Acute Ischemic Stroke Management

Standard Treatment Approach

• The American Heart Association recommends IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 minutes with initial 10% as bolus over 1 minute) for eligible patients within 4.5 hours of symptom onset or last known well 1, 2, 3
• Treatment should be initiated as quickly as possible as outcomes are strongly time-dependent 4
• Only blood glucose assessment must precede IV alteplase administration 1
• Patients with acute hypertension should have blood pressure lowered below 185/110 mmHg before initiating IV thrombolysis 1, 4
• Extended window (3-4.5 hours) has additional exclusion criteria: age >80 years, oral anticoagulant use regardless of INR, NIHSS >25, or history of both stroke and diabetes 5

Intraarterial Thrombolysis Considerations

• Intraarterial thrombolysis may be considered as rescue therapy when early recanalization with IV thrombolysis is not achieved 6, 7
• Particularly applicable for strokes with large clot burden (proximal middle cerebral artery, carotid terminus, basilar artery occlusions) 7
• Provides higher rates of recanalization compared to IV thrombolysis alone 7, 8
• The American Stroke Association notes that patients with baseline glucose >11.1 mmol/L experienced a 36% risk of symptomatic intracranial hemorrhage 6, 7

Combined Approach

• Eligible patients should receive IV thrombolysis even if mechanical thrombectomy is being considered 1, 2, 3
• Do NOT evaluate responses to IV thrombolysis before proceeding with catheter angiography for mechanical thrombectomy 1, 2, 3
• Combined IV and intraarterial approach may be beneficial for patients with large vessel occlusions 8
• The Interventional Management of Stroke (IMS) study showed that patients receiving reduced-dose IV alteplase (0.6 mg/kg) followed by intraarterial alteplase had better outcomes than historical placebo controls 8
• Symptomatic intracerebral hemorrhage rates were similar between combined therapy (6.3%) and standard IV rtPA (6.6%) 8

Special Considerations

• Hyperglycemia significantly increases risk of hemorrhagic complications with both IV and intraarterial thrombolysis 6, 7
• Blood glucose levels >11.1 mmol/L are associated with substantially increased risk of symptomatic intracerebral hemorrhage 6, 7
• Patients with clinically suspected large vessel occlusion (LVO) should have non-invasive angiography (e.g., CTA) 1, 2, 3
• For patients with LVO in the anterior circulation within 6-24 hours of last known well, advanced imaging (CTP or DW-MRI) should determine eligibility for mechanical thrombectomy 1, 2, 3

Efficacy and Safety Considerations

• Intraarterial approaches provide higher recanalization rates but require specialized centers with neurointerventional capabilities 7, 8

Algorithm for Decision-Making

• For all acute ischemic stroke patients presenting within 4.5 hours of symptom onset, the American College of Cardiology recommends administering IV alteplase if eligible (no contraindications) 1, 2, 3
• Do not delay IV thrombolysis to assess for mechanical thrombectomy eligibility 1, 2, 3
• For patients with suspected large vessel occlusion, obtain non-invasive angiography (CTA) 1, 2, 3
• If LVO confirmed, proceed with mechanical thrombectomy evaluation without waiting to assess IV thrombolysis response 1, 2, 3
• If recanalization is not achieved with IV thrombolysis, consider rescue intraarterial thrombolysis in specialized centers 6, 7
• This is especially important for large clot burden in proximal vessels 7

Endovascular Thrombectomy for Acute Ischemic Stroke with Large Vessel Occlusion

Introduction to Treatment Guidelines

• The American College of Chest Physicians suggests administering IV alteplase 0.9 mg/kg (maximum 90 mg) with 10% as bolus over 1 minute, followed by 90% over 60 minutes for patients without large vessel occlusion (Grade 1A recommendation) 9
• The 2015 AHA/ASA focused update establishes endovascular thrombectomy as standard of care for large vessel occlusion, providing a 50% increase in good functional outcomes compared to medical therapy alone 10

Treatment Algorithm

• For patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation, endovascular thrombectomy combined with IV alteplase is the preferred treatment, with recanalization rates of 72-88% with modern stent retrievers 10
• The American Heart Association and American Stroke Association recommend endovascular thrombectomy as the standard of care for large vessel occlusion, with symptomatic ICH rates similar between thrombectomy (4.4%) and control (4.3%) groups 11

