Are Direct Oral Anticoagulants Plasma Concentrations Associated with the Risk of Postoperative Bleeding? Results from the Real Life Cohort

Background

The perioperative management (PM) of direct oral anticoagulants (DOACs) is controversial. The role of assessing DOAC plasma levels in order to ensure a safe use of these anticoagulants is still unknown.

Aims

To examine the association between DOACs plasma concentrations obtained before surgery and the risk of postoperative bleeding in the perioperative setting.

Methods

From June 2014 to December 2015 we have consecutively included 99 patients treated with DOACs and referred to our Unit for PM. Management was performed following the PM recommendations from the Catalan Thrombosis Working Group (Tromboc@t) . Bleeding events were classified following the ISTH criteria. Plasma concentrations were measured in the day of invasive procedure using the Technoclone anti-Xa assay from Technoclone (Vienna-Austria) for Rivaroxaban and Apixaban, and the Direct Thrombin Inhibitor Assay from IL (Bedford-MA-USA) for Dabigatran; in each case, specific calibrators were used. Patients were systematically followed 30 days after the surgical procedure.

Results

A total of 99 patients were recruited. Median age was 76 years (range: 61-94) and 51 (51.5%) were female. Among them, 23 patients received dabigatran, 40 rivaroxaban and 36 apixaban. As per the risk scores, 66.7% of the patients had a CHA2DS2-VASc score >3, 57.6% had a HAS-BLED score >3, and 51 (51.5%) were considered high-risk procedures. Total bleeding events occurred in 23 patients (47.8% minor, 30.4% non-major clinically relevant, and 21.7% major bleeding). The median plasma NOACs concentration was 38.3 ng/ml (0.8-226 ng/ml), with 32 patients having levels >30 ng/mL. HASBLED score > 3 was associated with an increased risk of bleeding events within 30 days (hazard ratio (HR)= 3.9, 95% CI= 1.14-13.4, P=0.03). Plasma DOAC levels > 30 ng/ml were not significantly associated with an increased risk of bleeding events (HR=2.17, 95% CI=0.862-6.67, P=0.10). Major bleeding (n=5) was probably associated with the risk of the procedure than to the DOAC plasma concentrations.

Conclusion

In our cohort we found significant association between the individual bleeding risk before surgery with the risk of postoperative bleeding. In spite of that, this study will continue to reevaluate PM in high-risk procedures according to plasma DOAC levels.