Purpose: Direct oral anticoagulants (DOAC) and calcineurin inhibitors (CNI) are both substrates of CYP 3A metabolism; therefore, the purpose of this study is to assess the incidence of major bleeding in solid organ transplant (SOT) recipients taking CNI with a DOAC compared to patients taking warfarin.

Methods: A single center retrospective, observational chart review was performed in SOT recipients taking a CNI for immunosuppression, who required oral anticoagulation for DVT, PE, or nonvalvular atrial fibrillation between May 2013 and November 2016. Patients were stratified into two groups: those taking a CNI and a DOAC versus those taking a CNI and warfarin. The primary endpoint was the incidence of major bleeding in a critical site, defined as a decrease in hemoglobin of ≥ 2 g/dL, requiring transfusion of at least two units of blood. Patients were excluded if they were < 18 years old, taking a DOAC for off-label use, taking warfarin for an indication that a DOAC does not have an indication for, had valvular atrial fibrillation, baseline platelet count < 50,000/microliter, baseline INR > 1.5, or warfarin goal INR other than 2-3.

Results: The primary endpoint was reached in 10.8% (4/37) of patients in the DOAC group and 5% (2/40) of patients in the warfarin group. Using a fisher's exact test, no statistical difference was found between the two groups (P=0.419). The primary site of bleeding in the 4 DOAC patients was pericardial (2/4), gastrointestinal (1/4), and genitourinary (1/4). In the warfarin group, 1 patient had a retroperitoneal bleed and 1 patient had a genitourinary bleed. In 50% of patients who met the primary outcome, major bleeding occurred after allograft biopsies. Demographics consisted of mainly Caucasian males (61%), heart transplants (43.8%), and the CNI tacrolimus (97.4%). DOACs used were as follows: apixaban (59.5%) and rivaroxaban (40.5%), with a dose reduction in 48.6%. Of the 48.6% DOAC dose reductions, 16.2% were done following manufacturer recommendations.

Conclusion: In this retrospective chart review, we found no statistical difference in rates of major bleeding between SOT recipients taking a DOAC versus warfarin concomitantly with a CNI. It appears that the DOAC cohort did not experience excessive anticoagulation due to competition of drug metabolism with a CNI. However, further research is warranted to support this conclusion.

CITATION INFORMATION: Hazelcorn J, Yau R, Sabagha N, Moaddab M, Manson M. Risk of Major Bleeding in Solid Organ Transplant Recipients Taking Calcineurin Inhibitors Concomitantly with Direct Oral Anticoagulants Compared to Warfarin. Am J Transplant. 2017;17 (suppl 3).

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