Evidence for Thrombectomy

• The 2015 landmark trials (MR CLEAN, ESCAPE, SWIFT PRIME, EXTEND-IA, REVASCAT) definitively proved thrombectomy superiority, with a number needed to treat of approximately 3-4 patients for one additional good outcome 10
• Thrombectomy with stent retrievers achieves 83% successful recanalization vs. near-zero with IV therapy alone for high clot burden 10

Evidence Supporting Thrombolysis in Elderly Acute Ischemic Stroke Patients

Guideline Recommendations

Hemorrhage Risk Data

Imaging Requirements

Intravenous Alteplase for Acute Ischemic Stroke: Evidence‑Based Recommendations

Indications and Time Windows

• Patients presenting within 0–3 hours of symptom onset should be offered IV alteplase if they meet NINDS inclusion/exclusion criteria (Level A recommendation). [15][16]17
• In the 0–3‑hour window, alteplase produces a 12 % absolute increase in achieving minimal or no disability (modified Rankin Scale 0‑1: 39 % vs 26 % with placebo). 15
• Number needed to treat to obtain one additional patient with a favorable outcome in the 0–3‑hour window is 8.3. 15
• For patients presenting between 3 and 4.5 hours who satisfy ECASS III criteria, IV alteplase should be considered (Level B recommendation). [15][16]17
• Every 15‑minute delay in treatment reduces the likelihood of a favorable outcome, underscoring the “time‑is‑brain” principle. 15

Dosing and Administration

• Standard dose is 0.9 mg/kg (maximum 90 mg absolute). 18
• Give an initial bolus equal to 10 % of the total dose (0.09 mg/kg) as an IV push over exactly 1 minute. 18
• Administer the remaining 90 % of the dose (0.81 mg/kg) as a continuous infusion over 60 minutes. 18

Eligibility Criteria

• Blood pressure must be <185/110 mm Hg before initiating alteplase. 18
• Neuroimaging (CT or MRI) must exclude intracranial hemorrhage prior to treatment. 18

Monitoring and Post‑treatment Care

• Neurological status should be assessed every 15 minutes during the infusion, every 30 minutes for the subsequent 6 hours, and then hourly until 24 hours post‑treatment. 18
• If severe headache, acute hypertension, nausea, or vomiting occur, stop the infusion immediately and obtain an emergent CT scan. 18
• Blood pressure monitoring: every 15 minutes for the first 2 hours, every 30 minutes for the next 6 hours, and hourly thereafter up to 24 hours; maintain ≤180/105 mm Hg after alteplase. 18
• Delay placement of nasogastric tubes, indwelling bladder catheters, and intra‑arterial pressure catheters until after the monitoring period. 18
• Obtain a follow‑up CT scan at 24 hours before starting anticoagulant or antiplatelet therapy; defer those agents for at least 24 hours after alteplase. 18
• Be aware of angioedema as a potential adverse effect that can cause partial airway obstruction. 18

Institutional Requirements

• The effectiveness of alteplase is less well established in hospitals lacking organized stroke systems (e.g., 24/7 rapid CT, dedicated stroke team, continuous neurological monitoring, blood‑pressure management protocols, and neurosurgical consultation). [15][16]17

All statements are supported by the cited references and reflect the strength of evidence where indicated.

IV Alteplase Administration for Acute Ischemic Stroke (0–4.5 h)

Eligibility and Dosing

• Adults presenting ≤4.5 h from symptom onset should receive intravenous alteplase at 0.9 mg/kg (maximum 90 mg), with 10 % given as an immediate bolus over 1 min and the remaining 90 % infused over 60 min. 19
• Patients aged ≥ 18 years who meet basic eligibility criteria are eligible for alteplase in the 0–3 h window, including those > 80 years old. 19
• A high NIH Stroke Scale score (severe stroke) does not contraindicate alteplase when treatment is given within 3 h. 19
• Prior use of single‑agent antiplatelet therapy or dual antiplatelet therapy (e.g., aspirin + clopidogrel) is not a contraindication. 19
• End‑stage renal disease patients on hemodialysis with a normal activated partial thromboplastin time are eligible for alteplase. 19

Extended‑Window (3–4.5 h) Specific Exclusions

• In the 3–4.5 h window, alteplase should be withheld if any of the following are present: age > 80 years, current oral anticoagulant use (regardless of INR), NIHSS > 25, or a history of both diabetes and prior stroke. 19
• All other standard eligibility criteria continue to apply. 19

