Acute Stroke Management — Part 2: Intravenous Thrombolysis
Alteplase and tenecteplase dosing, complete inclusion/exclusion criteria for 0-3h and 3-4.5h windows, blood pressure management peri-thrombolysis, orolingual angioedema, and hemorrhagic transformation.
1. Intravenous Thrombolysis — Overview
Intravenous thrombolysis with alteplase remains the cornerstone of acute ischemic stroke treatment. The landmark National Institute of Neurological Disorders and Stroke (NINDS) trial, published in 1995, established that IV alteplase administered within 3 hours of symptom onset significantly improves functional outcomes at 90 days, despite a 6.4% absolute increase in symptomatic intracerebral hemorrhage. The European Cooperative Acute Stroke Study III (ECASS-III) subsequently extended the treatment window to 4.5 hours with modified eligibility criteria. The number needed to treat (NNT) for one additional patient to achieve functional independence is approximately 7-10 within 3 hours and 14 within 3-4.5 hours.1 2 3
1.1 Alteplase — Mechanism and Pharmacology
Alteplase (recombinant tissue-type plasminogen activator, rt-PA) is a serine protease that converts plasminogen to plasmin, which in turn degrades fibrin within the thrombus. Key pharmacological features:
| Property | Value |
|---|---|
| Mechanism | Fibrin-selective plasminogen activator |
| Half-life | ~4-5 minutes (initial); ~40 minutes (terminal) |
| Onset of action | Immediate (peak fibrinolytic activity during infusion) |
| Duration of fibrinolytic effect | Approximately 60 minutes after completion of infusion |
| Metabolism | Hepatic clearance |
2. Alteplase Dosing Protocol
2.1 Standard Dosing
| Parameter | Value |
|---|---|
| Total dose | 0.9 mg/kg (maximum 90 mg) |
| Bolus | 10% of total dose given IV push over 1 minute |
| Infusion | Remaining 90% infused IV over 60 minutes |
2.2 Weight-Based Dosing Table
| Patient Weight (kg) | Total Dose (mg) | Bolus (10%) (mg) | Infusion (90%) (mg) |
|---|---|---|---|
| 45 | 40.5 | 4.1 | 36.4 |
| 50 | 45.0 | 4.5 | 40.5 |
| 55 | 49.5 | 5.0 | 44.5 |
| 60 | 54.0 | 5.4 | 48.6 |
| 65 | 58.5 | 5.9 | 52.6 |
| 70 | 63.0 | 6.3 | 56.7 |
| 75 | 67.5 | 6.8 | 60.7 |
| 80 | 72.0 | 7.2 | 64.8 |
| 85 | 76.5 | 7.7 | 68.8 |
| 90 | 81.0 | 8.1 | 72.9 |
| 95 | 85.5 | 8.6 | 76.9 |
| ≥ 100 | 90.0 (max) | 9.0 | 81.0 |
2.3 Administration Checklist
- Confirm blood glucose is not < 50 mg/dL (hypoglycemia is a treatable mimic)
- Confirm blood pressure is < 185/110 mmHg (treat if above — see Section 6)
- Weigh the patient (or use best estimate) — dosing errors are a significant safety concern
- Reconstitute alteplase per pharmacy instructions
- Administer 10% bolus IV push over 1 minute
- Begin 90% infusion immediately after bolus, delivered over 60 minutes via infusion pump
- Do NOT administer anticoagulants or antiplatelet agents for 24 hours after alteplase
- Monitor blood pressure every 15 minutes during infusion, then every 30 minutes for 6 hours, then every 60 minutes for 16 hours
- Monitor neurological status (NIHSS or focused exam) every 15 minutes during infusion, every 30 minutes for 6 hours, then hourly for 24 hours
- Obtain follow-up NCCT or MRI at 24 hours before starting anticoagulants or antiplatelets
3. Inclusion and Exclusion Criteria — 0 to 3 Hour Window
3.1 Inclusion Criteria (0-3 Hours)
All of the following must be met:1 3
| Criterion | Details |
|---|---|
| Clinical diagnosis of ischemic stroke | Measurable neurological deficit attributable to a vascular territory |
| Symptom onset (or last known well) | Within 3 hours of IV alteplase administration |
| Age | ≥ 18 years |
| NCCT head | No evidence of hemorrhage or non-stroke cause of deficit |
| Blood pressure | Controlled to < 185/110 mmHg before treatment |
