THROMBOLYTICS


See also Acute MI, Cerebrovascular Disease, and Pulmonary Embolus

Promote conversion of plasminogen to plasmin, which lyses fibrin clots

Ones that are more "fibrin-specific" (i.e., affect fibrin-bound plasminogen more than circulating plasminogen) are theorized to be more effective and produce less bleeding 

I. Specific preparations:

  1. Streptokinase (Streptase) 1.5MU IV over 60min
  2. Reteplase (r-PA, Retavase) 10U IV bolus over 2min, repeated 30min later
  3. Alteplase (t-PA, Activase) 15mg IV bolus then 50mg over 30min then 35mg over 60min (if <67kg, 0.75mg/kg over 30min then 0.5mg/kg over 60min)
    1. More fibrin-specific than Reteplase
    2. Double-bolus (50mg bolus Q30min x2) vs. 90min infusion above found to not affect 30d mortality despite better acute patency rates assessed by angio in one study of 7,000 pts; the double-bolus group had nonsig. higher rates of mortality and CVA (NEJM 337:1124, 1997--UW Pharm Letter)
  4. Tenecteplast (TNKase) 30-50mg IV bolus over 5sec (based on weight)
    1. More fibrin-specific than Alteplase
    2. Longer half life than t-PA
    3. Similar outcomes in clinical trials to Alteplase as of 2000
  5. Anistreplase (anisoylated plasminogen streptokinase activator complex) 30U IV over 2-5min
  6.  
  7. Urokinase
  8. Duteplase (a double-chain TPA)
  9. Prourokinase
  10. Ancrod--A protease enzyme undergoing clinical trials as of 1999

II. Complications

  1. Minor bleeding is common
  2. Intracranial hemorrhage
    1. Incidence rate 0-1.4%
    2. Incidence is greater with bolus administation than with infusion or bolus + infusion (Lancet 356:449, 2000--Med. Lett.)
    3. In a study with 2,400 pts, the following were independent risk factors for ICH < 48h post-tx (J.Am.Coll.Card. 19:289, Feb '92):
  1. Oral anticoagulant before admiss.
  2. Body weight <70kg ("overdosage" may have contributed)
  3. Age >65y
  4. No effect seen of gender, in-house anticlotting therapy, h/o HTN, PVD, or smoking; or infarct location
  5. No effect seen of choice of thrombolytic agent, but in pooled data from randomized trials, risk was tied lowest for streptokinase & anistreplase and higher for TPA.
  6. Median time between tx & presentation of IC hemorrh. was 16h (range 3-36h); mort. was 66%
  1. In a study of 71,000 pts with acute MI who received t-PA, overal rate of imaging-confirmed ICH was 0.88%; 53% of these pts died during hospitalization; 25% had neurologic deficits at discharge. The following were independent risk factors for ICH (Ann. Int. Med. 129:597, 1998--JW):
  1. Female gender
  2. Black race
  3. Age > 64y
  4. BP > 139/99
  5. History of CVA
  6. Dose of t-PA > 1.5mg/kg

III. Contraindications (per Med. Letter 38:100, 1996 as above and Ann. Emerg. Med. 30:644, 1997--AFP):

  1. Age < 18y
  2. Onset of sx > 3h prior
  3. Intracranial hemorrhage (must do CT to r/o!) or other sig. bleeding (e.g. GI)
  4. Intracranial tumor or vascular lesion
  5. Major surgery in previous 14d
  6. CVA in previous 3mos
  7. Head trauma in previous 3mos
  8. Uncontrolled HTN (e.g. > 180/110)
  9. Arterial puncture at a noncompressible site in previous 7d
  10. LP in previous 7d
  11. Heparin in previous 48h or elevated PTT
  12. Warfarin with PT > 15sec
  13. Platelet count < 100
  14. Pregnancy (or lactation--??)
  15. Recent ASA is not an absolute contraindication
  16. Diabetic retinopathy is not, despite popuular belief, a contraindication (Among 41,000 who received with t-PA or streptokinase for acute MI, only 12 cases of ocular hemorrhage, only one was intraocular, and occurred in a pt w/o DM. None of the 6,000 pts w/DM had intraocular hemorrhage; JACC 30:1606, 1997--JW)