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PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS

PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS. James Huffman 11.13.2008 Thanks to Dr. Gil Curry, Dr. Nadim Lalani. Outline. Epidemiology / Pathophysiology DVT Anatomy Clinical Presentation Diagnostic Approach Pre-test probability Labs Imaging Real-Life Algorithm Treatment. Outline.

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PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS

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  1. PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS James Huffman 11.13.2008 Thanks to Dr. Gil Curry, Dr. Nadim Lalani

  2. Outline • Epidemiology / Pathophysiology • DVT • Anatomy • Clinical Presentation • Diagnostic Approach • Pre-test probability • Labs • Imaging • Real-Life Algorithm • Treatment

  3. Outline • PE • Clinical Presentation • Diagnostic Approach • Pre-test probability • Labs • EKG • Imaging • X-ray, CT, MR • Real-Life Algorithm

  4. Focus: the bottom line

  5. Epidemiology • VTE is a ‘spectrum’ : Simple superficial thrombophlebitis to fatal PE • Est incidence : 100 /100 000 • 1/3 of cases are PE • Increases dramatically with age (sharp increase after the age of 45) • DVT: • Only 1/3 of pts investigated for DVT have it • “silent” PE present in 40-60% of pts with DVT • In asymptomatic pts w/ proven DVT, up to 1/3 will have undiagnosed PE • With treatment 50% have residual clot up to 1y • Without treatment 50% recurrence w/ in 3 mo

  6. Epidemiology • PE: • 10% fatal w/ in 1st Hour • 75% pt w/ PE have DVT (2/3 proximal vein) • Classic presentations are less common than atypicals and asymptomatic VTE is common • 20% have “pleuritic CP” in ED • 5-10% PE have shock as initial presentation • Despite treatment, kills 1-8% • Complications: • postphlebitic syndrome [40%] • pulmonary HTN [4%]

  7. Pathophysiology of Thrombosis • Fibrinogen is converted to fibrin in response to vasc. Injury and inflammation • Fibrin is 1° structural framework of embolized clots and excessive fibrin deposition provides the nidus of VTE • VTE is the end-product of imbalanced clot formation and breakdown What promotes this imbalance of fibrin deposition and removal?

  8. Virchow’s TriadWhite, RH: The epidemiology of venous thromboembolism. Circulation 107(23 Suppl 1):I4, 2003. • Injury to the vascular endothelium • Alterations in blood flow • Hypercoagulability Anything else associated with imbalanced clot formation? Age – likely through a combination of the above mechanisms

  9. Coagulation Cascade

  10. Coagulation Cascade PTT Heparin PT/INR Warfarin

  11. Anatomy • Depth • Deep • Superficial* • Proximal • Popliteal v. or higher • Distal *Superficial femoral vein is a member of the deep group

  12. Case 1 • 55♀: Referred to ED for pain, redness and swelling of right calf • WIC today: Sent to ED with note:

  13. History • Started 3/7 ago • Denies previous DVT • Has been on IV combo chemotherapy for ovarian Ca diagnosed six months ago (extensive pelvic lymph node involvement – which has improved as per recent U/S) • Fell day before this started and “twisted her knee” • All this is good – what are your main goals with history? • Determine pre-test probability of DVT • Look for other causes

  14. DVT: History is Risk Assessment Hypercoagulability: • Autoimmune Disease and Immune Deficiency • Not just SLE! Remember IBD • Cancer • Chemotherapy: especially breast CA • Coagulopathy:  Factor V Leiden. Present in 7% pop = 50%  Protein C, protein S & antithrombin III deficiency = 15% DVT.  Resistance to aPC  Lupus anticoagulant  Prothrombin G20210A  antiphospholipid antibodies  others

  15. DVT: History is Risk Assessment Stasis: • Immobility: Not just surgery – remember other conditions (oldies!) • Heart Disease (AMI & CHF): independent of bedrest • Travel ?Duration / proximity? • Hyperlipiedmia • Polycythemia Endothelial Injury: • Stroke • Vascular surgery • PVD Others: • Age, race, prior DVT, blood types, tissue antigens, homocysteine

  16. Case 1 Continued • When you examine her what do you expect to find? • P/E: • Generalised tenderness to her calf • Exquisite pain in popliteal fossa along vein • Edema, erythema and warmth • Swollen 3.5 cm • Homan’s Sign + • What do you think of this?

  17. Physical is Risk AssessmentAnand, SS, Wells, PS, et al. 1998. Does this Patient have deep vein thrombosis? JAMA:279(14) • Classically: • Leg tenderness , Homan’s Sign • Swelling • Pitting edema • Dilated superficial veins • Erythema • Calor • Neither sensitive nor specific • OR’s between 2- 4

  18. Physical is Risk AssessmentAnand, SS, Wells, PS, et al. 1998. Does this Patient have deep vein thrombosis? JAMA:279(14)

  19. DVT: H&P Bottom Line • Neither is sensitive or specific • i.e. you can’t rule-in or rule-out a DVT • Use them to decide pre-test probability

  20. Clinical Prediction Rule: EvolutionLandefeld et. Al 1990 • 354 pts suspected of DVT that underwent venography • 5 clinical predictors identified: • 1 or more  95% Sens [92-100] 20% spec [15-25] • Swelling above the knee • Swelling below the knee • Recent immobility • Fever • Cancer • Absence of all  only 5% DVT

  21. Pretest ProbabilityWells, P., et al. 1995. Accuracy of Clinical Assessment of Deep Vein Thrombosis. Lancet:345; 1326-30 • First Wells Criteria • Based on literature review and clinical experience of investigators • Study showed value in stratifying pretest probability with respect to eliminating need for repeat u/s

  22. Pretest ProbabilityWells, P, et al. 1997. Lancet:350;1795. • Revised Wells score through logistic regression analysis • Prospectively validated using same treatment algorithm (next slide) • 593 patients from two Canadian tertiary care centres • Score ≥ 3 (high risk), 1 or 2 (moderate risk), <1 (low risk)

  23. Pretest ProbabilityWells, P, et al. 1997. Lancet:350;1795. • 593 pts w/ suspect DVT • Stratified low, mod, high risk  compression U/S /veno • 3% of Low risk, 17% of moderate risk, 75% of high risk pts had DVT • Concluded that Clinical probability + U/S safe [0.6% missed]

  24. Pretest Probability • This algorithm re-presented in JAMA rational clinical examination series Anand SS, Wells PS, Hunt D, Brill-Edwards P, Cook D, Ginsberg JS. Does this patient have deep vein thrombosis? JAMA. 1998 Dec 2;280(21):1828-9. • What’s missing? The N’Dimer!

  25. Assay Sensitivity Specificity Whole blood 80 - 85% 70 - 90% agglutination (SimpliRED) Latex 90 - 95% 40 - 90% agglutination R apid ELISA 95 - 100% 30 - 60% D-Dimer Testing • U/S not a perfect test • Degradation product of fibrin • Non-specific • PPV bad • +ve: surgery, trauma, hemorrhage, CA, pregnancy, sepsis, >80 yrs old • Sensitivity variable • Need Pre-test probability to r/o DVT CHR uses

  26. D-Dimer TestingWells, P., et al. 2003. NEJM: 349(13); pp1227-35 • RCT (N=1096) • D-Dimer vs no D-Dimer • DVT Likely = Wells ≥ 2 • # of U/S per pt decreased in D-dimer group (0.78 vs 1.34)

  27. D-Dimer TestingWells, P., et al. 2003. NEJM: 349(13); pp1227-35 • “Modified” Wells Criteria • Used SimpliRED and IL-Test assays (less sens) • Conclusion: • Clinical prediction rule + D-Dimer can safely r/o DVT

  28. Case 1 continued • Pretest probability? • Active cancer (1) • Localized tenderness (1) • Calf swelling (1) • Edema (1) • Other Diagnosis? Compression by pelvic nodes? (Doesn’t matter – score would still be “not low risk”) • What about the D-Dimer – Would you order it? • Doesn’t matter – it was sent already • Level positive at 1.77C • Both CMAJ and Well’s protocols would have you order it anyway (we’ll discuss) So she gets either 4 or 2 points = DVT likely

