Delayed versus non-delayed anticoagulation after systemic alteplase for high-risk and intermediate-risk pulmonary embolism – a retrospective observational study

Background The timing of therapeutic anticoagulation after systemic thrombolysis for high-risk and intermediate-risk pulmonary embolism has not been thoroughly studied regarding bleeding risk and other outcomes. Objectives This study aims to compare clinically relevant outcomes between two common approaches of anticoagulation after systemic alteplase for high-risk and intermediate-risk pulmonary embolism. Methods A retrospective, multicenter, cohort study was conducted for 77 patients with high-risk and intermediate-risk pulmonary embolism from 2013 to 2023. Delayed anticoagulation (DAC) was defined as therapeutic, parenteral anticoagulation ordered for administration after systemic alteplase when the partial thromboplastin time (PTT) was below two times the upper limit of normal or after a clinician-directed time delay. Non-delayed anticoagulation (NDAC) was defined as therapeutic, parenteral anticoagulation ordered for administration after systemic alteplase regardless of PTT value or time delay. The primary outcome was a composite of major bleeding or clinically relevant non-major (CRNM) bleeding. Secondary outcomes included minor bleeding, blood transfusion requirements, intracranial hemorrhage, readmission within 30 days, recurrent thrombotic events, intensive care unit length of stay, and survival to hospital discharge. Results DAC and NDAC were associated with similar occurrences of major or CRNM bleeding after adjusting for the number of baseline bleeding and clotting risk factors (adjusted odds ratio [aOR], 0.61; 95% confidence interval [CI], 0.13 – 1.85). No statistically significant differences in secondary outcomes were observed except for a lower odds of survival to hospital discharge with DAC (OR, 0.07; 95% CI, 0.00 – 0.47). Conclusion DAC and NDAC after systemic thrombolysis may be associated with similar bleeding risks.