NINDS Criteria
Inclusion:
- Acute ischemic stroke with clearly defined onset within 3 hours (at/after ) of proposed treatment
- Measurable deficit on NIH stroke scale
- Baseline CT head demonstrating no hemorrhage
Exclusion:
- Another stroke, intracranial/intraspinal surgery, or serious head injury ≤ 3 mo. ago
- Presence of known intracranial aneurism, AVM, or a brain mass which is known to increase the risk of bleeding
- Major surgery ≤ 14 days ago
- History of intracranial hemorrhage
- SBP > 185 or DBP > 100
- Rapidly improving or minor symptoms
- Symptoms suggestive of SAH
- GI or GU hemorrhage ≤ 21 days ago or current internal bleeding
- Arterial puncture at noncompressible site ≤ 7 days ago
- Seizure at onset of stroke
- Anticoagulation:
- Heparin ≤ 24hrs ago with ↑ PTT
- PT > 15 sec or INR > 1.6
- Platelets < 100k
- Glucose < 50mg/dL or > 400mg/dL
ECASS III
Inclusion:
- Acute ischemic stroke with clearly defined onset within 3 - 4.5 hours (at/after ) of proposed treatment
- Age 18-80 years old
- Stroke symptoms present for ≥ 30 minutes without significant improvement prior to treatment
- Baseline CT head demonstrating no hemorrhage
Exclusion: same as NINDS plus
- Age > 80 years old
- Severe stroke (NIHSS > 25 or > ⅓ of the middle cerebral artery territory)
- Both history of prior stroke and diabetes mellitus
- Any oral anticoagulant use
Relative contraindications:
- Pregnancy or post-partum period
- Myocardial infarction ≤ 3 months ago
- Known bleeding diathesis or recent lumbar puncture
- Recent pericarditis
Studies demonstrating benefit to tPA:
- NINDS
- ECASS III
- Japan Alteplase Clinical Trial (2006)
- SITS-MOST (2007)
- Third International Stroke Trial - 3 (2012)
Studies demonstrating no effect or harmful effect to tPA:
- MAST-I (1995): streptokinase < 6hrs, no benefit
- ECASS I (1995): streptokinase < 6hrs, no benefit
- MAST-E (1996): streptokinase < 6hrs, harm (stopped early)
- ASK (1996): streptokinase < 4hrs, harm (stopped early)
- ECASS II (1998): alteplase < 6hrs, no benefit
- ATLANTIS B (1999): alteplase < 6hrs, harm (stopped early)
- ATLANTIS A (2000): alteplase < 6hrs, harm (stopped early)
- DIAS-2 (2009): desmoteplase 3-9hrs, no benefit
- IST-3 (2012): alteplase < 6hrs, no benefit
Rate of intracranial hemorrhage after tPA: (Predicting sICH. J Neuro Sci. 2013.)
- Anterior circulation: 8%
- Posterior circulation: 1.2%
Dosing of tPA
Clinical Policy: Use of Intravenous tPA for the Management of Acute Ischemic Stroke in the Emergency Department. Ann Emerg Med. 2013; 61: 225-243.