Leukocyte activation: The link between inflammation and coagulation during heatstroke. A study of patients during the 2003 heat wave in Paris*

Abstract

These results suggest that neutrophil activation plays a key role in the acute activation of coagulation observed during severe heatstroke, despite a rapid and sustained antiinflammatory response. The comparison with a group of patients with severe sepsis suggests some common mechanisms, but more intense responses during heatstroke.

Hsp-72, a candidate prognostic indicator of heatstroke

“…Wang et al (2001) detected increased serum levels of Hsp-72 in patients with moderate heatstroke and healthy individuals exposed to heat wave, but not in patients with severe heatstroke. In contrast, in a recent study of patients with severe heatstroke, circulating Hsp-72 and Hsp-60 levels were found markedly elevated and were associated with increased morbidity and mortality (Huisse et al, 2008). However, both clinical studies had serious limitations including a single measurement of plasma Hsp levels, the presence of antibodies to Hsp that may have interfered with the assay and finally, variable characteristics of the population studied, particularly the age, which is known to affect the heat shock response (Moseley 1997;Gutsmann-Conrad et al 1998).…”

“…Until recently, heat shock proteins were considered intracellular proteins, however, the detection of Hsp-60 and Hsp-72 in the sera of normal individuals (Pockley et al 1999;Pockley et al 2002) and observations of increased circulating levels of Hsp-72 in various conditions such as cardiovascular (Wright et al 2000;(Dybdahl et al 2005), acute lung injury (Ganter et al 2006), heat illness (Wu et al 2001), and trauma (Wright et al 2000;Wu et al 2001;Pittet et al 2002;Pockley et al 2002) raised the question of a potential extracellular role. In classical heatstroke, two clinical studies so far have reported high circulating levels of Hsp-72 and Hsp-60 with conflicting findings (Wang et al 2001;Huisse et al, 2008). Wang et al (2001) detected increased serum levels of Hsp-72 in patients with moderate heatstroke and healthy individuals exposed to heat wave, but not in patients with severe heatstroke.…”

“…In humans, exercise associated heat stress was shown to be a potent inducer of Hsp-72 expression and release into the circulation (Moseley 1997;Febbraio and Koukoulas 2000;Walsh et al 2001). In human victims of heatstroke, conflicting findings were reported namely; that both low and high levels of Hsp-72 were observed and correlated with poor outcome (Wang et al 2001;Huisse et al, 2008). To date, there are no published data that assessed tissue expression and blood release of Hsps in a clinically relevant model of heatstroke.…”

Heat Stroke

“…Cytokine modulation of DIC is supported by several lines of evidence including: (i) increased plasma levels of IL-1β, IL-6, and TNF in patients with DIC, with high IL-6 correlating with organ failure (386-388), (ii) IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, and TNF-induced alteration in coagulation (23,169,264,293,379), and (iii) efficacy of neutralizing cytokine antibodies for attenuation of coagulation (282,327). In the Paris heat wave of 2003, a link was established between elevated circulating levels of proinflammatory cytokines, neutrophil activation, and coagulation in elderly classic heat stroke patients (162). HMGB1 is a 30 kDa protein constitutively expressed in the nuclei of eukaryotic cells.…”

Heat stroke: Role of the systemic inflammatory response

“…Consumptive coagulation may lead to excessive, prolonged bleeding from multiple tissue sites (e.g., venipuncture sites, gums) and is associated with fatal outcome (46). In the Paris heat wave of 2003, a link was established between elevated circulating levels of pro-inflammatory cytokines, neutrophil activation, and coagulation in elderly heat stroke patients (41). Endotoxin and cytokines are thought to activate leukocytes and endothelial cells to amplify the coagulation cascade and participate in the progression of DIC.…”