The Fellow on Call: The Heme/Onc Podcast

Episode 133: VTE Series – Perioperative Anticoagulation Management and Emergent Reversal
Date: April 9, 2025
Hosts: Ronak (A), Vivek (B), Dan (C)

Episode Overview

This episode dives into the perioperative management of anticoagulation, with a special focus on practical strategies for holding, bridging, and reversing anticoagulation in patients with venous thromboembolism (VTE), particularly around surgical procedures. The hosts walk through detailed case-based scenarios, evidence-based recommendations, and the nuances of emergent anticoagulant reversal. The discussion is geared toward guiding physicians, trainees, and advanced practice providers through “bread and butter” decision-making in hematology and oncology clinics.

Key Discussion Points and Insights

1. Importance of Perioperative Anticoagulation Management

• Routine in Clinical Practice: Managing anticoagulation around procedures is a daily practice in hematology clinics. (03:33)
• Early Planning: Always ask patients about upcoming procedures and aim for 4–6 weeks of advance notice when possible.

2. Collaborative Decision-Making

• Procedure Team’s Role: Only the proceduralists truly know the bleeding risks of the planned intervention.

  • “[They] have to tell me whether or not they need the blood thinner held during that procedure…they know when it’s safe to reintroduce anticoagulation based on what they experience during that procedure.” — Dan [03:33]

• Case Example:

  • 58-year-old man with a recent DVT/PE on apixaban, now requiring a biliary stent exchange.
  • GI proceduralist reaches out for anticoagulation guidance.
  • Interprofessional communication is crucial to tailor the plan.

3. Evidence-Based Approach to Holding Anticoagulation

• Warfarin/Fondaparinux: Hold for 5 days prior to most procedures.
• DOACs (Apixaban, Rivaroxaban, etc.):
  • PAUSE Trial: 1 day hold for low bleeding risk, 2 days for high risk.
    • In practice, proceduralists often request longer holds (up to 5 days) out of habit.
• Lovenox (Enoxaparin): 24-hour washout is typical.
• Heparin and Direct Thrombin Inhibitors (Argatroban/Bivalirudin): Hold for 1–2 hours prior to procedure, may extend to 4 hours depending on specifics.

4. Bridging Anticoagulation: Who Needs It?

• Most Patients Don’t:

  • “The moral of the story is the majority of patients will not need a bridge.” — Ronak [07:59]
  • Those with atrial fibrillation, atrial flutter, or VTE >3 months ago typically do not need bridging (supported by BRIDGE and PERIOP2 trials).

• Indications:

  • Recent VTE (<3 months) — Try to postpone procedures until after 3 months.
  • Recurrent VTE or high-risk conditions: e.g., antithrombin III deficiency, triple-positive antiphospholipid syndrome.
  • Mechanical heart valves and certain cardiac scenarios: Always involve cardiology.

• Absolute Bridging Indication: History of warfarin skin necrosis.

• Key Trials:

  • BRIDGE Trial: No difference in embolic events with or without bridging for AF on warfarin; bridging increased major bleeding. [08:24]
  • PERIOP2: Included patients with mechanical valves; again, no difference in events — but underpowered for this subgroup.

5. How to Bridge: Practical Details

• Agent of choice: Enoxaparin (Lovenox) for most.

• Timing:

  • For warfarin, first enoxaparin at the time of the second missed warfarin dose.
  • For DOACs, after the third missed dose.

• Clear Instructions: Use SmartPhrases or templates specifying exact dates, times, and dosages (“You don't want confusion when it comes to blood thinners.” — Dan [14:28])

• Special Situations:

  • Renal dysfunction or HIT: Enoxaparin may not be possible; admit for IV heparin or direct thrombin inhibitor (bivalirudin) bridging.
  • Providers may be surprised by the need for prolonged hospital admission even for elective/screening procedures in these complex cases.

