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

Abstract

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.

Low admission protein C levels are a risk factor for disease worsening and mortality in hospitalized patients with COVID-19

“…Depleted protein C (measured by chromogenic assays and/or ELISA) has been associated with DIC and poor prognosis in sepsis [ 5 ]. In a recent study, low protein C levels measured by ELISA was one of several variables that could identify the pre-DIC state in septic patients [ 6 ]. Of note, protein C and APC have short half-lives and situations with increased activation of the coagulation pathway thus result in acquired deficiency of protein C and the development of a thrombogenic state [ 7 ].…”

D-dimer kit with a High FDP/D-Dimer Ratio is Useful for Diagnosing Thrombotic Diseases

“… 16 Many studies have been performed using very low cut-off values such as 0.5 to 0.8 μg/ml. 21 – 23 Our findings showed that the D-dimer cut-off value that excluded DIC was 3.2 μg/ml, suggesting that the cut-off value of the ISTH overt-DIC scoring system should be ≥3.2μg/ml.…”

The prognostic utility of protein C as a biomarker for adult sepsis: a systematic review and meta-analysis

“…In total, 12 articles were included in our systematic review [ 27 – 38 ], and 8 articles were combined for meta-analysis [ 27 – 35 , 38 ]. The remaining 4 articles were not included in the meta-analysis due to limited available data; however, the study characteristics and available results have been reported in table format [ 28 , 32 , 36 , 37 ].

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