Hematology and Oncology Book

Tranfusion

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Thrombolysis in Massive Pulmonary Embolism

Aka: Thrombolysis in Massive Pulmonary Embolism, Pulmonary Embolism Thrombolysis, PE Thrombolysis
  1. See Also
    1. Thrombolysis contraindications
    2. Pulmonary Embolism
    3. Pulmonary Embolism Management
    4. Thrombolytic
    5. Thrombolysis in Cerebrovascular Accident
    6. Thrombolysis in ST Elevation Myocardial Infarction
    7. t-PA (Alteplase)
  2. Indications
    1. Massive Pulmonary Embolism (absolute indications)
      1. Hypotension
        1. Systolic Blood Pressure <90 mmHg or
        2. Systolic Blood Pressure drops >40 mmHg from baseline for at least 15 minutes
      2. Systemic hypoperfusion
      3. Cardiac Arrest with dilated right ventricle on Bedside Ultrasound (suggestive of PE)
        1. Thrombolytics are not indicated in undifferentiated Cardiac Arrest
    2. Submassive Pulmonary Embolism with significant cardiopulmonary findings (relative indications, treatment is controversial)
      1. Evidence does not support as of 2017 (see below)
      2. Right ventricular dysfunction (RV Strain)
        1. Serum Troponin elevation or
        2. ntBNP >900 pg/ml or (BNP >90 pg/ml) or
        3. Echocardiogram with right ventricular dilation or hypokinesis
      3. Pulmonary Hypertension
      4. Extensive Deep Vein Thrombosis
      5. Prevent recurrent Pulmonary Embolism
  3. Contraindications
    1. See Thrombolytic Contraindication
  4. Efficacy
    1. Local or directed Thrombolysis has had mixed efficacy in massive Pulmonary Embolism
      1. Early studies demonstrated no benefit over intravenous Thrombolysis
      2. However, as of 2015, catheter placement within the PE appears effective
        1. Piazza (2015) JACC Cardiovasc Interv 8(10): 1382-92 +PMID: 26315743 [PubMed]
        2. Kuo (2015) Chest 148(3):667-73 [PubMed]
    2. Only significant benefit for Thrombolysis may be in massive Pulmonary Embolism
      1. Thrombolysis offers faster clot lysis than Heparin
      2. Short-term better pulmonary artery perfusion
      3. Benefit is in first 24-48 hours
    3. Thrombolysis longterm outcomes are similar to Heparin in non-massive PE (intermediate risk PE)
      1. No difference in mortality
      2. No difference in Pulmonary Embolism resolution
      3. No difference in recurrent PE
      4. Dyspnea at 3 year follow-up is similar for those treated with Thrombolysis and those not treated
        1. Konstantinides (2017) J Am Coll Cardiol 69(12): 1536-44 +PMID:28335835 [PubMed]
      5. Exception: Right ventricular dysfunction may be less with Thrombolysis (see below)
    4. Quality of life may be improved with Thrombolysis for non-massive PE (intermediate risk PE)
      1. Right ventricular dysfunction and functional outcome may be improved with Thrombolysis (esp. younger patients)
      2. Lower risk of Pulmonary Embolism recurrence (less residual nidus)
      3. Weigh quality of life following submassive PE versus the bleeding risk (see below)
      4. Orman and Kline in Herbert (2015) EMRap 15(9):14-17
      5. Kline (2014) J Thromb Haemost 12(4):459-68 +PMID:24484241 [PubMed]
    5. Adverse effects of bleeding are substantial and likely to outweigh the benefits in intermediate risk PE
      1. Studies of patients with RV dysfunction but hemodynamically stable
      2. Number Needed to Treat (NNT) was 59 to prevent one death and 53 to prevent recurrence
      3. Number needed to harm (NNH) for major bleeding was 18 (NNH was 11 if over age 65)
      4. Number needed to harm (NNH) for Intracranial Hemorrhage was 78
      5. Chatterjee (2014) JAMA 311(23): 2414-21 [PubMed]
    6. References
      1. (1974) JAMA 229:1606-13 [PubMed]
      2. Levine (1990) Chest 98:1473-9 [PubMed]
      3. Dalla-Volta (1992) J Am Coll Cardiol 20:520-6 [PubMed]
  5. Protocol
    1. General
      1. Administered with Heparin
      2. Indicated within 14 days of severe PE onset
      3. Outcomes between agents are similar at 24 hours (however tPA is typically used)
      4. Meyer (1992) J Am Coll Cardiol 19:239-45 [PubMed]
    2. Agents
      1. T-PA (Alteplase) - preferred agent
        1. T-PA 100 mg IV peripheral infusion over 2 hours (first 10 mg over 1-2 minutes)
        2. Restart Heparin when PTT less than twice normal
      2. Streptokinase
        1. Load: 250,000 units over 30 minutes
        2. Maintenance: 100,000 units per hour for 24 hours
      3. Urokinase
        1. Load: 4400 units/kg over 10 minutes
        2. Maintenance: 4400 units/kg per hour for 12-24 hours
    3. Monitoring
      1. Obtain PTT after Thrombolytic infusion and q4 hours
      2. Protocols vary on whether to stop Heparin while TPA is infusing
      3. Restart Heparin when PTT falls below 2x to 2.5x normal (typically <80 seconds)
        1. Maintain PTT 1.5 to 2.5 times normal
        2. Standard Unfractionated Heparin is typically used (over LMWH) to allow for rapid stopping in case of bleeding
  6. Complications
    1. See Complications in Thrombolysis
  7. References
    1. (2000) Eur Heart J 21(16): 1301-36 [PubMed]
    2. Almoosa (2002) Am Fam Physician 65(6):1097-1102 [PubMed]
    3. Condliffe (2014) Thorax 69(2): 174-80 [PubMed]
    4. Jaff (2011) Circulation 123: 1788-830 [PubMed]

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