Biomarkers of Hemostatic Dysregulation, Inflammation, and Infection in Patients Diagnosed with Sepsis Associated Coagulopathy

Introduction: Sepsis associated coagulopathy (SAC) is one of the major pathophysiological mechanisms of sepsis and has been shown to greatly increase mortality in septic patients. SAC is characterized by the inappropriate activation of the coagulation cascade, leading to the formation of microthrombi and the potential for multiple organ failure. Additionally, the excessive consumption of platelets and coagulation factors can create a risk of excessive bleeding. SAC is a complex syndrome, involving coagulation factors, inflammatory cytokines, and several other notable factors of varied origin. In this study, our aim was to evaluate the levels of endocan, pentraxin, and procalcitonin in individuals with SAC diagnosed according to the ISTH criteria in comparison to healthy individuals. Endocan is a soluble, circulating proteoglycan that normally binds to LFA-1 and inhibits leukocyte diapedesis. It is produced by vascular endothelial cells as well as the lung and kidney and has been proposed as a marker of endothelial dysfunction and disease severity in patients with sepsis. Endocan may be useful in the evaluation and tracking of SAC as a marker of endothelial damage caused by excessive inflammation and coagulation. Pentraxin (PTX3) is a protein structurally similar to CRP that is produced by several cell types in response to inflammatory signals and is known to be a marker of inflammation in a number of disease processes. In addition to being the precursor of the hormone calcitonin, procalcitonin is produced by a variety of tissues and may correlate with degree of infection and response to treatment in individuals with sepsis. Taken together, endocan, pentraxin, and procalcitonin may be useful in the evaluation and monitoring of SAC as they are representative of endothelial damage, inflammation, and systemic infection, respectively.

Materials and Methods: Blood from 50 patients with SAC and 33 normal individuals obtained from a commercial source (George King Biomedical, Overland Park, KS) were evaluated. Levels of pentraxin, procalcitonin, endocan, and coagulation factors VII, IX, and X were measured using commercially available ELISA kits from Stago (Parsippany, NJ), Lunginnov (Lillie, France) and R&D Systems (Minneapolis, MN). All results are compiled as group mean and expressed as average mean + SD.  These values are compared with normal and results were computed as percent increase or decrease. 

Results: The levels of coagulation factors VII and X were found to be reduced in patients with SAC compared to normal individuals (p < 0.05); the level of factor IX was statistically unchanged. The reduction in factor X was relatively modest, less than a 20% reduction compared to normal, while the reduction in factor VII was more marked, with a greater than 40% reduction compared to normal.  The levels of pentraxin, proxalcitonin, and endocan were all found to be significantly elevated in blood from SAC patients compared to blood from normal healthy individuals (p < 0.05). All three markers exhibited a greater than 100% average increase when compared to normal.

 Discussion: These results indicate that endocan, pentraxin, procalcitonin, and factor VII are all candidates for further investigation in the identification of a more comprehensive molecular profile of SAC and in the development of diagnostic or prognostic tests. The significant degree of change observed in each marker from normal provides a baseline for future studies of these markers in SAC patients. Although these factors individually are not specific markers of SAC, each is a marker for a specific system that is dysregulated in SAC; endocan for endothelial damage, pentraxin for inflammation, procalcitonin for infection, and factor VII for coagulation. Taken together, these biomarkers may be useful in the diagnosis and monitoring of SAC.