The Relationship between the Initial Anti-factor Xa Measurement and the Duration of Direct Oral Anticoagulant Influence in Patients Transitioning to Heparin

Pharmacotherapy. 2020 Sep;40(9):880-888. doi: 10.1002/phar.2444. Epub 2020 Aug 14.


Background: Anticoagulation monitoring during transition from direct oral anticoagulants (DOAC) to heparin infusions is a significant challenge. Factor Xa inhibitors influence the heparin calibrated antifactor Xa assay. The University of Virginia (UVA) Medical Center utilized a corrected antifactor Xa assay (c-AXA) during this transition period, which removes DOAC-mediated antifactor Xa activity (d-AXA) and reflects heparin-specific activity. Currently, the duration of this influence is not well described.

Study objective: This study had two aims: to determine if the initial d-AXA is predictive of the duration of DOAC influence and to further characterize this influence among different patient populations.

Methods: This retrospective study included adult patients admitted to UVA Medical Center between September 2016 and March 2017, with c-AXA measurements, who received apixaban or rivaroxaban within 48 hours before heparin initiation. A Pearson correlation test, Kaplan-Meier Survival Analysis, and multivariate linear regression were used to assess the relationship between initial d-AXA and duration of influence.

Results: Sixty-eight patients met inclusion criteria and were maintained on either apixaban (85%) or rivaroxaban (15%) before heparin initiation. The initial d-AXA ranged from 0.11 to 3.27 IU/ml. The mean duration of influence was 69.3 ± 46.2 hours, with a median duration of 62.7 hours. No strong correlation was identified between initial d-AXA and duration of influence (R2 = 0.124). Presence of interacting medications significantly increased duration of influence (p=0.012). No significant difference in duration of influence existed between patients with normal renal function and those with dynamic renal function (p=0.84), or with body mass index (BMI) greater than 40 kg/m2 (p=0.16).

Conclusions: The initial d-AXA was not predictive of duration of influence in patients transitioning from DOACs to heparin infusion; however, the median duration of influence suggests influence may be present for longer than currently stated in the literature, especially in those taking interacting medications.

Keywords: anticoagulation; antifactor Xa assay; direct factor Xa inhibitors; hematology; heparin monitoring; laboratory interference; pharmacokinetics.

Publication types

  • Evaluation Study

MeSH terms

  • Administration, Oral
  • Anticoagulants / administration & dosage*
  • Anticoagulants / pharmacokinetics
  • Blood Coagulation Tests
  • Drug Administration Schedule
  • Factor Xa Inhibitors / blood*
  • Female
  • Heparin / administration & dosage*
  • Heparin / pharmacokinetics
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Retrospective Studies


  • Anticoagulants
  • Factor Xa Inhibitors
  • Heparin