1. Venous Thromboembolism Denise Watt January 3, 2002

2. Outline l epidemiology l pathophysiology l risk factors l diagnosis clinical labs diagnostic imaging algorithms l treatment

3. Case 1 l Rural ED l 72 yo male l fever, SOB, pleuritic CP x 2 days l HR 110, bp 140/90, RR 22, sat 90% l CXR unremarkable l what test/Rx?

4. Case 2 l 55 yo man l sudden central CP, SOB, presyncope l HR 120, bp 90/70, RR 30, sats 88% l ECG: sinus tach l what tests/Rx?

5. Case 3 l 33 yo healthy woman, 34 wks GA l syncope at home l EMS called l asystolic arrest en route l CPR x 5 min l what do you do?

6. Epidemiology l Lifetime incidence VTE 2-5% PE: 0.5/1,000/year DVT: 1/1,100/year l PE mortality: 10% die in 1st hour 30% untreated 2-8% if anticoagulated l >50% PEs undiagnosed

7. Risk Factors l Primary Factor V leiden Antithrombin III deficiency Prot C deficiency Prot S deficiency hyperhomo- cysteinemia anticardiolipin Ab dysfibrinogenemia l Secondary age trauma / surgery malignancy immobilization stroke smoking obesity OCP/HRT lupus anticoagulant pregnancy hyperviscosity heart failure

8. Risk Factors l 50% without risk factors l OCP/HRT: 3x baseline risk 0.3/10,000/yr; 15/10,000/yr higher in 3rd gen progesterones l pregnancy: 5x baseline risk 75% DVT antepartum, 66% PE postpartum

9. Pathophysiology: Source of VTE most start in calf, extend proximally 70% PE have DVT evidence at autopsy 70-90% known source: IVC, ileofemoral or pelvic veins, 10-20% SVC incidence of PE from DVT calf: 46% thigh: 67% pelvic: 77% other: UE, jugular, mesenteric, cerebral

10. Consequences of PE l Hemodynamic tachycardia hypotension RV overload and dilation  CVP  LV preload  myocardial flow pulmonary HTN pul A-V shunts l Respiratory hyperventilation PA HTN  compliance atelectasis broncho- constriction  airway resistance

11. Clinical Presentation: DVT l Calf-popliteal 80-90%, many asymptomatic pain & swelling spreads proximally l Ileofemoral pain in buttock, groin thigh swelling 10-20% cases

12. Clinical Prediction Model for DVT Wells et al. Ann Int Med, 1997

13. Clinical Model for DVT

14. Incidence of DVT by Clinical Probability

15. Clinical Presentation of PE: The great pretender l SOB, CP or tachypnea in 97% l individual s+s not sensitive/specific l peripheral (distal vessel) pleuritic CP, ± hemoptysis, ± SOBOE l central (lobar / segmental) SOBOE l massive (main pulmonary artery) syncope, hypotension, shock

16. Clinical Prediction Model for PE Wells. Ann Int Med, 1998

17. Incidence of PE by Clinical Probability

18. Ancillary tests for PE l CXR: r/o other diagnoses ‘classic’ signs non-specific l ABG: 20% have normal PaO2 15-20% have normal Aa gradient l ECG: remember???

19. D-dimer l degradation product of fibrin l PPV poor; NPV excellent l non-specific: +ve: surgery, trauma, hemorrhage, CA 90% +ve >80 yrs old l most useful in ED patients l NOT to r/o PE in high PTP

20. D-dimer Assays Van der Graaf. Thromb Haemost, 2000.

21. Diagnostic Imaging for DVT l Duplex / compression U/S non-invasive, portable direct visualization of veins and flow loss of compression = DVT 97% sensitive & specific for symptomatic proximal/popliteal DVT 62% sensitive for asymptomatic DVT +ve in 30-50% PE; 5% non-dx V/Q scans

22. Serial Venous U/S l 2 protocols: Wells & Hull l may avoid angiography in ?PE l 2% +ve in 2 weeks (?PE) l if U/S -ve 2 weeks apart, <2% have VTE in next 6 mos

23. Diagnostic Imaging for DVT l IPG detects changes in flow before and after cuff inflated sensitivity 60%

24. Algorithm for Suspected first DVT: Perrier. Lancet, 1999

25. Diagnostic Imaging for PE: V/Q scan l PIOPED: ventilation component adds little info l PISAPED criteria: normal, non-diagnostic, high probability 25%, 50%, 25% respectively high prob: 85-90% PPV non-diagnostic: 25% PE l interpret in context of PTP

