Thrombolysis and

Thrombectomy in acute
ischemic stroke
Amit prajapati Santosh Ghimire
Resident Resident
Thrombolysis
Prehospital Systems
• Public education programs focused on stroke systems and the need to
seek emergency care.
• Designed to decrease stroke onset to emergency department arrival
times and to increase timely use of thrombolysis and thrombectomy.
• EMS (Emergency medical services )systems.
• Mobile stroke units (MSUs).
Hospital Stroke Teams
• An organized protocol.
• Designation of an acute stroke team.
• Multicomponent quality improvement initiatives, which include ED
education and multidisciplinary teams with access to neurological
expertise
In-hospital timeline
• A door-to-needle time of ≤60 minutes is the benchmark for achieving
rapid treatment with IVT.
• Evaluation by physician – 10 minutes elapsed from arrival
• Stroke or neurologic expertise contacted (ie, stroke team) – ≤15 minutes
elapsed
• Head CT or MRI scan – ≤25 minutes elapsed
• Interpretation of neuroimaging scan – ≤45 minutes elapsed
• Start of IVT – ≤60 minutes elapsed
• Although IVT is the first priority, evaluation and preparation for
possible MT should proceed during and after IVT.
Emergency Evaluation and Treatment
• Stroke scales
• NIHSS (National institute of health stroke scale)
Disabling symptoms
• Complete hemianopia: ≥2 on NIHSS
• Severe aphasia: ≥2 on NIHSS
• Visual extinction: ≥1 on NIHSS
• Any weakness limiting sustained effort against gravity: ≥2 on NIHSS
• Any deficits that lead to a total NIHSS >5
• Any remaining deficit considered potentially disabling by the patient,
family, or the treating clinician
Head and neck imaging
• Systems should be established so that brain imaging studies can be
performed as quickly as possible.
• NCCT Head – effective to exclude ICH
• MRI – effective as NCCT to exclude ICH
• CTA with CTP or MRA with DWI with or without perfusion
• who awake with stroke or have unclear time of onset >4.5 hours from
baseline or last known well (can benefit from IV alteplase administration
within 4.5 hours of stroke symptom).
• selecting candidates for mechanical thrombectomy.
Inclusion criteria
• Clinical diagnosis of ischemic stroke causing measurable neurologic
deficit.
• Onset of symptoms <4.5 hours before beginning treatment; if the
exact time of stroke onset is not known, it is defined as the last time
the patient was known to be normal or at neurologic baseline.
• Age ≥18 years.
Inclusion criteria
• WAKE-UP or unknown time of onset–
- Who have a DW-MRI lesion smaller than one-third of MCA
territory and no visible signal change on FLAIR.
- Thrombolysis administered within 4.5 hour of stroke symptom
recognition can be beneficial.

AHA/ASA guideline: 2019 Update to the 2018 Guidelines for the Early Management of Acute
Ischemic Stroke
Wake-up stroke/unknown onset
Intravenous thrombolysis is recommended for those with
• Wakeup stroke, last seen well more than 4.5 h earlier
- who have MRI DWI-FLAIR mismatch, and for whom mechanical
thrombectomy is either not indicated or not planned

• Wakeup stroke, Within nine hours from the midpoint of sleep

- who have CT or MRI core/perfusion mismatch and for whom mechanical
thrombectomy is either not indicated or not planned

European Stroke Organisation (ESO) guidelines on intravenous thrombolysis

for acute ischaemic stroke 2021
• 4.5 – 9 h (known onset), perfusion mismatch
• Whom mechanical thrombectomy is either not indicated or not
planned, intravenous thrombolysis is recommended.
• No consensus – when eligible for MT
• Consensus for thrombolysis if MT is not available (6/9)

European Stroke Organisation (ESO) guidelines on intravenous thrombolysis

for acute ischaemic stroke 2021
MRI core/perfusion mismatch
In the individual participant data meta analysis by Campbell et al.,
core/perfusion mismatch was assessed with an automated processing
software and defined as follows:
• Infarct core** volume < 70 ml
• and Critically hypoperfused† volume/ Infarct core** volume > 1.2
• and Mismatch volume > 10 ml

** rCBF <30% (CT perfusion) or ADC < 620 µm2/s (Diffusion MRI)
† Tmax >6 s (perfusion CT or perfusion MRI)
Evidence-based Recommendation
Mothership, ≤4.5 hrs of symptom onset

For patients directly admitted to a thrombectomy-capable centre for an acute ischaemic stroke (≤4.5 hrs of
symptom onset) with anterior circulation large vessel occlusion and who are eligible for both treatments,
we recommend intravenous thrombolysis plus mechanical thrombectomy over mechanical thrombectomy
alone.

