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thrombolytics

thrombolytics

thrombolytic agents:

  • also called fibrinolysis or fibrinolytics

  • LMWH such as enoxaparin (30mg iv bolus, then 1mg/kg s/c bd), appears to be better than unfractionated heparin as an adjunct to thrombolysis in AMI although does increase major bleed rates, but net benefit appears to outweigh this risk 1) 2) 3)

streptokinase:

pharmacology:
  • acts on the inactive proenzyme plasminogen to produce the active enzyme plasmin
  • 1st used to lyse coronary clots: IV in 1958 & intracoronary in 1976
  • 1st demonstrated to recanalise an acutely occluded coronary artery in a living pt in early 1980's
  • usage in AMI:
    • aspirin x1, chewed;
    • no heparin as no added benefit with SK and only increases bleeding risk
    • 2 x IV cannulae;
    • 1.5million IU in 100ml NS over 1hr (CVS guidelines state 20-30min!)
    • if BP falls below 80mmHg:
      • place in Trendelenberg
      • consider IV fluid bolus
      • reduce infusion rate to half
    • if BP falls below 70mmHg:
      • cease infusion & recommence at half previous rate when BP > 70mmHg
  • Contraindications to SK in addition to usual C/I to thrombolytics:
    • SK has been administered within 3 years unless in past 3-5 days
    • PH HS reaction to SK
    • recent streptococcal infection
  • Adverse effects:
    • bleeding:
      • haemorrhagic stroke
    • hypotension (12%)
    • allergic reactions
    • anaphylaxis (rare)

APSAC:

pharmacology:
  • anisoylated plasminogen SK activator complex
  • clinical use 1st reported in 1984
  • a 2nd generation complex of SK, its active agent & acylated human lysplasminogen
  • rapid acting with prolonged half life ⇒ only bolus needed ⇒ 4-6hrs of activity
  • dose: 30U IV over 5min

r-tPA (alteplase):

reteplase:

  • the 1st 3rd generation thrombolytic
  • a deletion mutant of alteplase with slower plasma clearance
  • double bolus dosing rather than infusion:
    • give reteplase as double bolus injections over 2min, with 2nd bolus 30min after the 1st

tenecteplase:

  • a triple-combination mutant of alteplase derived via recombinant DNA established from Chinese Hampster Ovary cells
  • longer plasma half life (20min)
  • drug product info. sheet recommends lower heparin doses than are standard:
    • heparin 5000IU IV stat (4000IU if < 67kg) then infusion 25000IU in 500ml NS @ 16ml/hr (<67kg) or 20ml/hr (>67kg)
    • aim for aPTT of 50-75secs
  • single IV bolus dose dependent on weight, given over 10sec else Mx as for tPA:
    • dosages marked on syringe in ml or kg:
      • <60kg: 6ml (ie. 30mg = 6,000IU) USE 40mg size ampoule!
      • 60-70kg: 7ml (ie. 35mg = 7,000IU) USE 40mg size ampoule!
      • 70-80kg: 8ml (ie. 40mg = 8,000IU) USE 40mg size ampoule!
      • 80-90kg: 9ml (ie. 45mg = 9,000IU) USE 50mg size ampoule!
      • >= 90kg: 10ml (ie. 50mg = 10,000IU) USE 50mg size ampoule!
  • NB. incompatible with dextrose, use NSaline infusions only in that cannula concurrently
  • more fibrin-specific than alteplase ⇒ less non-cerebral bleed & better mortality in subgroup of pts where Rx started > 4hrs
  • less non-cerebral bleeding than r-TPA (ASSENT-2 trial)
  • introduced in Aust. 2000

contraindications to thrombolytic Rx of AMI:

Absolute contraindications to thrombolytic Rx:

  • within past 10 days:
    • active bleeding eg. GIT, genitourinary BUT not menstruation as compressible with vaginal packs
    • trauma
    • major surgery eg. CABG, obstetric delivery, organ Bx, puncture of noncompressible vessels
  • known haemorrhagic diathesis
  • thrombotic/haemorrhagic stroke CVA in last 6 months
  • severe uncontrolled HT with systolic BP > 200 or diastolic BP > 110mmHg despite use of IV GTN
  • SBE (eg. IV drug users with cocaine induced AMI)
  • acute pericarditis
  • high likelihood of left heart thrombus (eg. mitral stenosis with AF)
  • see also specific C/Is to SK

