A Systemwide Approach for Navigating the Dilemma of Oral Factor Xa Inhibitor Interference With Unfractionated Heparin Anti-Factor Xa Concentrations

Ann Pharmacother. 2021 May;55(5):618-623. doi: 10.1177/1060028020956271. Epub 2020 Sep 4.


Background: Oral factor Xa inhibitors are known to significantly increase heparin anti-Xa concentrations, which leads to inaccuracies when monitoring intravenous unfractionated heparin (IV UFH). Guidance for managing this laboratory interference is lacking, creating substantial uncertainty in clinical practice.

Objective: To describe a strategy used by a large academic institution for managing the controversy of laboratory interference in the setting of oral factor Xa inhibitor use and provide effectiveness and safety data for this approach.

Methods: In December 2016, a new Heparin IV Direct Oral Anticoagulant (DOAC) Interference PowerPlan (a comprehensive order set) was made available in the electronic health record (Cerner, North Kansas City, MO) throughout the health system. We retrospectively examined 169 patients with events reported in the error reporting system, RISKMASTER, and evaluated reports with and without the use of the PowerPlan. Effectiveness was determined through evaluation of thrombosis. The Naranjo criteria for causality were applied to assess thrombotic events.

Results: Of 56 events that were reported with apixaban when the PowerPlan was not ordered, 4 (7%) thrombotic events occurred within 7 days of UFH initiation. One out of the 4 events (25%) that occurred when the PowerPlan was not appropriately initiated was considered probable using the Naranjo Scale. Three additional events (75%) were possible using the Naranjo Scale.

Conclusion and relevance: The Heparin IV DOAC Interference PowerPlan appears to be conducive to positive patient outcomes when evaluating voluntary reported events and may assist clinicians with managing the therapeutic dilemma of this laboratory interference.

Keywords: anticoagulants; anticoagulation; cardiology; heparin; medication safety.

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / blood
  • Drug Monitoring / methods*
  • Factor Xa / metabolism
  • Factor Xa Inhibitors / administration & dosage*
  • Factor Xa Inhibitors / blood
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / blood
  • Heparin / administration & dosage*
  • Heparin / blood
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Thrombosis / blood
  • Thrombosis / drug therapy


  • Anticoagulants
  • Factor Xa Inhibitors
  • Fibrinolytic Agents
  • Heparin
  • Factor Xa