Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited. June 1, 2015 • Volume 4 • Number 11 cases-anesthesia-analgesia.org 151 Copyright © 2015 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000143 N ovel anticoagulation therapies include orally administered direct thrombin inhibitors and direct factor Xa inhibitors. These drugs have the poten- tial to address some of the limitations of vitamin K antag- onists, including fewer food and drug interactions, and more predictable anticoagulant effects. This may facilitate fxed dosing without continuous laboratory monitoring. However, some clinical situations require measuring anti- coagulant activity. Routine coagulation assays are help- ful with these novel drugs, but sensitivity varies among the reagents used. 1 More specifc anti-Xa chromogenic assays are now commercially available for routine clini- cal practice. Some studies demonstrate that the thrombin generation assay could be a useful tool for monitoring rivaroxaban’s anticoagulant activity, 2,3 which seems to have a dose-dependent effect. 4 Despite acceptable effectiveness for thromboprophy- laxis after total hip or knee replacement, a recent systematic review found that new oral anticoagulant drugs are associ- ated with an increased risk of major bleeding. 5 However, there is limited information on how to control bleeding or reverse the anticoagulation effects of these new drugs. The use of nonspecifc reversal agents (nonactivated or activated prothrombin complex concentrates, recombinant activated FVII) is proposed in the absence of a specifc anti- dote. The impact of nonspecifc reversal agents on thrombin generation is variable, 6,7 and little is known about their in vivo pattern in a hemorrhagic situation. We report a case of major bleeding diathesis reversed by a 4-factor prothrombin complex concentrate in a patient receiving rivaroxaban pro- phylaxis. Oral patient consent was obtained for publication of this report. CASE DESCRIPTION A 74-year-old man was admitted to our hospital for a spon- taneous acute subdural hematoma. His medical history included being overweight (body mass index 28 kg/m 2 ), hypertension, and dyslipidemia. The patient’s medications consisted of rilmenidil, lercanidipine, simvastatin, panto- prazole, and acetaminophen. One month before admission, rivaroxaban (10 mg once daily) was prescribed for venous thromboembolism prophylaxis after an uneventful total knee arthroplasty. The patient’s estimated creatinine clear- ance was 75 mL/min using the Modifcation of Diet in Renal Disease formula. On the day of admission, he presented with a sudden headache at 5:00 am associated with a spontaneous hyper- tensive episode, without vigilance disorder. At 9:45 am, his mental status declined, and he developed left hemiplegia, central facial paralysis, and vomiting. He was admitted with a Glasgow Coma Scale (GCS) of 12 (E2 V4 M6). Noncontrast brain computed tomography (CT) imaging revealed a right subdural hematoma with midline shift (Fig. 1). Initial labo- ratory assays included a 14.2 g/dL hemoglobin concentra- tion, a 461 G/L platelet count, a 34-second activated partial thromboplastin time (aPTT), and a 14.9-second prothrombin time (PT) (Table 1). aPTT and PT were within normal range. The plasma rivaroxaban concentration was 34 ng/mL, mea- sured 15 hours after the last dose. This is in agreement with the expected values found in the literature, ranging from 9 to 122 μg/mL. 8 The patient was admitted to the neuro- surgery unit for serial neurological examinations. The ini- tial treatment consisted of stopping anticoagulation therapy and administration of 50 UI per kg of 4-factor prothrombin The management of life-threatening bleeding associated with rivaroxaban remains a challenge for physicians due to the lack of evidence about clinically effective options for anticoagulation reversal. We report a favorable outcome in a patient receiving rivaroxaban prophylaxis, who developed a spontaneous subdural hematoma treated by a surgical evacuation and administra- tion of 4-factor prothrombin complex concentrate. Classical coagulation variables were asso- ciated with impaired thrombin generation. Reversal with prothrombin complex concentrates improved all thrombin generation measures. Thrombin generation tests may be suitable for assessing the clinical utility of reversal drugs on rivaroxaban-induced coagulopathy. (A&A Case Reports. 2015;4:151–4.) From the Departments of *Anesthesiology and Intensive Care, †Neurosur- gery, and ‡Hematology, and §Emergency Unit, University Hospital of Cler- mont-Ferrand, Clermont-Ferrand, France; and ‖Department of Anesthesiol- ogy and Intensive Care, Cochin University Hospital, Paris, France. Accepted for publication October 14, 2014. Funding: None. The authors declare no conficts of interest. Address correspondence to Aurélien Lebreton, MD, PhD, Department of Hematology, University Hospital of Clermont-Ferrand, CHU Clermont- Ferrand, Hôpital Estaing, 1 place Lucie et Raymond Aubrac, 63 003 Clermont- Ferrand cedex 1, France. Address e-mail to alebreton@chu-clermontferrand.fr. Favorable Outcome of Rivaroxaban-Associated Intracerebral Hemorrhage Reversed by 4-Factor Prothrombin Complex Concentrate: Impact on Thrombin Generation Sophie Kauffmann, MD,* Russell Chabanne, MD,* Aurélien Coste, MD,† François Longeras, MD,* Thomas Sinegre, MD,‡ Jeannot Schmidt, MD, PhD,§ Charles-Marc Samama, MD, PhD,‖ Jean-Michel Constantin, MD, PhD,* and Aurélien Lebreton, MD, PhD‡