title: A multicenter, prospective, observational study of warfarin-associated intracerebral hemorrhage: The SAMURAI-WAICH study.
abstract: BACKGROUND
  Because patients with warfarin-associated intracerebral hemorrhage (WAICH) have a high risk of ongoing bleeding, disability, and death, urgent coagulopathy reversal should be considered. On the other hand, thromboembolism may occur with reversal or withholding of anticoagulant therapy. The current status of acute hemostatic treatments and clinical outcomes in WAICH patients was investigated.
  
  
  METHODS
  WAICH patients admitted within 3 days of onset were prospectively enrolled in 10 stroke centers. Thromboembolic and hemorrhagic complications and functional outcomes were followed-up for one year.
  
  
  RESULTS
  Of 50 WAICH patients (31 men, 73 ± 9 years old) enrolled, all stopped warfarin on admission. Elevated prothrombin time-international normalized ratios (PT-INR) were normalized in 43 (86%). Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin followed by warfarin in 9 (18%), intravenous low-dose unfractionated heparin followed by warfarin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5 (IQR 1.25-9), 4 (2-5.5) and 6 (3-11) days after onset, respectively, after emergent admission. Onset-to-admission time (per 1-hour increase; OR 0.55, 95% CI 0.19-0.84) was inversely associated with hematoma expansion. Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin in 9 (18%), low-dose heparin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5, 4 and 6 days after onset, respectively. During one-year follow-up (n=47), 11 thromboembolic and 6 hemorrhagic complications were documented. Twenty four patients showed unfavorable outcomes, corresponding to a modified Rankin Scale score of 4-6. Thromboembolic complications (OR, 10.62; 95% CI, 1.05-227.85), as well as advanced age (per 1 year; OR, 1.27; 95% CI, 1.10-1.61) and higher National Institutes of Health Stroke Scale (NIHSS) score (per 1 point; OR, 1.24; 95% CI 1.07-1.55), were independently associated with unfavorable outcome.
  
  
  CONCLUSIONS
  PT-INR normalization on admission and early anticoagulant resumption were common in WAICH patients. Thromboembolic complications were independently associated with unfavorable outcome.
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Osaki
authors.affiliation: Division of Stroke Care Unit, National Cerebral and Cardiovascular Center, Suita, Japan. Electronic address: koga@ncvc.go.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Koga
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Neurology, St Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Neurosurgery, Nakamura Memorial Hospital, Sapporo, Japan.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Nakagawara
authors.affiliation: Department of Stroke Neurology, Kohnan Hospital, Sendai, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Furui
authors.affiliation: Department of Neurology, Kobe City Medical Center General Hospital, Kobe, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Todo
authors.affiliation: Department of Stroke Medicine, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Departments of Neurosurgery and Stroke Center, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shiokawa
authors.affiliation: Department of Cerebrovascular Disease, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Neurology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okuda
authors.affiliation: Department of Cardiovascular Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan.
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamagami
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minematsu
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Toyoda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000925:Anticoagulants / Q000627:therapeutic use; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy; D015331:Cohort Studies; D006406:Hematoma / Q000209:etiology; D019370:Observation; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Acute stroke; Anticoagulant therapy; Asia; Hematoma expansion; Hemorrhagic complication; Intracerebral hemorrhage; Thromboembolic complication; Warfarin