Leukocyte activation: the link between inflammation and coagulation during heatstroke. A study of patients during the 2003 heat wave in Paris.
OBJECTIVE
The mechanisms linking severe inflammation and coagulation during heatstroke are poorly understood. Here, we examined the roles of the tissue factor pathway, leukocyte activation, and mediators of innate immunity in patients admitted to an intensive care unit for heatstroke during an intense heat wave in Paris.


METHODS
Retrospective observational study.


METHODS
Intensive care unit of a university medical center.


METHODS
Eighteen critically ill severe patients with heatstroke were enrolled in the study and 14 age-matched patients with severe sepsis as controls.


METHODS
None.


RESULTS
High circulating levels of some inflammation and stress mediators (interleukin-6, -8, C5a, interleukin-1 receptor antagonist, heat shock protein 60 and 70) were observed. Blood leukocyte activation was shown by beta2 integrin up-regulation, L-selectin down-regulation, and strong production of reactive oxygen species and interleukin-8 ex vivo. High levels of circulating promatrix metalloproteinase-9 were detected in all the patients studied, and its active form was present in two patients. Overt disseminated intravascular coagulation according to the International Society of Thrombosis and Hemostasis score was present in five patients. Whole-blood tissue factor was present in all the patients and part of this activity was associated with microparticles in five patients. The degrees of inflammation and disseminated intravascular coagulation are correlated with clinical severity.


CONCLUSIONS
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.
Huisse
Marie-Geneviève
MG
Department of Hematology, AP-HP, Hospital Bichat, Paris, France. marie-genevieve.huisse@bch.ap-hop-paris.fr
Pease
Sebastian
S
Hurtado-Nedelec
Margarita
M
Arnaud
Bertrand
B
Malaquin
Cécile
C
Wolff
Michel
M
Gougerot-Pocidalo
Marie-Anne
MA
Kermarrec
Nathalie
N
Bezeaud
Annie
A
Guillin
Marie-Claude
MC
Paoletti
Xavier
X
Chollet-Martin
Sylvie
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000097:blood; D005260:Female; D018883:Heat Stroke / Q000097:blood* / Q000145:classification / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007962:Leukocytes / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010297:Paris; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D012720:Severity of Illness Index
D016207:Cytokines