title: Anticoagulant treatment with rivaroxaban in severe protein S deficiency.
abstract: 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 <4.0. Vitamin K antagonists decrease plasma level of vitamin K-dependent 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-dependent 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.
authors.affiliation: Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Pace, 9, 20122 Milan, Italy. martin@policlinico.mi.it.
authors.forename: Ida
authors.initials: I
authors.lastname: Martinelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Bucciarelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Artoni
authors.forename: Emilio F
authors.initials: EF
authors.lastname: Fossali
authors.forename: Serena M
authors.initials: SM
authors.lastname: Passamonti
authors.forename: Armando
authors.initials: A
authors.lastname: Tripodi
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D018455:Protein S Deficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000069552:Rivaroxaban; D012720:Severity of Illness Index; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban
keywords: anticoagulant; coagulation; protein S; rivaroxaban