Jul 152018

The new generation of oral anticoagulants have revolutionized management of venous thromboembolism and atrial fibrillation. The changes in clinical practice have also created new questions and confusion around management of bleeding associated with these newer anticoagulants. The American College of Cardiology issued an expert consensus document in December 2017 to help guide physicians on the management of bleeding in patients receiving oral anticoagulants.

Authors advise being vigilant to renal dysfunction in patients treated with direct oral anticoagulants, as all DOACs are cleared by the kidneys. Dosage adjustments may be required (see package inserts).

A normal activated partial thromboplastin time (aPTT) generally excludes the possibility of excess dabigatran (Pradaxa) levels. aPTT is not useful for monitoring other DOACs. Monitoring assays are not readily available for any of the new anticoagulants.

Dabigatran is reversible with the monoclonal antibody derived antidote, idarucizumab (Praxbind). The antidote is indicated for severe bleeding in patients taking Pradaxa.

Andexanet alfa, an antidote to factor Xa, was approved by the FDA in May 2018 with indications for patients with major bleeding while taking factor Xa inhibitors rivaroxaban (Xarelto) and apixaban (Eliquis). ANNEXA-4 investigators reported substantial reductions in anti-factor Xa activity among rivaroxaban and apixaban recipients within hours after andexanet alfa administration.

Although FDA-approved, andexanet alfa is not yet widely available; a major launch is planned for 2019 after its maker expands manufacturing processes.

Prothrombin complex concentrate has been suggested as a treatment for bleeding due to DOACs other than dabigatran, but good evidence is lacking as to the efficacy of this approach.

Bridging anticoagulation with enoxaparin or other low molecular weight heparin products in the perioperative period is not considered necessary or advisable for most patients taking DOACs. The drug can simply be stopped for a period of days prior to the procedure (see package inserts or consult a local expert for the ideal timing of interruption).

Most patients can be restarted on their oral anticoagulant 24 hours after undergoing a surgery or procedure that carries a low risk of post-procedure bleeding. Restarting anticoagulation after 2 to 3 days is advised for patients at higher risk for bleeding.

For reversal of warfarin, vitamin K is still considered the first-line agent, preferably to be infused by slow intravenous dosing.

Prothrombin complex concentrates have also been suggested for reversal of serious bleeding associated with warfarin, because unlike fresh frozen plasma, PCC does not require blood type compatibility testing, permitting it to be delivered faster.


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How to manage bleeding from oral anticoagulant drugs