The correct answer is: C. Stop apixaban two days before surgery and then resume two or three days after the procedure; consider bridging with LMWH after surgery if the patient is unable to take oral medications post-operatively.

The management of anticoagulation in AF patients undergoing surgery is challenging because it requires a balance between the competing risks of thromboembolism and bleeding. In fact, both thromboembolic and bleeding events are known to adversely affect mortality;¹ hence, both inadequate and excessive anticoagulation contribute to higher mortality.

In everyday clinical practice, a stepwise approach seems reasonable.² First, the patient's thromboembolic risk should be considered in order to minimize the interval without anticoagulation, or to delay elective surgery if the risk is transiently increased (i.e., in case of stroke or transient ischemic attack within three months). The thromboembolic high-risk stratum includes patients with a CHADS₂ score ≥5 (or CHA₂DS₂-VASc score ≥6), patients with prior thromboembolism during temporary interruption of anticoagulation, or patients undergoing surgery associated with an increased risk for thromboembolism (i.e., cardiac valve replacement, carotid endarterectomy, or major vascular surgery).³ Second, it is crucial to assess the bleeding risk, which is essentially related to the type of surgery and to specific patient features (i.e., kidney function, age, history of bleeding complications, and concomitant medication). Table 1 summarizes the bleeding risk according to type of surgery.⁴

Table 1: Bleeding Risk According to Type of Surgery

Low Bleeding Risk Procedure (2-day risk of major bleeding 0-2%)	High Bleeding Risk Procedure (2-day risk of major bleeding 2-4%)
Pacemaker and cardiac defibrillator insertion	Cardiac surgery
Electrophysiologic testing	Vascular surgery
Hydrocele repair	Neurosurgical surgery
Eye surgery	Urologic surgery
Knee/hip replacement	Bilateral knee replacement
Shoulder/foot/hand surgery and arthroscopy	Laminectomy
Cholecystectomy	Head and neck surgery
Abdominal hysterectomy	Surgery for breast cancer
Gastrointestinal endoscopy ± biopsy	Polypectomy
Abdominal hernia repair	Variceal treatment
Bronchoscopy ± biopsy	Biliary sphincterectomy
Hemorrhoidal surgery	Endoscopically-guided fine-needle aspiration
Skin cancer excision	Any major operation with a duration >45 min
Bladder/prostate/thyroid/breast/lymph node biopsies	Multiple tooth extractions

Unfortunately, data comparing the relative benefits of continuing versus interrupting anticoagulation are limited, and a case-by-case approach is advisable. Answer option E is incorrect because in general, anticoagulation should be discontinued if the surgical bleeding risk is high. However, for patients at high thromboembolic risk, the period without anticoagulation should be as short as possible. Conversely, in the case of selected procedures that carry a low bleeding risk, it may be reasonable to continue anticoagulation (i.e., cataract surgery or minor dermatologic or dental procedures).^3,5

Perioperative Management of Novel Oral Anticoagulants (NOACs)

With the introduction of NOACs (e.g., direct thrombin inhibitor dabigatran; factor Xa inhibitors rivaroxaban, apixaban, and edoxaban), health care providers are facing a radical change in the perioperative management of anticoagulation. In fact, these new agents have short half-lives, making them easier to discontinue and resume rapidly, and do not require routine laboratory monitoring.

A growing body of evidence has begun to provide guidance in this setting, although recommendations remain largely based on extrapolations from pharmacokinetic/dynamic data and expert opinions. Data from the Dresden NOAC Registry reassure that either continuation, or short-term interruption, of anticoagulation are safe strategies for most invasive procedures with 30-day rates of major cardiovascular events, and major bleeding of 1.0% and 1.2%, respectively.⁶

