1. How do you approach a patient you think may have a PE?

2. 6/28/20152 Case 1 42 yo female presents to ED with complaint of 3 weeks of congestion and several days of difficulty catching her breath No significant PMH, meds, non-smoker, no recent immobility or surgeries T 37.9, P 82, RR 20, room air sats 98% –Sinus tenderness, boggy turbinates, red throat –Lungs clear and no respiratory distress –CXR clear –Spiral CT reveals left lower lobe sub-segmental defect

3. How good is a CTA (-CTV) to rule in or out a PE? 6/28/20153

4. PIOPED II – NEJM, 2006 Prospective cohort study Consecutive inpatient and outpatients with suspected acute pulmonary embolism Composite reference standard –Clinical assessment, VQ scanning, CUS, if necessary DSA CTA-CTV – stringent standards 6/28/20154

5. PIOPED II – NEJM, 2006 No PE –Normal DSA –Normal VQ scan –Low or very low prob VQ scan, low prob Wells, normal CUS –PLUS telephone interviews at 3 and 6 months PE –High Prob VQ scan –Abnormal DSA –Abnormal CUS 6/28/20155

6. Wells Criteria 6/28/20156

7. Results CTA –Sensitivity 83% –Specificity 96% –+LR 19.6, -LR.19 CTA-CTV –Sensitivity 90% –Specificity 95% – +LR 16.5, -LR.11 6/28/20157

8. Problems Exclusions and dropouts –“inconclusive results” 6% for CTA 11% for CTV –Of 1090 enrolled, 238 did not receive reference diagnosis This represents best case scenario 6/28/20158

9. Discordant clinical and radiologic findings 6/28/20159

10. 10

11. Christopher study – JAMA 2006 Prospective cohort study of a sequential application of a clinical decision rule, D- Dimer testing, and CTA Consecutive patients – sudden onset dyspnea, sudden deterioration of existing dyspnea, or sudden pleuritic chest pain –ED and wards A modified Wells assessment, An elisa ddimer test, and Multirow detector CT scan 3 month follow up 6/28/201511

12. Modified Wells 6/28/201512

13. 6/28/201513 PE? D-Dimer Positive Wells - Likely Wells - Unlikely D-Dimer Negative CT - Angiogram Negative Positive Treat Observe, no therapy *

14. Copyright restrictions may apply. Writing Group for the Christopher Study Investigators, JAMA 2006;295:172-179. Venous Thromboembolic Events (VTEs) During 3-Month Follow-up (n = 3138)*

15. Summary Safety with concordant findings –Low PTP/normal D-Dimer/negative CTA Consider going further if discordant findings 6/28/201515

16. 6/28/201516 Lower Extremity Ultrasound Annals of Internal Medicine 01/98 Cohort study of consecutive patients presenting to referral center with suspected DVT All underwent CUS initially and if normal again in 5-7 days All followed for 3 months

17. 6/28/201517

18. Prevention 6/28/201518

19. 6/28/201519

20. Limitations of the literature DVT screening methods –Venography – 20-40% nondiagnostic, clinical relevance of small thrombi –DUS – poor accuracy for calf veins, operator dependent End points –Mortality > fatal PE > PE > Symptomatic DVT > Asymptomatic DVT Industry sponsorship 6/28/201520

21. Risk Factors Increasing age (>50) Malignancy – history, active, under therapy Medications –OCPs, HRT, SERM, Erythropoiesis stimulating compounds Medical condition –IBD, Nephrotic syndrome, history of MI, atrial fibrillation, ischemic stroke, diabetes mellitus, obesity, CHF, paralysis, previous VTE, varicosities Thrombophilia –FVL, Prothrombin gene mutation, Protein C, S, ATIII deficiencies 6/28/201521

22. Prevalence of DVT in hospitalized patients * Patient GroupDVT Prevalence (%) Medical Patients10-20 General Surgery15-40 Stroke20-50 Hip/Knee Arthroplasty, HFS40-60 Critical Care10-80 6/28/201522 * Objective screening for asymptomatic DVT in patients not receiving thromboprophylaxis

23. Medical Patients Pharmacologic Thromboprophylaxis (LMWH, LDUH, fondaparinux) recommended for… acutely ill hospitalized patients with CHF, severe respiratory disease or confined to bed PLUS one or more additional risk factors such as –Active cancer –Previous VTE –Sepsis –Acute neurologic disease –IBD 6/28/201523

24. Meta-analysis Annals of Internal Medicine, February, 2007 Anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients “Individual randomized trials of anticoagulant prophylaxis in medical patients have been underpowered to show a reduction in PE and have assessed treatment effects on asymptomatic, venography-detected DVT, which is a less compelling outcome.” 6/28/201524

25. Meta-analysis Well designed and described search strategy Two independent reviewers Treatment efficacy outcomes –All-cause mortality, fatal and non-fatal symptomatic PE, symptomatic DVT On-treatment period Anticoagulant Regimens –LDUH 5000IU bid/tid, Enoxaparin 40-60mg daily or 30mg bid, Nadroparin 4000/6000 IU daily, Dalteparin 5000IU daily or Fondaparinux 2.5mg daily 6/28/201525

26. Dentali, F. et. al. Ann Intern Med 2007;146:278-288 Meta-analysis: Identification of eligible studies

27. Dentali, F. et. al. Ann Intern Med 2007;146:278-288 Any pulmonary embolism during anticoagulant prophylaxis

28. Dentali, F. et. al. Ann Intern Med 2007;146:278-288 Fatal pulmonary embolism during anticoagulant prophylaxis

29. Dentali, F. et. al. Ann Intern Med 2007;146:278-288 All-cause mortality during anticoagulant prophylaxis

30. Dentali, F. et. al. Ann Intern Med 2007;146:278-288 Symptomatic deep venous thrombosis during anticoagulant prophylaxis

31. Dentali, F. et. al. Ann Intern Med 2007;146:278-288 Major bleeding during anticoagulant prophylaxis

32. Limitations Not all studies were double blind –Diagnostic suspicion bias Best agent? –No head to head comparisons in this study Lack of standardized definition for major bleeding Pharmaceutical support 6/28/201532

33. 6/28/201533

34. Summary Those at highest risk receive greatest benefit from an intervention –Risk stratify surgical and medical patients (Joint Commission Requirement) –Provide anticoagulant prophylaxis to moderate and high risk surgical patients –Provide anticoagulant prophylaxis to most** hospitalized medical patients 6/28/201534