key: cord-0858404-9viv0cdl
authors: Chiang, Kate Chander; Gupta, Ajay
title: Aspirin Resistance in Obese and Elderly Patients with COVID-19?
date: 2021-04-19
journal: Am J Med
DOI: 10.1016/j.amjmed.2020.09.006
sha: 85f749b1cf8c03e2a94d574a0d547623be0a6201
doc_id: 858404
cord_uid: 9viv0cdl

nan

To the Editor:

We read with great interest the recent publication by McCullough et al proposing a comprehensive management strategy for ambulatory patients with coronavirus disease 2019 (COVID-19). 1 The authors should be commended for proposing antiplatelet and antithrombotic therapy early in the disease. 2 McCullough et al recommend 81 mg aspirin daily for high-risk, ambulatory patients with COVID-19. 1 We suggest caution in relying on low-dose aspirin as chemoprophylaxis or treatment for immunothrombosis in COVID-19, especially in patients who are obese or elderly.

Plasma thromboxane B 2 levels are significantly increased, 2 and COX-2 expression is upregulated more than 50-fold in severe COVID-19. 3 COX-2 is inducible and expressed in megakaryocytes and platelets. 4 Low-dose aspirin effectively inhibits COX-1 but not COX-2 activity. 5 Increased expression of cytosolic phospholipase A 2 and COX-2 in the obese or the elderly leads to increased generation of thromboxane A 2 and resistance to aspirin. 6 Among aspirin-naïve subjects, the median urinary 11-dehydrothromboxane B 2 levels was 1433 pg/mg creatinine in the obese compared with 505 pg/mg creatinine in the nonobese, healthy controls (P < 0.01). 7 Furthermore, among subjects taking aspirin, serum thromboxane B 2 levels were positively correlated with body mass index (BMI) and body weight, suggesting that thromboxane generation in the obese is COX-2 dependent. 7 The effect of aging on thromboxane generation was studied in 3261 aspirin-treated subjects: the baseline urinary thromboxane B 2 levels increased with advancing age and were associated with higher risk of cardiovascular events (CHARISMA trial). 8 Marked increase in thromboxane generation and COX-2 expression in severe COVID-19 raises the specter of aspirin resistance, especially in patients who are elderly or obese. Though increasingly recommended, the efficacy of low-dose aspirin remains to be demonstrated in ambulatory or hospitalized patients with COVID-19. The critical role of immunothrombosis in the pathogenesis, progression, and multiorgan failure in COVID-19 underlines an urgent need for effective antithrombotic therapies to reduce the risk of hospitalization, morbidity, and mortality. 

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