37:41 症 例 報 告 37: 41 46, 2015 3 1 2 2 1 1 1 1 1 1 2 要 旨 1 71 15 mg 2 76 15 mg 3 3 80 10 mg 2 Xa Key words: rivaroxaban, anticoagulation therapy, intracerebral hemorrhage はじめに 2012 4 Xa ROCKET AF 0.5 vs. 0.7 p=0.02 1 2 3 2 1 71 症 例 1 2 2014 6 5 2014 6 23 15 mg 10 165 cm 52.3 kg 141/98 mmhg JCS I-1 GCS E4V5M6 3/5 4/5 NIHSS 7 110 mg/dl Cockcroft-Gault 74.0 ml/min PT 95 PT-INR 1.02 APTT 28.9 CT 10 ml 3 MRI 3 microbleeds Fig. 1
37:42 脳 卒 中 37 巻 1 号 (2015:1) Fig. 1 1 A: CT: B: MRI:T2 star weighted MR angiography microbleeds 4/5 14 2:76 : : 15 mg :20 : 174 cm 80.2 kg 209/96 mmhg A B JCS III-200 GCSE1V1M4 2.5 mm sluggish 1/5 NIHSS 38 : 204 mg/dl Cockcroft-Gault 100.4 ml/min PT 79 PT-INR 1.17 APTT 32.4 :3 ml 4 (Fig. 2) : K 20 mg IX 500 450 ml 140/70 mmhg CT CT 3 3:80 : : 10 mg : 11 : 163 cm 59.2 kg 151/81 mmhg JCS I-2 GCSE4V4M6 2/5 3/5 NIHSS 10 : RBC 3.52 10 6 /μl Hb 11.7 g/dl Hct 34.7 Plt 8.4 10 4 /μl BUN 24 mg/dl Cre 1.19 mg/dl Cockcroft-Gault
37:43 Fig. 2 2 A CT 2 B CT 16 C CT 25 A B C 41.5 ml/min 100 mg/dl PT 79 PT-INR 1.14 APTT 29.1 CT 15 ml MRI Fig. 3 90 120 mmhg 60 80 mmhg 6 II-1 GCSE3V5M6 CT 3 4 5 10 2 考 察 3 Cockcroft- Gault PT-INR <50 kg 3 3 2 2 3 MRI microbleeds 4 140/90 mmhg 2 3 new oral anticoagulants; NOAC RE-LY 5
37:44 脳 卒 中 37 巻 1 号 (2015:1) Fig. 3 3 A: CT( 3 ): B: CT( 7 ): C: CT( 13 ): D: CT( 24 ): E: MRI:T2 star weighted MR angiography microbleeds A B C D E ROCKET AF ( ) 1) ARISTOTLE ( ) 6) International Society of Thrombosis and Haemostasis(ISTH) ( 2 g/dl 2 ) J-ROCKET AF 7) ( ) NOAC 1 2 1 1 12:1 8) 3 2 3 4 Xa
37:45 C thrombin activatable fibrinolysis inhibitor TAFI TAFI 9 TAFI TAFI 10 Xa TAFI 11 Protease-activated receptor-1 PAR-1 12 PAR-1 PAR-1 Xa PAR-1 antagonist 13 Xa PAR-1 ROCKET AF 14 59 53 15 3 2 NOAC NOAC 結 論 3 2 参 考 文 献 1 Patel MR, Mahaffey KW, Garg J, et al: Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365: 883 891, 2011 2 Stöllberger C, Zuntner G, Bastovansky A, et al: Cerebral hemorrhage under rivaroxaban. Int J Cardiol 167: e179 181, 2013 3 Donzé J, Rodondi N, Waeber G, et al: Scores to predict major bleeding risk during oral anticoagulation therapy: a prospective validation study. Am J Med 125: 1095 1102, 2012 4 Jellinger KA, Lauda F, Attems J: Sporadic cerebral amyloid angiopathy is not a frequent cause of spontaneous brain hemorrhage. Eur J Neurol 14: 923 928, 2007 5 Reilly PA, Lehr T, Haertter S, et al: The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol 63: 321 328, 2014 6 Wallentin L, Lopes RD, Hanna M, et al: Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation 127: 2166 2176, 2013 7 Hori M, Matsumoto M, Tanahashi N, et al: Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation the J-ROCKET AF study. Circ J 76: 2104 2111, 2012 8 Suzuki S, Otsuka T, Sagara K, et al: Rivaroxaban in clinical practice for atrial fibrillation with special reference to prothrombin time. Circ J 78: 763 766, 2014 9 Ammollo CT, Semeraro F, Incampo F, et al: Dabigatran enhances clot susceptibility to fibrinolysis by mechanisms dependent on and