An Observational Pilot Study Investigating the Role of Coagulation in the Diagnosis of SEPSIS in the Emergency Department (SEPSIS-ED)

J. Arora1; J. A. Klowak1; S. Parpia2; M. Zapata-Canivilo1,3; W. Faidi1; C. Skappak4; V. Catenacci1; V. Stewart5; R. Gregoris1; C. A. Kretz1; K. Raajakesary1; D. J. Dwivedi1; P. Liaw1; K. de Wit1,4; M. Welsford4; A. Fox-Robichaud1,3; On behalf of the Canadian Critical Care Translational Biology Group

1Thrombosis & Atherosclerosis Research Institute (TaARI), Hamilton, Canada; 2Departments of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada; 3Department of Medicine, Division of Critical Care, Faculty of Health Sciences, McMaster University, Hamilton, Canada; 4Department of Medicine, Division Emergency Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Canada; 5Department of Surgery, Division of General surgery, Faculty of Health Sciences, McMaster University, Hamilton, Canada

Introduction: Inflammation and coagulation are linked to the innate immune response. Early recognition and diagnosis are essential to alter patient prognosis. We have shown that coagulation markers are important for prognosis in the intensive care unit. However, the role of coagulation markers to aid in sepsis diagnosis in the emergency department (ED) has had limited investigation.

Methods: SEPSIS-ED is an observational cohort study with a planned recruitment of 250 adult patients presenting to two ED’s with sepsis suspicion. Samples are collected at two-time points: initial patient presentation to the ED (time point one, T1) and four hours after the initial sample collection (time point two, T2). Plasma cell-free DNA (cfDNA) levels are determined by the silica-membrane-based DNA purification method and UV spectrophotometry. Procalcitonin, protein C (PC), DNase I (deoxyribonuclease I), ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13), and von Willebrand factor (VWF) levels are measured using enzyme-linked immunosorbent assays. Each case with suspected sepsis is adjudicated using Sepsis-3 definition.1 Data is reported as median (Interquartile range) depending on whether normally distributed.

Results: We report data on 200 patients with 52.7% males and a mean age of 69.8 ± 17.7 years, including 83 septic and 117 non-septic patients. Septic patients had a 9.6% mortality at 28 days and a SOFA score of 4 (4) which was higher than the non-septic patient group (SOFA score 2 (2)). Septic patients had elevated leukocyte (12.7 (8.4) × 109/L) and neutrophil counts (10.9 (7.5) × 109/L) compared to the hospital standard. CfDNA levels were higher in septic patients (n = 83) compared to the non-septic patients (n = 117) at time point two (p = 0.03), while no difference was seen at time point one (p = 0.11) between the two patient groups. DNase I levels at both time points were not significantly different between septic (n = 21) and non-septic patients (n = 44) (T1, p = 0.39 and T2, p = 0.79). Procalcitonin levels were significantly higher in septic patients (n = 83) compared to non-septic patients (n = 117) at both time points (T1, p = 0.0009 and T2, p = 0.0003). PC levels declined four hours after admission to the ED in septic patients (n = 83) (p = 0.007), with no significant difference seen in mean values compared to non-septic patients (n = 117) (T1, p = 0.95 and T2, p = 0.13). In addition, ADAMTS13 levels in septic levels (n = 58) were lower than the non-septic patients (n = 54) (T1, p = 0.04 and T2, p = 0.03), with no difference in VWF levels among septic patients (n = 74) compared to non-septic patients (n = 100) (T1, p = 0.50 and T2, p = 0.16).

Limitations: The study is limited by the moderate study size and presence of only two study sites. Even though we aim to evaluate patients early in the disease process using the ED, the precise onset of sepsis cannot be accurately determined due to the heterogeneity of the pathophysiological process.

Conclusion: Our preliminary data suggest suspected septic patients presenting to the ED have an associated coagulopathy (as demonstrated by a decrease in ADAMTS13) together with an initial inflammatory response. Our results provide a rationale to explore the impact of coagulation markers in facilitating earlier and accurate sepsis diagnosis.

Reference:

1. Singer M, Deutschman CS, Seymour C, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA - J Am Med Assoc. (2016). 315(8):801–10.