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

• See Stroke Thrombolysis

TPA in Acute Pulmonary Embolism

• faster reduction in thrombus size
•  reduction in pulmonary artery pressure

References and Links

• Resus Review — TPA mixing tutorial (2013)