1. Diagnosis and Treatment of Deep Venous Thrombosis and Pulmonary Embolism Beth Stuebing, MD, MPH

2. History Susruta (Ayurveda physician and surgeon, 600-1000 B.C.) – patient with a “swollen and painful leg that was difficult to treat” Susruta (Ayurveda physician and surgeon, 600-1000 B.C.) – patient with a “swollen and painful leg that was difficult to treat” Giovanni Battista Morgagni, 1761 – recognized clots in pulmonary arteries after sudden death, but didn’t make the connection to DVT Giovanni Battista Morgagni, 1761 – recognized clots in pulmonary arteries after sudden death, but didn’t make the connection to DVT

3. Virchow Strikes Again “Discovered” PE in 1846 – “the detachment of larger or smaller fragments from the end of a softening thrombus which are carried along the current of blood and driven into remote vessels. This gives rise to the very frequent process on which I have bestowed the name Embolia” “Discovered” PE in 1846 – “the detachment of larger or smaller fragments from the end of a softening thrombus which are carried along the current of blood and driven into remote vessels. This gives rise to the very frequent process on which I have bestowed the name Embolia”

4. Deep Venous Thrombosis - Epidemiology 1969 paper by Kakker 1969 paper by Kakker –30% of post-op patients develop clot in calf veins –35% of these lysed within 72 hrs –15% of pts with persistent thrombosis developed PE Recent studies put incidence at 50 per 100,000 person years Recent studies put incidence at 50 per 100,000 person years Incidence greatly increases with age, 18% of 80yr old patients have asymptomatic DVT Incidence greatly increases with age, 18% of 80yr old patients have asymptomatic DVT

5. DVT Diagnosis Wells clinical prediction rules Wells clinical prediction rules D dimer ELISA assay >90% sensitive, but 40- 50% specific D dimer ELISA assay >90% sensitive, but 40- 50% specific When D dimer is negative and clinical suspicion low, further studies are unwarranted When D dimer is negative and clinical suspicion low, further studies are unwarranted Ultrasound most sensitive and specific (>90%) for symptomatic, proximal vein Ultrasound most sensitive and specific (>90%) for symptomatic, proximal vein US only 50-70% sensitive for asymptomatic pts US only 50-70% sensitive for asymptomatic pts Sens. And spec. much lower for symptomatic arm DVT (60-90%) Sens. And spec. much lower for symptomatic arm DVT (60-90%)

6. DVT Treatment (medicine) Initial treatment with UFH or LMWH Initial treatment with UFH or LMWH Goal aptt (with heparin) 1.5-2.5x nl Goal aptt (with heparin) 1.5-2.5x nl 25% pts resistant to heparin, better to monitor anti-factor Xa instead 25% pts resistant to heparin, better to monitor anti-factor Xa instead LMWH monitoring not necessary, but can be done with goal anti Xa level 0.6-1 U/ml (drawn 4hr after dose) LMWH monitoring not necessary, but can be done with goal anti Xa level 0.6-1 U/ml (drawn 4hr after dose) Age increases bleeding risk Age increases bleeding risk Some studies suggest lower mortality with LMWH in elderly Some studies suggest lower mortality with LMWH in elderly Transition to warfarin (goal INR 2-3), or continue with LMWH Transition to warfarin (goal INR 2-3), or continue with LMWH Starting with large doses (10mg) NOT recommended Starting with large doses (10mg) NOT recommended 3 months treatment with temporary, known risk factor (fracture, pregnancy, air travel) 3 months treatment with temporary, known risk factor (fracture, pregnancy, air travel) At least 6 months treatment with no discernible cause At least 6 months treatment with no discernible cause Hypercoagulable workups not necessary in the elderly Hypercoagulable workups not necessary in the elderly Length of treatment a risk:benefit analysis Length of treatment a risk:benefit analysis Major bleeding risk 1-3% per year with INR 2-3 Major bleeding risk 1-3% per year with INR 2-3

7. DVT Treatment - Filters Consider in pts with contraindications to anticoagulation or develop recurrent DVT or PE despite adequate medical therapy Consider in pts with contraindications to anticoagulation or develop recurrent DVT or PE despite adequate medical therapy Randomized trial of anticoagulation +/- IVCF: Randomized trial of anticoagulation +/- IVCF: –PE at day 12 reduced with filter, but benefit didn’t persist –Double risk of recurrent DVT with IVCF

8. Pulmonary Embolism - Epidemiology 1/3 of people with DVT may develop symptomatic PE 1/3 of people with DVT may develop symptomatic PE 1975 paper 1975 paper –Incidence 630,000 per year –Death within 1 hour in 11% –Undiagnosed 1 hr survivors: eventual 30% mortality –Diagnosed 1 hr survivors (treated): 8% mortality

9. PE Diagnosis Clinical diagnosis is nonsensitive and nonspecific Clinical diagnosis is nonsensitive and nonspecific ECG ECG ABG ABG CXR CXR Angiogram Angiogram VQ scan VQ scan ECHO ECHO CT chest CT chest

10. ECG Changes “S1 Q3 T3” “S1 Q3 T3” S wave in lead I S wave in lead I Q wave in lead III Q wave in lead III Flipped T in lead III Flipped T in lead III Possible RBBB Possible RBBB Signs of cor pulmonale Signs of cor pulmonale Classic, but uncommon Classic, but uncommon

