When should apixaban (direct oral anticoagulant) be stopped prior to hepatic surgery for cancer?

Perioperative Management of Apixaban Before Hepatic Surgery for Cancer

Apixaban should be discontinued 2 days before hepatic surgery for cancer, as it is considered a high bleeding risk procedure involving a highly vascular organ. 1, 2

Classification of Hepatic Surgery for Cancer

• Hepatic surgery for cancer is classified as a high bleeding risk procedure due to the liver being a highly vascular organ 1
• Surgery in highly vascular organs like the liver falls into the high-bleed-risk category according to the American College of Chest Physicians guidelines 1

Preoperative Management of Apixaban

Standard Timing for Discontinuation

• For high bleeding risk procedures like hepatic surgery:
  • Stop apixaban 2 days before surgery (skip 4 doses) for patients with normal or mildly impaired renal function (CrCl ≥50 mL/min) 1, 2
  • This corresponds to approximately 4-5 half-lives of apixaban, allowing for minimal (≤6%) residual anticoagulant effect at the time of surgery 1, 2

Special Considerations

• For patients with moderate renal impairment (CrCl 30-50 mL/min):

  • Consider extending the interruption period to 3 days before surgery (skip 6 doses) 1, 2
  • Although apixaban is less dependent on renal clearance (25%) than other DOACs, longer interruption may be warranted in patients with impaired renal function 2

• For patients with hepatic impairment:

  • Consider longer discontinuation periods for patients with moderate hepatic impairment as the area under the plasma concentration-time curve (AUC) of apixaban may be increased by 1.09-fold 3
  • Apixaban should be used with caution in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment 3

Pharmacokinetic Considerations

• Apixaban has a half-life of 7-8 hours in patients with normal renal function 1, 2
• Approximately 25% of apixaban is cleared renally, making it less dependent on kidney function than some other DOACs 2, 3
• In a prospective observational study, discontinuation of apixaban for at least 48 hours before surgery resulted in clinically insignificant levels of anticoagulation (≤30 ng/mL in 94% of patients) 4

Postoperative Resumption

• Resume apixaban 2-3 days (48-72 hours) after hepatic surgery, once adequate hemostasis has been established 2, 5
• Wait at least 24 hours after the end of surgery before considering resumption of apixaban 1, 5
• For patients at high risk for thromboembolism, consider using a reduced dose (2.5 mg twice daily) for the first 2-3 days after resumption 2

Bridging Anticoagulation

• Bridging anticoagulation with heparin or low-molecular-weight heparin is not recommended during the perioperative period for patients on apixaban 1, 2
• The rapid offset and onset of action of apixaban obviates the need for bridging with short-acting anticoagulants 1

Monitoring Considerations

• Routine coagulation tests like INR or aPTT may be insensitive to residual apixaban effect 1
• If needed, DOAC-calibrated anti-factor Xa levels can be used to measure apixaban levels before surgery 1
• Consider measuring apixaban levels if surgery is urgent (within 24 hours) 1

Cancer-Specific Considerations

• Cancer patients have an increased risk of both thromboembolism and bleeding 6, 7
• Studies suggest that DOACs, including apixaban, are promising alternatives to LMWH for VTE prophylaxis after cancer surgery 6
• Apixaban has shown good adherence for extended thromboprophylaxis after major abdominal cancer surgery 7

By following these guidelines for perioperative management of apixaban before hepatic surgery for cancer, clinicians can minimize the risk of both perioperative bleeding and thrombotic complications.