The discontinuation algorithm suggests interrupting NOACs 24 hours before the elective procedure if the bleeding risk is low. In the case of procedures that carry a risk for major bleeding, it is recommended to take the last dose 48 hours before the procedure. For dabigatran, which is 80% renally cleared, a more graded pre-intervention termination depending on creatinine clearance is indicated both for low- and high-risk interventions. For oral factor Xa inhibitors, which are 30-50% renally cleared, a longer duration of cessation is necessary only for patients with a significant renal impairment (creatinine clearance <30 mL/min). The timing of postoperative resumption must account for patient-specific and operative factors, such as the type of procedure and adequacy of hemostasis. Moreover, physicians should keep in mind that NOACs reach their peak effect within one to four hours of administration, and to date, no specific reversal agents are available. Therefore, for patients undergoing low-risk procedures, the anticoagulant could be resumed after 24 hours. In contrast, in cases of interventions with a high risk of bleeding, resumption of anticoagulation should be deferred at a minimum of 48-72 hours, and only after adequate hemostasis is assured. Therefore, answer options A and B are incorrect. These recommendations are summarized in Table 2.^5,7-13

Table 2: Perioperative Management of NOACs According to Bleeding Risk^5,7-13

	DABIGATRAN	RIVAROXABAN	APIXABAN	EDOXABAN
Timing of Cessation Prior to Procedure
High Bleeding Risk	≥48 hours if CrCl >60 mL/min (i.e., skip 4 doses) OR ≥96 hours if CrCl 15-60 mL/min (i.e., skip 8 doses)	≥48 hours  (i.e., skip 2 doses)	≥48 hours  (i.e., skip 4 doses)	≥48 hours  (i.e., skip 2 doses)
Low Bleeding Risk	≥24 hours if CrCl >60 mL/min (i.e., skip 2 doses) OR ≥48 hours if CrCl 15-60 mL/min (i.e., skip 4 doses)	≥24 hours  (i.e., skip 1 dose) OR ≥36 hours if CrCl 15-30 mL/min (i.e., skip 1 dose)	≥24 hours  (i.e., skip 2 doses) OR ≥36 hours if CrCl 15-30 mL/min (i.e., skip 3 doses)	≥24 hours  (i.e., skip 1 dose) OR ≥36 hours if CrCl 15-30 mL/min (i.e., skip 1 dose)
Resumption After Procedure
High Bleeding Risk	Resume 48-72 hours after surgery
Low Bleeding Risk	Resume 24-hours after surgery

Coagulation testing, either specific (diluted thrombin time or specific anti-Xa activity), or non-specific (i.e., activated partial thromboplastin time and prothrombin time), may be helpful in the preoperative setting, especially in selected patients, such as those undergoing emergency procedures or surgery at high risk for bleeding. However, their role has not yet been validated, and as such, answer option A is incorrect.^7,10

Given some similar pharmacokinetic properties of NOACs compared to LMWH, such as short time to onset and short half-lives, the utility of bridging therapy becomes marginal. In this regard, a separate analysis of patients receiving dabigatran in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial confirmed that bridging significantly increases major bleeding (6.5% vs. 1.8%; p <0.001) with no effect on thromboembolic events (0.6% vs. 1.2%; p = 0.16).¹⁴ Moreover, the routine use of this strategy in vitamin K antagonist (VKA)-treated patients has been recently discouraged by results of the Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery (BRIDGE) trial, which randomized 1,884 patients to periprocedural bridging anticoagulation with LMWH or matching placebo.¹⁵ At 30-day follow-up, warfarin discontinuation was demonstrated to be non-inferior to the use of bridging anticoagulation for the prevention of thromboembolism (0.4% vs. 0.3%; p = 0.01 for non-inferiority); in addition, bridging conferred a three-fold risk of major bleeding compared to no bridging (3.2% vs. 1.3%; p = 0.005 for superiority).¹⁵ Therefore, according to current evidence, we may consider bridging only for patients unable to promptly resume NOACs in the postoperative period (i.e., those with post-operative ileus), and as such, answer option B is incorrect.

Finally, considering that cancer increases not only the risk of bleeding,especially if located in the gastrointestinal tract, but also the risk of stroke, full-dose anticoagulation should be resumed postoperatively; however, dose reduction due to recent surgery is not required since this exposes the patient to increased risk of thromboembolism at a time when the risk is high. For this reason, answer option D is incorrect.⁷ However, given the lack of specific data from randomized trials regarding this subgroup of patients, physicians should instruct them to carefully monitor and promptly report signs of bleeding (i.e., petechiae, hemoptysis, black stools).

References

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