{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T02:15:57Z","timestamp":1776910557529,"version":"3.51.2"},"reference-count":34,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: While anticoagulant and antiplatelet therapies are commonly combined in clinical settings, this combination increases the risk of hemorrhage. However, comparative data on the bleeding risks of different drug combinations remain limited. This study assesses hemorrhage risk associated with various anticoagulant\u2013antiplatelet combinations using data from the USFDA Adverse Event Reporting System (AERS). Methods: Hemorrhage-related reports were extracted from the AERS database (March 2004\u2013June 2024). Anticoagulants analyzed included warfarin, rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, and acenocoumarol; antiplatelets included aspirin, clopidogrel, ticagrelor, cilostazol, prasugrel, and dipyridamole. Disproportionality analysis using frequentist and Bayesian approaches was conducted to detect hemorrhage signals. Results: Out of 160,715 hemorrhage reports, rivaroxaban, warfarin, and apixaban were the most frequently reported anticoagulants, while aspirin and clopidogrel were the top antiplatelets. Apixaban had the lowest reporting odds ratio for hemorrhage. The rivaroxaban-aspirin combination showed the highest hemorrhage risk, while combinations with cilostazol were the lowest. Apixaban, alone and in combination, was associated with reduced hemorrhage and mortality risks. Conclusions: Combining anticoagulants with antiplatelets increases hemorrhage and mortality risk. While our findings highlight potential safety signals related to hemorrhage with antithrombotic drug combinations, they remain hypothesis-generating and should not be interpreted as causal associations. Instead, they provide an initial basis for further validation in well-designed clinical cohorts where comorbidities can be adequately accounted for.<\/jats:p>","DOI":"10.3390\/jcm14176262","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T07:46:17Z","timestamp":1757058377000},"page":"6262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hemorrhage Risk Associated with Anticoagulant and Antiplatelet Drug Combinations: Insights from the USFDA Adverse Event Reporting System"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3811-6503","authenticated-orcid":false,"given":"Kannan","family":"Sridharan","sequence":"first","affiliation":[{"name":"Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences, Arabian Gulf University, Manama 26671, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5877-205X","authenticated-orcid":false,"given":"Gowri","family":"Sivaramakrishnan","sequence":"additional","affiliation":[{"name":"Bahrain Defence Force Royal Medical Services, Riffa 28743, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1378\/chest.06-2374","article-title":"Warfarin and antiplatelet combination use among commercially insured patients enrolled in an anticoagulation management service","volume":"131","author":"Johnson","year":"2007","journal-title":"Chest"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1001\/jamainternmed.2018.7816","article-title":"Association of Adding Aspirin to Warfarin Therapy Without an Apparent Indication With Bleeding and Other Adverse Events","volume":"179","author":"Schaefer","year":"2019","journal-title":"JAMA Intern. 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