Thrombolytics for acute ischemic stroke


see list of all thrombolytic trials in CVA for more details

NINDS Trial (treated within 3hrs)


  • 12% absolute risk reduction benefit (NNT = 8-9) at 3 months
  • Lower percentage of patients who left hospital severely disabled
  • Comparable 3-month mortality rate (even with increased rate of ICH)


  • 1% increase in mortality
  • 5% increase in nonfatal intracranial hemorrhage

ECASS Trial (treated within 4.5hrs)

  • Confirmed NINDS findings even when therapeutic window extended to 4.5hr
  • As a result AHA/ASA now recommends tPA for patients presenting up to 4.5hr after symptom onset

Studies Required

  • Physical exam: NIH Stroke Scale
  • Head CT
  • CBC (hemoglobin, plt)
    • Only need to wait for result if suspicion of abnormal value, patient has received heparin or warfarin, or use of anticoagulants is unknown
  • Glucose
  • ECG
  • Urine pregnancy (pregnancy is relative contraindication)

tPA <3hr

Inclusion Criteria

  • Diagnosis of ischemic stroke causing measurable neuro deficit
  • Clear onset (last witnessed well) <3hr (see below for extension to <4.5hr)
  • Age >18yr

Exclusion Criteria

  • Historical
  • Clinical
    • Spontaneously clearing stroke symptoms
    • Only minor and isolated neurologic signs
    • Seizure at stroke onset
  • Persistent SBP >185 or DBP >110 despite treatment
  • Use of direct thrombin inhibitors (e.g. dabigatran, argatroban) or direct factor Xa inhibitors (e.g. rivaroxaban, apixaban) with elevated aPTT, INR, or factor Xa assay
  • Active bleeding or acute trauma (fracture) on exam
  • Labs
    • Platelets <100K
    • Serum glucose <50, >400
    • INR >1.7 or PT >15 sec if on warfarin
    • Elevated PTT if on heparin
  • Head CT
    • Evidence of hemorrhage
    • Evidence of multilobar infarction with hypodensity involving >33% of cerebral hemisphere
    • Intracranial neoplasm, AVM, or aneurysm
  • Use of dabigatran within 48hrs is relative contraindication

Relative Exclusion Criteria

  • Minor or rapidly improving stroke symptoms
  • Pregnancy
  • Seizure at onset with postictal residual neuro impairments

tPA between 3-4.5hrs

Inclusion Criteria

  • Same as for <3hr

Exclusion Criteria

  • All of the above plus:
    • Age >80yr
    • Combination of both previous stroke and DM
    • NIHSS score >25
    • Oral anticoagulant use regardless of INR



  • NOTE - in stroke, do not give aspirin until 24 hours after giving tPA, as ASA with tPA does not improve outcomes and increases bleed risk[1]
  • Do not give acutely heparin (or any anticoagulation) if giving tPA[2]


  • 0.9mg/kg IV (max 90mg total)
    • 10% of dose is administered as bolus; rest is given over 60min
  • Neuro check Q15min x 2hr
  • No anticoagulation/antiplatelets x 24hr
  • Blood pressure (keep SBP <180, DBP <105)

If SBP is >180-230 or DBP is >120:

  • Nicardipine 5 mg/hr by slow infusion (50 mL/hr) initially; may be increased by 2.5 mg/hr every 15 minutes; not to exceed 15 mg/hr OR
  • Labetalol 10mg IV over 1–2 min; repeat dose q10–20min up to 300mg max OR
  • Labetalol 10mg IV followed by infusion at 2–8 mg/min

If BP not controlled by above measures:

  • Nitroprusside 0.5–10mcg/kg/min
  • Continuous arterial monitoring advised
  • Use with caution in patients with hepatic or renal insufficiency

tPA Complications

See Also


  • Hacke W, Kaste M, Bluhmi E, et al: Thrombolysis with alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med 359(13): 1317, 2008
  • ACEP/AAN Guidelines
  • AHA/ASA Guidelines
  1. Zinkstok SM, Roos YB, ARTIS Investigators . Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet (2012) 380(9843):731–7.10.1016/S0140-6736(12)60949-0.
  2. Periprocedural Antithrombotic Treatment During Acute Mechanical Thrombectomy for Ischemic Stroke: A Systematic Review. Rob A. van de Graaf, Vicky Chalos, Gregory J. del Zoppo, Aad van der Lugt, Diederik W. J. Dippel, Bob Roozenbeek. Front Neurol. 2018; 9: 238.