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Natural History Conclusions Lancet, June 18, 1960, 1309-1312

Natural History Conclusions Lancet, June 18, 1960, 1309-1312. PE untreated has high mortality (5/19 in randomized trial consistent with 23-87% in retrospective analyses) Waiting is dangerous since death happened in first two weeks. Anticoagulation greatly decreased mortality.

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Natural History Conclusions Lancet, June 18, 1960, 1309-1312

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  1. Natural History ConclusionsLancet, June 18, 1960, 1309-1312 PE untreated has high mortality (5/19 in randomized trial consistent with 23-87% in retrospective analyses) Waiting is dangerous since death happened in first two weeks. Anticoagulation greatly decreased mortality

  2. Timing of PE Death Days after initial event in untreated group 4, 5, 12, 16, 6

  3. Bleeding ComplicationsHow Common Are They Really? Warfarin: Bleeding Complications/Year Fatal 0.6% Major 3.0 Minor 9.6 Landefeld, Am J Med 1993;95:315

  4. Bleeding ComplicationsRule for Risk Prediction • Outpatient Bleeding Risk Index • > 65 y.o. • h/o stroke • h/o GI bleed • Comorbidity: MI, anemia, kidney disease, DM • 0 = low risk, 1 or 2 = moderate Beyth,Am J Med 1998;105;91

  5. Bleeding Risk Index in PE Among 222 patients Risk # Minor bleed Major bleed Low 128 7 0 Moderate 92 5 5 High 2 1 0 Annualized major bleed in moderate 4.3% Wells, Arch Intern Med 2003;163;917

  6. Treatment Threshold? The bleeding risk to 90 treated who do not have PE is balanced by the benefit of RX to 10 patients with PE (reduce death from 2.5 patients to 0.2 patients) 90 without PE (1-2 major bleeds with Rx) 0.1 10 with PE (2.5 deaths without Rx)

  7. Wells Criteria Previous PE 1.5 HR>100 1.5 Recent surg/immob 1.5 Clin Signs DVT 3 Alt. Dx less likely 3 Hemoptysis 1 Cancer 1 0-1 Low likelihood, 2-6 Med, >6 High Wells : Thromb Haemost 2000;83:416

  8. % In Each Category with PE High 78% Medium 28% Low 3% Wells includes multiple regression coefficients. Allows programming you palm to spit out probability.

  9. Geneva (Wicki) Criteria Arch Intern Med. 2001;161:92 Previous PE/DVT 2 HR>100 1 Recent Surgery 3 Age 60-79 1 >80 2 PaCO2 <36 2 36-39 +1 PaO2 <49 4, 49-60 +3, 60-71 +2, 71-81 +1 Atelectasis 1 Elevated diaphragm 1 0-4 low, 5-8 Med, >8 High

  10. Combine Pretest and DD Wells: Thromb Haemost 2000;8:416 Divided patients into two groups based on clinical criteria: <4 or > 4 points and did D-dimer on all Bottom line: The D-dimer successfully ruled out PE in the low likelihood group

  11. Clinical Prediction Model(% rounded) Score Pretest -DD +DD <4 5-8% 2% 12-18% >4 40% 10-18% 60% (Caveat: Not all D-D methods are equally effective)

  12. From An Update on CUSKearon, Ginsberg, Hirsh, Ann Intern Med 1998;129:1044 • In patients with non-diagnostic lung scan, 5-10% have CUS + for DVT • Among those with non-diagnostic lung scan and CUS -, 20% have PE BUT • Not at high risk for recurrent PE unless redevelop proximal clot

  13. Strategy for CUS & Nondiagnostic (but not negative) lung scan • CUS + - Treat • CUS -, do serial CUS • 2% will become + • Result: <2% recurrent PE in 6 months with this strategy

  14. VQ ScanJAMA 1990;263:2753 PIOPED study was an excellent study with enough problems to make it a great journal club article. Defined usefulness of VQ Divided into categories of Negative, Intermediate, High Probability Compared with angiogram or clinical course

  15. Likelihood Ratios for VQ Results Result # with PE # no PE LR High 102 14 7.3 Intermed 105 217 0.48 Low 39 273 0.14 Nml/Near Nml 5 126 0.04 Normal 0 21 0

  16. Later Studies of Spiral CT • Overall Sensitivity 88%, Specificity 95% (reviewed in Chest 2001;119:1791) • Less good for small subsegmental PEs (but some argue these are less clinically important) • Likelihood ratios implied by above: LR+ 18, LR- 0.1

  17. What About Echocardiogram? The issue: Massive PE (>50% reduction in blood flow) may benefit from lytics. Can we define need based on RV strain?

  18. Massive PE Further defined by severe hypoxia and vascular collapse (shock and hypotension) In various studies, massive PE represents from <1% to 13% of all PE patients.

  19. The Randomized Controlled TrialJeres-Sanchez; Thromb Thrombolysis. 1995;2:227 RCT: Heparin or Heparin + Streptokinase Pts. With PE, systemic hypotension, PA hypertension, RV dysfunction. All with streptokinase lived, all without died. Four patients in each group.

  20. What about lytics based on ECHO?Circulation 1997;96:882 Pts with PE, RV dysfunction, no shock: 169 got lytics (L), 550 just heparin (H) Mortality 30 days: L 4.7%, H 11.1% Recurrent PE L 7.7%, H 18.7% But choice of therapy was at discretion of MD. Those getting lytics were younger with less lung and heart disease.

  21. Submassive PE and lyticsNEJM 2002;347:1143 Pts with PE and one of: ECHO-demonstrated RV dysfunction Pulmonary hypertension (R heart cath) ECG evidence of right heart strain Heparin (n = 118) vs. Heparin + alteplase (128) 24.6% treatment escalation with heparin vs 10.2% in H + alteplase. No difference in mortality!

  22. Recommendations • Set an accurate pretest probability through use of prediction rule • Use D-dimer to help R/O in patients with low probability • Helical CT for all (or at least those with abnormal chest X-ray) moderate or high

  23. Recommendations • 4. Compression US helpful to find clot (5-10%) or (serially) detect early reoccurence of clot (if CT negative) • Follow negative Helical CT (and negative CUS) with angiogram for high or medium risk • Echocardiogram: the jury is still out!

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