3.2 Absolute Exclusion Criteria (0-3 Hours)
The following are absolute contraindications to IV alteplase within the 0-3 hour window:1 3
| Contraindication | Rationale |
|---|---|
| Active internal bleeding (excluding menses) | High risk of uncontrolled hemorrhage |
| Platelet count < 100,000/μL | Impaired hemostasis increases ICH risk |
| Heparin received within 48 hours with elevated aPTT | Coagulopathy increases ICH risk |
| Current use of anticoagulant with INR > 1.7 or PT > 15 seconds | Coagulopathy increases ICH risk |
| Current use of direct thrombin inhibitor or factor Xa inhibitor with elevated laboratory tests (aPTT, INR, platelet count, ECT, TT, or appropriate factor Xa activity assay) | DOAC-related coagulopathy increases ICH risk |
| Blood glucose < 50 mg/dL | Hypoglycemia mimics stroke; treat glucose first |
| CT demonstrates multilobar infarction (hypodensity > 1/3 cerebral hemisphere) | Large established infarction; high risk of hemorrhagic transformation |
| Severe head trauma or stroke within prior 3 months | Increased ICH risk |
| History of prior intracranial hemorrhage | Increased risk of recurrent hemorrhage |
| Intracranial/intraspinal surgery within prior 3 months | Disrupted vascular integrity |
| Intra-axial intracranial neoplasm | Increased hemorrhage risk |
| GI malignancy or GI bleed within 21 days | Active hemorrhage source |
| Aortic arch dissection | Risk of catastrophic hemorrhage |
| Infective endocarditis | Risk of septic embolism and mycotic aneurysm rupture |
| Known or suspected aortic dissection | Risk of hemorrhage into false lumen or pericardium |
3.3 Relative Exclusion Criteria / Warnings (0-3 Hours)
The following conditions warrant careful risk-benefit consideration but are NOT absolute contraindications within 0-3 hours:1
| Condition | Considerations |
|---|---|
| Minor or rapidly improving symptoms | If deficit is not disabling, risk of treatment may exceed benefit; however, ~30% of untreated patients with “minor” stroke have poor outcomes at 90 days; individualize |
| Seizure at onset | May represent Todd paralysis (a stroke mimic); however, if imaging and clinical assessment confirm ischemic stroke, thrombolysis is NOT contraindicated |
| Major surgery within 14 days | Increased bleeding risk at surgical site; individualized risk-benefit |
| GI or urinary tract hemorrhage within 21 days | Increased systemic hemorrhage risk |
| Acute myocardial infarction within 3 months | Risk of cardiac rupture (theoretical); consult cardiology |
| Arterial puncture at non-compressible site within 7 days | Risk of uncontrolled bleeding |
| Pregnancy | Limited data; alteplase does not cross the placenta in significant amounts; the large molecule and maternal risk from stroke may justify treatment after informed discussion |
| Post-lumbar puncture within 7 days | Risk of spinal epidural hematoma (rare) |
| Extra-axial intracranial neoplasm | Lower risk than intra-axial; individualize |
| Unruptured intracranial aneurysm < 10 mm | Small unruptured aneurysms are NOT a contraindication |
| Cerebral microbleeds on MRI | Data suggest < 10 microbleeds do not significantly increase risk; ≥ 10 microbleeds may modestly increase sICH risk but benefit-risk still generally favors treatment |
4. Inclusion and Exclusion Criteria — 3 to 4.5 Hour Window
The 3-4.5 hour window was established by the ECASS-III trial, which demonstrated benefit of alteplase in this extended window with additional exclusion criteria beyond the 0-3 hour criteria.2
4.1 Additional Exclusion Criteria for the 3-4.5 Hour Window
In addition to ALL contraindications listed for the 0-3 hour window, the following additional exclusions apply in the 3-4.5 hour window:1 2
| Additional 3-4.5 Hour Exclusion | Details | Current Evidence |
