Venous Thromboembolic Disease

2. Venous Thromboembolic Disease Chris Hall, MD, FRCPC Emergency Medicine Resident Rounds January 12, 2012

3. One Night in the ED… • 36 yo Female • Sudden onset right-sided pleuritic CP • Feels SOB • Physical examination ‘normal’ • PMHx: Nil • Meds: None • ECG, CXR normal

5. WHY I HATE PE… • Potentially fatal (“can’t miss”) • Challenging to diagnose • Evidence base is HUGE… and growing • Rapid advances in technology: evidence is obsolete (?!)

6. Objectives • To simplify YOUR life when it comes to PE in the ED • To provide an update on the latest state of the evidence regarding PE: • Diagnosis • Management • Risk Stratification

7. Epidemiology • PE Incidence • 115 cases per 100,000 population / yr • Mortality Rate • 12 per 100,000 / yr • Case Fatality • 8% overall (30% if untreated!)

8. Pathophysiology • Virchow’s Triad • Stasis • Injury • Hypercoagulability • > 90% Deep venous source • Iliofemoral > Pelvic > Renal > IVC • Calf veins (< 10%)

9. Pathophysiology • Multiple mechanisms of hypoxia • V/Q mismatch • Inflammatory cascade  surfactant dysfxn • Functional intrapulmonary shunting • 75% obstruction of PA bed = reduced CO

10. Risk Factors • Malignancy • Immobilization / Paresis • Surgery / Trauma • Prior hx of VTE • Thrombophilia • Family history • Pregnancy • Estrogen use

11. PE: Our Worst Nightmare…? • Presentation often non-specific • Many clinical mimics • Up to 40% of fatal PE < 35 yo missed on first MD contact

12. …or an iatrogenic epidemic? • 1998 – 2006: • PE Indicence 86% • Case Fatality  36% • CTPA use > 10-fold  • Pop’n Mortality: NO CHANGE • More testing / treatment to get the same result?

13. A Balance of Risks • PE mortality: 8% • (?? 25-30% if untreated) • LAR for cancer from one CTPA • 25yF: 1 / 400 • 55yF: 1 / 950 • 25yM: 1/ 2000 • Contrast nephropathy • Overanticoagulation

14. Less Investigation More investigation Fewer missed PE More missed PE ?? ??

15. What Risk is ‘Acceptable’? • At what pre-test probability would you discharge your patient without further testing? • 10% • 5% • 2% • 1% • 0.5% • 0.1%

16. What Risk is ‘Acceptable’? • Lessler et al, Ann Emerg Med 2010 • Theoretical decision analysis • Risk of missed PE vs. risk of investigation / overtreatment • At 1.4% probability, risks are equal • If probability of PE < 1.4%, do not test

17. Can clinical exam achieve PTP < 1.4%?

18. PE: Clinical Presentation • What symptoms / signs make you think of PE? • What is the most common symptom / sign?

19. Clinical Presentation

20. Clinical Presentation

21. One Night in the ED… • 36 yo Female • Sudden onset right-sided pleuritic CP • Feels SOB • Physical examination ‘normal’ • PMHx: Nil • Meds: None • ECG, CXR normal

22. Would You… • Send a d-dimer? • Proceed directly to imaging? • Do nothing?

23. Is this patient’s pre-test probability of PE below the “no-test” threshold?

24. Wells Rule

25. Geneva Rule

27. 55,268 patients • 10 CDRs + MD gestalt reviewed

29. PERC • Pulmonary Embolism Rule-out Criteria • Derived 2004 • Validated 2008 (multi-center) • Provides CLINICAL basis to rule out PE • GOAL: < 1.5% probability

30. PERC

31. PERC Validation • 8138 patients • Results: • SN 97.4% (if MD gestalt ‘low-risk’) • Post-test prob: 1.0% • PE prevalence 7% (3% in low-risk pts) • Only useful in ‘low-risk’ population (MD gestalt) (BUT - who qualifies?? < 5% PTP?? )

32. Caveat Emptor… • Hugli et al. J ThrombHaemost., Feb 2011 • 1675 consecutive patients • 21.3% prevalence of PE • Low-risk revised Geneva: 6.4% PE • Low-risk Geveva + PERC (-): 5.8% PE • PERC NLR = 0.63 in LOW RISK pop’n

33. PERC Bottom Line • Achieves ‘no-test’ threshold in ‘low-risk’ patients • Endorsed in ACEP Clinical Policy (2011) • Select patients carefully

34. Back to our case • How many will now send a d-dimer?

35. The test you love to hate… • D-dimer = FDP • SN 75 – 97% • SP 43 – 99% • Depends on assay type • Depends on clinical context (CDRs) • Higher PTP = Lower SN

36. (-) Low (+) Not Low

37. ‘Wells Rule’

39. Quantitative D-dimer + CDR

40. D-dimer: Bottom Line • In low-intermed. probability patients, d-dimer rules out PE ACEP Clinical Policy 2011 • Efficiency of PERC + CDR / d-dimer strategy unknown

41. Yes No Not High High Positive Negative

42. Back to our case… • D-dimer result = 0.89 • Patient remains stable • Do you now: • Order a V/Q scan? • Order a CTPA? • Order U/S dopplers of the legs?

43. PE: Imaging • What is the ideal strategy for imaging in suspected pulmonary embolism?

44. V/Q Scan • Advantages • Lower radiation dose (7 – 10 x less than CTPA) • No iodinated contrast • Disadvantages • Harder to obtain ‘after hours’ • Higher rate of non-diagnostic scans • Cannot diagnose other causes for symptoms

45. CT diagnosed more PE • 19.2% vs 14.2% • LARGE non-diagnostic V/Q scan rate (> 50%) • V/Q noninferior to CT • VTE @ 3 mos 1.0% vs 0.4%

46. V/Q Scan: Don’t Bury it Yet! • Good option if: • Normal CXR • Younger patients • Lower PTP • Contraindications to CT

47. CT Pulmonary Angiogram • Advantages • Speed • Available after hours (in Calgary) • Confirms alternative diagnoses • Disadvantages • Contrast load • Radiation dose • Our ‘de facto’ gold standard

48. 3306 consecutive patients • Utilized dichotomous Wells (≤ 4 = “low”) • D-dimer if Wells low; MDCT if d-dimer (+) or Wells high • No Rx if d-dimer (-) or MDCT (-) • VTE rate @ 3 months: • 0.5% for Wells / d-dimer (-) • 1.3% for CT (-)

49. PIOPED II • CTPA SN: 85% • VTE @ 6 mos: 14% for Int. / High PTP if CTPA (-)

50. CTPA Bottom Line: • For Wells ≤ 4, CTPA (-) rules out PE • If PTP ‘intermediate’, consider additional testing** if still ‘concerned’ about PE • If PTP ‘high’, obtain additional testing** ACEP Clinical Policy, 2011 **(D-dimer acceptable)