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Prior Infection and Resultant Coagulopathy Increase Heat Stroke Severity
Author(s) -
Dineen Shauna Marie,
Plamper Mark L.,
Ward Jermaine A.,
Audet Gerald N,
Leon Lisa R
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1018.7
Subject(s) - coagulopathy , medicine , disseminated intravascular coagulation , fibrinolysis , heatstroke , antithrombin , gastroenterology , hypothermia , coagulation , heparin
Anecdotally, it has been suggested that prior viral infection increases heat stroke (HS) susceptibility and severity. HS and systemic infection have both been shown to induce disseminated intravascular coagulation (DIC), a condition associated with hypercoagulation, thrombocytopenia, multiorgan dysfunction, and higher mortality. We hypothesized that injection of the immunostimulant Polyinosinic: polycytidylic acid (PIC;100 μg) 48h or 72h prior to heat exposure (HE; 39.5±0.1°C) would exacerbate systemic inflammation and coagulopathy in a conscious C57BL/6J mouse model and increase HS morbidity. Prior to HE, mice injected with PIC showed significantly lower platelet counts at 48h (211 × 10^9/L) and 72h (324 × 10^9/L) compared to saline controls (604 × 10^9/L; P<0.05). In addition, PIC injected mice showed significantly elevated levels of D‐dimer (48h, 783212 pg/ml; 72h, 587265 pg/ml;P<0.05), thrombin‐antithrombin complexes (TAT) (48h, 8.18 ng/ml; P<0.05), thrombomodulin (48h, 28317 pg/ml; 72h, 28269 pg/ml; P<0.05), and decreased levels of antithrombin III (48h, 36527 ng/ml; P<0.05) compared to controls. These results indicate that prior to any HE, injection with PIC induced thrombocytopenia, coagulation, and fibrinolysis. Although PIC injected mice showed no outward signs of illness, HE 48h or 72h post injection was associated with increased mortality (30% and 10%, respectively), with survivors experiencing greater hypothermia depth (marker of HS severity; 29.5°C) compared to controls (30.9°C; P<0.01). HE also significantly increased D‐dimer levels (48h,953787 pg/ml; 72h, 864400 pg/ml; P<0.003) in PIC injected compared to mice exposed to either PIC or heat (601506 pg/ml) alone. Similarly, PIC plus heat induced significantly higher levels of thrombomodulin (48h, 32444 pg/ml; 72h, 33000pg/ml; P<0.02) than PIC or heat (28029 pg/ml) alone. Thus, PIC injection exacerbated systemic coagulation and fibrinolysis experienced during HE and was associated with increased HS severity and mortality. The thrombocytopenia observed in PIC injected mice may reflect a depression in platelet‐mediated immune function and a reduction in their overall capability to handle a second insult such as HE. Future studies will examine coagulation factors as potential biomarkers for predisposing conditions that increase HS susceptibility as well as any potential coagulopathy interventions or therapeutics to increase HS survival. Author views not official US Army or DOD policy.