Identification of Mechanistic Pathways that Lead to Disseminated Intravascular Coagulation (DIC) in Sepsis: Implications for Screening
CCCF ePoster library. Jackson Chornenki N. Nov 9, 2018; 233328; 121 Disclosure(s): Nothing to disclose
Nicholas Jackson Chornenki
Nicholas Jackson Chornenki
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Introduction: Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by widespread intravascular activation of coagulation complicating many conditions including sepsis, trauma, and malignancy. The International Society on Thrombosis and Haemostasis (ISTH) scoring system for diagnosis of DIC is based on the platelet count, prothrombin time, fibrinogen levels, and fibrin-related markers, with a score ≥5 indicating DIC. However, once identified, the condition may already be irreversible and thus may not be responsive to therapy. To date, no useful biomarkers have been identified to differentiate “non-DIC” (a transient hypercoagulable state that does not lead to DIC) from “pre-DIC” (a hypercoagulable state which will lead to DIC).  In sepsis, cell-free DNA (cfDNA) released from activated neutrophils have been shown to play an important role in the pathogenesis of DIC via pro-coagulant and anti-fibrinolytic effects which may contribute to microvascular thrombosis.  The hypercoagulable and anti-fibrinolytic state in sepsis-associated DIC is accompanied by the increased consumption of anticoagulants such as protein C (PC).  High lactate concentrations are indicative of tissue hypoperfusion and are also associated with poor outcome in sepsis.


Objectives: To identify mechanistic pathways that lead to DIC in sepsis.  Specifically, we will determine if abnormalities in cfDNA, PC, and/or lactate can be used to differentiate pre-DIC from non-DIC. 


Methods: We studied a cohort of 173 septic patients recruited from hospitals in Hamilton, Ontario as part of the the DYNAMICS Study (DNA as Prognostic Marker in ICU patients study, Clinical Identifier: NCT01355042).  Patient plasma samples were collected daily for the first week and then weekly thereafter. The development of DIC was scored using the ISTH diagnostic criteria on Day 1 and day a plasma sample was available. Potential markers of DIC development were either extracted from existing clinical data or measured using in-house laboratory assays.


Results: 62 of the 173 septic patients were classified as having DIC (n=42 on Day 1 and n=20 after Day 1). Multivariable analysis demonstrated that both the presence of DIC (HR=1.98; 95% CI=1.04 – 3.79, p =0.039) and a history of chronic lung disease (HR = 1.97; 95% CI = 1.02 –3.80; p = 0.044) significantly increased mortality. Patients with DIC had higher baseline APACHE II scores (28.38 vs. 24.2, p=0.016). Creatinine levels on Day 1 (p<0.001) and Day 4 (p<0.01) were significantly higher in patents with DIC, while lactate on Day 1 was significantly higher in patients with DIC (p<0.001). Levels of PC were significantly lower in patients with DIC on all days during the first week of admission (p<0.01), while cfDNA did not significantly differ between DIC and non-DIC patients at any time point. When considering those who developed DIC later, the area under the curve (AUC) for Receiver Operating Characteristic (ROC) Curves for the prediction of DIC are summarized in Table 1. The combination of PC, lactate, and platelet count yielded stronger predictive power (AUC=0.72; 95% CI, 0.59–0.85) than individual markers.


Conclusion:  DIC represents a significant cause of mortality in sepsis, and its pathophysiology reflects consumptive coagulopathy as indicated by reduced PC. Screening for DIC in septic patients using lactate, PC, and platelets may prove useful in identifying patients at risk of developing DIC.



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