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Pulmonary Embolism

Definition : Pulmonary Embolism (PE) is obstruction of pulmonary artery or its branches by material (thrombus, tumor, etc) that originated elsewhere in body. There are 2 types of PE:

1) Massive PE, or called Hemodynamically Unstable (SBP < 90 mmHg for > 15 minutes OR hypotension/shock requiring vasopressors). Note: Not all patients with massive PE develop hypotension.

2) Submassive PE, or called Hemodynamically stable (not meet the definition of massive PE)

Pathology : Most thrombi develop at sites of decreased flow in the lower extremity veins, such as valve cusps or bifurcations. Once thrombus lodges in the lung, a series of pathophysiologic response can occur:

Pulmonary Infarction (chest pain, hemoptysis presumed from an intense inflammatory) Abnormal gas exchange due to blockage may cause hypoxia, hypocapnia, and alkalosis. Cardiovascular compromise. Diminished stroke volume and cardiac output, resulting hypotension.

Clinical presentation: dyspnea, cough, SOB. Many patients including large PE are asymptomatic or have mild/nonspecific symptoms.

Risk Factors: obesity BMI > 29, heavy smoking > 25 cigarettes per day, hypertension.

Diagnosis / Laboratory indicators: definitive imaging (CT scan, ventilation perfusion scanning, etc)

Treatment:

Suspected Acute PE, initial therapy:

Respiratory supports: o Supplemental oxygen (target Sat O2 > 90%) o Intubation or mechanical ventilation (severe hypoxemia, hemodynamic collapse, or respiratory failure).

Hemodynamic supports: 500 – 1000 mL IV NS (avoid in RV dysfunction), if failed NS, use IV Vasopressor (NE, NE + DoBUTamine, Epi) Empiric anticoagulation:

o Risk of bleeding assessment Low risk = no risk factors for bleeding (age > 65, previous bleeding, cancer, metastatic cancer, renal/liver failure,

thrombocytopenia, previous stroke, diabetes, anemia, antiplatelet therapy, poor anticoagulant control, comorbidity, reduced functional capacity, recent surgery, falls, alcohol abuse), empiric anticoagulation should be considered.

Moderate risk = one or more risk factors for bleeding, empiric anticoagulation may be considered. Unacceptably high risk = absolute contraindications (recent surgery hemorrhagic stroke, active bleeding) or high risk

of bleeding (aortic dissection, intracranial, spinal cord tumors), avoid empiric anticoagulation. Note: Menstruation, epistaxis, minor hemoptysis are not contraindicated to anticoagulants, but should be monitored.

Definitive treatment:

o Submassive PE / Hemodynamically stable (without hypotension SBP > 90) Recommend against thrombolytic therapy (CHEST guideline 5.6.1.2) Parenteral anticoagulation = IV UFH, SQ UFH, LMWH, Fondaparinux (CHEST guideline 5.1)

Recommend LMWH or Fondaparinux over IV UFH and SC UFH (CHEST guideline 5.4.1) Recommend LMWH once daily over twice daily administration (CHEST guideline 5.4.2)

o Note: Same total daily dose. Discrepancy: Lovenox QD dose is 1.5 mg/kg, BID dose is 1 mg/kg Vitamin K antagonist (warfarin) started on same day as parenteral anticoagulation and continue parenteral

anticoagulation for a minimum of 5 days and until the INR > 2 for at least 24 hours (CHEST guideline 5.3) Suggest INR = 2.0 – 3.0 (target INR = 2.5) for all treatment durations (CHEST guideline 6.5)

o Massive PE / Hemodynamically unstable (with hypotension SBP < 90, and not high bleeding risk) Recommend thrombolytic and short infusion (2 hours) over long infusion (24 hours) (CHEST guideline 5.6.2.1) Embolectomy when thrombolysis is either contraindicated or unsuccessful (UpToDate)

UHF is preferred for thrombolysis / embolectomy (UpToDate) Avoid Direct thrombin and factor Xa inhibitors in hemodynamically unstable patients (UpToDate)

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o Anticoagulation duration for both types of PE: (UpToDate) Initial anticoagulation (0 – 10 days): important in prevention of recurrence and VTE-related death Long-term anticoagulation

10 days – 3 months: for transient risk factors, or 6 – 12 months: for persisting risk factors or unprovoked VTE

Indefinite anticoagulation: only for unprovoked symptomatic PE (to reduce recurrence), recurrent unprovoked VTE, recurrent provoked VTE, provoked VTE with persistent risk factors, unprovoked asymptomatic PE.

