Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Coagulopathy signature precedes and predicts severity of end-organ heat stroke pathology in a mouse model.

Authors: Proctor, Elizabeth A; Dineen, Shauna M; Van Nostrand, Stephen C; Kuhn, Madison K; Barrett, Christopher D; Brubaker, Douglas K; Yaffe, Michael B; Lauffenburger, Douglas A; Leon, Lisa R

Published In J Thromb Haemost, (2020 08)

Abstract: BACKGROUND: Immune challenge is known to increase heat stroke risk, although the mechanism of this increased risk is unclear. OBJECTIVES: We sought to understand the effect of immune challenge on heat stroke pathology. PATIENTS/METHODS: Using a mouse model of classic heat stroke, we examined the impact of prior viral or bacterial infection on hematological aspects of recovery. Mice were exposed to heat either 48 or 72 hours following polyinosinic:polycytidylic acid (poly I:C) or lipopolysaccharide injection, time points when symptoms of illness (fever, lethargy, anorexia) were minimized or completely absent. RESULTS: Employing multivariate supervised machine learning to identify patterns of molecular and cellular markers associated with heat stroke, we found that prior viral infection simulated with poly I:C injection resulted in heat stroke presenting with high levels of factors indicating coagulopathy. Despite a decreased number of platelets in the blood, platelets are large and non-uniform in size, suggesting younger, more active platelets. Levels of D-dimer and soluble thrombomodulin were increased in more severe heat stroke, and in cases of the highest level of organ damage markers D-dimer levels dropped, indicating potential fibrinolysis-resistant thrombosis. Genes corresponding to immune response, coagulation, hypoxia, and vessel repair were up-regulated in kidneys of heat-challenged animals; these correlated with both viral treatment and distal organ damage while appearing before discernible tissue damage to the kidney itself. CONCLUSIONS: Heat stroke-induced coagulopathy may be a driving mechanistic force in heat stroke pathology, especially when exacerbated by prior infection. Coagulation markers may serve as accessible biomarkers for heat stroke severity and therapeutic strategies.

PubMed ID: 32367690 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

Back
to Top