Anti-factor Xa as the preferred assay to monitor heparin for the treatment of pulmonary embolism

Abstract

Introduction: The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE-associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti-factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE-associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events.

Methods: This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3-0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE-associated mortality within 3 months.

Results: A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021].

Conclusion: We observed a low incidence of recurrent thromboembolism or PE-associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE.

Keywords: PERT; anti-Xa; anticoagulation; heparin; pulmonary embolism.