Pulmonary Embolism

1. Pulmonary Embolism Larissa Bornikova, MD July 21, 2006

2. Objectives • To know the spectrum and sequelae of VTE • To review the risk factors for VTE • To understand the decision paradigms in the diagnosis of PE • To develop a systematic approach to evaluating a patient with suspected PE • To outline the initial treatment strategies for PE

3. Epidemiology • Incidence of VTE is about 1 in 1000 per year. • DVT and PE should be considered part of the same pathological process. - 40% of patients with DVT have asymptomatic PE on lung scanning. - 29% of patients with PE have abnormal LE venous ultrasound. • More than 500,000 patients are diagnosed with PE annually in the United States. More than half of all patients with PE remain undiagnosed. • Mortality rate is up to 30% without treatment primarily due to recurrent embolism. • Therapy with anticoagulants decreases the mortality rate from PE to 2-8%. • Sudden death is the presenting clinical manifestation in nearly 25% of patients with PE.

4. Sequelae of VTE • Pulmonary embolism - flow obstruction → increased pulmonary vascular resistance → redistribution of blood flow → V/Q mismatch due to alveolar dead space → increased RV afterload and RV wall tension → RV dilatation, dysfunction and possible ischemia. If ASD or PFO present R → L shunting and paradoxical embolism may occur. - other clinical sequelae: chronic dyspnea, chronic pulmonary hypertension (<2%), right-sided heart failure, death • DVT - post-thrombotic syndrome in 25% (swelling, stasis dermatitis, ulceration, venous insufficiency and venous claudication) - paradoxical embolism/stroke - PE

5. Risk factors Understanding risk factors will increase likelihood that DVT and PE will be diagnosed and/or prevented. • Think of Virchow’s triad: venous stasis, endothelial damage, and hypercoagulable state. • Think of risk factors as modifiable and non-modifiable (important when considering cause of VTE and duration or therapy).

6. Immobility or prolonged travel Increasing age Obesity Cigarette smoking OCPs (including progesterone only pills) Pregnancy HRT Tamoxifen Stroke/limb paresis or paralysis Trauma Surgery PNH Nephrotic syndrome Previous PE or DVT Varicose veins Cancer Congestive heart failure COPD Diabetes Inflammatory bowel disease Antipsychotic drug use Chronic indwelling central venous catheters Permanent pacemaker/ICD Polycythemia Vera / ET Inherited Thrombophilias (see next slide) Acquired Thrombophilias (APS and LA) Hyperviscosity (myeloma, Waldenstrom’s) High concentrations of factor VIII or XI Risk factors (cont’d)

7. Inherited Thrombophilias Inherited Thrombophilias Prevalence in Relative Risk general population of thrombosis Factor V Leiden heterozygous 1% - 15% 7 homozygous ~ 1% 80 Prothrombin gene mutation 0.7 – 6.5 % 2.8 Protein C deficiency 1 : 200 to 500 7.3 * Protein S deficiency 1 : 1000 to 5000 8.5 * Antithrombin III deficiency 1 : 2000 to 5000 8.1 * * Martinelli, et al. Blood 1998

8. Case I CC: Shortness of breath HPI: MV is a 40-year old woman, chemical manufacturing executive, who comes to the Emergency Department with complaints of shortness of breath, right sided chest pain aggravated by breathing and coughing. Within the last week she has returned from an overseas trip to China. She has not noticed fever, chills or sputum production. PMH: No recent surgeries; no prior hospitalizations or serious illnesses Allergies: None Medications: MVI, Orho-Novum 1/50 for excessive menstrual bleeding Social History: No tobacco, alcohol, IVDU

9. Clinical Presentation • What is the most common symptom of PE? What are other symptoms of PE? Dyspnea (>70%), pleuritic chest pain, cough, hemoptysis, syncope, hypotension, PEA, but can be asymptomatic • What are the signs you may find on physical exam? Tachypnea, rales, tachycardia, loud P2, fever, pleural rub, hypotension, increased JVP, right-sided S3, parasternal lift, cyanosis. • What are the radiographic signs of PE? Normal CXR, Westermark’s signs, Hampton’s hump, Palla’s signs, pleural effusion. • What are the EKG findings? Sinus tachycardia, S1Q3T3, RAD, RBBB, T-wave inversion in V1-V4. • What will you see on ABG? Respiratory alkalosis, hypoxemia, widened A-a gradient.

