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DOACs Part 2: Bleeding and Reversal Agents

The most important principle to remember in the management of hemodynamically unstable patients who are bleeding and taking DOACs is that reversing or withholding a DOAC does not stop bleeding, but rather, returns the patient to an un-anticoagulated state. It is therefore imperative that resuscitative measures to stop the bleeding are taken as a priority over reversing the DOAC.

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  Anticoagulant reversal

We overestimate the risk of bleeding. Most bedside ICU procedures carry a very low risk of bleeding and don't require aggressive coagulation reversal (with the possible exception of lumbar puncture).

  Andexxa

Andexxa is the first and only specific reversal agent for apixaban or rivaroxaban treated patients with life-threatening or uncontrolled bleeding.

  Kcentra - Coumadin

The Kcentra dosage calculator can save you time when determining the recommended dose of Kcentra for your patients.

  Praxbind

PRAXBIND is a specific reversal agent for PRADAXA, with no impact on the effect of other anticoagulant or antithrombotic therapies. PRADAXA can be re-initiated after 24 hours following PRAXBIND administration.

  Protamine

Protamine dosing for neutralizing heparin and LMWH

 Factor Xa Inhibitor Reversal Agent Is Not Ready for Prime Time

This brings us to the elephant in the room: the lack of any meaningful comparison arm. While those designing this study seemed to feel that a control arm was unwarranted or unethical, there is an obvious and clear alternative available, prothrombin complex concentrate (PCC). The most typically used four-factor PCCs include factors II, VII, IX, and X, along with proteins C and S. While PCCs are indicated primarily for the urgent reversal of vitamin K antagonists, they are also recommended, by guidelines, for the treatment of anti–factor Xa–related hemorrhage

 One Thing Leads to Another – Idarucizumab for Dabigatran

We agree idarucizumab rapidly normalizes abnormal coagulation parameters associated with use, but its suspected clinical effectiveness and safety cannot be confirmed at this time.

 Reversing NOACs – Updates for Emergency Physicians

If the clinician is unable to determine which agent the patient is taking, PCC can be used. Dabigatran can be reversed with idarucizumab. Xabans can be reversed with PCC. If PCC is not available, FFP and TXA should be utilized. Charcoal can be used in select patients who present within 2 hours of dosing.

Articles of Interest

Reversing DOAC-Associated Major Bleeding—Follow the Data

Several anticoagulant reversal agents have been introduced. As a result, we’ve seen better overall better safety in this field, and the incidence of intracranial hemorrhage and other major hemorrhagic events has markedly decreased.

4-Factor Works for Factor Xa Inhibitors

4-Factor prothrombin concentrate complexes have been established as a treatment option in the setting of hemorrhagic complications during anticoagulation with the Factor Xa inhibitors.

A Case Example: Reversing Anticoagulant Dabigatran with Idarucizumab

You recall that there is a new drug out that specifically counters dabigatran. It is composed of monoclonal antibodies that bind to and inactivate the drug. It is made by the same company that makes dabigatran (Boehringer Ingelheim).

Evidence-Based Strategies for Reversing Direct-Acting Oral Anticoagulants

The anticoagulant effects of DOACs dissipate quickly after the drugs are discontinued because of their short half-lives.16 Intervention is sometimes needed to hasten the reduction in (i.e., provide reversal of) anticoagulant effects for patients with spontaneous or traumatic life-threatening or uncontrolled bleeding or an urgent (i.e., within 1 hour) need for surgery or another invasive procedure.

Management of Patients on Novel Oral Anticoagulants with Bleeding

There are limited options for the reversal of clinically significant bleeding in patients taking dabigatran. Prothrombin complex concentrates (PCC’s), which contain high doses of vitamin K dependent clotting factors as well as Protein C and S, may be effective for dabigatran reversal.11 Hemodialysis has also been shown to be effective in removal of dabigatran in patients with end-stage renal disease, but the benefit of dialysis in patients with normal renal function is controversial.

More antidotes for newer blood thinners

The wait is over for an antidote to stop rare uncontrolled bleeding linked to some newer blood thinners.

Reversal agents for direct-acting oral anticoagulants

DOACs have several benefits over vitamin K antagonists (VKAs) and heparins. DOACs have quicker onset of action, can be taken by mouth, in general do not require dosage adjustment, and have fewer dietary and lifestyle modifications, compared with VKAs and heparins.

Reversal agents for non-vitamin K antagonist oral anticoagulants

The non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban, and rivaroxaban, which inhibit coagulation factor Xa.

Reversing DOACs: New guidance

New guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, discusses indications for reversal, explains how the individual reversal agents should be administered, and offers suggestions for stewardship at the health system level.

Roles of Four-Factor Prothrombin Complex Concentrate in the Management of Critical Bleeding

4F-PCC has proven to be an effective hemostatic agent compared to plasma transfusion in several prospective randomized trials in acute warfarin reversal. In recent years, 4F-PCC has been used in various acquired coagulopathies including post-cardiopulmonary bypass bleeding, trauma-induced coagulopathy, coagulopathy in liver failure, and major bleeding due to anti-FXa (anti-Xa) inhibitors (eg, rivaroxaban and apixaban).