Safety and feasibility of a lower dose intravenous TPA therapy for ischemic stroke beyond the first three hours

Cerebrovasc Dis. 2005;19(4):260-6. doi: 10.1159/000084090. Epub 2005 Feb 22.


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.

Subjects and 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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / epidemiology
  • Feasibility Studies
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Injections, Intravenous
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Risk Factors
  • Stroke / drug therapy*
  • Stroke / epidemiology
  • Thrombolytic Therapy*
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects


  • Fibrinolytic Agents
  • Tissue Plasminogen Activator