Alteplase (rtPA)
OVERVIEW
- Alteplase is recombinant tissue plasminogen activator (rt-PA)
CLASS
- thrombolytic
MECHANISM OF ACTION
- selectively binds to fibrin and converts plasminogen -> plasmin -> degradation of fibrin matrix
PHARMACEUTICS
- recombinant human tissue-type plasminogen activator (rt-PA)
- trade names include activase and actilyse
- white powder for reconstitution
INDICATIONS
- STEACS within 90 min, 6 hours or 24 hours (different dosing regimes)
- PE with haemodynamic instability
- Acute Ischaemic CVA within 3 hours after exclusion of haemorrhage
- occlusive iliac venous thrombosis
CONTRAINDICATIONS
General
- current bleeding disorder or known haemorrhagic diathesis within last 6 months
- anticoagulation (INR > 1.3)
- history of CNS damage
- major within last 2 months
- prolonged CPR
- hepatic dysfunction
- active peptic ulcer disease
- arterial aneurysm
- previous haemorrhagic CVA
- TIA within last 6 months
CVA
- rapid resolution of symptoms
- seizure
- previous CVA or stroke within 3 months
- previous CVA and DM
- anticoagulated
- platelets < 100
- SBP > 185
- DBP > 110
- hyper or hypoglycaemia
DOSE
- MI: bolus and infusion depending on time frame (accelerated and 3 hour dosage)
- PE: 10mg over 2 minutes -> 90mg over 2 hours
- CVA: 0.9mg/kg (maximum 90mg) over 60 minutes (10% given as a bolus)
- various heparin protocols to follow
ADVERSE EFFECTS
- intracranial haemorrhage
- bleeding anywhere
- allergy
- cardiac arrhythmia with reperfusion
Management of Bleeding
- stop TPA
- if heparin given -> protamine
- cryoprecipitate (keep fibrinogen > 1)
- FFP
- platelets
PHARMACOKINETICS
- Absorption
- Distribution
- Metabolism – hepatic
- Elimination – t1/2 = 5 minutes
EVIDENCE
TPA in STEACS
GUSTO
- n = 40,000
- t-PA + heparin vs streptokinase
-> higher thrombolytic success
-> decreased 30 day mortality
LATE
- t-PA vs placebo (within 6-12 hours of symptom onset)
-> reduction in 30 day mortality
-> treatment within 24 hours may be beneficial
-> restores coronary patency
-> reduces infarct size
-> preserves ventricular function
-> reduces mortality
TPA in Acute Ischaemic CVA
TPA in Acute Pulmonary Embolism
- faster reduction in thrombus size
- reduction in pulmonary artery pressure
References and Links
- Resus Review — TPA mixing tutorial (2013)
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.
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