Pulmonary Embolism Diagnosis Treatment and Prevention Dr Yasser

Pulmonary Embolism Diagnosis, Treatment, and Prevention Dr. Yasser Mostafa; MD Prof. Of Pulmonary Medicine Ain Shams University

Pulmonary Embolism n Thrombosis (Thrombo-embolic) that originates in the venous system and embolizes to the pulmonary arterial circulation n n DVT in veins of leg above the knee (>90%) DVT elsewhere (pelvic, arm, calf veins, etc. ) Cardiac thrombi Air embolism. Fat embolism.

How Common? n n 650, 000 cases in the US each year 150, 000 – 200, 000 US deaths each year Most common preventable cause of hospital death 3 rd most common acute cardiovascular emergency (MI and stroke)

Risk Factors (for DVT) n Virchow’s Triad: n n Alterations in blood flow (stasis): Injury to endothelium: Thrombophilia: Others: n n n n Age >50 History of varicose veins History of MI History of malignancy History of atrial fibrillation History of ischemic stroke History of diabetes mellitus Previous VTE, obesity, pregnancy

n n n Stasis: mainly caused by heart failure, prolonged immobility Endothelial injury: mainly caused by either direct trauma (severed vein) or local irritation (by chemotherapy, past DVT, phlebitis) Hypercoagulability: inherited (AT III def. , protein C, S deficiency) or acquired (malignancy, pregnancy, AT III def. , protein C, S deficiency as in nephritic syndrome, DIC and liver failure.

Patho-clinical forms n n n Recurrent showers of pulmonary emboli: (CTPH) Pulmonary infarction: Diseased lung ex lung congestion. Massive Pulm. Embolism

Clinical Presentation n n n Asymptomatic Sudden onset of unexplained dyspnea Pleuritic chest pain Tachypnea Tachycardia Anxiety/agitation, cough, hemoptysis, syncope, fever, cyanosis, isolated crackles, pleural friction rub, loud P 2, right-sided S 3, pulmonary insufficiency murmur, elevated JVP, right ventricular heave, acute worsening of heart failure or lung disease

Differential Diagnosis n n n n n Pneumothorax Myocardial ischemia Pericarditis Asthma Pneumonia MI with cardiogenic shock Cardiac tamponade Aortic dissection etc, etc

Westermark Sign n n represents a focus of oligemia (vasoconstriction) seen distal to a pulmonary embolism. While the chest x-ray is normal in the majority of PE cases, the Westermark sign is seen in 2% of patients. The sign results from a combination of: n n The dilation of the pulmonary arteries proximal to the embolus and the collapse of the distal vasculature creating the appearance of a sharp cut . off on chest radiography

Hampton Hump Radiologic sign which consists of a shallow wedge-shaped opacity in the periphery of the lung with its base against the pleural surface.

EKG Findings

Evaluation and Diagnosis n n Evaluation and imaging is dependent upon estimated pretest probability (Modified Wells’ Criteria) Pretest probability: n n n Low (<2 points) Intermediate (2 -6 points) High (>6 points) VARIABLE POINTS S/S of DVT 3. 0 HR >100 1. 5 Immobilization (bed rest >/= 3 d) OR surgery within 4 weeks 1. 5 Prior DVT or PE 1. 5 Hemoptysis 1. 0 Malignancy (treated within the past 6 months or palliative 1. 0 Other diagnoses less likely than PE 3. 0

D-dimer in evaluation of PE n n High sensitivity but poor specificity Negative ELISA has >95% negative predictive value and can be used to r/o PE in low risk patients (less than 2 points) Low (<2) Intermediate (2 High (>6) -6) Overall 3% 20% 60% (-) D-dimer 2% 6% 20% (+) D-dimer 7% 36% 75%

Helical CT n n n Sensitivity 85% (more sensitive for proximal emboli) Specificity 95% Values vary widely in literature

Bilateral PE

V/Q Scan n Identifies mismatches between areas that are ventilated but not perfused Best initial test in patients with clear CXR Scan be interpreted as High, Intermediate, or Low probability of PE, or normal n n Normal rules out PE High-probability scan is diagnostic of PE if the clinical suspicion is also high Low-probability scan rules out PE only in a pt with low pretest clinical probability (because PE is found in roughly 15% of pts with lowprobability scans) Intermediate-probability scan requires further evaluation (16 -66% chance of PE depending on pretest probability)

