Alteplase

Chemical

Recombinant version of the naturally occurring glycoprotein (rtPA)

tPA = tissue plasminogen activator

Use

  1. Massive PE

Presentation

50mg vial + 50mL sterile H2O for reconstitution

Dose

PE: 10mg over 2 mins → 90mg over 2hrs

Route

IV

Onset / DoA

Immediate → t ½ 10 mins

MoA

  • Plasminogen = proenzyme synthesised by liver
  • Both fibrin & fibrinogen bind plasminogen
  • ∴ it is structured into clot
  • Alteplase binds to clot-bound-fibrin → activates Plasminogen to form PLASMIN → which will lyse fibrin clot

NOTE: plasmin is a protease → ∴breaks fibrin but also other proteins & also non-clot bound fibrinogen

  • Alteplase is selected because EPA is more specific for clot bound fibrin
  • ∴less breakdown of other proteins
  • Generates overall ‘systemic fibrinolysis state’
  • Normally α2-antiplasmin neutralises Plasmin, but the dose of rTPA overwhelms the α2

PK

A

Instant, IV route

100% bioavailability

D

VD 1.2L/kg

M

Liver

E

Renally excreted 10mL/min/kg

t 1/2 15 – 30mins

Needs dose adjustment in renal failure

Adverse Effects

  • Needs reconstitution
  • Intracranial bleeding
  • Serious bleeding
  • Superficial bleeding
  • Allergic reactions
  • Hypotension

Monitoring

Neuro, BP, ECG, for bleeding signs for 24hrs

Fibrin levels are unreliable to monitor

Reversal

FFP + PRBC + Cryoprecipitate

+/- Antifibrinolytics

Contraindications

  • Significant bleeds <6 month
  • Evidence of intracranial/SAH
  • CNS neoplasm
  • Severe uncontrolled HTN
  • CPR <10 day
  • Major surgery < 3 months
  • Ulcer disease < 3 months
  • Arterial aneurysms / AV malformations
  • Severe hepatic dysfunction

DOSE ADJUST FOR RENAL IMPAIRMENT