independent of thrombin-activatable fibrinolysis inhibitor. J Thromb Haemost 8: 790 798, 2010 10 Hoppensteadt D, Cunanan J, Lewis BE, et al: Effect of dabigatran and rivaroxaban on thrombomodulin mediated activation of protein c and thrombin activated fibrinolysis inhibitor (TAFI). Potential clinical implications. Blood 122 (21), 2013 11 Maruyama I, Bell CE, Majerus PW: Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblast of human placenta. J Cell Biol 101: 363 371, 1985 12 Maruyama I, Shigeta K, Miyahara H, et al: Thrombin activates NF-kappa B through thrombin receptor and results in proliferation of vascular smooth muscle cells: role of thrombin in atherosclerosis and restenosis. Ann N Y Acad Sci 811: 429 436, 1997 13 Lee M, Saver JL, Hong KS, et al: Risk of intracranial hemorrhage with protease-activated receptor-1 antagonists. Stroke 43: 3189 3195, 2012
37:46 脳 卒 中 37 巻 1 号 (2015:1) 14)Goodman SG, Wojdyla DM, Piccini JP, et al: Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation). J Am Coll Cardiol 63: 891 900, 2014 15)Hankey GJ, Stevens SR, Piccini JP, et al: Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation. Stroke 45: 1304 1312, 2014 Abstract Three cases of spontaneous intracerebral hemorrhage on rivaroxaban Ayumi Debata, M.D., 1) Yohei Tateishi, M.D., Ph.D., 2) Jumpei Hamabe, M.D., 2) Nobutaka Horie, M.D., Ph.D., 1) Tsuyoshi Izumo, M.D., Ph.D., 1) Kentaro Hayashi, M.D., Ph.D., 1) Kensaku Kamada, M.D., Ph.D., 1) Takayuki Matsuo, M.D., Ph.D., 1) Izumi Nagata, M.D., Ph.D., 1) and Akira Tsujino, M.D., Ph.D. 2) 1) Department of Neurosurgery, Nagasaki University Hospital 2) Cerebrovascular Center, Nagasaki University Hospital We here report three cases of intracerebral hemorrhage on rivaroxaban. Case 1: A 71-year-old man taking rivaroxaban 15 mg/day due to atrial fibrillation suffered 10 ml left thalamic hemorrhage. He was successfully managed nonoperatively. Case 2: An 80-year-old man presented with left hemiparesis and sensory deficit who took rivaroxaban 10 mg/day because of deep venous thrombosis. CT showed 15 ml right thalamic hemorrhage with obstructive hydrocephalus. Although he was performed cerebral ventricle drainage, he died of hematoma expansion and progression of hydrocephalus on day 2. Case 3: A 76-year-old man with atrial fibrillation using rivaroxaban 10 mg/day developed 3 ml caudate nucleus hemorrhage with obstructive hydrocephalus. External ventricular drainage and neuroendoscopic removal of intraventricular hematoma were performed. However, he died 3 days after presentation because of rebleeding and massive hydrocephalus despite reoperation using endoscopy. Rivaroxavan, a direct factor Xa inhibitor, is a new oral anticoagulant for nonvalvular atrial fibrillation. However, it has risks of hemorrhagic adverse events. Especially, we have to pay attention to the development of intracerebral hemorrhage that could be a fatal outcome. Key words: rivaroxaban, anticoagulation therapy, intracerebral hemorrhage (Jpn J Stroke 37: 41 46, 2015)