  29. What next Einstein?

  30. UltrasoundAmerican Journal of Respiratory Critical Care Medicine. 1999: 160; 1043-66 • Well studied • Widely available • Proven accurate for Dx symptomatic prox DVT • Like CT/PE provides other Dx: hematomas, baker’s cysts, lymphad, aneurism, thrombophlebitis and abscess • Has been advanced by the combination of compression and doppler Bottom line: U/S is the test of choice for DVT

  31. Duplex UltrasoundStork, A. 2005. Calgarian J of PPT Slides. 1(1) pp1 • Two parts i) Compression - Tech applies pressure - clot  not compressible ii) Doppler (B mode) • Shows blood flow

  32. Ultrasound Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

  33. EDE • Jolly BT, et al. Acad Emerg Med 1997;4(2):129–32. • Retrospective analysis 1994 • EPs trained to perform colour doppler US (20-30 studies each) • 100% sensitive, 75% specific for acute DVT • 2 false-positives were in chronic DVT • Frazee BW, et al. J Emerg Med 2001;20(2):107–12. • Prospectively demonstrated 95.7% NPV for EP performed LCUS

  34. Naughty by Nature - “Feel me flow”

  35. EDE – ED Flow • Blaivas M, et al. Acad Emerg Med. 2000;7(2):120–6. • Median exam time of 3m 28s • 98% correlation with vascular lab-performed studies on same pts • Theodoro D, et al. Am J Emerg Med. 2004;22(3):197–200. • 125m reduction in time to pt disposition with EP-performed US • Kappa = 0.9, 99% agreement (154/156 cases) • Jang T, et al. Acad Emerg Med. 2004;11(3):319–22. • 8 emerg residents (4 PGY-1, 2 PGY-2, 2 PGY-3) • 1h focused training (didactic and practice on 2 healthy volunteers) • SN = 100%, SP = 91.8%, avg scan time = 11.7min (self-reported) • 4 false-positives (chronic DVT), 0 false-negatives

  36. Ultrasound: Limitations • Obese, ++edema, immobilsation devices (x-fix) • Doesn’t see isolated thrombi in iliac or superficial femoral veins within abductor canal MRI better • Pelvic masses may cause noncompressibility in absence of thrombus  false +’ve • Most importantly: U/S doesn’t return to normal after acute DVT • Therefore use impedance plethysmography for recurrent DVT • U/S - 60-70% of studies return to normal at one year • IP – 90% return to normal within a year

  37. CT-VenographyGoodman LR, Stein PD, Matta F, et al. AJR Am J Roentgenol 2007;189(5): 1071–6 • PIOPED II Data • 711 pts with CT-V and sonography • Results: • 95.5% concordance for dx or exclusion of proximal DVT • Kappa = 0.809 • Simlar results across all subgroups (asymptomatic, symptomatic, previous DVT)

  38. Bottom Line Thus Far? • Hx/PE help us decide pretest probability (Wells) • We add in a sensitive Test (D-Dimer) • And a sensitive confirmatory test (U/S) ‘Cause Stone Cold says so!

  39. Real-Life ApproachScarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.

  40. Or…the 1620h approachFields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

  41. CHR Approach • The next 4 slides describe the current Calgary Health Region approach • Not many people use this as it is a bit outdated but I’ve kept the slides here for your interest

  42. Wells Criteria for Probability of DVT LOW PROB < 0 points MOD PROB 1 or 2 points HIGH PROB >3 points

  43. LOW PROBABILITY DVT D-Dimer Neg Positive STOP CUS legs DVT Normal STOP TREAT

  44. MODERATE PROBABILITY DVT D-Dimer Neg Positive STOP CUS legs Normal DVT CUS leg in 1 week TREAT Normal Positive STOP TREAT

  45. HIGH PROBABILITY DVT CUS legs Normal DVT Venography TREAT Normal Positive STOP TREAT

  46. Case 1 Continued • Okay back to it… • U/S shows popliteal vein DVT • Management Doctor?

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