title: Leukocyte activation: the link between inflammation and coagulation during heatstroke. A study of patients during the 2003 heat wave in Paris.
abstract: 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.
authors.affiliation: Department of Hematology, AP-HP, Hospital Bichat, Paris, France. marie-genevieve.huisse@bch.ap-hop-paris.fr
authors.forename: Marie-Geneviève
authors.initials: MG
authors.lastname: Huisse
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pease
authors.forename: Margarita
authors.initials: M
authors.lastname: Hurtado-Nedelec
authors.forename: Bertrand
authors.initials: B
authors.lastname: Arnaud
authors.forename: Cécile
authors.initials: C
authors.lastname: Malaquin
authors.forename: Michel
authors.initials: M
authors.lastname: Wolff
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Gougerot-Pocidalo
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kermarrec
authors.forename: Annie
authors.initials: A
authors.lastname: Bezeaud
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guillin
authors.forename: Xavier
authors.initials: X
authors.lastname: Paoletti
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chollet-Martin
mesh_terms: 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
chemical_list: D016207:Cytokines