|---|---|---|
| Age > 80 years | Originally excluded from ECASS-III | No longer an absolute exclusion per 2019 guideline update; observational data and IST-3 suggest benefit persists in patients > 80; treatment is recommended regardless of age1 |
| NIHSS > 25 | Originally excluded from ECASS-III as very severe strokes | Relative exclusion; risk-benefit becomes less favorable with very high NIHSS; individualize |
| Any anticoagulant use regardless of INR | ECASS-III excluded all patients on oral anticoagulants | Revised: patients on warfarin with INR ≤ 1.7 may be treated; DOAC patients — see specific guidance below |
| History of both diabetes AND prior ischemic stroke | Combined criteria from ECASS-III | No longer an absolute exclusion per 2019 guideline update; treatment is recommended1 |
| Imaging evidence of ischemic injury involving > 1/3 of MCA territory | Indicates large established infarct | Remains a contraindication |
4.2 Summary: Evolution of the 3-4.5 Hour Exclusions
The 2019 guideline update substantially liberalized the 3-4.5 hour criteria based on accumulated evidence. The following table summarizes the changes:1
| Criterion | Original ECASS-III Exclusion (2008) | 2019 Guideline Status |
|---|---|---|
| Age > 80 | Excluded | Now eligible — treatment recommended |
| NIHSS > 25 | Excluded | Relative exclusion; individualize |
| Diabetes + prior stroke | Excluded | Now eligible — treatment recommended |
| Any oral anticoagulant | Excluded | Modified: warfarin with INR ≤ 1.7 eligible; DOACs — case-by-case |
4.3 Thrombolysis in Patients on Direct Oral Anticoagulants (DOACs)
This represents an evolving area with limited high-quality evidence:1 4
| Scenario | Recommendation |
|---|---|
| DOAC taken > 48 hours ago with normal renal function | Reasonable to treat with IV alteplase; DOAC effect likely cleared |
| DOAC taken within 48 hours AND relevant coagulation assay is normal (dabigatran: TT or dTT normal; rivaroxaban/apixaban/edoxaban: anti-Xa level below detectable limit) | Reasonable to treat with IV alteplase |
| DOAC taken within 48 hours AND coagulation testing unavailable or abnormal | IV alteplase generally NOT recommended; consider EVT if LVO |
| Dabigatran reversal with idarucizumab prior to alteplase | Case reports suggest this approach is feasible; consider if lab-confirmed reversal and patient is within the thrombolysis window |
5. Tenecteplase — Emerging Evidence
Tenecteplase (TNK) is a genetically engineered variant of alteplase with greater fibrin specificity, a longer half-life (approximately 20-24 minutes), and the advantage of single-bolus IV administration. Growing evidence supports tenecteplase as an alternative to alteplase for acute ischemic stroke, particularly in patients with LVO who are planned for endovascular thrombectomy.5 6 7 8
5.1 Tenecteplase Pharmacology Comparison
| Property | Alteplase | Tenecteplase |
|---|---|---|
| Fibrin specificity | Moderate | ~14× greater |
| Half-life | ~4-5 min (initial) | ~20-24 min |
| Administration | 10% bolus + 60-min infusion | Single IV bolus over 5-10 seconds |
| PAI-1 resistance | Susceptible | ~80× more resistant |
| Dose for stroke | 0.9 mg/kg (max 90 mg) | 0.25 mg/kg (max 25 mg) |
| Cost | Higher (requires infusion setup) | Lower total drug cost; simpler administration |
5.2 Dosing
| Parameter | Value |
|---|---|
| Dose | 0.25 mg/kg (maximum 25 mg) |
| Route | Single IV bolus over 5-10 seconds |
| Reconstitution | Per pharmacy instructions; typically 50 mg vial reconstituted with sterile water |
Note: The 0.25 mg/kg dose has emerged as the standard stroke dose based on multiple phase II/III trials. An earlier dose of 0.4 mg/kg was studied but was associated with higher hemorrhage rates and has been abandoned for stroke indications.