V/Q Scan

Duplex US with compression of the lower extremities n n Non-invasive test that accurately detects proximal DVT in LE (70 -80% of pts with PE have concomitant proximal DVT) Often used in workup of PE before going to more invasive procedures

Pulmonary Angiography “Gold Standard” Invasive study 5% morbidity < 0. 5% mortality Indicated if the diagnosis remains uncertain after noninvasive testing n n n

PE on pulmonary angiogram

An approach to Prophylaxis 1/determine patient at risk n n n Low risk (<40 years old, ambulating, minor surgery) Moderate risk (>40 years old, abdominal, pelvic or thoracic surgery) High risk (>60 years old, prior DVTor PE malignancy, orthopedic surgery hypercoagulability state).

2/prohylaxis of choice n Encourage all patients to ambulate as soon as possible n Low risk patient don't need prophylaxis. n Moderate risk pneumatic compression boot or low dose heparin prophylaxis. n High risk combination of pneumatic compression boot and low dose heparin prophylaxis or Dextran. Coumadine or IVCfilter are considered. Ophthalmology or neurosurgery patient are NOT candidates for prophylaxis.

n For patients with objectively confirmed DVT or pulmonary embolism, grade 1 recommendations included: n n Anticoagulant therapy with subcutaneous low–molecular-weight heparin (LMWH), Monitored IV or subcutaneous unfractionated heparin, Unmonitored weight-based subcutaneous unfractionated heparin or subcutaneous fondaparinux. Physicians should treat patients who have a high suspicion of DVT or pulmonary embolism with anticoagulants while awaiting the outcome of diagnostic tests, according to the grade 1 guidelines. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8 th Edition). Chest. Jun 2008; 133(6 Suppl): 454 S-545 S

Unfractionated heparin therapy n n In patients with massive pulmonary embolism, if concerns regarding subcutaneous absorption arise, severe renal failure exists, or if thrombolytic therapy is being considered, IV UFH is the recommended form of initial anticoagulation (grade 2 C). The efficacy of heparin therapy depends on achieving a critical therapeutic level of heparin within the first 24 hours of treatment. The critical therapeutic level of heparin is 1. 5 times the baseline control value or the upper limit of normal range of the activated partial thromboplastin time (a. PTT).

Unfractionated heparin therapy n If IV UFH is chosen, an initial bolus of 80 U/kg or 5000 U followed by an infusion of 18 U/kg/h or 1300 U/h should be given, with the goal of rapidly achieving and maintaining the a. PTT at levels that correspond to therapeutic heparin levels. Fixed-dose and monitored regimens of subcutaneous UFH are available and are acceptable alternatives.

Low-molecular-weight heparin therapy n n Current guidelines for patients with acute nonmassive pulmonary embolism recommend LMWH over UFH (grade 1 A). LMWHs have many advantages over UFH: These agents have a greater bioavailability, n can be administered by subcutaneous injections, n and have a longer duration of anticoagulant effect. “A fixed dose of LMWH can be used, and laboratory monitoring of a. PTT is not necessary. ” n n Trials comparing LMWH with UFH have shown that LMWH is at least as effective and as safe as UFH. The studies have not pointed to any significant differences in recurrent thromboembolic events, major bleeding, or mortality between the 2 types of heparin. Chest. Jun 2008; 133(6 Suppl): 454 S-545 S

Low-molecular-weight heparin therapy n n LMWH can be administered safely in an outpatient setting. This has lead to the development of programs in which clinically stable patients with pulmonary embolism are treated at home, at substantial cost savings. An international, open-label, randomized trial compared outpatient and inpatient treatment (both using the LMWH enoxaparin as initial therapy) of low-risk patients with acute pulmonary embolism and concluded that outpatient treatment was non inferior to inpatient treatment. Lancet. Jul 2 2011; 378(9785): 41 -8

Fondaparinux n n n Fondaparinux is a synthetic polysaccharide derived from the antithrombin binding region of heparin. Fondaparinux catalyzes factor Xa inactivation by antithrombin without inhibiting thrombin. Fondaparinux has not been directly compared with subcutaneous UFH or LMWH. However, once-daily fondaparinux was found to have similar rates of recurrent pulmonary embolism, bleeding, and death as IV UFH, according to one randomized open-label study of 2213 patients with symptomatic pulmonary embolism. Br J Haematol. Nov 2005; 131(3): 301 -12.