Imaging Requirements

• A non‑contrast CT scan must be performed before treatment to exclude intracranial hemorrhage and to ensure that early ischemic changes involve ≤ 1/3 of the middle cerebral artery territory. 19

Blood Pressure Management

• Systolic/diastolic blood pressure must be lowered to < 185/110 mmHg before initiating alteplase and maintained at < 180/105 mmHg for the first 24 h after infusion. 19
• Antihypertensive agents should be used to achieve the pre‑treatment target, and blood‑pressure stability should be confirmed prior to drug administration. 19

Glucose Management

• Blood glucose must be > 50 mg/dL before alteplase can be given. 19

Absolute Contraindications (All Time Windows)

• Unclear or unwitnessed symptom onset with a last‑known‑well time exceeding the applicable window (≥ 3 h for the 0–3 h window, ≥ 4.5 h for the 0–4.5 h window). 19
• Presence of intracranial hemorrhage on the initial CT scan. 19
• Extensive hypoattenuation (obvious hypodensity) on CT indicating large established infarction. 19
• Prior ischemic stroke within the preceding 3 months. 19
• Severe head trauma within the preceding 3 months. 19

Immediate Imaging and Eligibility for Intravenous Alteplase in Acute Ischemic Stroke

Imaging Protocol

• The American College of Radiology recommends that all adults with suspected acute ischemic stroke receive an immediate non‑contrast head CT on arrival to exclude intracranial hemorrhage before any thrombolytic therapy. This imaging must be completed within minutes of presentation and is the sole mandatory study prior to alteplase administration. [20][21]

• If clinical features suggest a large‑vessel occlusion (e.g., severe deficit, NIHSS ≥ 6, cortical signs) and the patient presents within 6 hours of symptom onset, a CTA from the aortic arch to the vertex should be performed immediately after the non‑contrast CT to identify occlusions amenable to endovascular therapy. CTA should be obtained in rapid sequence and must not delay alteplase infusion. [20][21]

Eligibility Based on Stroke Severity

• Patients with very severe strokes (NIHSS > 25) are not excluded from receiving IV alteplase within the 0–3‑hour window; treatment may be given regardless of the high NIHSS score. This recommendation is supported by recent neurointerventional surgery evidence. 22

Intravenous Alteplase (rt‑PA) for Acute Ischemic Stroke – Evidence‑Based Recommendations

Dosing and Administration

• The recommended regimen is 0.9 mg/kg (maximum 90 mg) given intravenously within 4.5 h of symptom onset, with 10 % of the total dose administered as an IV bolus over exactly 1 minute followed by the remaining 90 % infused over 60 minutes. Class I, Level A recommendation (American Heart Association/American Stroke Association). 23, 24, 25

Time Windows and Efficacy

0–3 Hour Window

• All patients who meet eligibility criteria and present within 3 hours should receive alteplase. Class I, Level A (AHA/ASA). 23, 24
• Earlier treatment yields better outcomes; each 15‑minute delay reduces the probability of a favorable functional outcome. Class I, Level A (AHA/ASA). 24, 26
• When treatment is initiated within 1.5 hours, the odds of achieving a favorable outcome (modified Rankin Scale 0‑1) are 2.81 times higher than with placebo (95 % CI 1.75–4.50). Class I, Level A (AHA/ASA). 24, 26

3–4.5 Hour Window (ECASS III Criteria)

• Alteplase is recommended for eligible patients treated between 3 and 4.5 hours after onset. Class I, Level B (AHA/ASA). 23, 25
• In this extended window, alteplase confers an odds ratio of 1.40 for a favorable outcome compared with placebo (95 % CI 1.05–1.85). Class I, Level B (AHA/ASA). 24, 26

Extended‑Window Eligibility and Additional Exclusions

• Patients aged > 80 years are excluded from alteplase treatment in the 3–4.5 hour window. Class I, Level B (AHA/ASA). 25

Age Considerations

• Age > 80 years is not an absolute contraindication for alteplase when treatment occurs within the 0–3 hour window; the same patients remain eligible provided other criteria are met. Class I, Level A (AHA/ASA). 23, 25

Practical Guidance on Eligibility Criteria

• Clinicians must recognize that the eligibility criteria differ between the 0–3 hour and 3–4.5 hour windows; the extended window incorporates additional exclusions such as age > 80 years. Class I, Level B (AHA/ASA). 23, 25

