A Comprehensive Update on Aspirin Management During Noncardiac Surgery

Neal S. Gerstein, MD, FASE; Cory L. Albrechtsen, BS; Nestor Mercado, MD, PhD; Joaquin E. Cigarroa, MD; Peter M. Schulman, MD

Disclosures

Anesth Analg. 2020;131(4):1111-1123. 

In This Article

The Aspirin Withdrawal Syndrome

Given the importance of aspirin in managing CV disease, it is logical to postulate that its temporary discontinuation may increase CV risk. Concern for an "aspirin withdrawal syndrome" is supported by limited evidence.[19,21,34–36] Doutremepuich et al,[34] measuring intravascular thrombus and emboli in an animal model, demonstrated a prothrombotic state peaking 8–10 days after a single aspirin dose, consistent with a withdrawal syndrome. Vial et al[37] measured urine metabolites of TXA-2 (a product of activated platelets with prothrombotic and vasoconstrictor properties) before, during, and after cessation of a 1-week aspirin regimen and found these metabolites exceeded levels beyond those in controls. The peak metabolite concentrations occurred 7–14 days after aspirin withdrawal. Beving et al[36] measured a platelet metabolite (12-L-hydroxy5,8,10-heptadecatrienoic acid [12-HHT]) in 32 patients whose aspirin therapy was held 2 weeks before coronary bypass surgery. Fourteen days after cessation, 25% of the cohort had 12-HHT levels exceeding the normal range. These same investigators had previously reported a similar 12-HHT rebound in healthy subjects after cessation of a 1-week aspirin regimen.[35] In both trials by Beving et al,[36] the platelet function rebound effect was dose dependent, with a faster rebound associated with the withdrawal of low-dose aspirin.[35,36] In a clinical context, Rodríguez et al[38] completed a case-control study of nearly 40,000 adults prescribed aspirin for secondary prevention of CV disease. They found those who recently stopped taking aspirin had a significantly increased risk of nonfatal MI- or CAD-related death combined (rate ratio = 1.43, 95% CI, 1.12–1.84) and nonfatal MI alone (rate ratio = 1.63, 95% CI, 1.23–2.14). However, the association between recently stopping low-dose aspirin and the risk of death from CAD was not significant (rate ratio = 1.07, 95% CI, 0.67–1.69).[38] Another cohort study by Sundström et al[39] evaluated over 600,000 patients using aspirin for either primary or secondary prevention and found that discontinuing aspirin in the absence of major bleeding or surgery was associated with a >30% increased risk of CV events. Conversely, Alcock et al[21] administered daily aspirin to 11 healthy subjects and examined the impact on platelet function sampled at baseline and then at 7, 14, and 21 days after the final aspirin dose. At each of the time points when aspirin was stopped, no evidence of increased platelet aggregation or rebound effect was found.[21]

In summary, some limited evidence suggests that abrupt aspirin withdrawal leads to hyperthrombosis and some observational data have demonstrated an association between aspirin cessation and adverse CV events. Although the mechanism for an aspirin withdrawal syndrome has not been completely elucidated, it is likely related to platelet hyperactivity characterized by increased TXA production and decreased fibrinolysis. The true clinical significance of aspirin withdrawal remains unclear and ripe for further investigation.

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