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. Pediatrics 2013;132:e1435–e1439 AUTHORS: Ida Martinelli, MD, PhD,a Paolo Bucciarelli, MD,a Andrea Artoni, MD,a Emilio F. Fossali, MD,b Serena M. Passamonti, MD, PhD,a Armando Tripodi, PhD,a and Flora Peyvandi, MD, PhDa aA. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, and bDepartment of Maternal and Pediatric Sciences, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico and University of Milan, Milan, Italy