10. Case I (cont’d) Physical exam: BP 100/70 P 95 (recumbent) BP 95/80 P 120 (upright) RR 24 T 98.9 HEENT: WNL Chest: decreased breath sounds at the R base Cardiac: tachy; normal heart sounds; no m/r/g Abdomen: soft, NABS, NT, ND, no HSM Extremities: warm, w/o cyanosis, clubbing or edema CXR: ill defined pleural-based infiltrate at the fight posterior base Labs: ABG 7.49/29/80 (room air) WBC 10.2; Hgb 13; Hct 37; Plt 238,000

11. Approach to the patient with suspected PE. Clinical suspicion for PE should lead to diagnostic evaluation. Two steps: • To determine the patient’s clinical probability of PE. • To decide what diagnostic test you would you like to order. EKG, blood gases, CXR may help determine the pretest probability and focus the differential diagnosis.

12. Well’s Criteria Validated clinical risk factors that help to determine pre-test probability of a PE in outpatients who present to ED . Risk factorNo. of points Clinical signs and symptoms of DVT 3.0 An alternative diagnosis less likely than PE 3.0 Heart rate >100 beats/min 1.5 Immobilization or surgery in the previous 4 wks 1.5 Previous DVT or PE 1.5 Hemoptysis 1.0 Cancer (receiving treatment, treated in past 6 mo, 1.0 or palliative care) Patients can be classified into three groups on the basis of clinical probability of PE: Low (<2 points) prevalence 10% or less Intermediate (2-6 points) prevalence of about 30% High (> 6 points) prevalence of 70% or more

13. Case I (cont’d) • What is the probability that this patient has a pulmonary embolism? • What diagnostic test would you like to order?

14. Diagnostic Approach to a Patient with an Intermediate Clinical Probability of Embolism, Using Helical CT Scanning or Ventilation-Perfusion Scanning as the Initial Diagnostic Study Fedullo P and Tapson V. N Engl J Med 2003;349:1247-1256

15. Diagnostic tests EKG, blood gases, CXR may help to determine the pretest probability and focus the differential diagnosis. Diagnostic tests: • D-dimer • Imaging. Spiral CT with IV contrast vs. V/Q scan vs. pulmonary angiography • Echocardiogram (poor diagnostic test)

16. Treatment of acute PE: Risk stratification Prognostic tests: • Echocardiogram (RV dysfunction signifies increased risk of death during hospitalization). • BNP • Troponin (high risk of complicated hospital course) Adverse outcome also predicted by: cancer, heart failure, previous DVT, hypotension, hypoxemia, DVT on US.

17. Case I (cont’d) How would you treat this patient? • LMWH followed by warfarin • IV heparin followed by warfarin • Thrombolytic therapy • Warfarin alone

18. Treatment of acute PE • Unfractionated heparin • LMWH • Warfarin - initiate 5 mg rather than 10 mg 88% vs. 53% therapeutic on day 5 (Crowther et al Arch Intern Med 1999) • Thrombolysis • Pulmonary embolectomy or catheter thrombus extraction • IVC Filter (contraindication to AC, recurrent PE while on AC, complication of AC, poor cardiopulmonary reserve) - at 8 years fewer symptomatic PE (6 vs. 15%) but more DVT (21 vs. 12 %) (PREPIC trial Circulation 2005)

19. Duration of treatment of acute PE • Transient risk factors → 3 – 6 months • First VTE, idiopathic → 6 – 12 months • VTE + irreversible risk factor → 1 year to lifelong • Recurrent → lifelong Testing for inherited and acquired thrombophilia - AT III level depressed by heparin; Prot C and protein S level lowered by warfarin Age-appropriate cancer screening

20. References • Goldhaber, SZ. Pulmonary Embolism. Lancet 2004; 363: 1295 – 1305. • Goldhaber, SZ. Pulmonary Embolism. N Engl J Med 1998; 339: 93 – 104. • Fedullo, PF and Tapson VF. The Evaluation of Suspected Pulmonary Embolism. N Engl J Med 2003; 349: 1247 – 1256. • UpToDate • Summary of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126. • Piazza G and Goldhaber, SZ. Acute Pulmonary Embolism Part I: Epidemiology and Diagnosis. Circulation 2006; 114; 28 – 32. • Piazza G and Goldhaber, SZ. Acute Pulmonary Embolism Part II: Treatment and Prophylaxis. Circulation 2006; 114; 42 – 47.