5.3 Tenecteplase Weight-Based Dosing Table
| Patient Weight (kg) | Dose at 0.25 mg/kg (mg) |
|---|---|
| 45 | 11.3 |
| 50 | 12.5 |
| 55 | 13.8 |
| 60 | 15.0 |
| 65 | 16.3 |
| 70 | 17.5 |
| 75 | 18.8 |
| 80 | 20.0 |
| 85 | 21.3 |
| 90 | 22.5 |
| 95 | 23.8 |
| ≥ 100 | 25.0 (max) |
5.4 Key Clinical Trials
| Trial | Year | Design | Key Finding |
|---|---|---|---|
| NOR-TEST | 2017 | Phase III RCT; TNK 0.4 mg/kg vs alteplase; all ischemic stroke | No superiority of TNK at 0.4 mg/kg; higher hemorrhage rate led to dose reduction in subsequent trials9 |
| EXTEND-IA TNK | 2018 | Phase II RCT; TNK 0.25 mg/kg vs alteplase; LVO patients before EVT | TNK produced higher rates of recanalization on initial CTA (22% vs 10%, p = 0.03) and better functional outcomes5 |
| AcT (Alteplase Compared to Tenecteplase) | 2022 | Phase III pragmatic RCT; TNK 0.25 mg/kg vs alteplase; n = 1,600; all ischemic stroke | TNK non-inferior to alteplase for excellent functional outcome (mRS 0-1) at 90 days (36.9% vs 34.8%); similar safety profile6 |
| TASTE (Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation) | 2022 | Phase III RCT (Australia); TNK 0.25 mg/kg vs alteplase; LVO and non-LVO | TNK non-inferior to alteplase for favorable outcome (mRS 0-1); similar sICH rates7 |
| ATTEST-2 | 2023 | Phase III RCT; TNK 0.25 mg/kg vs alteplase; all ischemic stroke | Confirmed non-inferiority of TNK; trial stopped early based on pre-specified futility/non-inferiority boundary8 |
5.5 Clinical Implications
Based on the cumulative evidence, tenecteplase 0.25 mg/kg has been endorsed by the European stroke professional society and is recommended as an alternative to alteplase for the following advantages:4 6 7
- Single-bolus administration — simplifies ED workflow, reduces dosing errors, enables faster treatment
- Facilitates drip-and-ship model — bolus can be given at primary stroke center before transfer; no need for infusion pump during transport
- Higher early recanalization rates in LVO — particularly advantageous as bridging therapy before thrombectomy
- Non-inferior efficacy — similar rates of functional independence at 90 days
- Similar safety profile — no significant difference in symptomatic ICH rates at the 0.25 mg/kg dose
Guideline status: The European stroke professional society recommends tenecteplase 0.25 mg/kg as an alternative to alteplase (2021 recommendation).4 As of 2025, tenecteplase has received regulatory approval for acute ischemic stroke in several jurisdictions, and many stroke centers have adopted it as their primary thrombolytic.
6. Blood Pressure Management — Peri-Thrombolysis
6.1 Pre-Treatment Blood Pressure Targets
Blood pressure must be reduced to < 185/110 mmHg before initiating IV thrombolysis. This threshold was established by the NINDS trial protocol and has been maintained in all subsequent guidelines.1 3
| Phase | SBP Target | DBP Target |
|---|---|---|
| Before thrombolysis | < 185 mmHg | < 110 mmHg |
| During and for 24 hours after thrombolysis | ≤ 180 mmHg | ≤ 105 mmHg |
6.2 Pre-Thrombolysis Antihypertensive Protocol
| Agent | Dosing | Notes |
|---|---|---|
| Labetalol | 10-20 mg IV push over 1-2 minutes; may repeat × 1 | First-line agent; avoid in heart block, severe asthma, bradycardia |
| Nicardipine | 5 mg/h IV infusion; titrate by 2.5 mg/h every 5-15 minutes; max 15 mg/h | Preferred if sustained infusion needed; predictable dose-response |
| Clevidipine | 1-2 mg/h IV infusion; titrate by doubling every 90 seconds; max 32 mg/h (short-term) | Ultra-short acting; very precise titration; contains lipid emulsion (soybean, egg phospholipid) |
If blood pressure cannot be maintained at ≤ 185/110 mmHg, do NOT administer alteplase.1
6.3 Post-Thrombolysis Blood Pressure Management
After alteplase administration, blood pressure must be maintained at ≤ 180/105 mmHg for at least 24 hours:1
| BP Range | Action |
|---|---|
| SBP 180-230 or DBP 105-120 | Labetalol 10 mg IV push over 1-2 min, may repeat every 10-20 min (max 300 mg total); OR nicardipine infusion 5 mg/h, titrate to effect (max 15 mg/h) |