26. Diagnostic Imaging for PE: Pulmonary Angiography l Gold standard (imperfect) sens 98%, spec 95-98% l ED physicians reluctant to use: invasive, risks, requires expertise, not readily available, time consuming, $ l relative contraindications l indicated if non-invasive tests inconclusive

27. Diagnostic Imaging for PE: Spiral CT l IV contrast, direct visualization l subsegmental PE not well seen l more specific, underlying lung dx l sens depends on CT, experience l wide variation in studies Rathbun. Ann Intern Med, 2000 (review) sens 53-100%, spec 81-100% poor methodolgy of studies

28. Spiral CT l Perrier. Ann Intern Med, 2001 sens 70%, spec 91%, 4% inconclusive good interobserver agreement l CT venography: benefit over U/S not determined l role? no evidence to withold Rx if CT negative may replace angiography

29. Diagnostic Imaging in PE: Echocardiography l useful for patients in shock/arrest r/o DDx: tamponade, Ao dissection, AMI l indirect evidence of PE: RV overload, septal shift to L, TR,  PA pressure, RV wall motion abn sens 93%, spec 81% l ‘sub-massive’ PE: independent predictor of mortality (?significance)

30. Algorithm for suspected PE: Wells. Ann Int Med, 2001

31. Wells’ Algorithm: Criticism l Uses SimpliRED assay: lower sens. l sCT not included could replace angiography? l Low prevalence of PE (9%) l not validated by other RCTs

32. Treatment of VTE: Goals l reduce mortality l prevent extension/recurrence l restore pulmonary vascular resistance l prevent pulmonary hypertension

33. Treatment of VTE: Anticoagulation l Out-patient LMWH l LMWH superior to UFH? (Gould 1999) l out-pt Rx safe in PE ( Kovacs, 2000) l DVT: start Rx, definitive test in 24hr l baseline B/W

34. Anticoagulation l Enoxaparin 1mg/kg bid or 1.5 od l Tinzaparin 175 anti-Xa u/kg od l start warfarin 5mg on day 1 l d/c LMWH when INR >2.0 x 2 days l Rx 3 mos if 1st and reversible cause l 6 mos if non-reversbile l indefinite if recurrent, CA, genetic

35. Treatment of PE: Criteria for admission l Hemodynamic instability l O2 requirement l surgery < 48hr l risk of active bleeding l history of HIT l IV pain control

36. Treatment of massive PE l judicious fluids (500cc max) l NE, dopamine, dobutamine prn l O2, intubate if shock positive pressure worsens RV fn l anticoagulation if no contraindications UFH if hypotensive PTT 1.5-2.5 x normal

37. Treatment of massive PE: Thrombolytics l no evidence of mortality benefit including in cardiac arrest (case series) l no benefit in hemodynamically stable l improves pul. perfusion (15% vs 2%), RV function (34% vs. 17%) cf. heparin l t-PA faster hemodynamic effect l IV same as intrapulmonary l 5-10% major bleed, 1-2% ICH

38. Thrombolytics l 2 week window of opportunity! effect  with time l no advantage of t-PA bolus l protocols: t-PA: 100mg over 2 hr UK: 4400U/kg over 10min; rpt x 12-24hr SK: 250,000U over 30min; 100,000 x 24h arrest: t-PA 10mg/kg bolus x 2 q 30 min

39. Embolectomy l Indicated in acute, massive PE if: contraindication to thrombolytics unresponsive to medical mgt l moribund pt  poor results l no evidence cf. with thrombolytics l percutaneous vs. surgical ?role

40. IVC Filters l Indications: contraindication to anticoagulation recurrent VTE despite anticoagulation after surgical embolectomy l no long term adv vs. anticoagulation l anticoagulate if no contraindications DVT and IVC occlusion

41. Pregnancy l V/Q safe, no breastfeed x 15hr post l D-dimer  in pregnancy, wide Aa l angiography safer than empiric Rx l LMWH in DVT, not studied in PE l PE: UFH IV x 4-5 days, then s/c l treat x 3 months or 6 weeks postpartum l switch to oral postpartum