Stroke Thrombolysis with Alteplase

Introduction

Thrombolytic therapy with alteplase within 4.5 hours of symptom onset significantly reduces death and disability at 90 days. Alteplase (recombinant human tissue-type Plasminogen Activator or “rt-PA”) is a thrombolytic agent that binds to the fibrin clot and induces the conversion of plasminogen to plasmin. This in turn induces fibrinolysis of the clot.

Stroke thrombolysis is delivered jointly by stroke consultants in NHS Ayrshire & Arran and NHS Lanarkshire. In hours via face-to-face delivery and out of hours consultation with the patient via video conferencing. Stroke consultants will review the CT brain scan and make the decision whether to offer thrombolysis or not.

All potential stroke thrombolysis patients should be admitted to the emergency department at University Hospital Crosshouse.

Inclusion criteria

  • Clinical diagnosis of ischaemic stroke causing a measurable deficit
  • Onset of symptoms within 4.5 hours
  • CT appearances consistent with acute ischaemic stroke/normal CT
  • Risks and benefits explained to patient/relative and verbal consent given

Exclusion criteria

Absolute contraindications

  • Symptoms of stroke began >4.5 hours prior to start of infusion
  • Time of onset unknown
  • Hypersensitivity to alteplase or to any of the excipients

  • Alteplase is contraindicated in cases where there is a high risk of haemorrhage such as:

    • Significant bleeding disorder at present or within the past 6 months
    • Known haemorrhagic diathesis
    • Patients receiving effective oral anticoagulant treatment, e.g., DOAC or warfarin (INR ≥1.7)
    • Administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory
    • Manifest or recent severe/dangerous bleeding in the last 21 days
    • Known history of or suspected intracranial haemorrhage (ICH). Evidence of ICH on CT scan
    • Suspected subarachnoid haemorrhage (SAH) or condition after SAH from aneurysm
    • History suggestive of SAH even if CT scan is normal
    • Persistent uncontrolled arterial hypertension - systolic BP >185mmHg or diastolic BP >110mmHg despite aggressive management (i.e. IV labetalol or glyceryl trinitrate)
    • Bacterial endocarditis, pericarditis
    • Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial-aneurysm, arterial/venous malformations
    • Severe liver disease, including hepatic failure, cirrhosis, portal hypertension and active hepatitis
    • Major surgery or significant trauma in last 14 days
    • Platelet count below 100x109/L
    • Lumbar puncture in last 7 days
    • Significant stroke in the last 14 days
    • Treatment with alteplase within the last 14 days for ischaemic stroke

Relative contraindications

Treatment can go ahead if the benefits of alteplase appear to outweigh risks, provided patient and/or carers accept associated risk

  • Minor neurological deficit (NIHSS ≤4) or symptoms rapidly improving before start of infusion
  • Severe stroke as assessed clinically (e.g. NIHSS>25) and/or by appropriate imaging techniques
  • Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
  • Neoplasm with increased bleeding risk
  • Recent (less than 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood vessel (e.g. subclavian or jugular vein puncture)
  • Acute pancreatitis
  • Seizure at onset of stroke
  • Patients with any history of prior stroke and concomitant diabetes
  • Blood glucose (<2.8mmol/L or >22.3mmol/L)
  • Major surgery or significant trauma within the previous 3 months but not within the previous 14 days (which is an absolute contraindication)
  • Pregnancy
  • Recent (<10 days) of obstetric delivery

Drug management with alteplase

Treatment must be started within 4.5 hours of onset of stroke symptoms - decision to treat made by stroke consultant

Dosing

Alteplase is administered as an initial IV bolus injection, then immediately followed by an IV infusion as detailed in the table and chart below.

Alteplase IV bolus injection IV infusion
Dose Total dose is 0.9mg/kg body weight (maximum total dose 90mg)
Dosing schedule 10% of total dose over 2 minutes Remaining 90% of dose over 60 minutes

N.B. Alteplase should be prescribed on a high-risk infusion chart and on HEPMA system as ‘alteplase infusion as charted’.

Preparation

Reconstitute 50mg alteplase vial(s) with 50mls of Water for Injections provided in the pack via the transfer spike to give a solution with concentration 1mg/ml.

IV bolus injection: Withdraw required dose into syringe for bolus administration. 

IV infusion: Check IV infusion dose to be administered. Withdraw the equivalent volume of fluid from 100ml bag of sodium chloride 0.9% and discard. Add required IV infusion dose of reconstituted alteplase to this bag of sodium chloride 0.9% to make up to 100ml.

N.B. Alteplase is incompatible with glucose 5%. Alteplase should not be mixed with other medicinal products and should be administered via a dedicated line.

Adverse effects

There are significant risks with administration of thrombolysis which can be fatal. Risks include ICH, active bleeding, acute hypertension and anaphylaxis. Be alert to the early signs of complications and initiate treatment at the earliest opportunity.

Close monitoring and prompt response to deterioration are important in the safe administration of treatment. 

Close monitoring should be carried out prior to alteplase infusion, during infusion and after for 24 hours following administration as detailed in thrombolysis care plan documentation.

Complications

Complications can occur during and post alteplase delivery - see management guidelines below:

 

Guideline reviewed August 2023
Page updated May 2024



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