{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:28:46Z","timestamp":1761092926167,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T00:00:00Z","timestamp":1604793600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cutaneous small vessel vasculitis (CSVV) has been reported after exposure to direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to describe clinical characteristics associated with CSVV among DOAC\u2010exposed patients. Furthermore, we characterized this signal in the Sentinel System to relate the clinical data from the individual FAERS cases to population\u2010based electronic healthcare data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We queried FAERS for all cases of CSVV associated with DOACs from U.S. approval date of each DOAC through March 16, 2018. Within the Sentinel System, we identified incident CSVV cases using ICD\u20109 and ICD\u201010 diagnosis codes among adults aged\u00a0\u2265\u00a030\u00a0years who received a DOAC in the prior 90\u00a0days between January 1, 2010, and June 30, 2018. We excluded patients with evidence of select autoimmune diagnoses in the 183\u00a0days prior to their CSVV diagnoses and reported patient characteristics in the 183\u2010day period prior to CSVV diagnoses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In FAERS, we identified 50 cases of CSVV reported with rivaroxaban (n=26), apixaban (n=14), dabigatran (n=9), and edoxaban (n=1). Approximately 50% of the cases reported time to onset within 10\u00a0days after DOAC exposure. When specified, the predominant type of CSVV reported was leukocytoclastic vasculitis (n=31), followed by Henoch\u2010Schonlein purpura (n=4). Hospitalization occurred in most of the cases (n=37). Switching of the offending agent after the development of CSVV was reported (n=26). Three rivaroxaban (n=3) cases and one dabigatran case (n=1) reported positive rechallenge. In the Sentinel system, we identified 3659 CSVV cases with prior DOAC exposure, with 85% of events occurring within 10\u00a0days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The assessment of FAERS cases, combined with the temporal clustering of the Sentinel System cases suggest a possible causal relationship of DOACs and CSVV. Future efforts should characterize the risk of CSVV among the various DOAC users.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2468","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T03:25:29Z","timestamp":1602213929000},"page":"1099-1107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Complementary Use of U.S. FDA\u2019s Adverse Event Reporting System and Sentinel System to Characterize Direct Oral Anticoagulants\u2010Associated Cutaneous Small Vessel Vasculitis"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5997-4876","authenticated-orcid":false,"given":"Mohamed","family":"Mohamoud","sequence":"first","affiliation":[{"name":"Division of Pharmacovigilance Office of Surveillance and Epidemiology Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland 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