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Sepsis-associated disseminated intravascular coagulation (DIC) is related to marked hemostatic changes such as transient thrombocytopenia secondary to the endogenous activation and consumption of platelets. This study measured markers of platelet function in 103 adult ICU patients with clinically established sepsis-associated DIC to determine the biomarker association with disease severity. Patients were categorized as having no DIC, nonovert DIC, or overt DIC using the International Society of Thrombosis and Hemostasis scoring system. Plasma levels of CD40L, platelet factor 4 (PF4), platelet-derived microparticles, and microparticle-associated tissue factor were quantified. Markers of platelet activation were significantly elevated in patients with DIC compared to healthy individuals. This increase was independent of platelet count. Levels of PF4 differed based on the severity of DIC and differentiated nonsurvivors and survivors. These findings suggest that the markers of platelet activation in DIC may not be regulated by the number of circulating platelets and may be independent of the factors leading to their consumption.

Sepsis is a systemic response to infection with a high rate of mortality and complex pathophysiology involving inflammation, infection response, hemostasis, endothelium, and platelets. The purpose of this study was to develop an equation incorporating biomarker levels at intensive care unit (ICU) admission to predict mortality in patients with sepsis, based on the hypothesis that a combination of biomarkers representative of multiple physiological systems would provide improved predictive value. Plasma samples and clinical data were collected from 103 adult patients with sepsis at the time of ICU admission. Biomarker levels were measured using commercially available methods. A 28-day mortality was used as the primary end point. Stepwise linear regression modeling was performed to generate a predictive equation for mortality. Differences in biomarker levels between survivors were quantified using the Mann-Whitney test and the area under the receiver operating curve (AUC) was used to describe predictive ability. Significant differences ( P < .05) were observed between survivors and nonsurvivors for plasminogen activator inhibitor 1 (AUC = 0.70), procalcitonin (AUC = 0.77), high mobility group box 1 (AUC = 0.67), interleukin (IL) 6 (AUC = 0.70), IL-8 (AUC = 0.70), protein C (AUC = 0.71), angiopoietin-2 (AUC = 0.76), endocan (AUC = 0.58), and platelet factor 4 (AUC = 0.70). A predictive equation for mortality was generated using stepwise linear regression modeling, which incorporated procalcitonin, vascular endothelial growth factor, the IL-6:IL-10 ratio, endocan, and platelet factor 4, and demonstrated a better predictive value for patient outcome than any individual biomarker (AUC = 0.87). The use of mathematical modeling resulted in the development of a predictive equation for sepsis-associated mortality with performance than any individual biomarker or clinical scoring system which incorporated biomarkers representative of multiple systems.

The role of the endothelium in sepsis-associated disseminated intravascular coagulation (DIC) is multifaceted and may contribute substantially to disease severity and outcome. The purpose of this study was to quantify measures of endothelial function, including markers of activation (endocan, Angiopoietin-2 [Ang-2], and von Willebrand Factor), endogenous anticoagulants (tissue factor pathway inhibitor and protein C), and damage-associated factors (High Mobility Group Box 1 [HMGB-1]) in the plasma of patients with sepsis and DIC, and to determine the relationship of these factors with severity of illness and outcome. Plasma samples were collected from 103 adult patients with sepsis within 48 hours of intensive care unit admission. Biomarker levels were measured using commercially available, standardized methods. Disseminated intravascular coagulation was diagnosed according to the International Society of Thrombosis and Hemostasis scoring algorithm. Twenty-eight-day mortality was used as the primary end point. In this study, endothelial damage and dysfunction were associated with the severity of coagulopathy and mortality in DIC patients. Loss of the endogenous anticoagulant protein C and elevation in the vascular regulator Ang-2 were associated with the development of overt DIC. In addition to Ang-2 and protein C, endocan, a biomarker of endothelial activation, and HMGB-1, a mediator of endothelial damage and activation, were significantly associated with mortality. This underscores the contribution of the endothelium to the pathogenesis of sepsis-associated DIC.

Sepsis is a severe systemic inflammatory response to infection that manifests with widespread inflammation as well as endothelial and coagulation dysfunction that may lead to hypotension, organ failure, shock, and death. Disseminated intravascular coagulation (DIC) is a complication of sepsis involving systemic activation of the fibrinolytic and coagulation pathways that can lead to multi-organ dysfunction, thrombosis, and bleeding, with a 2-fold increase in mortality. This study demonstrates the diagnostic and prognostic value of profiling various biomarkers of inflammation and infection in patients with sepsis-associated DIC to assess the severity of illness. Deidentified samples were obtained from adult patients with sepsis and suspected DIC. Platelet count, prothrombin time, D-dimer, and fibrinogen levels were used to assign International Society of Thrombosis and Hemostasis DIC scores to plasma samples from 103 patients with sepsis and suspected DIC. Using commercially available enzyme-linked immunosorbent assay, chromogenic assay, and RANDOX Biochip methods, levels of procalcitonin (PCT), extracellular nucleosomes, interleukin (IL) 6, IL-8, IL-10, and tumor necrosis factor α (TNFα) were measured in patients with sepsis and DIC and compared to levels in healthy individuals. Elevated levels of PCT, IL-6, IL-8, IL-10, and TNFα were observed in most patients with sepsis and DIC. Additionally, the levels of these markers show significant positive correlations with each other and with DIC score. Currently, no single biomarker can effectively diagnose DIC in patients with sepsis. This study lays the groundwork for the development of a diagnostic algorithm using several markers of inflammation and infection and DIC score as parameters in assessing severity of sepsis-associated coagulopathy in a clinical setting.