Effectiveness of early heparin therapy on outcomes in critically ill patients with sepsis-induced coagulopathy

Abstract

Background: This study aimed to investigate whether early unfractionated heparin (UFH) administration provides a survival advantage for patients with sepsis-induced coagulopathy (SIC).Methods: Patients hospitalized with sepsis-induced coagulopathy from the Medical Information Mart for Intensive Care (MIMIC)-IV database were identified. Patients were divided into two groups, who received unfractionated heparin (UFH) subcutaneously within 24 h after intensive care unit (ICU) admission, and the control group, who received not. The primary endpoint was intensive care unit mortality, the secondary outcomes were 7, 14, and 28-day and hospital mortality. Propensity score matching (PSM) the marginal structural Cox model (MSCM) and E-value analysis were used to account for baseline differences, time-varying and unmeasured confounding factors.Results: A total of 3,377 patients with sepsis-induced coagulopathy were enrolled in the study, of which 815 in unfractionated heparin group and 2,562 in control group. There was significant effect on primary and secondary outcomes with unfractionated heparin after propensity score matching (intensive care unit mortality, hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.52–0.92; 7-day, HR 0.70, 95% CI 0.49–0.99; 14-day, HR 0.68.95% CI 0.50–0.92; 28-day, HR 0.72, 95% CI 0.54–0.96; hospital mortality, HR 0.74, 95% CI 0.57–0.96), marginal structural Cox model manifested unfractionated heparin associated with decreased intensive care unit mortality in all populations (HR 0.64, 95% CI 0.49–0.84), and stratification with the marginal structural Cox model indicated analysis further indicated the survival advantage only among patients with an sepsis-induced coagulopathy score of 4 (HR 0.56, 95% CI 0.38–0.81). Further analysis showed that treatment with 6,250–13750 IU/day of unfractionated heparin associated with a decreased risk of intensive care unit mortality. Similar results were replicated in subgroup analysis with propensity score matching only for patients with an sepsis-induced coagulopathy score of 4 (intensive care unit mortality, HR 0.51, 95% CI 0.34–0.76).Conclusion: This study found early unfractionated heparin therapy to patients with sepsis-induced coagulopathy appears to be associated with improved outcomes. Subgroup analysis further demonstrates heparin therapy decreased intensive care unit mortality primarily in patients only with SIC score of 4.

Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse

“…As administration heparin is time-dependence variable, so we employed MSCM model to adjust additional time-dependent interventions ( de Keyser et al, 2014 ; Karim et al, 2014 ; Huang et al, 2023 ). The MSCM further reinforces the efficacy of heparin in reducing ICU mortality.…”

“…The present study adopted propensity score matching (PSM) to interpret the basic differences in whether the patient received heparin treatment ( Huang et al, 2023 ). During PSM analysis, prophylactic heparin was administered to the heparin group 24 h post-ICU admission.…”

Research Progress of Macromolecules in the Prevention and Treatment of Sepsis

“…The anti-inflammatory effect of UFH is superior to that of NAH; however, UFH increases the risk of bleeding. A retrospective study of 3377 patients with SIC found that UFH (6250–13,750 IU/d) reduced the risk of death in patients with a SIC score of 4 points; however, UFH increased the risk of bleeding in clinical trials [ 73 , 95 , 96 ].…”

Impact of early heparin therapy on mortality in critically ill patients with sepsis associated acute kidney injury: a retrospective study from the MIMIC-IV database

“…Many studies have confirmed the therapeutic effects of heparin in sepsis, including the regulation of inflammatory reactions by antagonizing histones ( Wildhagen et al, 2014 ), inhibiting the generation of inflammatory factors ( Harada et al, 2006 ), immune regulation, and vascular protection ( Eggimann et al, 2003 ). Study by Huang and colleagues revealed that heparin administration was also associated with decreased ICU mortality in patients with an SIC score of 4 (HR 0.63, 95% CI 0.45-0.89) ( Huang et al, 2023 ). Whether heparin therapy is associated with reduced mortality in SAKI patients remains controversial.…”