Both treatments should be performed as early as possible after hospital arrival. Mechanical thrombectomy
should not prevent the initiation of intravenous thrombolysis, and intravenous thrombolysis should not delay
mechanical thrombectomy.

Quality of evidence: Moderate ⊕⊕⊕

Strength of recommendation: Strong ↑↑
Expert Consensus Statement
Mothership, wake-up stroke

For patients directly admitted to a thrombectomy-capable centre within 4.5 hours of symptom recognition
after wake-up stroke caused by anterior circulation large vessel occlusion, we suggest intravenous
thrombolysis plus mechanical thrombectomy over mechanical thrombectomy alone in selected patients.

The selection criteria are detailed in the corresponding European Guidelines. Notably, eligibility imaging
criteria for IVT include DWI-FLAIR mismatch or perfusion core/penumbra mismatch*.
*Perfusion core/penumbra mismatch:
- Infarct core** volume < 70 ml
- and Critically hypoperfused† volume / Infarct core** volume > 1.2
- and Mismatch volume > 10 ml

** rCBF <30% (CT perfusion) or ADC < 620 µm2/s (Diffusion MRI)
† Tmax >6s (perfusion CT or perfusion MRI)

2019 ESO-ESMINT Guidelines on mechanical thrombectomy (Turc G et al, Eur J Stroke 4(1):6-12)
2021 ESO Guidelines on intravenous thrombolysis (Berge E et al, Eur J Stroke 6(1):I-LXII)
Absolute contraindications
• NCCT head: intracranial hemorrhage or subarachnoid hemorrhage
• NCCT Head: extensive regions of hypodensity consistent with
irreversible injury
• Ischemic stroke or severe head trauma in previous 3 months
• Intracranial or intraspinal surgery within prior 3 months.
• History of intracranial hemorrhage.
Absolute contraindications
• GI malignancy or GI bleed within 21 days.
• Active internal bleeding (i.e., Aortic Dissection known or suspected)
• Unable to maintain BP < 185/110 despite aggressive antihypertensive
treatment.
• Infective endocarditis
• Intra-axial or intracranial neoplasm
Absolute contraindications
Laboratory
• Blood glucose <50 mg/dL (however should treat if stroke symptoms persist after
glucose normalized)
• Results not required before treatment unless patient is on anticoagulant therapy or
there is another reason to suspect an abnormality:
• INR >1.7
• Platelet count < 100,000 PT > 15 sec, aPTT > 40 sec
• Unknown coagulation tests those on VKA.
Medications
• Full dose LMWH within last 24 hours (patients on prophylactic dose of LMWH
should NOT be excluded)
• DOAC within last 48 hours
Relative contraindications
• Mild Non disabling stroke (NIHSS 0-5)
• Patient/family refusal
• Pregnancy
• Major surgery or major trauma within 14 days
• Past gastrointestinal or genitourinary bleeding
• Untreated intracranial vascular malformation
Relative contraindications
• Seizure at onset with postictal phenomenon (Reasonable if weakness
is due to stroke and not a postictal phenomenon)
• Myocardial infarction within last 3 months
• Blood glucose > 400 mg/dL (however should treat if stroke symptoms
persist after glucose normalized)
Drugs
• Alteplase
• The alteplase dose is calculated at 0.9 mg/kg of actual body weight, with a
maximum dose of 90 mg.