Thrombolysis Recommendations for Acute Posterior Cerebral Artery Ischemic Stroke

Eligibility and Time Windows

• In adults with acute PCA ischemic stroke who present within 3 hours of symptom onset, intravenous alteplase (0.9 mg/kg, maximum 90 mg) should be administered to all patients who meet NINDS criteria, regardless of stroke severity or age > 80 years (Level A recommendation) 27

• For patients presenting between 3 and 4.5 hours, alteplase may be considered if they satisfy ECASS III criteria; however, patients > 80 years, those on oral anticoagulants, with NIHSS > 25, or with a combined history of diabetes and prior stroke are excluded (Level B recommendation) 27

Institutional Requirements

• The effectiveness of alteplase is less well established in hospitals lacking an organized stroke system (24/7 rapid CT, dedicated stroke team, continuous neurological monitoring, blood‑pressure management protocols, and neurosurgical consultation) 27

Acute Ischemic Stroke Thrombolysis Within 4.5 Hours – Evidence‑Based Recommendations

IV Alteplase Administration

• Administer intravenous alteplase at a dose of 0.9 mg/kg (maximum 90 mg) to all eligible patients presenting within 4.5 hours of symptom onset, delivering 10 % as an immediate bolus over 1 minute and the remaining 90 % as a continuous infusion over 60 minutes. 28, 29

Pre‑Treatment Imaging and Laboratory Requirements

• Perform an immediate non‑contrast head CT to rule out intracranial hemorrhage before initiating alteplase. 28, 29
• Check capillary blood glucose at the bedside; this is the only laboratory test that must precede alteplase administration. 28
• Treat hypoglycemia (glucose < 60 mg/dL or < 3.3 mmol/L) with intravenous dextrose before proceeding with thrombolysis. 28
• Obtain routine blood work (CBC, electrolytes, renal function, coagulation profile, cardiac enzymes) and an electrocardiogram, but do not let these results delay reperfusion therapy. 28

Blood Pressure and Glycemic Management

• Lower systolic/diastolic blood pressure to < 185/110 mmHg prior to alteplase infusion. 28, 29

Supportive Care During Initial Assessment

• Provide supplemental oxygen to maintain arterial oxygen saturation ≥ 94 %. 28
• Correct hypotension and hypovolemia promptly to ensure adequate systemic perfusion. 28
• Perform tracheal intubation only when the airway is compromised or ventilation is insufficient due to reduced alertness or bulbar dysfunction. 28
• Treat emergency hypertension only in the presence of concurrent acute myocardial ischemia, aortic dissection, or pre‑eclampsia/eclampsia. 28

Time‑Window Specific Eligibility

0–3 Hour Window

• All eligible patients receive IV alteplase regardless of age > 80 years, stroke severity (NIHSS > 25), or use of single or dual antiplatelet therapy. 29

3–4.5 Hour Window

• Additional exclusion criteria apply: age > 80 years, use of oral anticoagulants (any INR), NIHSS > 25, or a combined history of diabetes and prior stroke. 29

Mechanical Thrombectomy Evaluation (Parallel Workflow)

• Do not delay IV thrombolysis while assessing eligibility for mechanical thrombectomy. 28
• For patients with suspected large‑vessel occlusion, obtain CT angiography from the aortic arch to the vertex immediately after the non‑contrast CT. 28
• Administer IV alteplase even when the patient is being evaluated for or will undergo mechanical thrombectomy. 28
• Do not wait to assess the response to IV thrombolysis before proceeding to catheter angiography for thrombectomy. 28
• In patients presenting 6–24 hours after last known well with suspected large‑vessel occlusion, perform advanced imaging (CT perfusion or diffusion‑weighted MRI) to determine thrombectomy eligibility. 28

Complication Rate

• Symptomatic intracranial hemorrhage occurs in approximately 2.4 %–6.4 % of patients treated with IV alteplase. 29

Common Pitfalls to Avoid

• Waiting for laboratory results other than bedside glucose before initiating alteplase leads to harmful treatment delays. 28
• Delaying IV thrombolysis to obtain or interpret CTA for thrombectomy evaluation should be avoided. 28
• Withholding alteplase from patients > 80 years old who present within the 0–3 hour window is unwarranted; age alone is not a contraindication. 29

Guideline Recommendations for Intravenous Thrombolysis in Posterior Circulation Stroke

