35 years and those in labor were excluded.…”

Prognostic value of tissue plasminogen activator (tPA) in patients with epithelial ovarian cancer undergoing chemotherapy

“…The impact of BMI on hemostatic markers has been widely discussed, although data concerning tPA is conflicting [20][21][22]. Smith et al found that plasma tPA concentration positively correlated with triglyceride levels and BMI and negatively with HDL cholesterol level whereas Morgan et al didn't confirm that relationship [23,24]. Our univariate analysis revealed that BMI > 25 kg/m 2 didn't increase the risk of death but was associated with shorter DFS.…”

Epidemiologie, Risikofaktoren und Risikostratifizierung venöser Thromboembolien (VTE) in Schwangerschaft und Wochenbett

“…Als Ursachen für diese Risikoerhöhung werden diskutiert [72,73]: erhöhte Thrombinbildung, erhöhte Plasminogen-Aktivator-Inhibitor I-Spiegel mit verminderter fibrinolytischer Aktivität und Erhöhung der Leptinspiegel (fördern Thrombozytenaggregation), erhöhter oxydativer Stress in Verbindung mit Thrombozytenaktivierung, endotheliale Dysfunktion mit Freisetzung von thrombogen-wirksamen Mikropartikeln subendothelialer Herkunft [74].…”

“…Eine vor kurzem publizierte Gerinnungsstudie bei Schwangeren mit unterschiedlichem BMI ergab keine signifikante Korrelation zwischen prothrombotischen Veränderungen und einem erhöhten BMI [74]. Die Autoren dieser Studie vermuten eine gesteigerte venöse Stase (fördert Hyperkoagulabilität und hemmt fibrinolytische Aktivität) und endotheliale Dysfunktion mit chronischer systemischer inflammatorischer Reaktion als wichtige pathogenetische Faktoren bei übergewichtigen Schwangeren.…”