How do medications affect clotting in GI bleed management?

Management of Anticoagulants and Antiplatelets in GI Bleeding

For patients presenting with acute GI bleeding on anticoagulants or antiplatelets, immediately interrupt direct oral anticoagulants (DOACs) and warfarin, continue aspirin if used for secondary cardiovascular prevention, and temporarily hold P2Y12 inhibitors (clopidogrel) while maintaining aspirin in patients on dual antiplatelet therapy. 1, 2

Initial Management by Drug Class

Direct Oral Anticoagulants (DOACs)

• Interrupt DOACs immediately at presentation for both upper and lower GI bleeding 1, 2
• Do NOT routinely give prothrombin complex concentrate (PCC) for DOAC-associated bleeding 1, 3, 4
• For life-threatening hemorrhage only, consider specific reversal agents:
  • Idarucizumab for dabigatran 1, 2
  • Andexanet alfa for rivaroxaban, apixaban, or edoxaban 1, 2
• Most cases resolve by withholding the drug and waiting for anticoagulant effects to dissipate (half-life 3-12 hours depending on renal function) 1

Warfarin

• Interrupt warfarin immediately at presentation 3, 4
• For severe or life-threatening bleeding:
  • Give four-factor PCC plus vitamin K 5-10 mg IV 3, 4
  • Avoid fresh frozen plasma as PCC provides more rapid and effective reversal 1, 3, 4

Antiplatelet Therapy

• For aspirin used for secondary cardiovascular prevention: DO NOT HOLD during GI bleeding 1, 2, 5
• For aspirin used for primary prevention: permanently discontinue as bleeding risk outweighs benefit 2
• For dual antiplatelet therapy (aspirin + P2Y12 inhibitor):
  • Continue aspirin 1, 2
  • Temporarily hold the P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel) 1, 2
  • Never hold both agents simultaneously due to high stent thrombosis risk 2
• Do NOT give platelet transfusions for antiplatelet-associated bleeding 4

Transfusion Thresholds

• Use restrictive transfusion strategy with hemoglobin threshold of 70 g/L, targeting 70-100 g/L 1, 3
• For patients with cardiovascular disease, consider higher threshold of 80 g/L 1, 3
• Up to 80% of transfusions in lower GI bleeding may be inappropriate or unnecessary 1

Timing of Anticoagulation Resumption

P2Y12 Inhibitors

• Resume within 5 days maximum after endoscopic hemostasis to prevent stent thrombosis 1, 2
• For ticagrelor, consider earlier resumption within 2-3 days due to reversible binding 2
• High thrombotic risk factors requiring earlier resumption include: recent coronary stent placement, left main or proximal LAD stenting, last remaining patent coronary artery, multiple/long stents, or history of stent thrombosis 2

Aspirin for Secondary Prevention

• Restart as soon as hemostasis is achieved (same day if endoscopically confirmed) 2, 4
• Discontinuation is associated with nearly sevenfold increase in death or acute cardiovascular events 2

Warfarin

• Low thrombotic risk: restart at 7 days after bleeding stops 2, 3
• High thrombotic risk (prosthetic metal mitral valve, AF with prosthetic valve or mitral stenosis): consider low molecular weight heparin bridging at 48 hours after hemostasis 2, 3

DOACs

• Resume at maximum of 7 days after bleeding stops 1, 2
• Remember DOACs have rapid onset (full anticoagulation within 3 hours), so timing is critical 1
• Consider warfarin instead of DOAC in patients at high rebleeding risk due to more effective reversal options 1

Protective Strategies

• Initiate high-dose PPI therapy for all patients with GI bleeding on antithrombotic therapy 2
• Continue PPI for the duration of combined antithrombotic therapy 2
• Consider PPI even with single antithrombotic agent based on individual GI bleeding risk 2

Critical Pitfalls to Avoid

• Never withhold aspirin for secondary prevention during non-life-threatening bleeding - the cardiovascular risk far exceeds bleeding risk 1, 2, 5
• Never hold both antiplatelet agents simultaneously in patients on DAPT - this dramatically increases stent thrombosis risk 2
• Do not delay P2Y12 inhibitor resumption beyond 5 days - thrombosis risk escalates sharply after this timeframe 1, 2
• Avoid routine reversal agents for DOACs - reserve for life-threatening hemorrhage only as most bleeding resolves with drug interruption alone 1, 4
• Be aware of PPI-clopidogrel interaction, particularly in Asian populations with high prevalence of CYP2C19 slow metabolizers, though clinical significance remains uncertain 1, 2