What are the anesthesia considerations for a patient with lymphoma taking zanubrutinib (Bruton's tyrosine kinase inhibitor) prior to elective surgery?

Anesthesia Considerations for Zanubrutinib Prior to Elective Surgery

Hold zanubrutinib 3-7 days before elective surgery and resume when hemostasis is secure and oral intake is tolerated postoperatively. This perioperative interruption minimizes bleeding risk while avoiding prolonged treatment gaps that could compromise disease control.

Preoperative Management

Timing of Discontinuation

• Discontinue zanubrutinib 3-7 days prior to elective surgical procedures to reduce perioperative bleeding risk 1, 2
• The specific duration within this window should be determined by:
  • Bleeding risk of the procedure (higher risk procedures warrant 7-day hold) 1
  • Patient's baseline platelet count and bleeding history 1
  • Concurrent anticoagulation or antiplatelet therapy 1

Critical Preoperative Assessment

• Obtain complete blood count with differential to assess for neutropenia, which occurs in 29% of patients (grade ≥3 in 20%) 3, 1
• Evaluate for thrombocytopenia, present in approximately 11% of patients 3
• Screen for anemia (occurs in 12% of patients) 3
• Assess cardiac status, particularly for atrial fibrillation, though zanubrutinib has a favorable 4% incidence compared to 17% with ibrutinib 3, 1

Anticoagulation Considerations

• Zanubrutinib should never be combined with warfarin due to excessive bleeding risk 1, 2
• If anticoagulation is required perioperatively, use alternative strategies rather than warfarin 1, 2
• Carefully evaluate benefit-risk in patients requiring any anticoagulation, as overall bleeding risk is 26-39% for any grade and 2% for grade ≥3 1

Intraoperative Considerations

Bleeding Risk Management

• Anticipate increased bleeding tendency even after appropriate drug discontinuation, as zanubrutinib affects platelet function through BTK inhibition 1, 4
• Have blood products readily available, particularly in patients with baseline cytopenias 3, 1
• Consider case reports of hemorrhagic complications, including rare but serious events like hemorrhagic pleural effusion 5

Anesthetic Technique Selection

• Regional anesthesia requires careful consideration due to bleeding risk, particularly neuraxial techniques 1
• General anesthesia may be preferred for procedures where regional techniques pose unacceptable bleeding risk 1

Postoperative Management

Resumption of Therapy

• Resume zanubrutinib as soon as hemostasis is secure and oral intake is tolerated 1, 2
• Do not delay resumption unnecessarily, as prolonged interruption risks disease progression in lymphoma patients 2
• No dose adjustment or bridging strategy is required upon resumption 2

Monitoring Requirements

• Monitor complete blood count closely postoperatively, as neutropenia may require granulocyte colony-stimulating factor support 3, 1, 2
• Assess for bleeding complications, particularly in the first 48-72 hours after resumption 1, 5
• Watch for infection, as 29% of patients experience grade 3-4 infections on long-term therapy 3

Common Pitfalls to Avoid

• Do not confuse zanubrutinib management with antiretroviral therapy, which should be continued perioperatively—these are entirely different drug classes requiring opposite approaches 6
• Do not assume zanubrutinib has the same cardiac toxicity profile as ibrutinib—zanubrutinib has a 4-fold lower atrial fibrillation rate (4% vs 17%) 3, 1
• Do not overlook the higher neutropenia risk with zanubrutinib compared to ibrutinib (29% vs 13% any grade; 20% vs 8% grade ≥3), which may complicate postoperative recovery 3, 1
• Do not combine with warfarin perioperatively—this combination is contraindicated 1, 2
• Do not hold the drug "just to be safe" for extended periods—balance bleeding risk against disease progression risk, particularly in aggressive lymphomas 2

Special Populations

Patients with Cardiac Risk Factors

• Zanubrutinib is preferred over ibrutinib in patients with pre-existing cardiac disease due to lower atrial fibrillation rates 3, 2
• Continue standard cardiac monitoring perioperatively, though cardiac toxicity is significantly reduced compared to first-generation BTK inhibitors 3, 1

Patients with Baseline Cytopenias

• Consider preoperative G-CSF support in patients with grade ≥3 neutropenia 3, 1, 2
• Delay elective surgery if possible in patients with severe thrombocytopenia until counts improve 3
• Coordinate with hematology/oncology for optimal timing of surgery relative to blood count nadirs 2