Thrombolysis following a stroke

What does tPA stand for ?

Tissue plasminogen activator

How does tPA work?

• It is a thrombolytic agent (clot buster).

• Binds to fibrin in a thrombus → converting to plasmin → which initiates local fibrinolysis.

• End effect is clot breakdown, possible re-perfusion to the ischemic area, reduced tissue damage, and potentially significant improvement in clinical outcomes.

• Patients who receive thrombolysis treatment are at least 30% more likely to have little or no disability at 3 months.

What is one major risk of thrombolysis?

Intracerebral hemorrhage

What are the inclusion criteria for thrombolysis?

• Age 18-85 years

• Clinical diagnosis of ischemic stroke causing measurable neurological deficit (impairment of language, motor function, cognition, vision, neglect)

• Clearly define onset of symptoms within 4.5hrs or treatment initiation (waking from a sleep with symptoms is not acceptable due to uncertainty in length of stroke

• A CT must be performed to rule out hemorrhage

What are the exclusion criteria for thrombolysis?

• Coma or severe obtundation with fixed eye deviation and complete hemiplegia

• Minor stroke symptoms that are rapidly improving (NIHSS >4)

• Stroke in previous 3 months

• TIA without a CT head in the recent 3 months

• MI in past 30 days

• Biopsy of organ or surgery in area that would increase risk of difficult to control bleeding in past 30 days

• Recent trauma past 30 days

• Current pregnancy or childbirth past 30 days

• INR >1.5 (on warfarin or due to liver disease), patient receiving dabigatran (last dose within last 12hrs or APTT, or dilute thrombin clotting time prolonged)

Preparation pre administration of tPA

• Weight → the dose is weight dependent

• Prescription → must be prescribed as actilyse or alteplase and no tPA or thrombolysis. tPA is also a treatment administered for other conditions i.e MI. The tPA that is used for MI is different to that used in strokes.

• Equipment

• IV access → ensure pt has x2 leurs, one dedicated for tPA only. Label line.

• Observation → ensure they are in the parameters as per the guideline

• Consent

• Dose of tPA → 0.9mg per kg up to a max of 90mg . Initially 10% of the dose is to be given as a bolus over 2-3 minutes, and the remaining dose is to be given as an infusion over 60minutes.

After 10minutes following an ischemic stroke how many neurons have died?

19 million

4 major complications from tPA

• Hemorrhage

• HTN

• Orolingual angio-oedema

• Anaphylaxis

Haemorrhage complications; why?

Following administration of 90mg actilyse, there is a decrease (16%-36%) in circulating fibrinogen. High risk of fragile blood vessels bleeding into the infarcted area of the brain

Haemorrhage complications; risk management?

• Close observation of the pt

• Bleeding can occur anywhere in the body

• Haemorrhage within the brain may cause change in GCS, agitation, and worsening symptoms

Haemorrhage complications; action?

• Stop infusion if during acute phase

• Call for help

• Urgent CT scan if GCS dropped

• Apply pressure if superficial bleeding

• May need blood transfusion

• Transfusion of cryoprecipitate, fresh frozen plasma, and platelets may be considered with clinical and laboratory reassessment after each administration

Hypertension complications pre-or during thrombolysis; Why

BP to be maintained <185/110 aim to reduce likelihood of hemorrhagic transformation/oedema formation

Hypertension complications pre-or during thrombolysis; Risk management?

• Regular recording of BP

• Accurate cuff size and placement

• Ensure other causes for high BP not present i.e. pain, discomfort, need to urinate etc.

Hypertension complications pre-or during thrombolysis; Action

If BP remains > parameters give labetalol 10-20mg intravenously over 1 to 2 minutes. The dose may be repeated and/or doubled every 10-20 minutes, up to 200mg (total cumulative dose)

Alternatively, following the first bolus of labetalol, an intravenous infusion of 2 to 8mg/minute labetalol may be inititated and continued until the desired BP is reached or as per your local guidelines

Hydralazine may be considered if Labetalol contraindicated - such as hx of asthma

Consider GTN/Clonidine patches

Orolingual angio-oedema complications; Why

Increased incidence when already taking ACE-inhibitors

Orolingual angio-oedema complications; Risk management

Closely observe mouth and lips intermittently, ask pt to show tongue

Listen for increased slurring of speech

Orolingual angio-oedema complications; Action

Anti-allergic medications/adrenaline

Ability to intubate if required

Anaphylaxis contraindications re tPA; Why

Can occur with any medication

Anaphylaxis contraindications re tPA; Risk management

May appear as rash, urticaria (hives), bronchospasm, angioodema (most commonly affects the face), hypotension, shock or other symptom associated with allergic reactions

Anaphylaxis contraindications re tPA; Action

Conventional anti-allergic therapy should be initiated. Be aware that some anti-histamines can cause drowsiness and may effect GCS