Thromboelastogrpahy Reveals Kinetics of LPS- Induced Coagulopathy and Correlates to Fetal Outcome in a Rat Model of Pregnancy Complications.
Authors: Othman Maha , Renaud Stephen , Quirt Jill , MacDonald-Goodfellow Shannyn , Graham Charles 
Published: October 2019

Abstract 4200

Pre-eclampsia, intrauterine growth restriction (IUGR) and spontaneous abortion constitute the majority of serious complications of pregnancy. Women affected with these complications often exhibit excessive systemic inflammation, coagulopathies, and an increased risk of subsequent cardiovascular disease (CVD). Thromboelastography (TEG) has proven efficiency as a global test for monitoring hemostasis in hematological and non hematological conditions including pre-eclampsia. systemic administration of low doses of the immunogenic agent lipopolysaccharide (LPS) to pregnant rats has been shown to cause complications that recapitulate many of the features associated with human pregnancy disorders such as IUGR, hypertension, proteinuria, and pregnancy loss. In this study we investigated the acute hemsotatic events using TEG in pregnant rats at day 14 following injection of 100ug/ kg of LPS and correlated this to fetal outcome. Blood samples were withdrawn from 12 rats and tested for TEG at 1h (n=6) and 4h (n=3) post LPS and the results were compared to saline injected control rats (n=3). At 1h after LPS injection, 3 rats showed a DIC- like condition stage I (hypercoagulability with secondary fibrinolysis): in comparison to saline injected rats, there was significant shortening of R time (2.2 min. compared to 10.2 min. in saline control), increase in alpha angle, increase in overall clot index and significant increase in LY30 (p= 0.0001, 0.002, 0.03 and 0.05 respectively). The three other rats showed DIC stage II (hyperfibrinolysis): compared to saline control, there was significant shortening of R time, reduction in clot index, increase of LY 30 with no significant changes in alpha angle or MA (p=0.02, 0.03, 0.03, 0.3 and 0.6 respectively). After 4h of LPS injection, rats showed enhanced hyperfibrinolysis/ hypocoagulability indicating DIC stage III. In these rats, there were no significant changes in R time or alpha angle, significant reduction in MA, significant reduction in clot index and highly significant increase in LY30 (p=0.9, 0.8, 0.03, 0.03 and 0.001 respectively). The average lysis time was 13% in stage 1, 17 % in stage II and 39% in stage III compared to 1.7 % in saline control. Using ultrasound to determine fetal parameters, we observed fetal death occurring approximately 3-4 h after LPS administration as determined by loss of detection of heart rate and severe hypoxia. Doppler recordings also showed that fetal death was also associated with reduced blood flow through the spiral arterioles, which supply blood to the placenta. These data indicate that the acute LPS- induced hemostatic changes (both coagulation and fibrinolysis) in pregnant rats can be detected and monitored using thromboelastography and that these changes contribute to the negative fetal outcome. To our knowledge this is the first study that investigates LPS- induced acute hemostatic events in pregnant rats using TEG and correlates the changes over 4h hours period with the foetal outcome. The study provides potential for TEG utilization as a point of care device to predict both fetal and maternal outcomes in complicated pregnancies.

Disclosures:

No relevant conflicts of interest to declare.