Duration: The ACCP recommended n Initial treatment with low–molecular-weight heparin, unfractionated heparin or fondaparinux for at least five days in patients with acute DVT or pulmonary embolism; this is plus vitamin K antagonists (VKA). The heparin preparations should be discontinued when international normalized ratio reaches ≥ 2 for at least 24 hours.

VKA: Warfarin therapy n n The anticoagulant effect of warfarin is mediated by the inhibition of vitamin K–dependent factors, which are II, VII, IX, and X. The peak effect does not occur until 36 -72 hours after drug administration, and the dosage is difficult to titrate. A prothrombin time ratio is expressed as an INR and is monitored to assess the adequacy of warfarin therapy. The recommended therapeutic range for venous thromboembolism is an INR of 2 -3. Initially, INR measurements are performed on a daily basis; once the patient is stabilized on a specific dose of warfarin, the INR determinations may be performed every 1 -2 weeks or at longer intervals.

Duration of anticoagulation therapy n n A patient with a first thromboembolic event occurring in the setting of reversible risk factors, such as immobilization, surgery, or trauma, should receive warfarin therapy for at least 3 months. No difference in the rate of recurrence was observed in either of 2 studies comparing 3 versus 6 months of anticoagulant therapy in patients with idiopathic (or unprovoked) first event. BMJ. Mar 31 2007; 334(7595): 674 “The current recommendation is anticoagulation for at least 3 months in these patients; the need for extending the duration of anticoagulation should be reevaluated at that time. ”

Duration of anticoagulation therapy n n The current ACCP guidelines recommend that all patients with unprovoked pulmonary embolism should undergo a risk-to-benefit evaluation to determine if long-term therapy is needed (grade 1 C). Long-term treatment is recommended for these patients who do not have risk factors for bleeding and in whom accurate anticoagulant monitoring is possible (grade 1 A). .

Duration of anticoagulation therapy n Patients who have pulmonary embolism and preexisting irreversible risk factors, such as deficiency of antithrombin III, protein S and C, factor V Leiden mutation, or the presence of antiphospholipid antibodies, should be placed on long-term anticoagulation.

Recommendations for Fibrinolysis for Acute PE n n 1. Fibrinolysis is reasonable for patients with massive acute PE and acceptable risk of bleeding complications (Class IIa; Level of Evidence B). 2. Fibrinolysis may be considered for patients with submassive acute PE judged to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening respiratory insufficiency, severe RV dysfunction, or major myocardial necrosis) and low risk of bleeding complications (Class IIb; Level of Evidence C). 3. Fibrinolysis is not recommended for patients with low-risk PE (Class III; Level of Evidence B) or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening (Class III; Level of Evidence B). 4. Fibrinolysis is not recommended for undifferentiated cardiac arrest (Class III; Level of Evidence B).

IVC Filter: if anticoagulation is contraindicated (ie, active GI bleed, intracranial neoplasm, know bleeding diathesis), if thrombus formed despite adequate anticoagulation, or with a large burden of thrombosis in the LE that could be fatal if embolized

Antithrombotic Therapy for Venous Thromboembolic Diseases ----Antithrombotic Therapy and Prevention of Thrombosis: ACCP Evidence-Based Clinical Practice Guidelines, 9 th ed Copyright: American College of Chest Physicians 2012 ©

Parenteral Anticoagulation Prior to Receipt of the Results of Diagnostic Workup for PE In patients with a high clinical suspicion of acute PE, we suggest treatment with parenteral anticoagulants compared with no treatment while awaiting the results of diagnostic tests (Grade 2 C).

Parenteral Anticoagulation Prior to Receipt of the Results of Diagnostic Work-up for PE In patients with an intermediate clinical suspicion of acute PE, we suggest treatment with parenteral anticoagulants compared with no treatment if the results of diagnostic tests are expected to be delayed for more than 4 h (Grade 2 C).