If PE provoked by surgery Recommend anticoagulation for 3 months over shorter period and over longer period (6 – 12 months) or

extended therapy (CHEST guideline 6.0) If PE provoked by a non-surgery (estrogen therapy, etc)

Recommend anticoagulation for 3 months over shorter period and over longer period (6 – 12 months) or extended therapy (CHEST guideline 6.2)

o Treatment Algorithm for PE: (UpToDate)

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CHEST guidelines 5.6.1.2 recommend against thrombolytic in hemodynamically stable PE

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Monitoring:

Therapeutics levels of anticoagulation (UpToDate)o UFH = aPTT with target range of 1.5 to 2.5 times upper normal limito Warfarin = PT/INR with target INR = 2 – 3o LMWH, Factor Xa inhibitor, Direct thrombin inhibitor = no monitoring

Renal dosing adjustment (Lovenox, Fondaparinux) Conditions that affect half-life of anticoagulant (renal failure, pregnancy, weight gain/loss, drug interactions) Early complications of PE (recurrence) Late complications of PE (recurrence, chronic thromboembolic pulmonary hypertension) Bleeding, ADR Risk of recurrence and bleeding Predisposing risk factors for PE (malignancy, inherited thrombotic disorder, surgery)

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Drug Classes for Anticoagulation and Lab

Anticoagulant Example Lab

Vitamin K Antagonist (VKA) Warfarin (PO) PT/INR

Unfractionated heparin (UHF) Heparin (IV/SQ) Hgb, HCT, aPTT, ACT, Platelet (only if HIT risk >1%)

Low Molecular Weight Heparin (LMWH)

Enoxaparin (SQ) Dalteparin (IV/SQ)

Cr, Platelet, Anti Xa (only if pregnancy, mechanical heart valve, weight > 190 kg if test available)

Factor Xa InhibitorApixaban (PO) Rivaroxaban (PO) Fondaparinux (SQ)

Renal/Liver function, weight < 60 kg

Direct Thrombin InhibitorBivalirudin (IV) Argatroban (IV) Dabigatran (PO)

Bivalirudin = ACT, aPTTArgatroban = Hgb, HCT, aPTT if HIT, ACT if PCIDabigatran = Platelet, PT, aPTT, Cr, plasma concentration (suggest)

Antiplatelet

Aspirin Aspirin (PO) Renal/Liver function

Thienopyridine Clopidogrel (PO) Prasugrel (PO)

Clopidogrel = Hgb, HCT, Platelet, Renal/Liver functionPrasugrel = Hgb, HCT, Platelet function (optional)

GP 2B/3A InihibitorAbciximab (IV) Eptifibatide (IV) Tirofiban (IV)

- Abciximab = PT, aPTT, Hgb, HCT, Platelet, Fibrinogen, Fibrin split product- Eptifibatide = Hgb, HCT, Cr, PT, aPTT, ACT if during PCI, platelet (2-4 hrs after initiation or 24 hours before D/C)- Tirofiban = Platelet (6 hours after initiation then daily), Hgb, HCT

Non-thienopyridine Cangrelor (IV) S&S of bleeding

Thrombolytic agents Alteplase (IV) Tenecteplase (IV)

Alteplase- Ischemic stroke = BP, CBC, aPTT, PT/INR, glucose- PE = BP, HR at least 24 hours after administration- STEMI = BP, cardiac biomarkers, CBC, PT/INR, aPTT

Tenecteplase = CBC, aPTT, EKG

Dosing reference for acute PE : (LexiComp)

Warfarin (VKA) = individualized according to INR. Range from 2 – 10 mg once daily UFH = 80 U/kg IV push, then IV infusion 18 U/kg/hr OR 333 U/kg SQ, then 250 U/kg SQ q12 Enoxaparin (LMWH) = 1 mg/kg SQ q12 OR 1.5 mg/kg SQ qd Fondaparinux (Xa inhibitor):

o < 50 kg: 5 mg qdo 50 – 100 kg: 7.5 mg qdo > 100 kg: 10 mg qd

Alteplase (thrombolytic): IV 100 mg over 2 hours OR 10 mg IV bolus followed by 90 mg IV over 2 hours.

Reference

1. Tapson, VF. Overview of the treatment, prognosis, and follow-up of acute pulmonary embolism in adults. UpToDate Inc. http://www.uptodate.com/contents/overview-of-the-treatment-prognosis-and-follow-up-of-acute-pulmonary-embolism-in-adults?source=machineLearning&search=pe&selectedTitle=3%7E150&sectionRank=3&anchor=H21434574#H21434574. Accessed 8/18/2015.

2. Guyatt, GH, Akl, EA, Crowther M, et al. Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2012; 141 (2)(Suppl): e419S-e494S http://journal.publications.chestnet.org/pdfaccess.ashx?ResourceID=6568310&PDFSource=13. Accessed 8/20/15

3. Lexi-Comp, Inc. (Lexi-Drugs). http://online.lexi.com/lco/action/home/switch. Accessed 8/19/2015