Delayed anticoagulation is associated with lower mortality in sepsis-induced coagulopathy: a large-scale, propensity-score-matched cohort study from MIMIC-IV.

BACKGROUND

This study aimed to investigate the relationship between the timing of anticoagulation initiation and clinical outcomes in critically ill patients with sepsis-induced coagulopathy (SIC).

METHODS

We conducted a retrospective cohort study using the MIMIC-IV database. Adult patients diagnosed with SIC (ISTH-SIC score ≥ 4) and receiving anticoagulation therapy during their ICU stay were included. Anticoagulation therapy was defined as administration of unfractionated heparin, low-molecular-weight heparin, vitamin K antagonists, or direct oral anticoagulants, as captured in medication records; additionally, a heparin-only analysis was performed given its predominant use in this population. Patients were stratified into early (≤ 48 hours post-ICU admission) or delayed (> 48 hours) anticoagulation groups. Baseline characteristics were balanced using propensity score matching (PSM). Primary outcomes included 28-day, 60-day, and 90-day mortality. Cox proportional hazard models were applied to assess survival differences across subgroups.

RESULTS

Among 12 738 eligible patients, 10 689 received early anticoagulation and 2049 received delayed treatment. After PSM (n = 3986), delayed anticoagulation was associated with significantly lower 28-day mortality (15% vs 19%, P < 0.001), and similar reductions were observed at 60 and 90 days. Kaplan-Meier survival curves showed significantly better survival in the delayed group (P < 0.001). Subgroup analyses revealed that the survival benefit was more pronounced in patients aged >65 years, those without acute kidney injury (AKI), platelet count ≥ 100 × 109/L, Sequential Organ Failure Assessment score ≥ 6, and those treated with unfractionated heparin.

CONCLUSIONS

Among critically ill patients with SIC, delayed initiation of anticoagulation was independently associated with improved short- and medium-term survival. These findings support a phenotype-guided, time-stratified approach to anticoagulation in sepsis and highlight the need for prospective trials to validate optimal timing strategies.