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Alteplase: Catheter Directed Thrombolysis for Limb Deep Vein Thrombosis

Who can administer

Important information

  • Patients are under the care of a consultant interventional radiologist (IR) who is available 24/7 to answer questions related to the catheters, drugs etc
  • See also - Attached protocols from Gerard O'Sullivan, Consultant Interventional Radiologist
  • Purpose
    • Thrombolytic agent - tissue plasminogen activator (tPa) Actilyse® Alteplase (unlicensed indication)
    • To chemically dissolve thrombus by attacking the fibrin within the thrombus, thereby clearing the affected region of deep venous thrombus
  • For use in thrombolysis (acute MI)acute massive PEacute ischaemic stroke - see separate monograph
  • For use in PE (low dose for intermediate/high risk)- unlicensed- see separate monograph 

Available preparations

  • Actilyse 10mg vial (with 10ml Water for Injection provided)

Reconstitution

  • Use 10ml Water for Injection provided

Infusion fluids

  • Use Sodium Chloride 0.9% only
  Dilution Concentration produced
Preferred concentration 10mg added to 40ml infusion fluid to produce a final volume of 50ml 0.2mg per ml
  • Syringe must be changed after 8 hours (no stability data beyond 8 hours at room temperature) (ref 2)

Dose in adults

  • Administer via catheter as per consultants instructions
  • Dose range is 2.5ml/hour (0.5mg/hour) to 10ml/hour (2mg/hour)
  • Usual rate is 5ml/hour (1mg/hour)
  • In general, two catheters are inserted, one for tPA and one for unfractionated heparin
    • These are labelled appropriately
  • The infusion could be infused for up to five days but generally is infused for 24 to 72 hours
  • A dose reduction may be required for longer infusion durations

Heparin infusion

  • The patient is also anti-coagulated with unfractionated heparin (patients receive heparin bolus during procedure)
  • Run through side arm of 6F sheath
  • An optimum target APTT of between 55 and 80 is suggested based on a mean average aPTT of 28 in GUH (prescribe on the green Heparin prescription)
  • The mean aPTT is specific to each laboratory, and is reagent and analyser specific.  It is also important to look at the patient's baseline APTT.  Aim for APTT ratio or 2 to 3 times the patient's or laboratory baseline
  • Note:  in certain circumstances, patients may remain on LMWH instead of UFH after discussion with consultant haematologist

Monitoring

Blood tests

  • Inform laboratory that patient is receiving alteplase (tPA) infusion as this interferes with assays
  • Check FBC, PT, APTT, CLAUSS fibrinogen before starting the infusion
  • Recheck above after 4 to 6 hours
  • Then recheck every eight hours for first 24 hours
  • If stable, need to recheck bloods every 12 hours, but this depends on the clinical situation
  • Monitor for bleeding
  • If Hb or CLAUSS fibrinogen falls, more frequent monitoring is required
  • Stop alteplase and heparin infusions if major bleeding 
  • Consider halving alteplase rate if Fibrinogin falls precipitously and is less than 1.5g/L
  • Stop alteplase if CLAUSS fibrinogen is less than 1g/L (continue UFH unless bleeding)
  • Consider restarting alteplase at half original rate if CLAUSS fibrinogen is greater than 1g/L as long as no bleeding.  Clinical judgement required

What to watch out for: see protocol below

  • HeadacheIntracranial bleeding occurs in approximately 2/1000 patients.  CT scan is indicated as an emergency for any patient complaining of a new or unusual headache.  Call the Interventional Radiologist if in doubt.
  • Low BP: could signal internal bleeding.  Approximately 2-4/100 patients.  Watch Hb carefully. Appropriate fluid challenge. Call the Interventional Radiologist if in doubt.
  • Increased heart rate: may signal early bleeding

What to expect:

  • Oozing around puncture sites
  • Drop in Hb by 0.5 to 1g/day

What to avoid:

  • Intramuscular injections
  • Arterial puncture/blood gases while on infusion
  • If venous access may be an issue, consider an arterial line prior to starting heparin and tPA infusion 

Recommendations:

  • Strict bed rest
  • Regular diet
  • Good analgesia - PCA ideal

Storage

Store below 25°C

References

  • 1. Guideline prepared in consultation with Dr Ruth Gilmore (Consultant haematologist)and Dr Gerry O'Sullivan (Consultant interventional radiologist)
  • 2. Actilyse (SPC). 06/2021. Accessed at https://www.medicines.org.uk/emc/medicine/308#gref on 01/09/2021.