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• W3154881210 abstract "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).1McCullough PA Kelly RJ Ruocco G et al.Pathophysiological basis and rationale for early outpatient treatment of SARS-CoV-2 (COVID-19) infection [e-pub ahead of print].Am J Med. 2021; (Accessed August 25, 2020): 16-22https://doi.org/10.1016/j.amjmed.2020.07.003Abstract Full Text Full Text PDF Scopus (79) Google Scholar The authors should be commended for proposing antiplatelet and antithrombotic therapy early in the disease.2Hottz ED Azevedo-Quintanilha IG Palhinha L et al.Platelet activation and platelet-monocyte aggregates formation trigger tissue factor expression in severe COVID-19 patients.Blood. 2020; 136: 1330-1341https://doi.org/10.1182/blood.2020007252Crossref PubMed Scopus (454) Google Scholar McCullough et al recommend 81 mg aspirin daily for high-risk, ambulatory patients with COVID-19.1McCullough PA Kelly RJ Ruocco G et al.Pathophysiological basis and rationale for early outpatient treatment of SARS-CoV-2 (COVID-19) infection [e-pub ahead of print].Am J Med. 2021; (Accessed August 25, 2020): 16-22https://doi.org/10.1016/j.amjmed.2020.07.003Abstract Full Text Full Text PDF Scopus (79) Google Scholar 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 B2 levels are significantly increased,2Hottz ED Azevedo-Quintanilha IG Palhinha L et al.Platelet activation and platelet-monocyte aggregates formation trigger tissue factor expression in severe COVID-19 patients.Blood. 2020; 136: 1330-1341https://doi.org/10.1182/blood.2020007252Crossref PubMed Scopus (454) Google Scholar and COX-2 expression is upregulated more than 50-fold in severe COVID-19.3Sharma A Garcia GJ Wang Y et al.Human iPSC-derived cardiomyocytes are susceptible to SARS-CoV-2 infection.Cell Rep Med. 2020; 1100052https://doi.org/10.1016/j.xcrm.2020.100052Abstract Full Text Full Text PDF Scopus (168) Google Scholar COX-2 is inducible and expressed in megakaryocytes and platelets.4Rocca B Secchiero P Ciabattoni G et al.Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets.Proc Natl Acad Sci U S A. 2002; 99: 7634-7639https://doi.org/10.1073/pnas.112202999Crossref PubMed Scopus (313) Google Scholar Low-dose aspirin effectively inhibits COX-1 but not COX-2 activity.5Ornelas A Zacharias-Millward N Menter DG et al.Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention.Cancer Metastasis Rev. 2017; 36: 289-303https://doi.org/10.1007/s10555-017-9675-zCrossref PubMed Scopus (127) Google Scholar Increased expression of cytosolic phospholipase A2 and COX-2 in the obese or the elderly leads to increased generation of thromboxane A2 and resistance to aspirin.6Kim JW Zou Y Yoon S et al.Vascular aging: molecular modulation of the prostanoid cascade by calorie restriction.J Gerontol A Biol Sci Med Sci. 2004; 59: B876-B885https://doi.org/10.1093/gerona/59.9.b876Crossref Scopus (43) Google Scholar Among aspirin-naïve subjects, the median urinary 11-dehydro-thromboxane B2 levels was 1433 pg/mg creatinine in the obese compared with 505 pg/mg creatinine in the nonobese, healthy controls (P < 0.01).7Petrucci G Zaccardi F Giaretta A et al.Obesity is associated with impaired responsiveness to once‐daily low‐dose aspirin and in vivo platelet activation.J Thromb Haemost. 2019; 17: 885-895https://doi.org/10.1111/jth.14445Crossref PubMed Scopus (35) Google Scholar Furthermore, among subjects taking aspirin, serum thromboxane B2 levels were positively correlated with body mass index (BMI) and body weight, suggesting that thromboxane generation in the obese is COX-2 dependent.7Petrucci G Zaccardi F Giaretta A et al.Obesity is associated with impaired responsiveness to once‐daily low‐dose aspirin and in vivo platelet activation.J Thromb Haemost. 2019; 17: 885-895https://doi.org/10.1111/jth.14445Crossref PubMed Scopus (35) Google Scholar The effect of aging on thromboxane generation was studied in 3261 aspirin-treated subjects: the baseline urinary thromboxane B2 levels increased with advancing age and were associated with higher risk of cardiovascular events (CHARISMA trial).8Eikelboom JW Hankey GJ Thom J et al.Incomplete inhibition of thromboxane biosynthesis by acetylsalicylic acid.Circulation. 2008; 118: 1705-1712https://doi.org/10.1161/circulationaha.108.768283Crossref PubMed Scopus (0) Google Scholar 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." @default.
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• W3154881210 title "Aspirin Resistance in Obese and Elderly Patients with COVID-19?" @default.
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