Mediating Role of Platelet Count Increase in Unfractionated Heparin Treatment for Sepsis Patients: A Retrospective Cohort Analysis

Aims/Background The role of heparin in sepsis therapy has been widely debated. The controversy surrounding heparin's use as an anticoagulant in sepsis may stem from differences in sepsis definitions, study designs, timing and dosage of drug administration, treatment duration, complications, and patient severity. In this study, we aimed to determine the optimal timing and dosage of heparin in patients with sepsis, identify specific subgroups that could benefit from heparin therapy, and explore laboratory markers to assess its efficacy. Methods This retrospective cohort study was conducted using the Medical Information Mart for Intensive Care-IV dataset. Data from patients with sepsis were extracted based on the Sepsis 3.0 criteria. Patients were categorized according to heparin use. The effectiveness of early and appropriate heparin administration was assessed, and a subgroup analysis was performed to identify patients most likely to benefit from heparin therapy. Additionally, factors mediating the improvement in sepsis prognosis following heparin treatment were analyzed. Results We recruited 4149 participants who met the inclusion criteria, with an overall 28-day mortality rate of 19.5%. There were 2192 individuals in the heparin group and 1957 in the non-heparin group. After propensity score matching, heparin therapy demonstrated a significantly greater effect on reducing both 28-day and 90-day mortality compared to the non-heparin treatment (18.1% vs. 10.7%, p < 0.001; 18.8% vs. 12.6%, p < 0.001). However, the heparin group had a higher incidence of major bleeding (10.9% vs. 6.3%, p = 0.001), increased use of mechanical ventilation (54.3% vs. 45.1%, p < 0.001), and a longer intensive care unit stay (3.6 vs. 2.5 days, p < 0.001) compared to the non-heparin group. Early administration of high-dose heparin improved 28-day survival. Early and adequate heparin administration was more effective than late and insufficient dosing (p < 0.01), except in patients with sepsis who had low white blood cell counts, alkalosis, or reduced platelet counts. The increase in platelet count had a significant mediating effect on the entire cohort (p < 0.001 for the causal mediation effect), with a mediation proportion of 14%. Conclusion Early and adequate heparin administration can significantly improve the prognosis of sepsis. An increase in platelet count may serve as a potential indicator of the effectiveness of heparin therapy in sepsis.