Periprocedural Management of Chronically Anticoagulated Patients: A Practical Approach to Use of Novel Anticoagulants in Orthopedic Surgery

Conclusion

Compared with warfarin, the NOACs dabigatran, rivaroxaban, and apixaban are efficacious and safe. Because of their steady pharmacokinetics, they do not require regular coagulation testing, as is the case with warfarin. These NOACs have been approved for the prevention of stroke and thromboembolic events in patients with nonvalvular AF; rivaroxaban has also been approved for VTE prevention after total hip or knee arthroplasty, for DVT treatment, and for prevention of recurrent VTE after acute DVT. Other options for VTE prophylaxis after hip and knee surgery are addressed in the guidelines issued by the American Academy of Orthopaedic Surgeons in 2011.¹² As the incidence of chronic anticoagulation continues to increase among patients undergoing TJA, orthopedic surgeons need to be aware of the mechanism of action of these NOACs, as well as their pharmacokinetics and available reversal agents. Aggarwal and colleagues1 found that AF patients undergoing TJA had longer hospital stays, increased transfusion requirements, and increased risk for periprosthetic joint infection and unplanned hospital readmission.

The anticoagulation tests recommended for evaluation of hemostasis and drug reversal are normalization of aPTT for dabigatran; PT for rivaroxaban; and chromogenic anti–factor Xa activity for apixaban³ (Table 2). Although several research projects are being planned to develop an antidote for these medications, no antidote has been approved for human trials. The coagulation agents currently being used for reversal of NOACs are nonactivated PCC (Kcentra, Bebulin) and aPCC. Kcentra is a 4-factor PCC (II, VII, IX, X), and Bebulin is a 3-factor PCC (II, IX, X). Most authors recommend using 4-factor PCC 25 to 50 IU/kg. In vivo studies and animal studies have shown that nanofiltered aPCC (Feiba NF) at doses of 30 to 50 IU/kg can to some extent reverse anticoagulation in patients receiving NOACs. The current, limited data support use of reversal agent PCC for rivaroxaban and apixaban (no human studies for apixaban) and use of aPCC for dabigatran.^3,6,8 Activated charcoal can be used for patients who have taken dabigatran <6 hours before presentation.³ Hemodialysis is another option for dabigatran removal. Hemodialysis, however, takes 4 to 6 hours or longer to remove about 60% of the medication (Table 2).^3,5

In major orthopedic surgeries, such as TJA, bleeding is a critical concern. Using reversal agents to overcome the anticoagulation effect adds to the potential concern for thromboembolism secondary to these agents. Therefore, in cases in which surgery cannot be delayed any longer, the decision to use reversal agents should be made on a case-by-case basis. For most patients on rivaroxaban or apixaban, it is sufficient to delay for 24 to 48 hours before proceeding safely with surgery; for dabigatran, a delay of 3 to 4 days is recommended. Delay before surgery may need to be extended for the elderly and for patients with renal failure. The pharmacokinetics of these medications is summarized in Table 1.

There are no guidelines for perioperative management of patients undergoing elective, urgent, or emergent surgeries while on NOACs. As discussed, Pernod and colleagues6 proposed better perioperative management of major bleeding risks in patients receiving rivaroxaban or dabigatran. Adapting their approach, and using the data available from the medical literature, we propose a perioperative algorithm that can guide practicing orthopedic surgeons performing urgent and emergent surgeries (Figure).

The population of patients receiving chronic anticoagulation therapy is growing, and anticoagulant and antiplatelet options are increasing in the United States and around the world. We propose a team approach for patient care, with orthopedic surgeon and cardiologist or vascular medicine specialist collaborating to ensure the safety and effectiveness of this treatment.