1. Deep vein thrombosis Pulmonary embolism Deep vein thrombosis Pulmonary embolism Venous Thromboembolism TreatmentTreatment …All the same?

2. Acute DVT Management What is the goal of therapy?

3. Reduce CVI Acute DVT Therapeutic Goals/Options No Rx Caval Filter Anticoagulation Thrombolytic Rx Thrombectomy Reduce PE X X X X X X X X Prevent Extension X X X X + + Reduce Recurrence X X X X + + Restore Patency X X X X Preserve Valve Function X X X X X X X X + +

4. Langerstedt CI, et al. Lancet 1985. Isolated Calf DVT 51 patients randomized Rx 51 patients randomized Rx Heparin x 5 days Warfarin x 3 mos Heparin x 5 days Warfarin x 3 mos No recurrent VTE 29% recurrent VTE 19% proximal DVT 4% pulmonary emboli

5. Initial treatment –Importance of therapeutic levels –Compression –Ambulation Long-term treatment –5 patient categories Initial treatment –Importance of therapeutic levels –Compression –Ambulation Long-term treatment –5 patient categories TreatmentTreatment Deep Vein Thrombosis

6. Acute DVT Importance of Early Rx Recurrent VTE* Hull, RD et al NEJM 1990 Hull, RD et al NEJM 1990 * most occur > 4 weeks association with poor initial response not appreciated by attending MDs * most occur > 4 weeks association with poor initial response not appreciated by attending MDs PTT <1.5x (24 hrs.) PTT >1.5x 24.5% (15:1) <0.001 1.6%

7. Heparin/LMWH Bioavailability Heparin for Acute DVT Bratt G, et al. Thromb Rea 1986;42(5):613-620. Bara L, et al. Thromb Res. 1985;39(5):631-636. Bratt G, et al. Thromb Rea 1986;42(5):613-620. Bara L, et al. Thromb Res. 1985;39(5):631-636. Plasma Recovery Plasma Level After SQ - Volunteers Single Subcutaneous Injection Unfractionated heparin (UFH) LMWH 20% 90%

8. Prospective Adjusted dose unfractionated heparin Fixed dose SQ LMWH Objective outcome measures Symptomatic recurrent DVT Change in thrombus size Major bleeding Mortality Prospective Adjusted dose unfractionated heparin Fixed dose SQ LMWH Objective outcome measures Symptomatic recurrent DVT Change in thrombus size Major bleeding Mortality LMWH vs. UFH for Acute DVT A Meta-Analysis of 10 Studies (n=759) Bratt G, et al. Thromb Rea 1986;42(5):613-620. Bara L, et al. Thromb Res. 1985;39(5):631-636. Bratt G, et al. Thromb Rea 1986;42(5):613-620. Bara L, et al. Thromb Res. 1985;39(5):631-636.

9. LMWH vs. UFH for Acute DVT A Meta-Analysis of 10 Studies (n=759) Lensing AWA, et al Arch Intern Med 1995 Lensing AWA, et al Arch Intern Med 1995 Venographic Change 6.5% 3.1% 53% <0.01 Improved 52% 63% - - Worse 12% 6% <0.001 Major Bleed 2.8% 0.8% 68% <0.005 Mortality 7.1% 3.9% 47% <0.04 UFH LMWH Risk Reduction Risk Reduction P-value

10. Proximal DVT- 53 patients LMWH...then randomize: –Bed rest –Ambulation + 35 mm Hg stocking –Ambulation + 50 mm Hg compression bandage Activity measured - pedometer Venous duplex days 0 & 9 Proximal DVT- 53 patients LMWH...then randomize: –Bed rest –Ambulation + 35 mm Hg stocking –Ambulation + 50 mm Hg compression bandage Activity measured - pedometer Venous duplex days 0 & 9 Deep Vein Thrombosis Initial Treatment: Compression & Ambulation 1.Blattler W., et al Int’l Angiol. 2003; 32: 861-9 2.Partsch H. et al J Vasc Surg 2000; 32: 861-9 1.Blattler W., et al Int’l Angiol. 2003; 32: 861-9 2.Partsch H. et al J Vasc Surg 2000; 32: 861-9