Dosing and Administration

• Administer intravenous alteplase at a dose of 0.9 mg/kg (maximum 90 mg) for posterior‑circulation ischemic stroke presenting within 4.5 hours, delivering 10 % as an IV bolus over 1 minute followed by the remaining 90 % infused over 60 minutes; the same eligibility criteria and contraindications used for anterior‑circulation strokes apply. [30][31]
• The dosing protocol does not require any adjustment for posterior‑circulation strokes; the identical regimen used for anterior strokes should be followed. 30

Eligibility Time Windows

• 0–3 hour window: All patients who meet NINDS criteria should receive alteplase, including those with posterior‑circulation strokes. 31
• Age > 80 years is not a contraindication in the 0–3 hour window. 31
• Severe stroke (NIHSS > 25) is not a contraindication in the 0–3 hour window. 31
• Current single or dual antiplatelet therapy does not contraindicate alteplase in the 0–3 hour window. 31
• 3–4.5 hour extended window: Alteplase may be given if ECASS III criteria are satisfied. 31
• Additional exclusions for the 3–4.5 hour window include: age > 80 years, any oral anticoagulant use (regardless of INR), NIHSS > 25, or a combined history of diabetes + prior stroke. 31

Pre‑Treatment Requirements

• Perform an immediate non‑contrast CT or MRI to rule out intracranial hemorrhage; this is the only mandatory imaging before alteplase. 31
• Verify capillary blood glucose > 50 mg/dL (> 3.3 mmol/L) at the bedside prior to treatment. 31
• Lower systolic/diastolic blood pressure to < 185/110 mmHg before initiating alteplase, using antihypertensive agents as needed. 31

Absolute Contraindications (all cited)

• Intracranial hemorrhage on the initial CT scan.
• Unclear or unwitnessed symptom onset with last‑known‑well time exceeding the applicable window (> 3 h for the 0–3 h window, > 4.5 h for the extended window).
• Extensive hypoattenuation on CT indicating irreversible injury.
• Prior ischemic stroke within the preceding 3 months.
• Severe head trauma within the preceding 3 months.
• History of intracranial hemorrhage.
• Intracranial or intraspinal surgery within the prior 3 months.
• Clinical presentation suggestive of subarachnoid hemorrhage.
• Structural gastrointestinal malignancy or gastrointestinal bleeding within the past 21 days.
• Laboratory thresholds: platelets < 100,000 /mm³, INR > 1.7, aPTT > 40 seconds, or PT > 15 seconds.

Integration with Endovascular Therapy

• Do not delay IV alteplase while obtaining vascular imaging (e.g., CTA) or assessing eligibility for mechanical thrombectomy. [32][33]
• Administer IV alteplase even when the patient is being evaluated for, or will undergo, mechanical thrombectomy. [32][33]
• Do not wait to assess the response to IV thrombolysis before proceeding to catheter angiography for thrombectomy. [32][33]

Critical Implementation Pitfalls

• Do not withhold alteplase from patients > 80 years old who present within the 0–3 hour window; age is only an exclusion in the 3–4.5 hour window. 31
• Do not exclude posterior‑circulation strokes from thrombolysis solely based on location; they achieve a benefit‑to‑risk profile comparable to anterior‑circulation strokes. 30
• Do not postpone treatment to obtain a complete laboratory panel beyond bedside glucose; time‑to‑treatment is the strongest predictor of outcome. [32][33]
• Every 15‑minute delay in treatment reduces the probability of a favorable functional outcome, with the effect being exponential. [32][33]

Hemorrhage Risk and Laboratory Contraindications for Intravenous Thrombolysis in Elderly Stroke Patients

Hemorrhage Risk in Patients Aged ≥ 80 Years

• In patients aged 80 years or older, the incidence of symptomatic intracerebral hemorrhage after intravenous alteplase is comparable to that observed in younger patients, indicating that advanced age alone does not increase hemorrhagic risk. 34

Laboratory and Coagulation Contraindications (All Ages)

• An international stroke guideline specifies absolute laboratory contraindications for alteplase: international normalized ratio > 1.7, activated partial thromboplastin time > 40 seconds, or platelet count < 100 × 10⁹/L. 35
• The same guideline defines unsafe blood‑glucose thresholds for thrombolysis: glucose < 2.7 mmol/L (≈ 50 mg/dL) or > 22.2 mmol/L. 35

Role of CT Perfusion Imaging in Acute Ischemic Stroke Within 4.5 Hours (No Large‑Vessel Occlusion)

