Thrombolytics for acute ischemic stroke
Background
see list of all thrombolytic trials in CVA for more details
NINDS Trial (treated within 3hrs)
Benefits:
- 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)
Risks:
- 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)
- PT/PTT/INR
- 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
- Stroke or head trauma in previous 3 months
- Any history of intracranial hemorrhage
- Major surgery in the previous 14 days
- GI or urinary tract bleeding in previous 21 days
- Myocardial infarction in previous 3 months
- Arterial puncture at noncompressible site in previous 7 days
- 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
Administration
Alteplase
- 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]
Dosing:
- 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
- CVA (Main)
- Post-tPA Hemorrhage in CVA
- NIH Stroke Scale
- List of studies: Thrombolytics in CVA
- Thrombolytics
References
- 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
- ↑ 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.
- ↑ 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.