Relative contraindications:

  • clinical evidence or history of TIA's
  • concomitant use of oral anticoagulants with INR > 2
  • prolonged (>10min) or traumatic CPR
  • recent non-compressible vascular puncture eg. CVC
  • pregnancy
  • systolic BP > 175mmHg - consider angioplasty instead
  • PH CABG as these patients may be relatively resistant to thrombolytic Rx & thus should be considered for direct angioplasty or combined thrombolytic Rx and rescue angioplasty
  • haemorrhagic ophthalmic conditions eg. active diabetic haemorrhagic retinopathy

Indications and Contraindications of thrombolysis in stroke

Complications of thrombolytic Rx:

bleeding:

  • haemorrhagic stroke 0.5-1.0% (slightly more with tPA than with SK):
    • comparable to incidence of all types of stroke in AMI without thrombolytic Rx (mostly embolic)
    • if have haemorrhagic stroke during AMI then mortality increases from 12% to 47%
    • risk of haemorrhagic stroke:
      • 3.4% if PH CNS disease, TIA's or CVA
      • 0.5% if no PH neurologic disease
      • 0.5% with SK vs 1.0% with tPA
  • systemic bleeding (slightly more with SK than with tPA):
    • GIT bleed or drop in h'crit by > 15% - 3% pts
    • minor bleeding 19%
  • significant bleeding if given post-pulmonary angiography (14%)
  • see Mx of bleeding (below)

hypotension:

  • esp. with SK (12% vs tPA 7%) usually due to vasodilatation:
    • responds to IV fluids
    • if BP falls below 80mmHg:
      • place in Trendelenberg
      • consider IV fluid bolus
      • reduce infusion rate to half
    • if BP falls below 70mmHg:
      • cease infusion & recommence at half previous rate when BP > 70mmHg

allergic reactions (urticaria, bronchospasm & serum sickness):

  • consider IV fluids & Trendelenberg position if hypotension

Bleeding whilst on thrombolytic Rx:

Management

  • local pressure
  • IV fluid replacement
  • cease thrombolytic &/or anticoagulant Rx
  • maintain h'crit above 30% in pts with AMI & compromised coronary perfusion:
  • blood transfusion prn
  • if on heparin, give protamine sulphate 1mg per 100U of heparin may be given to decrease half-life of heparin from 90 to 45min
  • if bleed causing haemodynamic compromise but not immediately life-threatening:
  • if pt still bleeding then give 2-6U FFP
  • if still bleeding, then 6-8U platelets
  • if new focal neurologic deficits develop, or new headache or decreased GCS:
    • stop thrombolytic & anticoagulant Rx
    • protamine as above if on heparin
    • FFP if INR prolonged
    • urgent non-contrast CT brain scan
    • if intracranial bleed:
      • elevate head to 30 degrees— target PaCO2 35-40 mmHg
      • BP control e.g. SBP <160 mmHg and MAP <110 mmHg
      • urgent neurosurgical consult to decide on options vs palliation
        • consider mannitol or hypertonic saline to control raised ICP
      • inform parent unit (eg. stroke consultant if patient is a stroke patient)
      • monitor BP every 15min
      • FFP 2 units q6h for 24h
      • cryoprecipitate 10 units if not already given for a target fibrinogen level of 1g/L, then,
      • 1 adult bag platelets if not already given
      • DDAVP 0.3 microg/kg
      • if significant circulating thrombolytic levels then consider:
        • antifibrinolytics:
          • epsilon-aminocaproic acid 5g in 15-60min
            • inhibits activation of plasminogen
            • risk of serious thrombotic complications!
          • tranexamic acid 1g IV
      • fibrinogen levels should be rechecked every Q 4 hours & cryoprecipitate transfused PRN to maintain fibrinogen levels
      • rpt CT brain may be indicated to assess progression
thrombolytics.txt · Last modified: 2019/11/20 05:44 by wh