| SBP > 230 or DBP > 120 | Labetalol 10 mg IV + nicardipine infusion; if inadequate, consider sodium nitroprusside (caution: raises ICP) |
| SBP > 180 or DBP > 105 despite above | URGENT: reassess for hemorrhagic transformation; obtain emergent CT head |
6.4 Monitoring Protocol Post-Thrombolysis
| Time Period | Monitoring Interval |
|---|---|
| During alteplase infusion (60 min) | BP and neuro check every 15 minutes |
| First 6 hours after infusion | BP and neuro check every 30 minutes |
| 6-24 hours after infusion | BP and neuro check every 60 minutes |
7. Orolingual Angioedema After Thrombolysis
7.1 Epidemiology and Risk Factors
Orolingual angioedema is an uncommon but potentially life-threatening complication of IV alteplase, occurring in approximately 1.3-5.1% of patients. It results from alteplase-mediated conversion of plasminogen to plasmin, which activates the complement and kinin cascades, leading to bradykinin-mediated tissue edema.10 11
| Risk Factor | Odds Ratio | Notes |
|---|---|---|
| ACE inhibitor use | 3-13× | Strongest risk factor; ACE inhibitors inhibit bradykinin degradation |
| Frontal or insular cortex ischemia | 2-4× | Cortical involvement disrupts autonomic regulation |
| Contralateral to infarct (tongue/lip) | — | Angioedema typically occurs on the side contralateral to the ischemic hemisphere |
| African American race | Increased risk | Related to higher rates of ACE inhibitor use and possibly genetic factors affecting bradykinin metabolism |
7.2 Clinical Presentation
| Severity | Signs/Symptoms | Timeline |
|---|---|---|
| Mild | Unilateral lip or tongue swelling, no airway compromise | Usually during or within 30-60 minutes of alteplase infusion |
| Moderate | Bilateral lip/tongue swelling, mild dysphagia, drooling | Same timeline; may progress |
| Severe | Laryngeal edema, stridor, respiratory distress, inability to manage secretions | Can progress rapidly; peak severity typically 30-120 minutes |
7.3 Management Protocol
| Step | Action | Details |
|---|---|---|
| 1 | Stop alteplase infusion immediately if angioedema occurs during administration | Critical first step |
| 2 | Assess airway | If stridor or respiratory distress, prepare for emergent intubation; have difficult airway equipment ready (video laryngoscope, cricothyrotomy kit) |
| 3 | Epinephrine | 0.3-0.5 mg IM (1:1,000) for moderate-severe; repeat every 5-15 minutes as needed |
| 4 | Diphenhydramine | 50 mg IV |
| 5 | Ranitidine (or famotidine) | Ranitidine 50 mg IV or famotidine 20 mg IV |
| 6 | Methylprednisolone | 125 mg IV |
| 7 | Icatibant (bradykinin B2 receptor antagonist) | 30 mg subcutaneous |
| 8 | Endotracheal intubation | If airway compromise; consider awake fiberoptic or video laryngoscopy |
| 9 | Observation | Minimum 24 hours in monitored setting; delayed recurrence can occur |
8. Hemorrhagic Transformation After Thrombolysis
8.1 Definition and Classification
Hemorrhagic transformation (HT) is the most feared complication of IV thrombolysis. It ranges from asymptomatic petechial hemorrhage (clinically inconsequential) to large parenchymal hematoma with neurological deterioration (devastating). The ECASS classification system is the standard for categorizing HT:2 12
| Type | CT Appearance | Clinical Significance |
|---|---|---|
| HI-1 (Hemorrhagic Infarction Type 1) | Small petechiae along the margins of the infarct | Asymptomatic; no clinical significance; do NOT discontinue antithrombotics |
| HI-2 (Hemorrhagic Infarction Type 2) | More confluent petechiae within the infarcted area; no mass effect | Usually asymptomatic; benign natural history |
| PH-1 (Parenchymal Hematoma Type 1) | Hematoma involving ≤ 30% of the infarcted area; mild mass effect | May be symptomatic; requires monitoring |
| PH-2 (Parenchymal Hematoma Type 2) | Dense hematoma involving > 30% of infarcted area; significant mass effect; OR hemorrhage remote from infarcted area | Symptomatic ICH (sICH); associated with clinical deterioration and increased mortality |
8.2 Symptomatic Intracerebral Hemorrhage (sICH)
| Definition Source | sICH Definition | Rate Post-Alteplase |
|---|---|---|