6. Emergent Reversal of Anticoagulation

Workup

• First Step: Check if the anticoagulant is still active using anti-10A levels or modified thrombin time for dabigatran, as appropriate. Only reverse if the drug is present. [19:39]

Reversal Agents

• DOACs (Factor Xa inhibitors like apixaban, rivaroxaban):
  • Limited options: Practical reversal is usually with prothrombin complex concentrate (PCC).
  • Andexanet alfa (Andexxa): Technically available, but limited by cost, continuous infusion requirements, and ambiguous clinical benefit. Not on formulary at many centers. [22:32]
• Dabigatran: Reversed by idarucizumab (Praxbind), where available.
• Warfarin:
  • Vitamin K (to restart synthesis),
  • PCC (for rapid effect),
  • Plasma in specific scenarios.
• Heparins:
  • Protamine sulfate reverses unfractionated heparin (fully) and enoxaparin (partially). Calculation for dosing is complex and risk of overshooting/instability.
• Fondaparinux: No good reversal; treat like DOACs — use PCC, accept limitations.

Risks of Reversal

• Thrombotic Risk: Both PCC and andexanet alfa increase risk of thrombotic events post-reversal.
  • "When you give something like andexanet alfa, you’re getting double the rates of thrombotic events." — Vivek [22:57]
  • PCC also carries a non-trivial risk; should be reserved for life-threatening bleeding, not minor events. [31:52]

Real-World Constraints

• Andexanet alfa data:
  • ANNEXA-4 (single-arm study) showed good hemostasis but high rates of thrombosis.
  • ANNEXA-I (RCT): Better hematoma stability for intracranial hemorrhage, but double the rate of thrombosis without clear improvement in long-term clinical outcomes.

7. Closing Management Pearls

• Reversal isn’t always indicated: Only attempt reversal for life-threatening or critical bleeding, not for minor bleeds.
• Anticoagulation should be resumed only after multidisciplinary discussion, especially if the patient’s goals of care have shifted, as in the presented case.

Notable Quotes & Memorable Moments

• On the procedural team’s role:

  • “Only the team doing the procedure truly knows the full extent of the bleeding risk associated with that procedure.” — Dan [03:33]

• On bridging necessity:

  • “The moral of the story is the majority of patients will not need a bridge.” — Ronak [07:59]

• On using andexanet alfa:

  • “It’s very costly... you have to have this continuous infusion... what we found was the patients who got this andexanet alpha... yes, we were able to normalize the activity of their factor 10A... but there’s also an increased risk of thrombosis.” — Vivek [22:59]

• Reversing heparin is tricky:

  • “[Protamine] at higher doses can actually cause hemodynamic instability...eventually has an anticoagulant effect if you overshoot by too much, so making a situation that was already bad even worse.” — Dan [28:39]

• Clinical decision-making:

  • “We don’t just reverse anticoagulation because someone nicks themselves shaving...This has to be life threatening in order for us to take the measures because they’re on blood thinners for a reason.” — Dan [31:52]

Timestamps for Important Segments

• Case introduction: [02:49]
• Approach to holding anticoagulation for procedures: [03:33]
• Bridging: evidence & practicalities: [07:59]
• How and whom to bridge: [13:15]
• Bridging in special populations: [16:28]
• Complex bridging/hospitalization needs: [16:56]
• Emergent reversal: approach & agents: [19:39]
• Andexanet alfa evidence & controversy: [22:32]
• Reversal of warfarin and heparins: [26:36]
• Reversal protocol math: [28:39]
• Case wrap-up and pearls: [30:57]
• Final summary and main takeaways: [31:52, 33:36]

Final Recap / Summary

• Advance planning and interdisciplinary collaboration are vital for safe perioperative management.
• The need for bridging anticoagulation is uncommon and should be reserved for high-risk scenarios.
• Clear, unambiguous instructions for medication management around procedures are essential to avoid dangerous errors.
• Emergent reversal should only be attempted in life-threatening bleeding, with awareness of the limitations and risks of available agents.
• Always weigh the risks and benefits and involve the whole care team—including cardiology and proceduralists—when making decisions.
• Stay updated on protocols and newer reversal agents, but apply with caution given evolving evidence and significant risks.

For practical tools and specific dosage templates, refer to the episode show notes linked on [the podcast’s website].