11. Arterial Blood Gas Hyperventilation leads to low pCO2 Hyperventilation leads to low pCO2 Difficulty in oxygenation Difficulty in oxygenation Alveolar-arterial gradient may be elevated (80% of cases) Alveolar-arterial gradient may be elevated (80% of cases) A-a O2 Gradient = [ (FiO2) * (Atmospheric Pressure - H2O Pressure) - (PaCO2/0.8) ] - PaO2 from ABG Nl Gradient Estimate = (Age/4) + 4 A-a O2 Gradient = [ (FiO2) * (Atmospheric Pressure - H2O Pressure) - (PaCO2/0.8) ] - PaO2 from ABG Nl Gradient Estimate = (Age/4) + 4

12. CXR – even post mortem! Westermark sign - Westermark sign - ischemia appeared as a clarified area with diminished vascularity corresponding to the extent of the embolized artery

13. Pulmonary Angiography Started in 1950s Started in 1950s 47% positive studies had no signs on CXR 47% positive studies had no signs on CXR 1 st confirmatory test other than autopsy 1 st confirmatory test other than autopsy

14. VQ scan Started in 1960s Started in 1960s Correlated well with angiogram and autopsy Correlated well with angiogram and autopsy “High probability” scans: 41% sensitive, 97% specific “High probability” scans: 41% sensitive, 97% specific Adequate for diagnosis in a minority of patients Adequate for diagnosis in a minority of patients

15. ECHO for PE RV dilates and LV is smaller in most patients RV dilates and LV is smaller in most patients Unreliable in pts with prior cardiac dysfunction Unreliable in pts with prior cardiac dysfunction TEE reported to be >90% sensitive and specific TEE reported to be >90% sensitive and specific Right heart dysfunction resolves after thrombolytic therapy Right heart dysfunction resolves after thrombolytic therapy

16. CT Chest Spiral CT chest introduced in early 1990s Spiral CT chest introduced in early 1990s Sensitivity 86- 100%, specificity 92-96% for central PE Sensitivity 86- 100%, specificity 92-96% for central PE 63% sensitive for subsegmental PE 63% sensitive for subsegmental PE

17. PE Treatment Heparin Heparin Embolectomy Embolectomy Thrombolytics Thrombolytics Venous interruption Venous interruption IVC filter IVC filter

18. Heparin - Warfarin Not used until 1940s Not used until 1940s Only prospective randomized trial in 1960s Only prospective randomized trial in 1960s –2 weeks of anticoagulation after PE –No deaths or nonfatal PE in treatment group 1990s - LMWH found equally effective 1990s - LMWH found equally effective

19. Trendelenburg’s Procedure Thromboembolectomy, described in 1908 Thromboembolectomy, described in 1908 First survivor of the procedure not until 1924 First survivor of the procedure not until 1924 Via left chest thoracotomy Via left chest thoracotomy

20. Thrombolytics Introduced in 1960s Introduced in 1960s Unclear benefit over heparin, significant bleeding risk Unclear benefit over heparin, significant bleeding risk Now used for massive PE with hemodynamic deterioration Now used for massive PE with hemodynamic deterioration Can be direct or systemic Can be direct or systemic 2-3% risk intracranial hemorrhage 2-3% risk intracranial hemorrhage

21. Venous Interruption Started with femoral vein ligation in 1930s Started with femoral vein ligation in 1930s 1940s, Homan suggested IVC ligation instead 1940s, Homan suggested IVC ligation instead Led to the first IVC nonextractable filter in 1969 Led to the first IVC nonextractable filter in 1969

22. IVC Filters Decousus, et.al., 1998 randomized trial for DVT: heparin/warfarin alone versus heparin/warfarin plus IVCF Decousus, et.al., 1998 randomized trial for DVT: heparin/warfarin alone versus heparin/warfarin plus IVCF –No difference in 2 year mortality –Less PE but more recurrent DVT in filter group

23. Prevention 1960s study: heparin q12h for 7 days after major surgery decreased DVT from 42% to 8% 1960s study: heparin q12h for 7 days after major surgery decreased DVT from 42% to 8% Established as standard of care after 1975 study with similar results Established as standard of care after 1975 study with similar results 60-70% relative risk reduction for DVT and fatal PE post-op 60-70% relative risk reduction for DVT and fatal PE post-op

24. DVT and PE in the ICU One study: routine Doppler shows DVT in up to 30-40% of all ICU patients, regardless of prophylaxis One study: routine Doppler shows DVT in up to 30-40% of all ICU patients, regardless of prophylaxis Much less likely to have physical exam findings Much less likely to have physical exam findings One study showed 38% of ICU pts with known DVT had undiagnosed PE on VQ scan One study showed 38% of ICU pts with known DVT had undiagnosed PE on VQ scan One autopsy study: 84% of PE were not diagnosed antemortem One autopsy study: 84% of PE were not diagnosed antemortem

25. DVT and PE in the ICU Chemical prevention has similar risk reduction of 60-70%, variety of meds studied Chemical prevention has similar risk reduction of 60-70%, variety of meds studied CT chest is higher risk (contrast load, travel with critical patient) and often unfeasible CT chest is higher risk (contrast load, travel with critical patient) and often unfeasible VQ scans essentially uninterpretable given multitude of pulmonary pathology VQ scans essentially uninterpretable given multitude of pulmonary pathology Higher risk: personal or family history, renal failure, platelet transfusion, vasopressor use, longer time on ventilator Higher risk: personal or family history, renal failure, platelet transfusion, vasopressor use, longer time on ventilator

26. Thanks, and Questions?