title: Proposed approach to thrombolysis in dabigatran-treated patients presenting with ischemic stroke.
abstract: BACKGROUND
  Acute ischemic stroke thrombolysis in patients taking dabigatran is controversial because of a presumed increased risk of symptomatic hemorrhagic transformation. Using data from our local hematopathology laboratory, we developed a thrombolysis protocol for acute ischemic stroke patients taking dabigatran.
  
  
  METHODS
  A local thrombin time (TT)-dabigatran concentration relationship was calculated using dabigatran calibrators. The effect of dabigatran on activated partial thromboplastin time (aPTT) and prothrombin time (PT) (international normalized ratio [INR]) was also measured. A protocol was developed, in which a dabigatran concentration less than 10 ng/mL (corresponding to a TT<38 seconds or a normal aPTT) was selected as the upper limit for thrombolysis. Consecutive patients presenting with acute stroke were then enrolled in this prospective study.
  
  
  RESULTS
  In the 8 months after development of the protocol, 13 potential thrombolysis candidates taking dabigatran were assessed at a median (interquartile range) time of 192 (143) minutes. The median National Institutes of Health Stroke Scale score was 18 (20). The mean time from arrival to TT, aPTT, and PT (INR) results were 39±4.1 minutes, 21±6.5 minutes, and 21±6.5 minutes, respectively. Based on TT/aPTT, 4 patients were ineligible for thrombolysis. Six patients were not treated because of minor or resolving symptoms and another presented with intracerebral hemorrhage. Two patients were treated with intravenous tissue plasminogen activator (tPA), without symptomatic hemorrhagic transformation in either case. In 3 patients (42.8%), aPTT was normal, despite a prolonged TT.
  
  
  CONCLUSIONS
  Administration of intravenous tPA in dabigatran-treated patients is feasible. Although, the relationship between dabigatran concentrations and coagulation measures varies between laboratories, individual protocols, preferably based on TT, can be developed at acute stroke treatment centers.
authors.affiliation: Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kate
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
authors.forename: Artur
authors.initials: A
authors.lastname: Szkotak
authors.affiliation: Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Witt
authors.affiliation: Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Ashfaq
authors.initials: A
authors.lastname: Shuaib
authors.affiliation: Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada. Electronic address: ken.butcher@ualberta.ca.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Butcher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000517:prevention & control; D000069604:Dabigatran; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D020521:Stroke / Q000188:drug therapy* / Q000517:prevention & control; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D005343:Fibrinolytic Agents; D015091:beta-Alanine; D010959:Tissue Plasminogen Activator; D000069604:Dabigatran
keywords: Thrombolysis; anticoagulation; dabigatran; partial thromboplastin time; stroke; thrombin time