• 10 % of the dose is given as an intravenous bolus over one minute and the
remainder is infused over one hour.
Tenecteplase
• ESO 2021 / ASA 2019
Tenecteplase as a reasonable alternative
- Acute ischemic stroke of < 4.5 h duration and with large vessel
occlusion who are candidates for mechanical thrombectomy and for whom
intravenous thrombolysis is considered before thrombectomy.
• ESO 2021
• Acute ischemic stroke of <4.5 h duration and not eligible for thrombectomy,
intravenous thrombolysis with alteplase over Tenecteplase is suggested.
ESO recommendation on Tenecteplase for AIS 2023
Tenecteplase
• The dose of Tenecteplase is 0.25 mg/kg (maximum total dose 25 mg)
given in a single intravenous bolus over 5 seconds, followed by a
saline flush.
Blood pressure
• Hypotension and hypovolemia should be corrected to maintain
systemic perfusion levels necessary to support organ function.
• Target BP before initiating thrombolysis : SBP <185 mm Hg , diastolic
BP <110 mm Hg
• Labetalol 10–20 mg IV over 1–2 min, may repeat 1 time; or
• Nicardipine 5 mg/h IV, titrate up by 2.5 mg/h every 5–15 min,
maximum 15 mg/h; when desired BP reached, adjust to maintain
proper BP limits; or
• Clevidipine 1–2 mg/h IV, titrate by doubling the dose every 2–5 min
until desired BP reached; maximum 21 mg/h
• Other agents (eg, hydralazine, enalaprilat) may also be considered
• If BP is not maintained ≤185/110 mm Hg, do not administer alteplase
• Maintain BP ≤180/105 mm Hg during and after thrombolysis.
• Monitor BP every 15 min for 2 h from the start of therapy, then every
30 min for 6 h, and then every hour for 16 h.
• If BP not controlled consider labetalol, Nicardipine, Clevidioine.
• If BP not controlled or diastolic BP >140 mm Hg, consider IV sodium
nitroprusside.
Special population
Sonothrombolysis
Age > 80y
Multimorbid, frailty, pre-stroke disability
Minor stroke (disabling)
Minor stroke (non disabling)
Rapidly improving symptoms
Thrombolysis recommendation
Not recommended
Recommended – high, strong
Suggest – very low, weak
Recommended - Mod, strong
Not recommended
Consensus – thrombolysis
Special population Thrombolysis recommendation
Antiplatelet prior to stroke Suggested
Anticoagulants before stroke
VKA, INR ≤ 1.7 Recommended – low, strong
INR > 1.7 , or unknown coagulation testing Not recommended
NOAC during last 48 h, no coagulation test Not recommended
available

Thrombocytopenia (<100k/mL) Not recommended

Monitoring
• Vital signs and neurologic status - every 15 minutes for two hours,
then every 30 minutes for six hours, then every 60 minutes until 24
hours.
• Blood pressure ≤ 180/105 mmHg during the first 24 hours.
• Antithrombotic agents, such as heparin, warfarin, direct oral
anticoagulants, or antiplatelet drugs, should not be administered for
at least 24 hours.
• Intra-arterial catheters, indwelling bladder catheters, and nasogastric
tubes - avoid for at least 24 hours.
Complication: ICH
• 5 to 7 percent
• Suspected in any patient who develops sudden neurologic
deterioration, a decline in level of consciousness, new headache,
nausea and vomiting, or a sudden rise in blood pressure after
thrombolytic therapy is administered, especially within the first 24
hours of treatment.
• Consider bleeding the likely cause of neurologic worsening after use
of a thrombolytic drug until a brain scan confirms or refutes
hemorrhage.
ICH
• Immediately discontinue ongoing infusion of thrombolytic drug.
• Obtain stat noncontract head CT or MRI.
• Obtain blood samples for type and cross match, complete blood
count, platelet count, PT, INR, aPTT, and fibrinogen
 ICH : Management
If symptomatic intracerebral hemorrhage is confirmed by imaging:
• Cryoprecipitate 10 units over 10 to 30 minutes and more as needed to achieve a
serum fibrinogen level of 150 to 200 mg/dL.
• Aminocaproic acid 4 to 5 g IV over one hour followed by 1 g/hour for 8 hours until
bleeding is controlled, or tranexamic acid 10 to 15 mg/kg IV over 10 to 20 minutes.
• For patients on VKA - vitamin K and PCC as adjunctive therapy to cryoprecipitate, or
FFP if PCC is not available.
• PRP for thrombocytopenia.
• For patients receiving UFH - give 1 mg of protamine for every 100 units of UFH
received in the preceding four hours.
• Neurosurgery and hematology consultations; consider evacuation of the hematoma.
Angioedema
Summarizing thrombolysis
• Well functioning hospital stroke response team
• NIHSS assessment
• Eligibility criteria
• < 4.5 hours of duration
• Wake up stroke within 4.5 h symptom recognition with DWI FLAIR mismatch
• 4.5 h – 9 h with small core and large salvageable penumbra
• Tenecteplase as better alternative.
• Evaluation for MT.
 Mechanical
Thrombectomy
(MT) for acute ischemic stroke

Dr. Santosh Ghimire

Resident, IM PAHS
• Benefit of reperfusion decreases over
time.

