New guidelines recommend specific tests to monitor the activity of direct oral anticoagulant drugs / imtmphoto

An American College of Cardiology (ACC) task force has issued expert guidance on managing bleeds from oral anticoagulants, including new direct oral anticoagulant (DOAC) drugs—Xarelto (rivaroxaban), Eliquis (apixaban), Pradaxa (dabigatran etexilate), and Savaysa (edoxaban). This consensus document, published in the Journal of the American College of Cardiology, recommends which tests to perform for specific DOACs and which tests to use when the ideal test is not available.

More than 6 million Americans at risk of deep venous thrombosis, pulmonary embolism, and post-surgical clots rely on anticoagulants to help prevent blood clots and stroke. While they pose certain advantages to warfarin, the downside of these drugs is they can increase patients’ risk of bleeding, and subsequently, raise their risk of morbidity and mortality.

The guidance document advises clinicians on managing patients who experience acute bleeding when taking DOACs or vitamin K antagonists (VKA) for any medical purpose. “My hope is that lab specialists, other clinicians, and patients will find this document extremely useful to help mitigate one of the most common adverse drug reactions we deal with, namely hemorrhage complicating anticoagulant use,” James L. Januzzi Jr., MD, FACC, chair of the ACC Task Force on Expert Consensus Decision Pathways, told CLN Stat.

The guidance also supplements the 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular AF, which is geared toward patients undergoing interventional procedures or surgery.

As Clinical Laboratory News reported in 2016, labs don’t always have access to optimal tests for measuring the effects of DOACs. The U.S. Food and Drug Administration has yet to approve an assay that specifically measures DOAC concentrations, and currently available assays such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) aren’t that proficient in measuring the anticoagulant effects of these drugs. Other options such as mass spectrometry are effective at measuring DOAC concentrations, but not all labs offer these methods.

Measuring anticoagulant activity is crucial in evaluating patients who experience acute bleeding or immediately need an unplanned procedure, the authors emphasized. For these patients, clinicians should request either a PT or an aPTT. “Interpretation of the PT and aPTT as well as the potential need to request specialized coagulation tests will depend on the clinical situation, the anticoagulant, and test availability,” they suggested. Determining the PT/ international normalized ratio (INR) in patients taking VKA will help in either managing bleeding or guiding perioperative care, unless a clinician suspects a concomitant defect in coagulation.

The most optimal tests for measuring anticoagulant activity of dabigatran—dilute thrombin time, ecarin clotting time, and ecarin chromogenic assays—are not always available to labs. The authors suggest as alternative qualitative tests thrombin time (TT) and aPTT. “The TT is exquisitely sensitive to dabigatran, even at very low drug concentrations. Thus, a normal TT excludes clinically relevant dabigatran levels, but a prolonged TT does not discriminate between clinically important and insignificant drug concentrations,” the authors explained. They also recommend that labs use TT to rapidly exclude clinically significant dabigatran levels, in the event they don’t offer a 24/7 assay for quantifying dabigatran.

In other recommendations, the authors suggest using a PT test to assess the anticoagulant activity of edoxaban and rivaroxaban, in the event chromogenic anti-Xa assay, the test optimal for apixaban, edoxaban, and rivaroxaban, isn’t available. “A prolonged PT suggests on-therapy or above on-therapy levels for these agents. However, depending on the sensitivity of the PT reagent, a normal PT may not exclude on-therapy levels,” according to the authors.

Because PT and aPTT are insensitive to apixaban, they aren’t useful for assessing this anticoagulant. As the authors explained, “a prolonged PT suggests the presence of clinically important apixaban levels, but a normal PT and aPTT do not exclude on-therapy or even above on-therapy levels of the drug.”