{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T22:41:48Z","timestamp":1772232108309,"version":"3.50.1"},"reference-count":16,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:p>We report a case of a 6-year-old girl with severe protein S deficiency due to a homozygous mutation and recurrent episodes of skin necrosis. She developed purpura fulminans at birth and a catheter-related venous thrombosis complicated by massive pulmonary embolism at the sixth day of life. Long-term oral anticoagulant therapy with a vitamin K-antagonist was started with a therapeutic range of the international normalized ratio of prothrombin time between 2.0 and 3.0. Unfortunately, this common range was not sufficient because recurrent episodes of warfarin-induced skin necrosis developed if the international normalized ratio was &amp;lt;4.0. Vitamin K antagonists decrease plasma level of vitamin K\u2013dependent coagulation proteins, including the natural anticoagulant protein C. In our patient, the hypercoagulable state due to warfarin-induced reduction of protein C, other than severe protein S deficiency, outweighed the anticoagulant efficacy of the inhibition of procoagulant factors II, VII, IX, and X. The switch of anticoagulant therapy from warfarin to rivaroxaban, a direct inhibitor of activated factor X that does not inhibit other vitamin K\u2013dependent proteins, resulted in the disappearance of skin necrosis at 1 year of follow-up. Rivaroxaban may be considered as a valid anticoagulant alternative in patients with severe inherited protein S deficiency and warfarin-induced skin necrosis.<\/jats:p>","DOI":"10.1542\/peds.2013-1156","type":"journal-article","created":{"date-parts":[[2013,10,21]],"date-time":"2013-10-21T20:48:33Z","timestamp":1382388513000},"page":"e1435-e1439","source":"Crossref","is-referenced-by-count":33,"title":["Anticoagulant Treatment With Rivaroxaban in Severe Protein S Deficiency"],"prefix":"10.1542","volume":"132","author":[{"given":"Ida","family":"Martinelli","sequence":"first","affiliation":[{"name":"A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Bucciarelli","sequence":"additional","affiliation":[{"name":"A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Artoni","sequence":"additional","affiliation":[{"name":"A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio F.","family":"Fossali","sequence":"additional","affiliation":[{"name":"Department of Maternal and Pediatric Sciences, Fondazione IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico and University of Milan, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena M.","family":"Passamonti","sequence":"additional","affiliation":[{"name":"A. 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