Parenteral Anticoagulation Prior to Receipt of the Results of Diagnostic Work-up for PE In patients with a low clinical suspicion of acute PE, we suggest not treating with parenteral anticoagulants while awaiting the results of diagnostic tests, provided test results are expected within 24 h (Grade 2 C).

Timing of Initiation of VKA and Associated Duration of Parenteral Anticoagulant Therapy In patients with acute PE, we recommend early initiation of VKA (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the INR is 2. 0 or above for at least 24 h (Grade 1 B).

Choice of Initial Parenteral Anticoagulant Regimen in Patients With PE In patients with acute PE, we suggest LMWH or fondaparinux over IV UFH (Grade 2 C for LMWH; Grade 2 B for fondaparinux) and over SC UFH (Grade 2 B for LMWH; Grade 2 C for fondaparinux). Remarks: Local considerations such as cost, availability, and familiarity of use dictate the choice between fondaparinux and LMWH and fondaparinux are retained in patients with renal impairment, whereas this is not a concern with UFH. In patients with PE where there is concern about the adequacy of SC absorption or in patients in whom thrombolytic therapy is being considered or planned, initial treatment with IV UFH is preferred to use of SC therapies.

Choice of Initial Parenteral Anticoagulant Regimen in Patients With PE In patients with acute PE treated with LMWH, we suggest once - over twice-daily administration (Grade 2 C). Remarks: This recommendation only applies when the approved once-daily regimen uses the same daily dose as the twice-daily regimen (ie, the once-daily injection contains double the dose of each twice-daily injection). It also places value on avoiding an extra injection per day.

Early vs Standard Discharge of Patients With Acute PE In patients with low-risk PE and whose home circumstances are adequate, we suggest early discharge over standard discharge (eg, after first 5 days of treatment) (Grade 2 B). Remarks: Patients who prefer the security of the hospital to the convenience and comfort of home are likely to choose hospitalization over home treatment.

Systemic Thrombolytic Therapy for Patients With PE In patients with acute PE associated with hypotension (eg, systolic BP < 90 mm Hg) who do not have a high bleeding risk, we suggest systemically administered thrombolytic therapy over no such therapy (Grade 2 C).

Systemic Thrombolytic Therapy for Patients With PE In most patients with acute PE not associated with hypotension, we recommend against systemically administered thrombolytic therapy (Grade 1 C).

Systemic Thrombolytic Therapy for Patients With PE In selected patients with acute PE not associated with hypotension and with a low bleeding risk whose initial clinical presentation, or clinical course after starting anticoagulant therapy, suggests a high risk of developing hypotension, we suggest administration of thrombolytic therapy (Grade 2 C).

Systemic Thrombolytic Therapy for Patients With PE In patients with acute PE, when a thrombolytic agent is used, we suggest short infusion times (eg, a 2 -h infusion) over prolonged infusion times (eg, a 24 -h infusion) (Grade 2 C).

Systemic Thrombolytic Therapy for Patients With PE In patients with acute PE when a thrombolytic agent is used, we suggest administration through a peripheral vein over a pulmonary artery catheter (Grade 2 C).

Catheter-Based Thrombus Removal for the Initial Treatment of Patients With PE In patients with acute PE associated with hypotension and who have (i) contraindications to thrombolysis, (ii) failed thrombolysis, or (iii) shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours), if appropriate expertise and resources are available, we suggest catheter-assisted thrombus removal over no such intervention (Grade 2 C).

Choice of Anticoagulant Regimen for Long-term Therapy In patients with acute PE associated with hypotension, we suggest surgical pulmonary embolectomy over no such intervention if they have (i) contraindications to thrombolysis, (ii) failed thrombolysis or catheter-assisted embolectomy, or (iii) shock that is likely to cause death before thrombolysis can take effect (eg, within hours), provided surgical expertise and resources are available (Grade 2 C).

New Drugs: Rivaroxaban n n Oral factor Xa inhibitor provide a simple, fixeddose regimen for treating acute DVT and for cntinued treatment, without the need for lab. Monitoring. Approved (FDA) for prophylaxis in post-operative period after knee & hip replacement and chronic AF. Nearly it will approved for treatment of acute PE. Antidote: Thrombin Complex Concintrate.