title: Safety and feasibility of a lower dose intravenous TPA therapy for ischemic stroke beyond the first three hours.
abstract: BACKGROUND
  The most common reason that patients do not receive intravenous tissue plasminogen activator (TPA) is the inability to meet the strict 3-hour treatment window. The risk/benefit ratio is more unfavorable beyond this time, but some patients might still benefit. We designed a pilot study with the hypothesis that lower dose TPA might be safe in selected patients treated beyond 3 h.
  
  
  METHODS
  To determine the range of symptomatic hemorrhage and good outcome, we prospectively gave i.v. TPA 0.6 mg/kg up to 60 mg (15% bolus, 85% infusion over 30 min) to patients with ischemic stroke beyond the first 3 h after last known to be normal. Other eligibility criteria were: NIH Stroke Scale > or =4, normal head CT scan, and clinical suspicion or transcranial Doppler (TCD) evidence of a proximal arterial occlusion.
  
  
  RESULTS
  28 patients were treated, median age 65 (range 24-88) years, median baseline NIHSS score 18 (range 7-34) points. TPA bolus was given 372 +/- 158 min after stroke onset (range 189-720). Symptomatic hemorrhage occurred in 3/28 (11%) patients, including 1 fatal bleed. Overall mortality was 6/28 (21%). Partial or complete recanalization was found in 8/20 (40%) TCD monitored patients within 2 h after TPA bolus. Early major improvement occurred in 4/28 (14%) patients.
  
  
  CONCLUSIONS
  Lower dose i.v. TPA in patients presenting beyond 3 h carries a risk of intracerebral hemorrhage. However, recanalization with dramatic recovery can still occur.
authors.affiliation: Stroke Program, Department of Neurology, University of Texas-Houston Medical School, USA. uchinok@upmc.edu
authors.forename: Ken
authors.initials: K
authors.lastname: Uchino
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Garami
authors.forename: Ashraf
authors.initials: A
authors.lastname: El-Mitwalli
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Morgenstern
authors.forename: James C
authors.initials: JC
authors.lastname: Grotta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy* / Q000453:epidemiology; D005240:Feasibility Studies; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator