Atrial Fibrillation and Anticoagulation: Bleeds Happen, Antidotes Needed

Several new anticoagulants have entered the US market in recent years, but research to find reversal agents for these drugs is ongoing.

Patients who have atrial fibrillation (AF) often require anticoagulation. A review article published in the August issue of Clinical and Applied Thrombosis/Hemostasis sheds light on our growing selection of anticoagulants and their most frequent side effect: bleeding. Researchers from Albany College of Pharmacy and Health Sciences assembled available information to address bleeding with approved or experimental antidotes or supportive care.

The researchers discuss the 50 years of experience we have with the vitamin K antagonist warfarin. Vitamin K antagonists are effective, available in oral and intravenous dosage forms, and have known antidotes (withholding a dose, administering vitamin K or plasma-derived products) if hemorrhage occurs. Their limitations—food/drug interactions and the need for frequent monitoring—are well documented. Research has found that patients are in the therapeutic window only slightly more than 60% of the time. The authors stress using conservative approaches when warfarin is employed, as its aggressive use is more likely to result in bleeding.

The oral Factor Xa inhibitors rivaroxaban and apixaban have been approved for fewer indications than warfarin, but the list is growing as research results become available. These agents are quite similar, and also increase bleeding risk. The FDA has not approved an agent to reverse bleeding associated with oral Factor Xa inhibitors. The authors review supportive care and plasma-derived products that have been used in healthy volunteers; more research is needed in clinical trials settings.

One direct thrombin inhibitor, dabigatran, is available. Should uncontrolled bleeding occur, several interventions to decrease blood loss may be employed after aPTT and TT levels are determined. Activated charcoal reduces dabigatran absorption from the gastrointestinal tract if the patient’s last dose was within the previous 2 hours. In mild bleeds, clinicians can use tranexamic acid to inhibit the binding of plasmin to fibrin. Supportive measures to maintain renal perfusion and urine output can accelerate dabigatran elimination.

Several studies are underway to identify appropriate antidotes for use when bleeding occurs with the newer agents.

The article provides a comprehensive review of available information, discussing clinical situations that are apt to occur and potential patient concerns about interventions.