Answer
The American Heart Association/American Stroke Association (AHA/ASA) inclusion guidelines for the administration of rt-PA in under 3 hours are as follows [7] :
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Diagnosis of ischemic stroke causing measurable neurologic deficit
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Neurologic signs not clearing spontaneously
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Neurologic signs not minor and isolated
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Symptoms not suggestive of subarachnoid hemorrhage
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Onset of symptoms less than 3 hours hours before beginning treatment
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No head trauma or prior stroke in past 3 months
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No MI in prior 3 months
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No GI/GU hemorrhage in previous 21 days
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No arterial puncture in noncompressible site during prior 7 days
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No major surgery in prior 14 days
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No history of prior intracranial bleed
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Systolic blood pressure under 185 mm Hg, diastolic blood pressure under 110 mm Hg
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No evidence of acute trauma or bleeding
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Not taking an oral anticoagulant, or if so, INR under 1.7
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If taking heparin within 48 hours, a normal activated prothrombin time (aPT)
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Platelet count of more than 100,000/μL
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Blood glucose greater than 50 mg/dL (2.7 mmol)
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No seizure with residual postictal impairments
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Computed tomography (CT) scan does not show evidence of multilobar infarction (hypodensity over one-third hemisphere)
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The patient and family understand the potential risks and benefits of therapy
In May 2009, and again in March 2013, the AHA/ASA guidelines for the administration of rt-PA following acute stroke were revised to expand the window of treatment from 3 hours to 4.5 hours to provide more patients with an opportunity to receive benefit from this effective therapy. [4, 8, 9] Eligible patients should receive rtPA therapy as soon as possible, ideally within 60 minutes of hospital arrival. IV fibrinolysis can be considered in patients with rapidly improving symptoms, mild stroke deficits, major surgery within the past 3 months, and recent myocardial infarction; risks should be weighed against benefits. [19]
Eligibility criteria for treatment in the 3 to 4.5 hours after acute stroke are similar to those for treatment at earlier time periods, with any 1 of the following additional exclusion criteria:
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Patients older than 80 years
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All patients taking oral anticoagulants are excluded regardless of the international normalized ratio (INR)
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Patients with baseline National Institutes of Health Stroke Scale (NIHSS) score > 25
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Patients with a history of stroke and diabetes
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Patients with imaging evidence of ischemic damage to more than one third of the middle cerebral artery (MCA) territory [19]
A Scientific Statement from the AHA/ASA, “Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke,” published in 2015, contained recommendations further elucidating the eligibility criteria for rtPA (alteplase) therapy in patients with acute ischemic stroke. Those recommendations included, but were not limited to, the following [38] :
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For otherwise medically eligible patients aged 18 years or older, intravenous alteplase administration within 3 hours is equally recommended for patients under age 80 years and older than age 80 years
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For severe stroke symptoms, intravenous alteplase is indicated within 3 hours from symptom onset of ischemic stroke
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For patients with mild but disabling stroke symptoms, intravenous alteplase is indicated within 3 hours from symptom onset of ischemic stroke
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Intravenous alteplase treatment in the 3- to 4.5-hour time window is recommended for those patients under age 80 years who have no history of both diabetes mellitus and prior stroke, who have a NIHSS score under 25, who are not taking any oral anticoagulants, and who have no imaging evidence of ischemic injury involving more than one third of the middle cerebral artery territory
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Intravenous alteplase treatment is reasonable for patients who present with moderate to severe ischemic stroke and demonstrate early improvement but remain moderately impaired and potentially disabled in the judgment of the examiner
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The time from last seen normal to treatment with intravenous alteplase should be under 3 hours for eligible patients with the use of standard eligibility criteria
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Intravenous alteplase administration is recommended in the setting of early ischemic changes (EICs), seen on CT scan, of mild to moderate extent (other than frank hypodensity)
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For EICs on CT scan, administering intravenous alteplase to patients whose CT brain imaging exhibits extensive regions of clear hypoattenuation is not recommended
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Intravenous alteplase is reasonable for the treatment of acute ischemic stroke complications of cardiac or cerebral angiographic procedures, depending on the usual eligibility criteria
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Intravenous alteplase is recommended for patients taking antiplatelet drug monotherapy before stroke on the basis of evidence that the benefit of alteplase outweighs a possible small increased risk of symptomatic intracerebral hemorrhage (sICH)
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The bar graphs show the percent of patients with different outcomes on the modified Rankin Scale of global disability 3 months following treatment with tPA or placebo in the NINDS-tPA Trials 1 and 2. Rankin 0 = no symptoms; 1 = No significant disability, despite symptoms; able to perform all usual duties and activities; 2 = Slight disability; unable to perform all previous activities but able to look after own affairs without assistance; 3 = Moderate disability; requires some help, but able to walk without assistance; 4 = Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5 = Severe disability; bedridden, incontinent, and requires constant nursing care and attention; 6 = Dead. Image courtesy of UCLA Stroke Center.
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Visual decision aid to help patients and families assess benefits and risks of thrombolytic therapy within the first 3 hours of onset. Image publicly available under a Creative Commons Use with Attribution license.
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Thrombolytic therapy carries a small, but significant, risk of life-threatening hemorrhage. For this reason, it is important to carefully screen for exclusionary criteria prior to administering t-PA, including hemorrhage, large areas of infarction and patient presentation beyond the 3-hour window for IV t-PA or possibly beyond 6 hours for IA TPA. This case illustrates this point in a patient with normal NCCT who was treated with IV t-PA for acute stroke and over the next 2 days, developed significant hemorrhage. Hemorrhage is noted to progressively increase in size along the medial margin of the right thalamus and the third ventricle. There is obstructive hydrocephalus with hemorrhage layering in the dependent portions of the occipital horns.
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This 48-year-old male presented with acute left-sided hemiplegia, facial palsy, and right-sided gaze preference. Angiogram with selective injection of the right internal carotid artery demonstrates occlusion of the M1 segment of the right MCA and A2 segment of the right ACA. Image courtesy of Concentric Medical.
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Follow-up imaging in the same patient as in the previous image after mechanical embolectomy demonstrates complete recanalization of the right middle cerebral artery and partial recanalization of the right A2 segment. Image courtesy of Concentric Medical.
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Cerebral angiogram demonstrates an occlusion of the distal basilar artery in this 31-year-old male approximately 4.5 hours after symptom onset. Image courtesy of Concentric Medical.
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Image on the left demonstrates deployment of a clot retrieval device in the same patient as in the previous image. Follow-up angiogram after embolectomy demonstrates recanalization of the distal basilar artery with filling of the superior cerebellar arteries and posterior cerebral arteries. The patient had complete resolution of symptoms following embolectomy. Image courtesy of Concentric Medical.
