Alteplase (Activase)

Indications

Acute Pulmonary Embolism (PE) with Hypotension (see Acute Pulmonary Embolism, [[Acute Pulmonary Embolism]])

  • Meta-Analysis of Thrombolyis in Acute PE (2014) [MEDLINE]: meta-analysis (16 trials, n = 2115)
    • Thrombolysis decreased mortality rate (2.17%), as compared to anticoagulation alone (3.89%)
      • No mortality benefit was observed in patients >65 y/o, a population in whom the risk of hemorrhage was greatest
    • Thrombolysis decreased the risk of recurrent PE (1.17%) as compared to anticoagulation alone (3.04%)
    • Thrombolysis increased the risk of major hemorrhage (9.2%), as compared to anticoagulation alone (3.4%)
      • No significant difference in major hemorrhage in patients 65 y/o and younger
    • Thrombolysis increased the risk of intracranial hemorrhage (1.5%), as compared to anticoagulation alone (0.2%)
  • PEITHO Trial (2014) [MEDLINE]: RCT of tenecteplase (n = 1006), intention-to-treat analysis in normotensive, intermediate-risk PE patients
    • Thrombolysis decreased hemodynamic decompensation (2.6%), as compared to placebo group (5.6%)
    • No difference in 30-day mortality rate
    • Thrombolysis increased risk of major hemorrhage and stroke
  • Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines [MEDLINE]: thrombolytics are recommended (Grade 2B recommendation)
    • Systemic Therapy is Recommended Over Catheter-Directed Thrombolysis (Grade 2C recommendation): however, bleeding risk may indicate catheter-directed thrombolysis in centers where expertise is present
    • Systemic thrombolytics can also be considered in patient who deteriorate after starting anticoagulation (significant hypoxemia, poor tissue perfusion, etc), but who have not developed hypotension yet

Acute Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident, [[Ischemic Cerebrovascular Accident]])

  • xxx

Acute ST Elevation Myocardial Infarction (STEMI) (see Coronary Artery Disease, [[Coronary Artery Disease]])

  • xxx

Contraindications

  • Major Contraindications to Systemic Thrombolytic Therapy
    • Active Bleeding
    • Bleeding Diathesis
    • Diabetic Retinopathy
    • History of Intracranial hemorrhage
    • History of Ischemic Stroke Within 3 mo
    • Recent Brain/Spinal Surgery
    • Recent Head Trauma with Fracture/Traumatic Brain Injury
    • Structural Intracranial Disease
  • Relative Contraindications to Systemic Thrombolytic Therapy
    • Age >75 y/o
    • Anticoagulation: coumadin, etc
    • Black Race
    • Diastolic BP >110
    • Female Sex
    • History of Ischemic CVA 3 mo Ago
    • Low Body Weight
    • Pericarditis/Pericardial Effusion
    • Pregnancy
    • Recent Invasive Procedure
    • Recent Non-Intracranial Hemorrhage
    • Recent Surgery
    • Systolic BP >180
    • Traumatic Cardiopulmonary Resuscitation

Pharmacology

  • Induces Acquired Von Willebrand Disease: hyperfibrinolytic state -> VWF degradation by proteolytic enzymes (such as plasmin)

Metabolism

  • xxx

Administration

  • IV Bolus Dosing in Acute Pulmonary Embolism: 100 mg over 2 hrs
  • IV Dosing in Acute Thrombotic Cerebrovascular Accident (CVA): xxx
  • IV Dosing in Acute ST Elevation Myocardial Infarction (STEMI): xxx

Dose Adjustment

  • Hepatic:
  • Renal:

Adverse Effects

Hematologic Adverse Effects

  • Hemorrhage

Other Adverse Effects

  • xxx
  • xxx
  • xxx

References

  • Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149(2):315-52. doi: 10.1016/j.chest.2015.11.026. Epub 2016 Jan 7 [MEDLINE]