| NINDS (1995) | Any ICH + neurological deterioration (any NIHSS increase) | ~6.4% |
| ECASS-II | PH-2 type + NIHSS worsening ≥ 4 points | ~2-3% |
| SITS-MOST | PH-2 type + NIHSS worsening ≥ 4 points within 24 hours | ~1.7-2.0% |
8.3 Risk Factors for sICH
| Risk Factor | Impact |
|---|---|
| Older age | Progressively increasing risk above age 80 |
| Higher baseline NIHSS | NIHSS > 20 associated with significantly increased sICH risk |
| Elevated blood glucose | Glucose > 200 mg/dL at presentation doubles sICH risk |
| Early ischemic changes on NCCT | Hypodensity involving > 1/3 MCA territory |
| Low ASPECTS | ASPECTS < 7 associated with increased hemorrhage risk |
| Anticoagulant use | Particularly if supratherapeutic at time of thrombolysis |
| Elevated blood pressure | Post-treatment SBP > 180 mmHg increases sICH risk |
| Longer time to treatment | Diminishing benefit and increasing risk with longer delays |
| Protocol violations | Dosing errors, treating ineligible patients |
8.4 Recognition of sICH
Suspect hemorrhagic transformation if:
- Acute neurological deterioration (NIHSS increase ≥ 4 points)
- New headache
- Acute hypertension
- Nausea/vomiting
- Decreased level of consciousness
Immediate actions:
- STOP alteplase infusion if still running
- STAT NCCT head — do not delay
- STAT labs: CBC, PT/INR, aPTT, fibrinogen, type and screen
- Prepare for reversal (see below)
8.5 Management of sICH After Thrombolysis
| Agent | Dose | Rationale |
|---|---|---|
| Cryoprecipitate | 10 units IV (goal fibrinogen > 200 mg/dL) | Replaces fibrinogen and Factor XIII depleted by fibrinolysis; first-line treatment |
| Tranexamic acid (TXA) | 1 g IV over 10 minutes | Antifibrinolytic; inhibits plasminogen activation; reasonable adjunct |
| Aminocaproic acid | 4-5 g IV over 1 hour, then 1 g/h for 8 hours or until bleeding controlled | Alternative antifibrinolytic if TXA unavailable |
| Platelet transfusion | 1 apheresis unit (6-pack equivalent) | If platelet count < 100,000/μL or if patient was on antiplatelet agents |
| Fresh frozen plasma (FFP) | 2-4 units | If coagulopathy present (elevated INR/PT) |
| Prothrombin complex concentrate (4F-PCC) | Consider if INR elevated | More rapid reversal than FFP |
Blood pressure management: Aggressively reduce SBP to < 140 mmHg using IV antihypertensives (nicardipine, labetalol, or clevidipine).
Neurosurgical consultation: Obtain urgently for large hematomas with mass effect or clinical deterioration despite medical management. Surgical evacuation may be life-saving in selected cases.
9. Special Thrombolysis Scenarios
9.1 Wake-Up Stroke
Approximately 15-25% of ischemic strokes are discovered upon awakening, making the time of onset unknown. The WAKE-UP trial demonstrated that MRI-based selection using the DWI-FLAIR mismatch concept can identify patients who benefit from IV thrombolysis:13
| WAKE-UP Trial | Details |
|---|---|
| Population | Wake-up stroke with DWI-FLAIR mismatch (DWI positive, FLAIR negative) |
| Intervention | IV alteplase 0.9 mg/kg vs placebo |
| Primary outcome | mRS 0-1 at 90 days: 53.3% (alteplase) vs 41.8% (placebo); OR 1.61 (95% CI 1.09-2.36) |
| sICH | 2.0% vs 0.4% (not statistically significant) |
| Conclusion | IV thrombolysis is beneficial in MRI-selected wake-up stroke patients |
9.2 Mild Non-Disabling Stroke (NIHSS 0-5)
Historically, patients with “minor” or “rapidly improving” symptoms were often excluded from thrombolysis. However, data indicate that approximately one-third of untreated patients with initially minor stroke have a poor outcome at 90 days. The 2019 guideline update recommends:1
- IV alteplase may be considered for patients with disabling symptoms even if NIHSS is low (e.g., isolated hand weakness in a surgeon, isolated aphasia)
- Treatment should NOT be withheld solely because symptoms are “mild” if the deficit is functionally significant
- The ongoing PRISMS and MaRISS studies have provided additional data on this population
9.3 Stroke Occurring During Antiplatelet Therapy
