Tissue Plasminogen Activator

Tissue Plasminogen Activator (tPA)
1. Serine protease binds Fibrin and activates Fibrin-bound plasminogen to plasmin
2. Plasmin breaks down both Fibrin and Fibrinogen to Fibrin
  1. Fibrin Degradation Products result, which in turn also act to inhibit Fibrin formation
3. tPA has been replaced by recombinant products (r-tPA)
  1. tPA was originally synthesized and extracted from cultured mammalian cells
Recombinant Tissue Plasminogen Activator (r-tPA)
1. Alteplase (Activase)
2. Reteplase (Retavase)
3. Tenectaplase (TNKase, TNK tPA)

Myocardial Infarction
1. See Thrombolysis in ST Elevation Myocardial Infarction
2. Bolus: 15 mg IV THEN
3. Next: 0.75 mg/kg (max 50 mg) over 30 minutes THEN
4. Next: 0.5 mg/kg (max 35 mg) over next 60 minutes
5. Administer adjunctive Heparin concurrently
  1. See Thrombolysis
Acute Ischemic Cerebrovascular Accident
1. See Thrombolysis in Cerebrovascular Accident
2. Calculate total dose: 0.9 mg/kg (max 90 mg)
3. Bolus: Give 10% total dose as IV bolus over 1 minute
4. Next: Give remainder of total dose over 60 minutes
Acute Massive Pulmonary Embolus
1. See Thrombolysis in Massive Pulmonary Embolism
2. Pulse present
  1. First: 10 mg IV bolus
  2. Next: 90 mg IV over 2 hours
3. Pulse absent
  1. tPA 50 mg IV bolus and continue CPR for at least 30 minutes (to allow for tPA circulation)
4. Restart Heparin when PTT below twice normal
Occluded central venous access
1. Administer 2 mg/ml via occluded catheter for 2 hours
2. May repeat once if refractory to first dose

Disadvantages (compared with other Thrombolytics)
1. Increased bleeding risk
  1. 3-4% greater risk of bleeding in older than age 75
2. Re-occludes earlier than other Thrombolytics
  1. Needs Heparin concurrently and afterward
Advantages (compared with other Thrombolytics)
1. Probably reperfuses arteries earlier
2. Superior in large, anterior Myocardial Infarctions