How to reverse the effects of Aspirin (acetylsalicylic acid) and Plavix (clopidogrel) during a gastrointestinal (GI) bleed?

From the Guidelines

To reverse aspirin and Plavix (clopidogrel) during a GI bleed, immediately discontinue both medications and provide supportive care, with platelet transfusions being the primary reversal strategy for severe bleeding, as recommended by the French working group on perioperative haemostasis 1.

Reversal Strategies

For aspirin, there is no specific reversal agent, but platelet transfusions (typically 0.5 to 0.7 x 10^11 per 10 kg of body weight) can be given if bleeding is severe, as proposed by the French working group on perioperative haemostasis 1. For Plavix, platelet transfusions are also the primary reversal strategy, with a recommended dose of 2 x standard dose, as its antiplatelet effects last 5-7 days after discontinuation 1. Desmopressin (DDAVP) at 0.3 mcg/kg IV over 30 minutes can be considered as an adjunct therapy to improve platelet function.

Management of GI Bleed

Volume resuscitation with crystalloids or blood products is essential, with packed red blood cells transfused to maintain hemoglobin above 7-8 g/dL (or higher in patients with cardiovascular disease) 1. Endoscopic intervention should be performed promptly to identify and treat the bleeding source.

Restarting Antiplatelet Therapy

The decision to restart antiplatelet therapy should be individualized based on thrombotic risk versus bleeding risk, typically resuming 3-7 days after bleeding has stopped and hemodynamic stability is achieved, as recommended by the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy (APSDE) 1. Aspirin and Plavix work by irreversibly inhibiting platelet function through different mechanisms, which is why new platelet production (taking about 7-10 days) is necessary for complete reversal of their effects.

Key Considerations

• The risk of GI bleeding associated with thienopyridines, such as clopidogrel, has been assessed in several case-control studies and randomized trials, with a relative risk increase of 2- to 3-fold compared with aspirin alone 1.
• The mortality attributable to GI bleeding in patients on clopidogrel alone or on dual antiplatelet therapy is low, but GI bleeding appears to be a significant predictor of death, even after adjustment for CV morbidity, age, sex, diabetes, PCI status, and concomitant therapy 1.

From the FDA Drug Label

Because the half-life of clopidogrel’s active metabolite is short, it may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 4 hours of the loading dose or 2 hours of the maintenance dose may be less effective

• Reversal of aspirin and clopidogrel (Plavix) during a GI bleed:
  • The use of platelet transfusions may be considered to reverse the effects of clopidogrel.
  • However, the effectiveness of platelet transfusions may be reduced if administered within 4 hours of the loading dose or 2 hours of the maintenance dose of clopidogrel.
  • There is no specific information on how to reverse aspirin in this context.
  • It is essential to weigh the risks and benefits of platelet transfusions and consider alternative strategies to manage the GI bleed 2

From the Research

Reversal of Aspirin and Plavix during GI Bleed

• The management of anticoagulants and antiplatelets during acute gastrointestinal bleeding is a complex issue, and there is limited evidence to guide the reversal of aspirin and Plavix (clopidogrel) in this setting 3, 4.
• For patients on antiplatelet agents, such as aspirin and Plavix, the American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline suggests against platelet transfusions 3.
• In patients with acute GI bleeding, the guideline suggests against holding cardiac acetylsalicylic acid (ASA) for secondary prevention, but if the ASA has been interrupted, resumption is suggested on the day hemostasis is endoscopically confirmed 3.
• There is limited evidence on the specific reversal strategies for aspirin and Plavix in the setting of GI bleeding, and the decision to restart antithrombotic therapy after upper GI bleeding is difficult due to the lack of sufficient data 5.
• A case report highlights the risk of gastrointestinal bleed with the combination of clopidogrel and aspirin, and recommends caution when combining these medications 6.

Management of GI Bleed

• The management of upper GI bleeding involves evaluation and management of the patient, including assessment of hemodynamic stability, laboratory tests, and endoscopy 5.
• Clinical prediction guides, such as the Glasgow-Blatchford bleeding score, are necessary for upper GI bleeding risk stratification and to determine therapy 5.
• Proton pump inhibitors should be initiated upon presentation with upper GI bleeding, and high-dose treatment is recommended for the first 72 hours post-endoscopy 5.