Limits...
Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569].

Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, Um SL, Utterback B, Laterre PF, Dhainaut JF, PROWESS Sepsis Study Gro - Crit Care (2004)

Bottom Line: At study entry, elevated D-dimer, thrombin-antithrombin complexes, IL-6, and prolonged prothrombin time were present in 99.7%, 95.5%, 98.5%, and 93.4% of patients, respectively.Markers of endothelial injury (soluble thrombomodulin) and deficient protein C, protein S, and antithrombin were apparent in 72%, 87.6%, 77.8%, and 81.7%, respectively.During the first 7 days, increased prothrombin time (which is readily measurable in most clinical settings) was highly evident among patients who were not alive at 28 days.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Physiology and Biophysics, University of Oklahoma Health Science Center, and Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.

ABSTRACT

Introduction: PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) was a phase III, randomized, double blind, placebo controlled, multicenter trial conducted in patients with severe sepsis from 164 medical centers. Here we report data collected at study entry for 1690 patients and over the following 7 days for the 840 patients who received placebo (in addition to usual standard of care).

Methods: Nineteen biomarkers of coagulation activation, anticoagulation, fibrinolysis, endothelial injury, and inflammation were analyzed to determine the relationships between baseline values and their change over time, with 28-day survival, and type of infecting causative micro-organism.

Results: Levels of 13 of the 19 biomarkers at baseline correlated with Acute Physiology and Chronic Health Evaluation II scores, and nearly all patients exhibited coagulopathy, endothelial injury, and inflammation at baseline. At study entry, elevated D-dimer, thrombin-antithrombin complexes, IL-6, and prolonged prothrombin time were present in 99.7%, 95.5%, 98.5%, and 93.4% of patients, respectively. Markers of endothelial injury (soluble thrombomodulin) and deficient protein C, protein S, and antithrombin were apparent in 72%, 87.6%, 77.8%, and 81.7%, respectively. Impaired fibrinolysis (elevated plasminogen activator inhibitor-1) was observed in 44% of patients. During the first 7 days, increased prothrombin time (which is readily measurable in most clinical settings) was highly evident among patients who were not alive at 28 days.

Conclusion: Abnormalities in biomarkers of inflammation and coagulation were related to disease severity and mortality outcome in patients with severe sepsis. Coagulopathy and inflammation were universal host responses to infection in patients with severe sepsis, which were similar across causative micro-organism groups.

Show MeSH

Related in: MedlinePlus

Time courses of biomarkers of anticoagulants in placebo-treated patients with severe sepsis in the PROWESS study are shown here as means and 95% confidence intervals, using standard error of the mean and repeated measures analysis without imputing for missing data. The number of observations for each time point appears below the x-axis for (●) survivors and (○) nonsurvivors. *P < 0.05 versus nonsurvivors.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC420030&req=5

Figure 2: Time courses of biomarkers of anticoagulants in placebo-treated patients with severe sepsis in the PROWESS study are shown here as means and 95% confidence intervals, using standard error of the mean and repeated measures analysis without imputing for missing data. The number of observations for each time point appears below the x-axis for (●) survivors and (○) nonsurvivors. *P < 0.05 versus nonsurvivors.

Mentions: Biomarker levels in placebo patients over time by 28-day survival are shown in Figs 1, 2, 3, 4. Nonsurvivors exhibited greater coagulopathy and less normalization over the first week (Fig. 1). Nonsurvivors also showed more severe acquired deficiency of anticoagulant factors at study entry and minimal recovery over the first 7 study days as compared with survivors (Fig. 2). With respect to thrombin generation, survivors had significantly lower levels of TAT and F1.2 over study days 1–5 than did nonsurvivors (Fig. 3). Survivors also had significantly less consumption of fibrinolytic factors or impairment of fibrinolysis (less consumption of plasminogen and α-2AP and less elevation in PAI-1) than did nonsurvivors over study days 1–5 (Fig. 3). Additionally, nonsurvivors exhibited greater levels of sTM (marker of endothelial injury) and IL-6 (marker of inflammation) than did survivors throughout the observation period (Fig. 4).


Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569].

Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, Um SL, Utterback B, Laterre PF, Dhainaut JF, PROWESS Sepsis Study Gro - Crit Care (2004)

Time courses of biomarkers of anticoagulants in placebo-treated patients with severe sepsis in the PROWESS study are shown here as means and 95% confidence intervals, using standard error of the mean and repeated measures analysis without imputing for missing data. The number of observations for each time point appears below the x-axis for (●) survivors and (○) nonsurvivors. *P < 0.05 versus nonsurvivors.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC420030&req=5

Figure 2: Time courses of biomarkers of anticoagulants in placebo-treated patients with severe sepsis in the PROWESS study are shown here as means and 95% confidence intervals, using standard error of the mean and repeated measures analysis without imputing for missing data. The number of observations for each time point appears below the x-axis for (●) survivors and (○) nonsurvivors. *P < 0.05 versus nonsurvivors.
Mentions: Biomarker levels in placebo patients over time by 28-day survival are shown in Figs 1, 2, 3, 4. Nonsurvivors exhibited greater coagulopathy and less normalization over the first week (Fig. 1). Nonsurvivors also showed more severe acquired deficiency of anticoagulant factors at study entry and minimal recovery over the first 7 study days as compared with survivors (Fig. 2). With respect to thrombin generation, survivors had significantly lower levels of TAT and F1.2 over study days 1–5 than did nonsurvivors (Fig. 3). Survivors also had significantly less consumption of fibrinolytic factors or impairment of fibrinolysis (less consumption of plasminogen and α-2AP and less elevation in PAI-1) than did nonsurvivors over study days 1–5 (Fig. 3). Additionally, nonsurvivors exhibited greater levels of sTM (marker of endothelial injury) and IL-6 (marker of inflammation) than did survivors throughout the observation period (Fig. 4).

Bottom Line: At study entry, elevated D-dimer, thrombin-antithrombin complexes, IL-6, and prolonged prothrombin time were present in 99.7%, 95.5%, 98.5%, and 93.4% of patients, respectively.Markers of endothelial injury (soluble thrombomodulin) and deficient protein C, protein S, and antithrombin were apparent in 72%, 87.6%, 77.8%, and 81.7%, respectively.During the first 7 days, increased prothrombin time (which is readily measurable in most clinical settings) was highly evident among patients who were not alive at 28 days.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Physiology and Biophysics, University of Oklahoma Health Science Center, and Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.

ABSTRACT

Introduction: PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) was a phase III, randomized, double blind, placebo controlled, multicenter trial conducted in patients with severe sepsis from 164 medical centers. Here we report data collected at study entry for 1690 patients and over the following 7 days for the 840 patients who received placebo (in addition to usual standard of care).

Methods: Nineteen biomarkers of coagulation activation, anticoagulation, fibrinolysis, endothelial injury, and inflammation were analyzed to determine the relationships between baseline values and their change over time, with 28-day survival, and type of infecting causative micro-organism.

Results: Levels of 13 of the 19 biomarkers at baseline correlated with Acute Physiology and Chronic Health Evaluation II scores, and nearly all patients exhibited coagulopathy, endothelial injury, and inflammation at baseline. At study entry, elevated D-dimer, thrombin-antithrombin complexes, IL-6, and prolonged prothrombin time were present in 99.7%, 95.5%, 98.5%, and 93.4% of patients, respectively. Markers of endothelial injury (soluble thrombomodulin) and deficient protein C, protein S, and antithrombin were apparent in 72%, 87.6%, 77.8%, and 81.7%, respectively. Impaired fibrinolysis (elevated plasminogen activator inhibitor-1) was observed in 44% of patients. During the first 7 days, increased prothrombin time (which is readily measurable in most clinical settings) was highly evident among patients who were not alive at 28 days.

Conclusion: Abnormalities in biomarkers of inflammation and coagulation were related to disease severity and mortality outcome in patients with severe sepsis. Coagulopathy and inflammation were universal host responses to infection in patients with severe sepsis, which were similar across causative micro-organism groups.

Show MeSH
Related in: MedlinePlus