Blood samples

Blood samples selleck screening library were obtained from 168 consecutive major trauma patients immediately upon …Recent experimental studies have indicated that alarmins, a family of early danger signal mediators to which HMGB1 belongs, and complement appear to be the early mediators of the sterile inflammatory response associated with hemorrhagic shock [14]. Furthermore, a recent experimental study has suggested that complement can activate the release of HMGB1 [27]. Finally, we have previously reported that there is an activation of complement within 45 minutes after severe trauma in humans [9]. We thus determined whether there was a correlation between activation of complement and plasma levels of HMGB1 within 45 minutes after trauma.

The results indicate that trauma patients who had the higher plasma levels of HMGB1 had significantly higher plasma levels of C5b-9 (membrane attack complex) generated as the final common pathway of complement activation (P = 0.0001 by rank and trend, Spearman correlation r = 0.33, P = 0.0001; Figure Figure2e2e).Plasma levels of HMBG1 and early coagulation derangements in trauma patientsCoagulation abnormalities are common following major trauma and are directly related to worse clinical outcome [28]. We have recently shown that only patients who are severely injured and in shock are coagulopathic at the admission to the Emergency Department within 45 minutes after injury and that the development of this coagulopathy correlates with the activation of the protein C pathway rather than with the consumption of coagulation factors [20].

We next sought to identify whether the release of HMGB1 in our patients was related to coagulation abnormalities. Patients with clinically significant coagulation abnormalities (international nationalized ratio (INR) >1.5) had significantly higher plasma levels of HMGB1 (P = 0.01; Figure Figure3a).3a). Furthermore, increasing plasma levels of HMGB1 were associated with a rise in INR (Spearman correlation r = 0.20, P = 0.008) the levels of soluble PF 1+2, a marker of thrombin generation (P = 0.001 by rank and P < 0.0001 by trend Spearman correlation r = 0.53 P �� 0.0001), soluble thrombomodulin (P = 0.06 by rank and P = 0.02 by trend, Spearman correlation r = 0.24 P = 0.002) and a fall in protein C levels (P = 0.002 by rank and trend Spearman correlation -.39, P �� 0.0001; Figures Figures3b3b to to3d).

3d). Finally, plasma levels of HMGB1 were negatively correlated with those of PAI-1 (P = 0.04 by rank and P = 0.03 by trend, Spearman correlation r = -.23, P = 0.004), and positively correlated with t-PA (P = 0.0001 by rank and trend, Spearman correlation r = 0.46, P �� 0.0001 and D-Dimer levels (P = 0.001 by rank and trend, Spearman correlation r = 0.50, P Entinostat �� 0.0001; Figures Figures4a4a to to4c),4c), suggesting an increased fibrinolytic activity in patients with elevated plasma levels of HMGB1.

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