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

J Thromb Haemost. 2020 Oct;18(10):2524-2531. doi: 10.1111/jth.14973. Epub 2020 Jul 23.


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 international normalized ratio (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 in the ROC analysis was 0.83 (95% confidence interval, 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.

Keywords: NETosis; antithrombin; disseminated intravascular coagulation (DIC); protein C; sepsis.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antithrombin III
  • Blood Coagulation Tests
  • Disseminated Intravascular Coagulation* / diagnosis
  • Disseminated Intravascular Coagulation* / epidemiology
  • Hemostasis
  • Hemostatics*
  • Humans


  • Hemostatics
  • Antithrombin III