How to reverse dabigatran (direct oral anticoagulant, DOAC) anticoagulation?

From the Guidelines

To reverse dabigatran anticoagulation, idarucizumab is the recommended antidote, administered at a dose of 5g, which has been shown to rapidly reverse the anticoagulant effects of dabigatran in patients with life-threatening bleeding or requiring urgent surgery 1. The use of idarucizumab has been evaluated in several studies, including the RE-VERSE AD study, which demonstrated a median reversal of 100% of the anticoagulant effect of dabigatran within four hours of administration 1. Key points to consider when using idarucizumab include:

• Idarucizumab has a half-life of 45 minutes, which may be prolonged in patients with renal dysfunction 1
• The recommended dose of idarucizumab is 5g, without adjustment for age, plasma concentration of dabigatran, renal or hepatic function 1
• Idarucizumab can cause the patient to develop antibodies, which may limit its repeated use 1
• In some cases, a second dose of idarucizumab may be necessary, such as in patients with ongoing bleeding or those requiring a second surgical procedure 1 Overall, idarucizumab is a highly effective antidote for reversing dabigatran anticoagulation, and its use is recommended in patients with life-threatening bleeding or requiring urgent surgery.

From the FDA Drug Label

Reversal of Anticoagulant Effect: In adults, a specific reversal agent (idarucizumab) for dabigatran etexilate is available when reversal of the anticoagulant effect of dabigatran is needed: For emergency surgery/urgent procedures In life-threatening or uncontrolled bleeding In pediatric patients, the efficacy and safety of idarucizumab have not been established Hemodialysis can remove dabigatran; however the clinical experience supporting the use of hemodialysis as a treatment for bleeding is limited [see Overdosage (10)]. Prothrombin complex concentrates, or recombinant Factor VIIa may be considered but their use has not been evaluated in clinical trials. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of dabigatran Consider administration of platelet concentrates in cases where thrombocytopenia is present or long-acting antiplatelet drugs have been used.

The anticoagulation effect of dabigatran can be reversed using idarucizumab, a specific reversal agent, in adults. This is recommended for:

• Emergency surgery or urgent procedures
• Life-threatening or uncontrolled bleeding Other options that may be considered include:
• Hemodialysis to remove dabigatran, although clinical experience is limited
• Prothrombin complex concentrates or recombinant Factor VIIa, although their use has not been evaluated in clinical trials
• Platelet concentrates in cases of thrombocytopenia or use of long-acting antiplatelet drugs Note that protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of dabigatran. 2

From the Research

Reversing Dabigatran Anticoagulation

To reverse dabigatran anticoagulation, the following methods can be considered:

• Discontinuation of dabigatran: In patients with normal renal function, discontinuation of dabigatran 24 hours before standard elective surgery is sufficient to normalize the bleeding risk 3.
• Haemodialysis: Dabigatran can be effectively removed from the circulation by haemodialysis, which can be used in cases of severe or life-threatening bleeding 3.
• Prothrombin complex concentrates: In cases of moderate or major bleeding, prothrombin complex concentrates can be administered to help stabilize the circulation, but their effect should be monitored clinically rather than relying on standard laboratory coagulation parameters 3.

Perioperative Management

Perioperative management of dabigatran involves:

• Standardized interruption protocol: A standardized interruption protocol can yield 80-86% of patients with no residual anticoagulant effect at the time of surgery or procedure 4.
• Assessment of coagulation tests: Coagulation tests such as aPTT, TT, and dTT can be used to assess the residual anticoagulant effect, but their utility may be limited in determining whether dabigatran concentrations are below a 'safe' threshold for surgery 5.
• Bridging therapy: Dabigatran can be used as bridging therapy while optimizing warfarin dosage for cardioembolic stroke, offering the advantage of oral administration, lower cost, and possibly lower bleeding risks compared to heparin 6.

Considerations

When reversing dabigatran anticoagulation, the following considerations should be taken into account:

• Renal function: Patients with renal impairment may require a longer duration of dabigatran discontinuation before surgery or procedure 3.
• Bleeding risk: The risk of bleeding should be weighed against the risk of thrombosis, and the management plan should be individualized based on the patient's constitution and the planned intervention 7.
• Monitoring: Patients should be monitored for bleeding and thromboembolic events after dabigatran discontinuation or reversal 4, 5.