Thrombolytic

Aka: Thrombolytic, Thrombolysis, Thrombolytic Contraindication

1. See Also
   1. Thrombolysis in Massive Pulmonary Embolism
   2. CVA Thrombolysis
2. Mechanism
   1. Activates plasminogen to form plasmin
   2. Plasmin digests fibrin and dissolves clot
3. Indications
   1. Myocardial Infarction Protocol
      1. Symptoms present for under 12 hours
      2. ST segment elevation
         1. Two anatomically contiguous leads
         2. Elevation > 0.1 mV (1 mm when EKG 10 mm/1 mV)
      3. Under Age 75 (no absolute age cut-off)
      4. Absence of other disease to explain symptoms
   2. Ischemic Cerebrovascular Accident
      1. See Ischemic CVA Management
4. Epidemiology: Thrombolytic in Acute MI
   1. Goal: Thrombolytics in Acute MI within 30-60 min
   2. Mortality related to delay in Thrombolytic use
      1. Meta-analysis: 50,246 patients in 22 trials 1983-1993
         1. Thrombolytic delayed 0-1 hours: 65/1000 lives saved
         2. Thrombolytic delayed 1-2 hours: 37/1000 lives saved
         3. Thrombolytic delayed 2-3 hours: 26/1000 lives saved
         4. Thrombolytic delayed 3-6 hours: 29/1000 lives saved
      2. Reference
         1. Boersma (1996) Lancet 348:771-5
5. Efficacy
   1. Myocardial Infarction mortality
      1. Reduced 25% if Thrombolytic given in first 6 hours
   2. Thrombolytics are 75% effective revascularization
6. Absolute Contraindications
   1. Active Internal Bleeding
   2. Suspect Aortic Dissection
   3. Known traumatic Cardiopulmonary Resuscitation (CPR)
   4. Severe Hypertension despite Medication (>180/110)
   5. Major Intracranial Events
      1. Recent Head Trauma or intracranial neoplasm
      2. Known arteriovenous malformation or aneurysm
      3. Intracranial Hemorrhage on CT (CVA protocol)
      4. High suspicion SAH despite normal CT (CVA protocol)
      5. Cerebrovascular Accident (or TIA) in last 6 months
   6. Major surgery within last 14 days
   7. Pregnancy
7. Relative Contraindications
   1. Recent trauma or major surgery in last 2 months
   2. Initial presenting BP > 180/110, but controlled now
   3. Peptic Ulcer Disease
   4. Remote history of Cerebrovascular Accident
   5. Known Bleeding Disorder
   6. Renal disease
   7. Prolonged Cardiopulmonary Resuscitation (CPR)
   8. Streptokinase in last 6 months
8. Preparations
   1. Non-clot selective Thrombolytic agents
      1. Streptokinase
      2. Urokinase
      3. AniStreplase (anisoylated plasminogen Streptokinase)
      4. STAR (Recombinant Staphylokinase)
   2. Clot-Specific Thrombolytic agents
      1. T-PA (Alteplase, Activase)
         1. Recombinant tissue Plasminogen activator
      2. Recombinant Urokinase plasminogen activator
   3. Adjunctive Heparin (in acute Myocardial Infarction)
      1. Used in combination with Thrombolytic
      2. Contraindications to adjunctive Heparin
         1. Discharge from major surgery with prior 14 days
         2. History of Cerebrovascular Accident
         3. Chronic Atrial Fibrillation
         4. Chronic Mitral Stenosis
         5. Acute Gastrointestinal Hemorrhage
      3. Cases where adjunctive Heparin is most beneficial
         1. Acute anterior Myocardial Infarction
         2. Left ventricular thrombus by echocardiogram
9. Complications and adverse effects
   1. Bleeding
      1. Not reduced by clot-specific agents
      2. Overall bleeding (Incidence: 20-25%)
         1. Occurs at catheter puncture sites most often
      3. Major bleeding (Incidence: 5-10%)
         1. Gastrointestinal tract
         2. Retroperitoneum
         3. Intracranial Hemorrhage (1-2% of cases)
            1. Occurs more often with bolus than with infusion
   2. Acute Myocardial Infarction specific effects
      1. Reperfusion Chest Pain
      2. Reperfusion arrhythmia
         1. Accelerated Idioventricular Rhythm
         2. Sinus Bradycardia
         3. Second or third degree AV Block
   3. Hypotension (Streptokinase)
   4. Nausea and Vomiting
   5. Allergic Reactions or Anaphylaxis (Streptokinase)
10. References
    1. Mehta (2000) Lancet 356:449-54
    2. Lewandowski (2001) Ann Emerg Med 37:211