Management of Special Situations That May Arise in the Use of Dabigatran
Switching From Warfarin to Dabigatran and Vice Versa
When converting patients from warfarin to dabigatran, it is recommended that dabigatran be started once the INR falls below the lower limit of the desired therapeutic range. Conversely, when switching from dabigatran to warfarin, the manufacturer recommends starting warfarin based on renal function ( Table 2 ). It should be noted that because dabigatran can increase the INR, the INR will better reflect warfarin's effect after dabigatran has been stopped for at least 2 days.
Bridging From Dabigatran to Parenteral Anticoagulants and Vice Versa
For patients currently receiving a parenteral anticoagulant, the manufacturer recommends starting dabigatran 0–2 hours before the next administration time for parenteral anticoagulants (eg, LMWH) or at the time of discontinuation for continuously infused parenteral drugs (eg, intravenous UFH). For patients currently taking dabigatran who are transitioning to a parenteral anticoagulant, it is recommended to wait 12 hours (CrCl ≥30 mL/min) or 24 hours (CrCl <30 mL/min) after the last dose of dabigatran before initiating treatment with a parenteral anticoagulant.
Management of Dabigatran Before Elective and Urgent Invasive Procedures
Patients who undergo invasive procedures in the presence of therapeutic levels of dabigatran are at an increased risk of bleeding. The manufacturer recommends holding dabigatran for at least 24 hours before elective surgery depending on the degree of renal impairment and the risk of bleeding.Table 3 lists recommendations on the timing of discontinuation of dabigatran before a procedure. If emergent/urgent surgery is necessary for a patient who is on dabigatran, the risk of bleeding should be weighed against the urgency of the intervention. As mentioned earlier, the ECT or the Hemoclot® Thrombin Inhibitor assay are the preferred tests for measurement of dabigatran effects, but they are not standardized or widely clinically available. Instead, prolongation of the TT (preferably) or the aPTT can be used to determine the presence of dabigatran.
Overdose and Toxicity With Dabigatran
Accidental or intentional overdose, or accumulation of dabigatran due to renal impairment, may lead to hemorrhagic complications. Unlike warfarin and heparin, there is no antidote for dabigatran. There are no widely available, reliable laboratory tests to measure the anticoagulant activity of dabigatran, and evidence-based guidelines to manage dabigatran toxicity do not exist. Therefore, in the event of dabigatran toxicity, treatment is largely supportive. Management of toxicity is dependent on whether the overdose/accumulation is accompanied by bleeding or not. For overdose, interventions include adequate diuresis and the use of activated charcoal to reduce the absorption of dabigatran (within 2 hours of ingestion). In the event of bleeding, proposed measures include application of mechanical pressure to the sites of bleeding and infusion of pro-coagulant blood products such as activated prothrombin complex concentrates (eg, FEIBA VH®, Baxter) or recombinant human activated factor VIIa (NovoSeven®, Novo-Nordisk) (reviewed in references 26 and 42). In life-threatening situations, hemodialysis could be considered, because it can remove ≈60% of the drug within 2–3 hours. Hemoperfusion over a charcoal filter or large volume hemofiltration have also been suggested in extreme situations. Acknowledging their limitations, the ECT, TT, or aPTT may be used to direct therapy.
Pregnancy and Dabigatran Therapy
Dabigatran is a class C drug during pregnancy, and there are no studies of dabigatran in pregnant women. Animal studies with dabigatran showed decreased fertility of pregnant rats; therefore, the risks and benefits of dabigatran therapy during pregnancy should be weighed carefully.