What are the mechanisms to reverse the effects of Acetylsalicylic acid (Aspirin)?

From the Guidelines

The most effective mechanism to reverse the effects of aspirin is platelet transfusion, which should be administered at a dose of 0.5 to 0.7 x 10^11 platelets per 10 kg body weight, as this introduces fresh, functional platelets to restore normal clotting ability. For patients with serious bleeding due to aspirin therapy, this dose is recommended to correct the platelet function evaluated with VerifyNow1 aspirin 1. The ability of platelet transfusion to correct the effects of aspirin has been well documented, with in vitro supplementation by noninhibited platelets in a proportion of 30% to 40% restoring platelet aggregation studied by light transmission and induced with arachidonic acid 1.

Some key points to consider when using platelet transfusion to reverse the effects of aspirin include:

• The time during which aspirin resides in the blood is brief, with a half-life of around 20 minutes, which makes platelet transfusion an effective strategy for immediate reversal 1.
• The effect of platelet transfusion to correct the effects of thienopyridines, such as clopidogrel, is less documented, but higher doses of platelets than for aspirin may be necessary 1.
• Platelet transfusion can probably not neutralize the effect of ticagrelor, as this directly active APA and its first metabolite are present in plasma at high concentrations and can inhibit platelets provided by transfusion for up to 24 hours after the last intake 1.

In less urgent situations, simply discontinuing aspirin will allow natural reversal as the body produces new platelets over 7-10 days, with partial recovery of hemostatic function occurring within 2-3 days. However, platelet transfusion remains the most effective immediate reversal strategy for critical bleeding situations, as it introduces fresh, functional platelets to restore normal clotting ability 1.

From the Research

Mechanisms to Reverse Effects of Aspirin

• The antihemostatic effect of aspirin can be corrected by the administration of platelet concentrate and/or desmopressin 2.
• Guidelines recommend stopping aspirin 7 to 10 days before surgery to allow time for replacement of permanently inhibited platelets by newly released uninhibited platelets 3.
• Arachidonic acid (AA)-induced light transmission aggregation (LTA) returns to baseline levels in all subjects within 4 days of stopping aspirin, coinciding with the partial recovery of plasma thromboxane B(2) concentrations 3.
• Platelet aggregation recovers within 4 days of stopping aspirin 3.
• Aspirin's effect upon the cyclooxygenase pathway is a key aspect of its mechanism, and understanding this is crucial for reversing its effects 4.

Reversal Strategies

• Administration of platelet concentrate and/or desmopressin can reverse the antihemostatic effect of aspirin 2.
• Stopping aspirin 7 to 10 days before surgery can allow for replacement of permanently inhibited platelets by newly released uninhibited platelets 3.
• Mixing with 30% untreated donor platelets can reverse the effects of aspirin on AA-induced LTA 3.

Comparison with Other Antiplatelet Agents

• Clopidogrel must be stopped for 10 days to achieve a normal aggregatory response, compared to 4 days for aspirin 3.
• ADP-induced LTA in patients treated with clopidogrel requires the addition of 90% or more donor platelets to reach control levels, compared to 30% for aspirin 3.