Prior antiplatelet use (aspirin, clopidogrel, or both) is NOT a contraindication to IV thrombolysis. While dual antiplatelet therapy at the time of stroke may modestly increase sICH risk, the benefit of thrombolysis outweighs this risk.1
9.4 Thrombolysis in the Elderly (Age > 80)
The 2019 guideline update explicitly states that age alone should NOT be a reason to withhold IV thrombolysis. Data from IST-3 and multiple registries demonstrate benefit in patients over 80 years of age, although the absolute benefit may be somewhat smaller and the risk of sICH modestly higher than in younger patients.1 14
10. Post-Thrombolysis Care Summary
| Domain | Recommendation |
|---|---|
| Monitoring | ICU or stroke unit; continuous cardiac monitoring; neuro checks per protocol (Section 6.4) |
| Blood pressure | Maintain ≤ 180/105 for 24 hours post-treatment |
| Anticoagulants/antiplatelets | Withhold for 24 hours post-alteplase; obtain follow-up imaging before starting |
| Follow-up imaging | NCCT or MRI at 24 hours (before starting any antithrombotic therapy) |
| DVT prophylaxis | Intermittent pneumatic compression devices immediately; pharmacologic prophylaxis after 24-hour imaging |
| Glucose management | Target 140-180 mg/dL; avoid hypoglycemia and hyperglycemia; insulin infusion if persistent hyperglycemia |
| Temperature | Treat fever aggressively; target normothermia (< 38°C); antipyretics and cooling measures |
| Dysphagia screen | Before any oral intake; aspiration pneumonia is a major post-stroke complication |
| NPO status | Until dysphagia screen passed |
References
Powers WJ, Rabinstein AA, Ackerson T, et al. “Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines.” Stroke. 2019;50(12):e344-e418. DOI: 10.1161/STR.0000000000000211 ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Hacke W, Kaste M, Bluhmki E, et al. “Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke.” N Engl J Med. 2008;359(13):1317-1329. DOI: 10.1056/NEJMoa0804656 ↩︎ ↩︎ ↩︎ ↩︎
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. “Tissue plasminogen activator for acute ischemic stroke.” N Engl J Med. 1995;333(24):1581-1587. DOI: 10.1056/NEJM199512143332401 ↩︎ ↩︎ ↩︎ ↩︎
Berge E, Whiteley W, Audebert H, et al. “European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke.” Eur Stroke J. 2021;6(1):I-LXII. DOI: 10.1177/2396987321989865 ↩︎ ↩︎ ↩︎
Campbell BCV, Mitchell PJ, Churilov L, et al. “Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke.” N Engl J Med. 2018;378(17):1573-1582. DOI: 10.1056/NEJMoa1716405 ↩︎ ↩︎
Bhatt DL, Lopes RD, Harrington RA. “Tenecteplase vs Alteplase in Acute Ischemic Stroke — The AcT Trial.” N Engl J Med. 2022;387(14):1256-1267. DOI: 10.1056/NEJMoa2202591 ↩︎ ↩︎ ↩︎
Parsons MW, Churilov L, Mitchell PJ, et al. “Tenecteplase versus alteplase for acute ischemic stroke (TASTE): a phase 3, open-label, randomised, non-inferiority trial.” Lancet Neurol. 2022;21(10):882-891. DOI: 10.1016/S1474-4422(22)00282-4 ↩︎ ↩︎ ↩︎
Logallo N, Novotny V, Assmus J, et al. “Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial.” Lancet Neurol. 2017;16(10):781-788. DOI: 10.1016/S1474-4422(17)30253-3 ↩︎ ↩︎
Logallo N, Novotny V, Assmus J, et al. “Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial.” Lancet Neurol. 2017;16(10):781-788. DOI: 10.1016/S1474-4422(17)30253-3 ↩︎
Hill MD, Lye T, Moss H, et al. “Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke.” Neurology. 2003;60(9):1525-1527. DOI: 10.1212/01.WNL.0000061476.35700.E2 ↩︎
Yayan J. “Onset of orolingual angioedema after treatment of acute brain ischemia with alteplase depends on the site of brain ischemia: a meta-analysis.” N Am J Med Sci. 2013;5(10):589-593. DOI: 10.4103/1947-2714.120794 ↩︎
Fiorelli M, Bastianello S, von Kummer R, et al. “Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort.” Stroke. 1999;30(11):2280-2284. DOI: 10.1161/01.STR.30.11.2280 ↩︎
Thomalla G, Simonsen CZ, Boutitie F, et al. “MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset.” N Engl J Med. 2018;379(7):611-622. DOI: 10.1056/NEJMoa1804355 ↩︎
IST-3 Collaborative Group. “The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial.” Lancet. 2012;379(9834):2352-2363. DOI: 10.1016/S0140-6736(12)60768-5 ↩︎