title: High-dose argatroban therapy for stroke: novel treatment for delayed treatment and the recanalization mechanism.
abstract: BACKGROUND
  There has been little effective treatment in patients with cerebral infarction at >24 hours after onset. We assessed the effects of high-dose argatroban therapy in delayed administration, and investigated the mechanism based on our clinical findings.
  
  
  METHODS
  Argatroban 30 mg was first administered for 15 minutes intravenously, and then 90 mg for 60 minutes followed by 60 mg for 60 minutes were infused continuously. The change of vascular obstruction caused by the treatment was assessed with magnetic resonance angiography.
  
  
  RESULTS
  In 4 patients studied, high-dose argatroban resulted in 100% recanalization of occluded vessels (5/5), even though argatroban was administrated >24 hours after onset. On the other hand, when an inadequate dose of argatroban was administered, a hemorrhage was identified. This supports our hypothesis that high-dose argatroban promotes recanalization by deactivating thrombin and exerting an anticoagulant effect on the vascular endothelium.
  
  
  CONCLUSIONS
  High-dose argatroban is an effective treatment for cerebral infarction and offers a novel therapeutic approach for delayed hospitalized patients at >24 hours after onset. Additional studies are necessary to identify the cellular and molecular mechanisms and determine the adequate dose in order to reduce risks of complication.
authors.affiliation: Department of Neurology, Iwate Prefectural Chubu Hospital, Iwate, Japan. i-hiroaki@hb.tp1.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Mizuho
authors.initials: M
authors.lastname: Koide
authors.forename: Satoko
authors.initials: S
authors.lastname: Obara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kumasaka
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects; D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation / Q000187:drug effects; D003251:Constriction, Pathologic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D007262:Infusions, Intravenous; D018810:Magnetic Resonance Angiography; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000473:pathology; D010875:Pipecolic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban