4/23/2009. September 15, 2008

Transcription

1 The Current Treatment of Deep Venous Thrombosis: Are We Doing Enough? George H. Meier, MD Professor and Chief Division of Vascular Surgery University of Cincinnati College of Medicine Cincinnati, Ohio 1

2 Disclosure I have no conflicts of interest relevant to this presentation. I have biases, but these are mine alone. The FDA and Peripheral Thrombolysis All peripheral thrombolysis is off-label Clinical research difficult since the standard of care is anticoagulation alone Combination with mechanical devices complex from FDA viewpoint Usually done on IND, not IDE 2

3 Outline The Tradition of DVT Treatment New Options for Treatment of DVT September 15, 2008 Venous Thrombolysis What is it? What are the indications? What outcomes can we expect? 3

4 Treatment of DVT Anticoagulation versus Thrombolysis In the beginning, there was heparin. The Coagulation Cascade INTRINSIC Surface contact (collagen, platelets) Prekallikrein High-molecular-weight kininogen XII Platelet surface? XI XIIa IX XIa IXa VIIIa PL Ca++ X IIa V Prothrombin (II) Va Xa VIIa Fibrinogen EXTRINSIC Tissue Damage Tissue Factor VII Thrombin (IIa) Fibrin The multistep process is activated by vessel injury and exposure of platelets to subendothelial elements (intrinsic pathway) and by tissue damage, leading to the production of tissue factor by macrophages (extrinsic pathway). Both pathways result in the conversion of prothrombin to thrombin, which then converts soluble fibrinogen to insoluble strands of fibrin, the protein that forms the scaffolding upon which platelets and blood cells aggregate to form a thrombus. Adapted with permission from Fuster V, Verstraete M. Hemostasis, thrombosis, fibrinolysis, and cardiovascular disease. In: Braunwald E, Heart Disease: A Textbook of Cardiovascular Medicine. 5th ed. Philadelphia, Pa: WB Saunders;1997: Origins of Thrombolysis For years the focus was on coagulation. Why? Better understanding of coagulation Better testing for coagulation Clinical observation: : patients started on heparin improved although heparin only stopped new thrombosis. Why? Presumed shift toward thrombolysis What happens if we increase thrombolysis independent of coagulation? 4

5 DVT Management Mostly unchanged for 70 years High rate of post-phlebitic phlebitic syndrome particularly with complete occlusions Chronically debilitating outcomes Main technique: prevent clot propagation, long term external compression Why Do We Need a New Treatment for DVT? Risk of post-phlebitic phlebitic syndrome high in iliofemoral DVT using current regimens In young patients, significant morbidity long term Venous Patency after UK Mewissen, Radiology 1999:211,

6 CDT Recommendations 6

7 Removing Clot in DVT Traditional Catheter-based Open Mechanical Thrombectomy Problems Incomplete clot removal Blood loss Vessel trauma Do percutaneous devices offer any advantages? Percutaneous Mechanical Adjuncts for Clot Removal Possis AngioJet Edwards Oasis Spectranetics - Eximer Laser Bacchus Trellis Ekos 7

8 4/23/2009 AngioJet Percutaneous Thrombectomy Mechanical Adjuncts in Venous Thrombosis Less vessel trauma Less blood loss But is clot removal adequate using this modality alone? EKOS 8

9 4/23/2009 Traditional Management of Venous Thrombus Old version Standard treatment usually includes anticoagulation to prevent further propagation of thrombus New version Goal is to preserve valve function Catheter--directed thrombolysis Catheter Mechanical adjuncts to speed up the process and lower risk SB 43 yo WF with history of BCPs x 4 years Acute onset left leg swelling and pain Ultrasound: occlusive iliofemoral DVT After AngioJet 9

10 4/23/2009 Six hours later Heparin stopped secondary to PTT > 120 seconds Popliteal sheath had been shut off, no infusion for 4 hours Back for catheter check 10

11 4/23/2009 After Angiojet Characteristics of Patients in Whom Catheter--Directed Fibrinolysis Works Best Catheter Those with threatened extremity (phlegmasia cerulea dolens) Those with swollen legs Acute DVT ( ( 10 days) regardless of the location of the thrombus Those with no prior history of DVT have a greater incidence of complete lysis than those with a history of DVT (36% vs 20%, P<0.03) Those with iliofemoral DVT than those with femoralfemoralpopliteal DVT (64% vs 47%, P<0.01) Patients who achieve complete lysis have significant long--term patency benefits long 11

12 What Have We Learned? Thrombolysis for DVT seems to work and provide reasonable patency Long duration thrombolytic infusions associated with significant bleeding Acute clot (<10 day old) responds better to thrombolysis than chronic Ideal Indications for Thrombolysis in DVT Occlusive iliofemoral or femoropopliteal DVT with no contraindications to thrombolysis Symptomatic Young patient Acute clot (<10 days old) No prior DVT Left leg? Left to Right Ratios for DVT Ouriel,J Vasc Surg 2000;31:

13 Normal Compression of the Left Iliac Vein Kibbe, JVS, 2004 :39 (5), Outcome of Venous Stents Outcome of Venous Stents Neglen and Raju, JVS 2004:39(1), Neglen and Raju, JVS 2004:39(1),

14 Conclusions Venous thrombolysis is an area for significant growth in the near term The combination of catheter directed thrombolysis with mechanical adjuncts is the current focus New thrombolytic agents may alter the balance further Summary Both diagnosis and treatment of DVT are changing! Better diagnosis may allow more tailoring of therapy to individual patients Preservation of valve function may be possible in many DVT patients VASCULAR VASCULAR 14

15 VASCULAR 15