Reversal of anticoagulation requires basic knowledge of underlying physiology of hemostasis, as well as obtaining a thorough history. A key piece of information is the timing of the last dose of anticoagulant agent. This is particularly important for DOAC agents where testing for degree of anticoagulation is not easily obtained or timely. Reversal agents for DOAC drugs are generally not indicated if the last known dose was greater than 18 hours prior to presentation. When real-time anti-Xa activity testing becomes widely available it will be very helpful in guiding the need for reversal when the last known dose is not available. If TEG/ROTEM is available, the results may likewise be helpful in this setting.
One of the most important overriding questions is this: "Does reversal of anticoagulation really have a clinically relevant benefit to the patient?" Most of the literature published on specific reversal agents such as 4-factor PCC, idarucizumab and andexanet focus on the agent's ability to normalize tests of coagulation (INR, PTT, etc). Improvement in predetermined clinical markers of bleeding has been demonstrated by looking at the decrease in hematoma growth and limitation of a drop in hemoglobin. Finally, there are suggestions in the literature, mostly based on observation, that there appears to be less bleeding in patients for whom anticoagulation is reversed. A leap is then often made to imply that less bleeding directly translates into improved morbidity and/or mortality. A morbidity or mortality benefit, however, has not yet been definitively demonstrated. It is critical to determine if expensive reversal agents that may promote thrombosis are actually beneficial.
Randomized studies of a particular reversal agent vs placebo in bleeding patients will likely never be performed due to ethical concerns. Future studies should report individual patient data and describe detailed outcomes of patients receiving reversal agents, possibly comparing them to historical controls in the era prior to specific reversal agents. Future directions, including further evaluation of ciraparantag and andexanet alfa, especially regarding morbidity and mortality are hopefully in the pipeline. Additional research into the utility of TEG/ROTEM to guide transfusion of blood products and its effects on mortality are also warranted.
Western J Emerg Med. 2019;20(5):770-783. © 2019 Western Journal of Emergency Medicine