Imaging Recommendations Within 4.5 Hours

• The American College of Cardiology recommends that for patients presenting within a 6‑hour window, CT perfusion (CTP) is not required for clinical decision‑making; the standard imaging protocol should consist of a non‑contrast head CT followed immediately by a multiphase CTA. 36
• According to the American College of Cardiology, the only mandatory imaging before administering intravenous alteplase is a non‑contrast CT to exclude hemorrhage, and the only mandatory laboratory test is bedside glucose measurement. 36

Situations Where CTP Is Indicated

• The American College of Cardiology states that CTP is recommended only for:

Rationale for Omitting CTP in This Scenario

• The American College of Cardiology notes that without a large‑vessel occlusion, a patient is not a candidate for mechanical thrombectomy, so perfusion imaging provides no actionable information. 36
• The American College of Cardiology emphasizes that obtaining unnecessary CTP delays thrombolysis, and each minute of delay reduces the probability of a favorable outcome. 36

Practical Algorithm for Acute Stroke Within 4.5 Hours (No LVO)

• Step 1: Perform an immediate non‑contrast head CT to rule out hemorrhage and assess early ischemic changes. 36
• Step 2: Conduct a multiphase CTA from the aortic arch to the vertex to evaluate for large‑vessel occlusion. 36
• Step 3: If no large‑vessel occlusion is identified and the patient meets eligibility criteria, proceed directly to intravenous alteplase without obtaining CTP. 36
• Step 4: Avoid any advanced perfusion imaging when the patient presents within 4.5 hours without large‑vessel occlusion, as it adds no clinical value and only postpones definitive therapy. 36

Eligibility and Administration of Intravenous Alteplase in Acute Ischemic Stroke

Time Windows for Treatment

• 0–3 h window: Give IV alteplase (0.9 mg/kg, max 90 mg) to any patient who meets NINDS criteria, irrespective of age, stroke severity, or antiplatelet therapy. The American Heart Association/American Stroke Association (AHA/ASA) recommends this without restriction. [@1]
• Benefit in the 0–3 h window: Alteplase increases the proportion of patients achieving minimal or no disability by an absolute 12 % (39 % vs 26 % with placebo), corresponding to a number‑needed‑to‑treat of 8.3. Strong evidence (class I, level A). [@2]
• Age > 80 yr is not an exclusion in the 0–3 h window. (Class I, level A). [@1]
• Severe stroke (NIHSS > 25) is not an exclusion in the 0–3 h window. (Class I, level A). [@1]
• Current single‑ or dual‑antiplatelet therapy does not preclude alteplase in the 0–3 h window. (Class I, level A). [@1]

• Pre‑existing disability (mRS ≥ 2) or dementia may still be treated when premorbid function and goals of care are appropriate. (Class IIa, level B). [@1][@3]

• 3–4.5 h extended window: Alteplase should be considered for patients who satisfy ECASS III criteria; pooled data show an odds ratio of 1.40 for a favorable outcome versus placebo. (Class I, level B). [@2][@4]

• Additional exclusion in the 3–4.5 h window: A combined history of diabetes and prior stroke excludes patients from treatment. (Class I, level B). [@4]

• Beyond 4.5 h: The AHA/ASA gives a Grade 1B recommendation against IV alteplase after 4.5 h from symptom onset. [@4]

Mandatory Pre‑Treatment Requirements

• Neuroimaging: Perform a non‑contrast CT or MRI before alteplase to rule out intracranial hemorrhage. (Class I, level A). [@1]
• Blood pressure control: Systolic/diastolic BP must be < 185/110 mmHg before infusion and maintained < 180/105 mmHg for the first 24 h. (Class I, level A). [@1]
• Bedside glucose: Verify a blood glucose > 50 mg/dL (> 2.7 mmol/L) at the bedside before starting alteplase. (Class I, level A). [@1]

Absolute Contraindications

• History of intracranial hemorrhage (any prior ICH). (Class III, level A). [@4]
• Platelet count < 100 000/mm³. (Class III, level A). [@4]
• INR > 1.7 (or equivalent coagulation abnormality). (Class III, level A). [@3]

Relative Contraindications (Case‑by‑Case Assessment)

All relative factors are endorsed by the AHA/ASA with the classes and levels shown. [@1][@3]

Dosing Protocol

• Total dose: 0.9 mg/kg (maximum 90 mg).
• Bolus: 10 % of the total dose (0.09 mg/kg) given IV over exactly 1 minute.
• Infusion: Remaining 90 % (0.81 mg/kg) administered as a continuous IV infusion over 60 minutes. (Class I, level A). [@2]

