Identification of hemostatic markers that define the pre-DIC state: A multi-centre observational study.

BACKGROUND A limitation of diagnostic scoring systems for disseminated intravascular coagulation (DIC) is that once DIC is identified, it may be in a state of irreversible deterioration. OBJECTIVES To identify hemostatic markers that can identify the pre-DIC state. METHODS This was a multi-center observational study of 357 septic patients. The incidence of DIC was determined using the International Society on Thrombosis and Haemostasis (ISTH) DIC Score. Markers of interest include components of the DIC score, protein C (PC), antithrombin (AT), and citrullinated histones (H3Cit) which is a marker of NETosis. RESULTS Out of 357 sepsis patients, 236 patients did not develop DIC (without-DIC), 79 patients had DIC on Day 1 (overt-DIC), and 42 patients developed DIC after Day 1 (pre-DIC). Compared to without-DIC patients, pre-DIC patients had decreased platelet count, increased INR, decreased PC and AT, and increased H3Cit. In contrast, D-dimer and fibrinogen levels did not differ between pre-DIC and without-DIC patients. Using Receiver Operating Characteristics (ROC) analysis, we found that platelet count and INR in combination with PC and AT could discriminate pre-DIC from without-DIC. The Area under the Curve (AUC) in the ROC analysis was 0.83 (95% CI, 0.76 to 0.89). CONCLUSION Our study suggests that platelets and INR in combination with PC and AT can identify the pre-DIC state in septic patients. In contrast, D-dimer increased and fibrinogen decreased in the late (ie. overt) stages of DIC. Our data also suggest that NETosis contributes to the onset of DIC in sepsis.