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Thromb Haemost 2012; 107(05): 864-874
DOI: 10.1160/TH11-10-0730
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Nitroglycerin prevents coagulopathies and foetal death associated with abnormal maternal inflammation in rats

Tiziana Cotechini
1   Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada
,
Maha Othman
1   Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada
,
Charles H. Graham
1   Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada
› Author Affiliations Financial support: This research was supported by The Heart and Stroke Foundation of Canada and Queen’s University Special Research Funds and the Canadian Hemophilia Society.
Further Information

Publication History

Received: 21 October 2011

Accepted after major revision: 22 January 2011

Publication Date:
25 November 2017 (online)

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Summary

Inflammation-associated foetal loss is often linked to maternal coagulopathies. Here, we characterised the role of maternal inflammation in the development of various systemic maternal coagulopathies and foetal death during mid-to-late gestation in rats. Since nitric oxide (NO) functions as an inhibitor of platelet aggregation and antioxidant, we also tested whether the NO mimetic nitroglycerin (glyceryl trinitrate, GTN) prevents inflammation-associated coagulopathies and foetal death. To induce chronic inflammation, pregnant Wistar rats were injected with low-doses of lipopolysaccharide (LPS; 10–40 μg/kg) on gestational days (GD) 13.5–16.5. To determine whether the effects of inflammation are mediated by tumour necrosis factor-α (TNF-α), the TNF-α inhibitor etanercept was injected on GD 13.5 and 15.5. Controls consisted of rats injected with saline. GTN was administered to LPS-treated rats via daily application of a transdermal patch on GD 12.5–16.5. Using thromboelastography (TEG), various coagulation parameters were assessed on GD 17.5; foetal viability was determined morphologically. Reference coagulation parameters were established based on TEG results obtained from control animals. LPS-treated rats exhibited distinct systemic coagulopathies: hypercoagulability, hypocoagulability, hyperfibrinolysis, and disseminated intravascular coagulation (DIC) stages I and III. A specific foetal death coagulation phenotype was observed, implicating TEG as a potential tool to identify inflammation-induced haemostatic alterations associated with pregnancy loss. Treatment with etanercept reduced the incidence of coagulopathy by 47%, while continuous delivery of GTN prevented foetal death and the inflammation-induced coagulopathies. These findings provide a rationale for investigating the use of GTN in the prevention of maternal coagulopathies and inflammation-mediated foetal death.

Keywords

Thromboelastography - pregnancy - disseminated intravascular coagulation (DIC) - nitric oxide/NO - etanercept
 

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