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

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

3. Epidemiology Incidence of VTE is about 1 in 1000 per year.Incidence of VTE is about 1 in 1000 per year. DVT and PE should be considered part of the same pathological process.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.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.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%.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.Sudden death is the presenting clinical manifestation in nearly 25% of patients with PE.

4. Sequelae of VTE Pulmonary embolismPulmonary 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 DVTDVT - post-thrombotic syndrome in 25% (swelling, stasis dermatitis, ulceration, venous insufficiency and venous claudication) - paradoxical embolism/stroke - paradoxical embolism/stroke - PE - 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: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).Think of risk factors as modifiable and non-modifiable (important when considering cause of VTE and duration or therapy).

6. Risk factors (cont’d) Immobility or prolonged travelImmobility or prolonged travel Increasing ageIncreasing age ObesityObesity Cigarette smokingCigarette smoking OCPs (including progesterone only pills)OCPs (including progesterone only pills) PregnancyPregnancy HRTHRT TamoxifenTamoxifen Stroke/limb paresis or paralysisStroke/limb paresis or paralysis TraumaTrauma SurgerySurgery PNHPNH Nephrotic syndromeNephrotic syndrome Previous PE or DVTPrevious PE or DVT Varicose veinsVaricose 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

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 5007.3 * Protein S deficiency1 : 1000 to 50008.5 * Antithrombin III deficiency1 : 2000 to 50008.1 * * 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?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?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?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?What are the EKG findings? Sinus tachycardia, S1Q3T3, RAD, RBBB, T-wave inversion in V1- V4. What will you see on ABG?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 determine the patient’s clinical probability of PE. To decide what diagnostic test you would you like to order.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 DVT3.0 An alternative diagnosis less likely than PE3.0 Heart rate >100 beats/min1.5 Immobilization or surgery in the previous 4 wks1.5 Previous DVT or PE 1.5 Hemoptysis 1.0 Cancer (receiving treatment, treated in past 6 mo,1.0 or palliative care) 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. Fedullo P and Tapson V. N Engl J Med 2003;349:1247-1256 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

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

16. Treatment of acute PE: Risk stratification Prognostic tests: Echocardiogram (RV dysfunction signifies increased risk of death during hospitalization).Echocardiogram (RV dysfunction signifies increased risk of death during hospitalization). BNPBNP Troponin (high risk of complicated hospital course)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? a.LMWH followed by warfarin b.IV heparin followed by warfarin c.Thrombolytic therapy d.Warfarin alone

18. Treatment of acute PE Unfractionated heparinUnfractionated heparin LMWHLMWH WarfarinWarfarin - initiate 5 mg rather than 10 mg 88% vs. 53% therapeutic on day 5 (Crowther et al Arch Intern Med 1999) ThrombolysisThrombolysis Pulmonary embolectomy or catheter thrombus extractionPulmonary embolectomy or catheter thrombus extraction IVC Filter (contraindication to AC, recurrent PE while on AC, complication of AC, poor cardiopulmonary reserve)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 monthsTransient risk factors → 3 – 6 months First VTE, idiopathic → 6 – 12 monthsFirst VTE, idiopathic → 6 – 12 months VTE + irreversible risk factor → 1 year to lifelongVTE + irreversible risk factor → 1 year to lifelong Recurrent → lifelongRecurrent → 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. Lancet 2004; 363: 1295 – 1305. Goldhaber, SZ. Pulmonary Embolism. N Engl J Med 1998; 339: 93 – 104.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.Fedullo, PF and Tapson VF. The Evaluation of Suspected Pulmonary Embolism. N Engl J Med 2003; 349: 1247 – 1256. UpToDateUpToDate Summary of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126.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 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.Piazza G and Goldhaber, SZ. Acute Pulmonary Embolism Part II: Treatment and Prophylaxis. Circulation 2006; 114; 42 – 47.