Longitudinal sepsis-induced coagulopathy score trajectories and mortality in relation to early prophylactic heparin: a multicentre cohort study.

BACKGROUND

Sepsis-induced coagulopathy (SIC) evolves dynamically, and a single-timepoint score may not capture its longitudinal course. This study characterised SIC score trajectories, evaluated their associations with mortality, and conducted exploratory analyses of early prophylactic unfractionated heparin exposure.

METHODS

SIC score trajectories were characterised using a latent class mixed model. Trajectory-class prediction models were developed from baseline features within the first 24 hours of ICU admission using five algorithms. Heparin analysis used a 48-hour landmark design; weighted Fine-Gray models and cumulative incidence functions estimated 28-day post-landmark in-hospital mortality.

RESULTS

The study enrolled 20,168 patients from MIMIC-IV and 5,829 from eICU-CRD. Three SIC trajectories were identified-Persistently High, Rising-then-Falling, and Resolving-comprising 31.9%, 10.6%, and 57.5% of patients in MIMIC-IV and 49.1%, 7.2%, and 43.7% in eICU-CRD. Relative to the Resolving trajectory, adjusted subdistribution hazard ratios (sHR) for mortality were 1.65 (95% CI 1.52-1.78) and 1.33 (1.18-1.49) for Persistently High and Rising-then-Falling in MIMIC-IV, and 1.73 (1.51-1.99) and 1.67 (1.33-2.11) in eICU-CRD. Prophylactic heparin was associated with a lower subdistribution hazard of 28-day post-landmark mortality in MIMIC-IV (sHR=0.908, 95% CI 0.839-0.983, P = 0.018); in an exploratory interaction analysis, the point estimate was more pronounced at higher predicted probabilities of the Persistently High trajectory, but this pattern was not replicated in eICU-CRD (sHR 0.877, 95% CI 0.744-1.034, P = 0.118).

CONCLUSION

SIC score trajectories stratify septic patients into three trajectory classes-Persistently High, Rising-then-Falling, and Resolving-each showing a graded association with 28-day mortality. Early prophylactic unfractionated heparin showed an exploratory association with lower post-landmark mortality in MIMIC-IV that was not independently replicated in eICU-CRD. Although these findings do not support treatment recommendations or trajectory-based anticoagulation decisions, they provide a basis for formulating hypotheses for future prospective studies.