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.