How to manage bleeding risk in a patient with atrial fibrillation or deep vein thrombosis on anti-thrombotic therapy, such as warfarin (Coumadin) or novel oral anticoagulants (NOACs) like apixaban (Eliquis) or rivaroxaban (Xarelto), with a high risk of thrombotic events and a high HAS-BLED score?

Managing Bleeding Risk vs. Antithrombotic Drug Withdrawal

In patients with atrial fibrillation or deep vein thrombosis on anticoagulation who have both high thrombotic risk and high HAS-BLED scores, continuing anticoagulation with risk mitigation strategies is strongly recommended over withdrawal, as the mortality benefit from preventing thromboembolism outweighs bleeding risk in most cases. 1

Risk Stratification Framework

High Thrombotic Risk Conditions

The following conditions mandate continued anticoagulation despite bleeding concerns 1:

• Atrial fibrillation with CHA₂DS₂-VASc ≥4: Annual stroke risk of 2.4-5.4%, which is unacceptably high without anticoagulation 2
• Mechanical heart valves: Particularly mitral position, caged ball or tilting disc valves, or any valve with prior stroke/TIA within 6 months 1
• Recent VTE (within 3 months): Includes unprovoked VTE, recurrent VTE, or cancer-associated VTE 1
• Left ventricular or left atrial thrombus 1

HAS-BLED Score Interpretation

A high HAS-BLED score (≥3) should not be used as a reason to withhold anticoagulation, but rather to identify modifiable bleeding risk factors and intensify monitoring. 1 The score includes: Hypertension, Abnormal renal/liver function, Stroke history, Bleeding history, Labile INR, Elderly (>65 years), and Drugs/alcohol 1

Anticoagulant Selection Strategy

For Patients with Normal to Moderate Renal Function

NOACs are preferred over warfarin in patients with high bleeding risk due to lower rates of intracranial hemorrhage and fatal bleeding. 1, 3

• Apixaban 5 mg twice daily (or 2.5 mg twice daily if ≥2 dose-reduction criteria): Lowest overall major bleeding rate among NOACs, particularly favorable for gastrointestinal safety 3, 4
• Dabigatran 110 mg twice daily: Lower bleeding risk than warfarin, though less data in high-risk bleeding populations 1
• Rivaroxaban 20 mg daily: Non-inferior to warfarin for efficacy but with less intracranial hemorrhage (0.5% vs 0.7%) and fatal bleeding (0.2% vs 0.5%) 5

For Patients with Severe Renal Impairment

In end-stage renal disease or dialysis patients, warfarin remains the only recommended anticoagulant (INR target 2.0-3.0), as NOACs lack safety data in this population. 2

• DOACs are contraindicated in CrCl <15 mL/min 2
• For CrCl 15-29 mL/min, apixaban 2.5 mg twice daily may be used with extreme caution 4
• Renal function must be monitored at least annually, or 2-3 times yearly with moderate impairment 4

Risk Mitigation Strategies While Continuing Anticoagulation

Modifiable Bleeding Risk Factors 1

• Blood pressure control: Maintain BP <140/90 mmHg; uncontrolled hypertension significantly increases intracranial hemorrhage risk 1
• Optimize INR control if using warfarin: Target TTR ≥65% (ideally 100%); INR >3.5 dramatically increases intracranial hemorrhage risk 1
• Discontinue NSAIDs and limit aspirin: Avoid concomitant antiplatelet therapy unless absolutely necessary for recent ACS/PCI 1
• Proton pump inhibitor therapy: Mandatory for all patients on anticoagulation, especially with prior GI bleeding 1
• Limit alcohol consumption: Reduces both bleeding risk and medication adherence issues 1

Monitoring Intensity

• Warfarin: INR monitoring weekly during initiation, then monthly once stable 2
• NOACs: Renal function before initiation and annually (more frequently if CrCl 30-49 mL/min) 4
• All patients: Reassess bleeding risk dynamically at every visit, as risk changes over time 1

Management of Active Bleeding While on Anticoagulation

Minor Bleeding

Do not interrupt anticoagulation for self-limiting epistaxis, bruising, or minor hematuria. 1 However, recognize that minor bleeding predicts future major bleeding and warrants risk factor reassessment 1

Major Bleeding

For life-threatening bleeding, immediate reversal is indicated: 1

• Warfarin: 4-factor prothrombin complex concentrate (preferred over fresh frozen plasma) plus vitamin K for sustained reversal 1
• Dabigatran: Idarucizumab 5g IV provides complete reversal within minutes 1
• Factor Xa inhibitors: Consider 4-factor PCC or recombinant factor VIIa 1

Timing of Anticoagulation Resumption After Major Bleeding

The decision to restart anticoagulation balances thrombotic risk against rebleeding risk, with high thrombotic risk favoring early resumption once hemostasis is achieved. 1

Stepwise Approach 1:

1. Days 1-3 post-hemostasis (high thrombotic risk):

   • Start unfractionated heparin IV infusion (short half-life, reversible with protamine) 1
   • Alternative: prophylactic-dose LMWH or UFH subcutaneously to balance risks 1

2. Days 3-7 (moderate-high thrombotic risk):

   • Transition to therapeutic parenteral anticoagulation with close monitoring 1

3. After 7-14 days (stable patients):

   • Resume oral anticoagulation at full therapeutic dose 1
   • For NOACs, can restart within 24 hours of idarucizumab if clinically stable 1

High Rebleeding Risk Exceptions

If rebleeding risk remains prohibitively high despite high thrombotic risk, consider non-pharmacological alternatives: 1

• Left atrial appendage closure devices for AF: Epicardial devices preferred (no post-procedure anticoagulation required) over endocardial devices (require 45 days of therapeutic anticoagulation) 1
• Retrievable IVC filters for acute proximal DVT: Use judiciously and temporarily only 1

Special Consideration: Triple Therapy After PCI

In AF patients requiring PCI, minimize triple therapy duration to reduce bleeding while maintaining thrombotic protection: 1

• 0-6 months post-PCI: OAC + clopidogrel 75 mg + aspirin ≤100 mg (duration based on bleeding/thrombotic risk stratification) 1
• 6-12 months: OAC + clopidogrel 75 mg only (omit aspirin) 1
• After 12 months: OAC monotherapy 1
• Avoid prasugrel or ticagrelor in this setting due to excessive bleeding 1

Critical Pitfalls to Avoid

• Never withhold anticoagulation based solely on HAS-BLED score: High scores identify patients needing closer monitoring, not anticoagulation avoidance 1
• Do not use fresh frozen plasma for warfarin reversal: Ineffective and high adverse event rate; use PCC instead 1
• Avoid aspirin doses >100 mg: No additional efficacy but significantly increased bleeding 1
• Do not assume all NOACs are equivalent: Apixaban has the most favorable bleeding profile, particularly for extracranial hemorrhage 3