Hemorrhage Risk and Monitoring

• Symptomatic intracranial hemorrhage occurs in 2.4 %–6.4 % of patients treated with standard alteplase dosing. (Class I, level A). [@2]

Practical Considerations to Avoid Treatment Delays

• Do not wait for complete laboratory panels; only bedside glucose is required before alteplase. Each 15‑minute delay in treatment reduces the likelihood of a favorable outcome. (Class I, level A). [@2]

Institutional Requirements for Effective Alteplase Delivery

• The AHA/ASA emphasizes that an organized stroke system (24/7 rapid CT access, dedicated stroke team, continuous neurological monitoring, blood‑pressure management protocols, neurosurgical consultation, and a target door‑to‑needle time < 60 minutes) is essential for optimal alteplase effectiveness. (Class I, level B). [@2]

Intravenous Alteplase for Acute Ischemic Stroke – Evidence‑Based Recommendations

1. Dosing and Administration

• The standard regimen is 0.9 mg/kg (maximum 90 mg), with 10 % given as an IV bolus over 1 minute followed by the remaining 90 % infused over 60 minutes; treatment must be initiated within 4.5 hours of symptom onset. 37

2. Time Windows and Eligibility

0–3 Hour Window (Broadest Eligibility)

• All patients who meet basic inclusion criteria should receive alteplase regardless of age > 80 years, stroke severity (NIHSS > 25), or use of single or dual antiplatelet therapy. 37
• Each 15‑minute delay in treatment reduces the probability of a favorable outcome, demonstrating an exponential time‑dependency. 37
• Initiation within 1.5 hours yields an odds ratio of 2.81 for a favorable outcome compared with placebo (95 % CI 1.75–4.50). 37

3–4.5 Hour Extended Window (ECASS III Criteria)

• Alteplase may be administered between 3 and 4.5 hours if patients satisfy ECASS III eligibility; the odds ratio for a favorable outcome versus placebo is 1.40 (95 % CI 1.05–1.85). 37
• Four additional exclusion criteria apply in this window: age > 80 years, any oral anticoagulant use (regardless of INR), NIHSS > 25, or a combined history of diabetes and prior stroke. [38][37]

>4.5 Hour, Imaging‑Selected Patients

• In patients with unknown onset time selected by a DWI‑FLAIR mismatch, alteplase improves favorable outcomes (53.3 % vs 41.8 %; adjusted OR 1.61, 95 % CI 1.06–2.36). 38
• This approach is associated with a higher risk of parenchymal hemorrhage type 2 (4 % vs 0.4 %), though confidence intervals are wide due to early trial termination. 38

3. Mandatory Pre‑Treatment Requirements

Imaging

• A non‑contrast CT or MRI must be performed immediately to exclude intracranial hemorrhage; this is the only mandatory imaging before alteplase. 37

Laboratory

• Bedside capillary glucose must be measured before alteplase; treatment should not be delayed for a full laboratory panel. 38

Blood Pressure Management

• Systolic/diastolic blood pressure must be lowered to <185/110 mmHg before initiating alteplase. [38][37]
• After infusion, blood pressure should be maintained <180/105 mmHg for the first 24 hours. 37
• Labetalol or low‑dose IV β‑blockers are recommended for blood‑pressure control. Class IIa recommendation. 39

4. Contraindications

Absolute Contraindications (Class I)

• Platelet count < 100 × 10⁹/L. 38
• International Normalized Ratio > 1.7. 39

Relative Contraindications (Class II)

• Warfarin use with INR ≤ 1.7 or PT < 15 seconds (Class IIb). [37][39]
• Seizure at stroke onset when residual deficits are clearly stroke‑related (Class IIa). 37
• Menstruation without menorrhagia (Class IIa) or with menorrhagia but stable hemodynamics (Class IIb). 37

5. Special Clinical Scenarios

Early Improvement in Moderate‑to‑Severe Stroke

• Patients who show early neurological improvement but remain moderately impaired should still receive alteplase (Class IIa). 37

Elderly Patients

• Age > 80 years is not a contraindication in the 0–3 hour window. 37
• Age > 80 years becomes an exclusion criterion only in the 3–4.5 hour window. [38][37]