• Timely restoration of cerebral blood

flow is important.

• Intravenous thrombolytic therapy

with alteplase or tenecteplase is first-
line therapy (<4.5 Hr) even if MT is
being considered.
 Patient Selection
• Ischemic stroke
• Within 24 hours of the time last known to be well
• First, give intravenous thrombolysis if eligible
• Consider Additional MT in following patients
• CT or DWI
• No haemorrhage, Alberta Stroke Program Early CT Score (ASPECTS)
≥3.
• CTA or MRA
• Proximal large vessel occlusion (including the intracranial internal
carotid artery or middle cerebral artery extending to the proximal
M2 segment) in the anterior circulation.
• Persistent, potentially disabling neurologic deficit(NIHSS ≥ 6)
To compute the
ASPECTS, 1 point
is subtracted from
10 for any
evidence of early
ischemic change
for each of the
defined regions.
https://jour-nals.sagepub.com/doi/full/10.1177/2396987319832140
Age stratified 90‐day outcomes of the STRATIS registry
(n=984)

https://doi.org/10.1161/STROKEAHA.117.016456
 Who not to Treat !

• Presence of a large established hypodensity on head CT.

• No ischemic penumbra (ie, no mismatch suggesting no salvageable

brain tissue) on CTP or DWI/PWI if these studies are performed.

• Presence of a large core infarct (eg, defined by an ASPECTS 3 to 5 or

imaging showing a core volume ≥50 mL) and severe pre-stroke
comorbidities (eg, pre-existing severe disability such as mRS 4 to 5, or
life expectancy less than six months).
 Individualized Decisions
• Salvageable brain tissue who are beyond the 24-hour time
window

• Medium vessel occlusion (eg, anterior cerebral artery,

middle cerebral artery beyond the proximal M2 segment,
and posterior cerebral artery)

• minor stroke (NIHSS ≤5)

• deficits that appear disabling
• clinical worsening despite intravenous thrombolysis
Visual decision aid Visual decision aid
depicting the depicting the
benefits and risks benefits and risks
of endovascular of endovascular
thrombectomy thrombectomy for
added to IV tPA patients ineligible
versus IV tPA for IV tPA
alone

https://www.ahajour
nals.org/doi/full/10.1
161/STROKEAHA.110.
581058
 Basilar Artery Occlusion

• Beneficial for patients of Chinese

ancestry

• NIHSS score ≥10

• Posterior circulation ASPECTS (pc-

ASPECTS) score is consistent with
a limited extent of ischemia
One point each is
subtracted from 10 for
early ischemic changes in
the left or right
thalamus, cerebellum, or
posterior cerebral artery
(PCA) territory,
respectively, and two
points in any part of the
midbrain or pons
 Procedure
• General anaesthesia or conscious sedation
• Catheterization: femoral artery puncture
• The stent retriever is then inserted through the catheter to reach the
clot.
• Stent retrievers
• Catheter aspiration devices
• Device is pulled back.
• Goal: modified Thrombolysis in Cerebral Infarction (mTICI) perfusion
grade 3>2b
 antegrade reperfusion
no perfusion
past the initial occlusion,
with limited distal branch
filling and minimal or
slow distal reperfusion
antegrade reperfusion antegrade reperfusion complete antegrade
of less than half of the
of more than half of the reperfusion of the
previously occluded previously occluded previously occluded
target artery´s ischemic target artery´s ischemic target artery´s ischemic
territory territory territory
• Antithrombotic agents?
• no indication for the routine use.

• BP ?
• keep SBP between 150 and 180 mmHg
prior to reperfusion
• Some suggest no use of
antihypertensives prior to reperfusion
unless SBP exceeds 200 mmHg
• If treated with IV thrombolytics
maintain BP ≤180/105 mmHg during
and for 24 hours following alteplase.
Tandem lesion: simultaneous presence of high-grade stenosis or occlusion of the
cervical internal carotid artery and thromboembolic occlusion of the intracranial
terminal internal carotid artery or its branches
Thank You

http://www.uptodate.com/2023
https://jour-nals.sagepub.com/doi/full/10.1177/2396987319832140
https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.110.581058
Thrombectomy Animation – YouTube
https://doi.org/10.1161/STROKEAHA.117.016456