Analysis of no bolus versus bolus unfractionated heparin nomograms in the management of pulmonary embolism: Insights from a real-world cohort

Abstract

Abstract Background: Unfractionated heparin (UFH) is a cornerstone of acute pulmonary embolism (PE) management. A weight-based UFH nomogram, with an initial bolus followed by continuous infusion (“bolus nomogram”) titrated to target activated partial thromboplastin time (aPTT), has been established as standard dosing. Despite the use of standardized nomograms, UFH pharmacokinetics are variable: studies have shown difficulty of achieving and maintaining therapeutic aPTT values. Increased time in subtherapeutic range is associated with increased rates of recurrent venous thromboembolism (VTE) and mortality. Patient factors may lead clinicians to withhold the initial UFH bolus (“no bolus nomogram”) (e.g. recent surgery and/or bleed). There are few data describing the effects of withholding the initial UFH bolus on aPTT values. We aimed to measure the association between no bolus versus bolus UFH nomograms and percent time with subtherapeutic aPTT values within the first 24 hours of treatment for acute PE. Methods We conducted a retrospective analysis of the Barnes-Jewish Hospital PE Response Team (PERT) database. We identified patients with radiographically confirmed acute PE treated with UFH as initial therapy between January 1, 2021, and July 1, 2025. The primary outcome was the percent time with a subtherapeutic aPTT value in the first 24 hours of UFH treatment defined using our institution's heparin nomogram target aPTT range (i.e. aPTT <60 prior to September 27, 2023 or <66 on or after September 27, 2023). Results Of 261 patients eligible for inclusion, the initial UFH bolus was withheld from 63 patients (24%), and given to 198 patients (76%). In logistic regression, surgery within 12 weeks prior to PE diagnosis (Odds Ratio [OR] 0.37; 95% confidence interval [CI] 0.20-0.71; p = 0.002), history of major bleed (OR 0.14; 95% CI 0.04-0.47; p= 0.002), and each 1-unit decrease in hemoglobin (OR 0.85; 95% CI 0.75-0.96; p = 0.014) were associated with omission of the initial bolus. 5 patients (8%) in the no bolus group and 42 patients (21.2%) in the bolus group were treated with catheter-directed or surgical intervention, and withholding the bolus was associated with decreased rates of these interventions (OR 0.32; 95% CI 0.12-0.85; p = 0.022). Patients in the no bolus group spent a median 15.3 hours (Interquartile Range [IQR]: 6.1-24.0) in subtherapeutic range versus 8.1 hours (IQR: 0.0-8.6) for those treated per the initial bolus nomogram (p = 0.01). Withholding the initial bolus was associated with a 63% mean increase in the percent time in subtherapeutic range (95% CI 24.2%-100%; p= 0.001). Results remained unchanged when accounting for estimated glomerular filtration rate (eGFR), bilirubin, baseline aPTT, and thrombectomy. The median time to achieve an aPTT ≥ therapeutic range was 18.5 hours (IQR: 7.0-24.0) in the no bolus group compared to 6.7 hours (IQR: 5.8-12.7) in the initial bolus group (p = 0.015). Omission of an initial bolus was associated with a 58% decrease in likelihood of achieving a therapeutic or greater aPTT within 24 hours of UFH initiation (Hazard Ratio [HR] 0.42; 95% CI 0.30-0.59; p < 0.001). At 24 hours after UFH initiation, 24 patients (38%) in the no bolus compared to 21 patients (11%) in the bolus group still had not achieved a therapeutic or greater aPTT. Conclusion Withholding the initial UFH bolus in the treatment of acute PE is associated with an increased percentage of time in subtherapeutic aPTT range within the first 24 hours of therapy. Prior studies have demonstrated an association between delay to therapeutic anticoagulation and risk of adverse outcomes. Evaluation of the risk of PE-related mortality and recurrent VTE after bolus omission is needed.