Thrombolytic

Aka: Thrombolytic, Thrombolysis, Thrombolytic Contraindication

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II. Mechanism

  1. Activates plasminogen to form plasmin
  2. Plasmin digests Fibrin and dissolves clot

III. 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

IV. Efficacy

  1. Myocardial Infarction mortality
    1. Reduced 25% if Thrombolytic given in first 6 hours
  2. Thrombolytics are 75% effective revascularization

V. Contraindications: Absolute

  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
    1. Highest risk surgeries for post-op bleeding: Brain or Spine Surgery
    2. Risk of major Hemorrhage within 1 week of surgery: 50%
    3. Risk of major Hemorrhage within 1-2 weeks of surgery: 20%
  7. Pregnancy
    1. Risk of bleeding 2.6%
    2. Consider in life-threatening massive Pulmonary Embolism if not near term
    3. Gartman (2013) Obstet Med 6:105-11 [PubMed]

VI. Contraindications: Relative

  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

VII. Medications

  1. Non-clot selective Thrombolytic agents
    1. Streptokinase
    2. Urokinase
    3. AniStreplase (anisoylated plasminogen Streptokinase)
    4. STAR (Recombinant Staphylokinase)
  2. Clot-Specific Thrombolytic agents (bind Fibrin and then activate plasminogen to plasmin)
    1. Recombinant Urokinase plasminogen activator (uPA)
    2. 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
    3. Recombinant Tissue Plasminogen Activator (r-tPA)
      1. Alteplase (Activase)
      2. Reteplase (Retavase)
      3. Tenecteplase (TNKase, TNK tPA)
  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

VIII. Adverse Effects

  1. Bleeding
    1. Rescue agents for Thrombolytic-related life threatening bleeding (e.g. Intracranial Hemorrhage)
      1. See Emergent Reversal of Anticoagulation
      2. Not reduced by clot-specific agents
      3. Consider infusing Fibrinogen Concentrate or Cryoprecipitate 10 pack
      4. Consider Fresh Frozen Plasma
      5. Consider Tranexamic Acid (TXA)
      6. Swaminathan and Weingart in Herbert (2020) EMRap 20(4):5-6
    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)

IX. References

  1. Condliffe (2014) Thorax 69(2): 174-80 [PubMed]
  2. Mehta (2000) Lancet 356:449-54 [PubMed]
  3. Lewandowski (2001) Ann Emerg Med 37:211 [PubMed]

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