Major bleeding owing to the residual effect of apixaban was the major concern in the present case; however, the volume of blood loss was 440 mL, and red blood cell transfusion was not required perioperatively. Although a percutaneous technique for posterior spine fusion might contribute to the moderate amount of bleeding, the perioperative bleeding risk for spine surgery is usually recognized as high [6]. The principles of perioperative management of antithrombotic therapy are interruption of antithrombotic drugs before surgery and prompt resumption after confirmation of surgical hemostasis. The European Heart Rhythm Association recommends 48 h or longer for the interruption period for direct oral anticoagulants before high-bleeding-risk interventions including spine surgery [7], although the timing of resumption depends on the balance between the risks of thrombosis and postprocedural bleeding in each patient. The present patient continued apixaban until the night before surgery; the duration between the last apixaban dose and the first blood sample collection in the operating room (after anesthesia induction) was 15 h. Given the plasma terminal half-life of apixaban of approximately 10 h [8], we expected that the apixaban plasma concentration would be at approximately trough level at the start of surgery.
The values for PT and APTT after anesthesia induction were slightly prolonged, consistent with the increased plasma concentration of apixaban [9]. However, the relation between the plasma concentration of apixaban and PT or APTT is poor; the slopes of the regression lines are relatively small, indicating that PT and APTT are not particularly sensitive to apixaban [1, 10]. The chromogenic anti-Xa assay is a functional test for anti-Xa activity, which has been reported to correlate well with plasma apixaban concentration [10, 11]. The values of plasma anti-Xa activity after anesthesia induction and at the end of surgery were 1.69 IU/mL and 1.12 IU/mL, respectively, in the present case (Table 1). It has been reported that the trough level of apixaban in patients with a dosage of 5 mg twice daily is 1.0 IU/mL [12,13,14]. Hence, the antithrombotic property of apixaban was considered to be in the therapeutic range during the present surgery. It might be desirable to perform a chromogenic anti-Xa assay to estimate perioperative bleeding risk owing to apixaban; however, it is usually feasible only in a specialized laboratory and has a long turnaround time. We sent blood samples for anti-Xa assay to an outside institution and obtained results several days later.
We examined the potential of an RVV test performed with ClotPro for evaluation of the antithrombotic effect of apixaban because a point-of-care device with a short turnaround time is suitable for the perioperative period. The RVV test has been developed on the same principle as RVV time (RVVT), which is another functional test for the evaluation of anti-Xa activity; RVVT is an assay for the detection of lupus anticoagulants, but it is also affected by anti-Xa drugs, including apixaban, because RVV specifically cleaves factor X to Xa [3, 4, 15]. As shown in Table 1, the results of the RVV test after anesthesia induction showed prolonged CT, which also showed a proportional linear relation to anti-Xa activity in the therapeutic range of apixaban (Fig. 2). These results might indicate feasibility of the RVV test as a point-of-care assay for evaluation of the anticoagulant effect of apixaban, although an appropriate observational study is required to validate its clinical usefulness.
Because the end point for determination of CT is fibrin clot formation, similar to other viscoelastic tests, prolonged CT with an RVV test might not always reflect anti-Xa activity. Considering the coagulation cascade, it could be also affected by anti-thrombin drugs, such as argatroban or dabigatran, or by hypofibrinogenemia. Thus, we also estimated anti-thrombin activity with the ECA and examined the plasma fibrinogen level [5]. The results were consistently in the normal range during the perioperative period, confirming that the prolongation of CT in the RVV test reflected anti-Xa activity owing to apixaban. Thus, it is reasonable to perform the RVV test in combination with the ECA to specifically evaluate anti-Xa activity.
In conclusion, we described the evaluation of the residual anti-Xa effect of apixaban with an RVV test using ClotPro for a patient who had a minimal interruption period of apixaban perioperatively. Given that continuation of anti-Xa drugs is generally accompanied by increased risks of bleeding and transfusion, the point-of-care evaluation of anti-Xa effect could help physicians prepare for massive bleeding. The short turnaround time for the RVV test using ClotPro might be useful for evaluation of the anti-Xa level induced by apixaban during the perioperative period. A future prospective study should elucidate the clinical usefulness of the RVV test.
