Early systemic heparin exposure is associated with lower mortality, reduced disseminated intravascular coagulation, and fewer thrombotic complications in septic shock.

Introduction: Septic shock is characterized by thrombo-inflammatory dysregulation and disseminated intravascular coagulation (DIC), contributing to organ failure and mortality. The clinical impact of heparin in septic shock remains uncertain. This study evaluated the association between early systemic heparin exposure and clinical outcomes. Methods: A retrospective multicenter cohort study was conducted using the TriNetX federated electronic health record network. Adult patients with septic shock receiving early systemic heparin exposure were compared with patients without heparin exposure. Propensity score matching balanced demographics, comorbidities, infection characteristics, organ dysfunction markers, and severity-related variables. Outcomes included mortality, DIC, thrombotic complications, renal outcomes, hematologic complications, and bleeding-related events. Clinical outcomes were assessed over a predefined 30-day follow-up period using risk-based and time-to-event analyses. Results: A total of 105,472 patients per cohort were included. Early systemic heparin exposure was associated with lower mortality (15.3% vs. 20.8%; Discussion: Early systemic heparin exposure was associated with lower mortality, reduced DIC, and fewer thrombotic complications, but increased rates of renal dysfunction and bleeding-related adverse events. These findings highlight a clinically relevant trade-off between potential benefit and harm. Prospective randomized studies are needed to define optimal patient selection and treatment timing.