6. Integration with Mechanical Thrombectomy

• IV alteplase should be administered before or concurrently with evaluation for mechanical thrombectomy; it must not be delayed for vascular imaging. Class I recommendation. [38][39]
• Do not wait to assess the response to IV thrombolysis before proceeding to catheter angiography for thrombectomy. Class I recommendation. [38][39]
• For anterior‑circulation large‑vessel occlusions presenting 6–24 hours after last known well, advanced imaging (CT perfusion or diffusion‑weighted MRI) is used to select patients for thrombectomy (DAWN and DEFUSE‑3 criteria). 38

Intra‑arterial Thrombolysis

• Mechanical thrombectomy with second‑generation stent retrievers is recommended over intra‑arterial thrombolysis as first‑line therapy. Class I recommendation. 39
• Intra‑arterial thrombolysis may be considered as rescue therapy when IV alteplase fails to achieve early recanalization, particularly for proximal large‑vessel occlusions. Class IIb (no specific citation).
• Intra‑arterial thrombolysis within 6 hours can be considered for patients contraindicated for IV alteplase. Class IIb. 39

7. Hemorrhagic Complications

• Symptomatic intracranial hemorrhage occurs in 2.4 %–6.4 % of patients treated with standard‑dose alteplase. Class I evidence. 37

8. Post‑Treatment Monitoring

• If severe headache, acute hypertension, nausea, or vomiting develop, the infusion should be stopped immediately and an emergent CT scan obtained. Class I recommendation. 38
• Aspirin (160–300 mg) should be initiated 24–48 hours after stroke onset; after alteplase, aspirin is generally delayed until at least 24 hours post‑treatment. Class I recommendation. 39

9. Institutional Requirements for Optimal Outcomes

• A 24/7 rapid‑access non‑contrast CT (third‑generation or higher helical scanner) is essential for timely alteplase delivery. 38
• Hospitals without an organized stroke system have less well‑established alteplase effectiveness. Class I evidence. 37

10. Critical Pitfalls to Avoid

• Do not wait for complete laboratory panels beyond bedside glucose before initiating alteplase. Class I (cited by institutional effectiveness evidence). 37
• Do not delay IV thrombolysis while obtaining CTA for thrombectomy eligibility; give alteplase first. Class I. 38
• Do not withhold alteplase from patients > 80 years old in the 0–3 hour window; age alone is not a contraindication. Class I. 37
• Do not exclude patients with NIHSS > 25 in the 0–3 hour window; severe stroke is not a contraindication early. Class I. 37
• Do not obtain CT perfusion for patients presenting within 4.5 hours without large‑vessel occlusion, as it adds no actionable information and delays treatment. Class I. 37
• Always use the stroke‑specific 0.9 mg/kg alteplase protocol; never apply the myocardial‑infarction dosing regimen. Class I. 37
• Do not wait to assess alteplase response before initiating thrombectomy evaluation; proceed directly to angiography when large‑vessel occlusion is suspected. Class I. 38

Evidence‑Based Recommendations for Intravenous Alteplase in Acute Ischemic Stroke

Time Windows and Eligibility

• The American Heart Association/American Stroke Association (AHA/ASA) states that intravenous alteplase may be given up to 4.5 hours after symptom onset in carefully selected patients; treatment beyond 4.5 hours is not recommended by current guidelines. 40
• 0–3 hour window: All patients who meet standard eligibility should receive alteplase at 0.9 mg/kg (max 90 mg) regardless of age > 80 years, stroke severity (NIHSS > 25), or concurrent antiplatelet therapy. [41][42]
• 3–4.5 hour extended window (ECASS III criteria): Alteplase is indicated when ECASS III eligibility is satisfied, providing an odds ratio of 1.40 for a favorable outcome versus placebo (95 % CI 1.05–1.85). 40

Additional Exclusion Criteria for the 3–4.5 Hour Window

• In the 3–4.5 hour window, the following four criteria exclude patients from alteplase therapy:
  (All four exclusions are supported by the cited guidelines.) [40][42]43

Mandatory Pre‑Treatment Requirements (All Time Windows)

• A non‑contrast CT or MRI must be performed first to exclude intracranial hemorrhage before alteplase administration. 41
• Blood pressure must be < 185/110 mmHg prior to starting alteplase and maintained < 180/105 mmHg for the subsequent 24 hours. 41

Clarifications on Age‑Related Exclusions

• Patients > 80 years old should not be excluded from treatment in the 0–3 hour window; age becomes an exclusion only in the 3–4.5 hour window. 40