In a patient with non-major bleeding on anticoagulant (e.g. warfarin, apixaban, rivaroxaban, or dabigatran) and antiplatelet (e.g. aspirin or P2Y12 inhibitor like clopidogrel) therapy, which one should be stopped first?

Management of Non-Major Bleeding in Patients on Anticoagulant and Antiplatelet Therapy

In a patient with non-major bleeding on both anticoagulant and antiplatelet therapy, the antiplatelet agent should be stopped first while continuing the anticoagulant, unless the bleeding is at a critical site or life-threatening. 1

Assessment of Bleeding Severity

First, determine if the bleeding is major or non-major:

• Major bleeding is defined as:

  • Bleeding at a critical site
  • Hemodynamic instability
  • Clinically overt bleeding with hemoglobin decrease ≥2 g/dL or requiring ≥2 units of RBCs

• Non-major bleeding is any bleeding that doesn't meet the above criteria

Management Algorithm for Non-Major Bleeding

Step 1: Assess the bleeding site and severity

• If bleeding is at a critical site or life-threatening → Stop both anticoagulant and antiplatelet
• If bleeding is non-major and not at a critical site → Continue anticoagulant but consider stopping antiplatelet agent

Step 2: Management based on medication combination

For patients on anticoagulant + single antiplatelet:

1. Stop the antiplatelet agent first while maintaining anticoagulation
2. Provide local therapy/manual compression
3. Assess for and manage comorbidities that could contribute to bleeding
4. Determine if anticoagulant dosing is appropriate

For patients on anticoagulant + dual antiplatelet therapy:

1. Stop one of the antiplatelet agents (preferably the P2Y12 inhibitor such as clopidogrel)
2. Continue anticoagulant and aspirin if possible
3. Provide local therapy/manual compression
4. Reassess bleeding control

Rationale for This Approach

The 2020 ACC Expert Consensus Decision Pathway recommends that for non-major bleeding that is not at a critical site, the anticoagulant can be continued while the antiplatelet agent(s) should be assessed for risks and benefits of stopping 1. This approach is supported by several key considerations:

1. Thrombotic risk: Anticoagulants are typically prescribed for conditions with high thrombotic risk (e.g., atrial fibrillation, mechanical heart valves, venous thromboembolism), where interruption could lead to serious thrombotic events

2. Reversibility of effect: Antiplatelet agents like aspirin and clopidogrel have irreversible effects on platelets, meaning that even after stopping the medication, the antiplatelet effect persists until new platelets are generated (7-10 days) 2

3. Bleeding risk hierarchy: The European Society of Cardiology Working Group on Thrombosis recommends that in patients who develop bleeding on triple therapy (dual antiplatelet + anticoagulant), either aspirin or clopidogrel should be stopped first 1

Special Considerations

For patients on warfarin:

• If INR is supratherapeutic (>3.5), consider dose adjustment rather than complete discontinuation 1
• For non-major bleeding, consider 2-5 mg PO/IV vitamin K if needed 1

For patients on DOACs (apixaban, rivaroxaban, dabigatran):

• Consider temporary dose reduction rather than complete discontinuation
• Assess renal function, as impaired renal function can increase DOAC levels 3
• No reversal agent is recommended for non-major bleeding 1

For antiplatelet therapy:

• If on dual antiplatelet therapy, the P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel) should be stopped first while continuing aspirin 1
• For patients on aspirin monotherapy for secondary prevention, consider continuing unless bleeding is significant 1

When to Resume Antiplatelet Therapy

Once adequate hemostasis has been achieved:

• Resume P2Y12 receptor inhibitor when bleeding is controlled 1
• For patients with high thrombotic risk (recent coronary stent placement), consult with a cardiologist regarding the timing of resumption

Common Pitfalls to Avoid

1. Stopping both medications simultaneously - This increases thrombotic risk unnecessarily in non-major bleeding

2. Stopping anticoagulant while continuing antiplatelet - This approach is contrary to guidelines and increases thrombotic risk while potentially not addressing the bleeding adequately

3. Failing to reassess medication dosing - Sometimes bleeding occurs due to inappropriate dosing of anticoagulants, particularly in patients with changing renal function

4. Not considering drug interactions - P-glycoprotein inhibitors and CYP3A4 inhibitors can increase DOAC levels and contribute to bleeding 3

By following this approach, you can effectively manage non-major bleeding while minimizing both bleeding and thrombotic risks in patients requiring both anticoagulant and antiplatelet therapy.