April 8-9, 2011 New York LaGuardia Marriott COMPLETE MANAGEMENT OF VENOUS DISEASE Optimal Utilization of Thrombolytics Anthony J. Comerota, MD, FACS, FACC Director, Jobst Vascular Institute Adjunct Professor of Surgery, University of Michigan
Disclosure Anthony Comerota, M.D., FACS, FACC I disclose the following financial relationship(s): Speaker/Honoraria: BMS, Covidien
Optimal Utilization of Thrombolytics Issues - Patient Related - 1. Can plasmin be generated within clot? (clot age) 2. Is there underlying venous disease? (correct underlying lesions) 3. Presence of thrombophilia (not an issue!)
Optimal Utilization of Thrombolytics Issues - Technical - 1. Can a guideline pass through thrombus? 2. Can intra-thrombus delivery of lytic agent be performed? 3. Bolus delivery vs. continuous infusion 4. Correction of underlying stenosis 5. Adequate inflow to lysed venous segment 6. Addition of IPC 7. Pharmacomechanical techniques
Optimal Utilization of Thrombolytics Mechanisms of clot dissolution is activation of fibrin-bound plasminogen (Plasminogen within the clot) Anthony Fletcher Norma Alkjaersig Sol Sherry Diminishes with time!
Optimal Utilization of Thrombolytics Intra-Arterial CDT - Randomized Trial - Intra-arterial CDT: More effective than systemic Rx Intra-arterial rt-pa More effective than intra-arterial SK Berridge D et al Br J Surg 1991; 78(8):998
Catheter-Directed Thrombolysis Importance of Underlying Lesion Patency at 1 year Intra-Arterial CDT Lesion Corrected McNamara et al, 1986 Yes 80% No 7% Gardiner Same et al, principle 1989 applies to 86% veins (CFV and above) 37%
Optimal Utilization of Thrombolytics Presence of Thrombophilia Will not alter management of any patient (for 6-12 months) Might consider evaluation of first degree female relatives of child bearing potential (more during discussion)
Catheter-Directed Thrombolysis Determinants of Success Successful Lysis Guidewire Penetration Yes No McNamara et al (N=62) 100% 10% Ouriel et al (N=103) 89% 16% If guidewire passage fails, a chronic venous obstruction exists! McNamara T, et al. AJR 1985;14:764 Ouriel K, et al. Radiol 1994;193:561
Catheter-Directed Thrombolysis Intra-Arterial CDT - Bolus vs No Bolus - Infusion time Bolus Yes No 14 hrs. 27 hrs. P = 0.0005 Bolus infusion reduces overall infusion time Ward AS et al JVS 1994; 19:503
Catheter-Directed Thrombolysis Intra-Arterial CDT - Bolus vs No Bolus - Successful Lysis at 24 Hours Pulse Spray 78% Slow Infusion <50% Speed of lysis appears related to amount and distribution of plasminogen activator in thrombus Kandarpa K. et al JVIR 1995; 6: 558
Optimal Utilization of Thrombolytics Importance of good inflow to lysed proximal veins
Phlegmasia Cerulea Dolens 65 yo Caucasian male Chronic low back pain worse x one month Phlegmasia cerulea dolens Venous duplex: Clot post tib Ext. iliac vein
Phlegmasia Cerulea Dolens Femoral Popliteal
Phlegmasia Cerulea Dolens Posterior Tibial Vein Catheter
Phlegmasia Cerulea Dolens US Guided Venous Access Trellis catheter Lysus catheter Isolated segment between balloons Ultrasound transducers
Phlegmasia Cerulea Dolens Post Ultrasound Lysis
Phlegmasia Cerulea Dolens Post Trellis, LysUS, Angiojet and Stent
Phlegmasia Cerulea Dolens 16 Month Follow-up Asymptomatic No PTS symptoms All veins patent Normal deep valve function
Catheter-Directed Thrombolysis for IFDVT Is long-term outcome dependent upon lytic success? YES! OK result is NOT good enough!
Outcome Measures after IFDVT Lysis Results: Villalta Score vs Percent Lysis Villalte Score Villalta Score Villalta Score Distribution 14 12 10 8 6 4 0.5 p=0.025 Group <=50% > 50% Group 50% >50% 2 0 Essentially NO PTS with 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 90% Percent clot Lysis lysis! Mean Villalta score difference (7.13 versus 2.21) with p-value 0.025 1.0 Grewal P et al Am Ven Forum 2010
Optimal Utilization of Thrombolytics Intermittent Pneumatic Compression Prospective, nonrandomized, pilot study Concept: Immobility during CDT IPC increases venous flow 24 patients with CDT for DVT - 10-CDT alone - 14 ODT + IPC (with IVC filter) Low dose urokinase: 240,000 IU X 1hr, 120,000 IU thereafter Pre Rx and post Rx pulmonary angio or CTA chest CDT + IPC post Rx cavagram Post Rx: Venogram Venous disability score Venous duplex Ogawa T et al J Vas Surg 2005
Optimal Utilization of Thrombolytics Intermittent Pneumatic Compression Variable - Post Rx Evaluation - CDT Alone (N=6) CDT/IPC (N=14) No Obstruction/Reflux 17% 43% Obstruction 50% 36% Obstruction + reflux 33% 7% Ogawa T et al J Vas Surg 2005
Optimal Utilization of Thrombolytics Intermittent Pneumatic Compression Venous Disability Score CDT Alone (N=10) CDT/IPC (N=14) 0 2 9 1 4 5 2 3 0 3 1 0 Ogawa T et al J Vas Surg 2005
Optimal Utilization of Thrombolytics Pharmacomechanical Techniques Proper use of pharmacomechanical techniques will optimize lytic success
Pharmacomechanical Thrombolysis Isolated, Segmental, Pharmacomechanical Thrombolysis rtpa infusion Maceration Trellis Catheter
Pharmacomechanical Thrombolysis Ultrasound-Accelerated Thrombolysis EkoSonic Control Unit EkoSonic Mach4 Endovascular Device 5.2 fr Intelligent side-hole drug delivery catheter
Pharmacomechanical Thrombolysis Angiojet - Rheolytic Segmental Thrombus
CDT Vs PMT Discussion Pharmacomechanical Thrombolysis Martinez J et al JVS 2008; 48:1532 Technique Observations p-value ISPMT Improved lysis Shorter Rx time Reduced tpa dose.0058.0001.007 Lin P H et al Am J Surg 2006; 192:782 Rheolytic Reduced ICU stay Reduced hospital stay Reduced transfusion <.04 <.02 <.05 Parikh S et al JVIR 2008; US Lysis Reduced lytic agent Shorter Rx time <.05 <.05
Optimal Utilization of Thrombolytics Summary Guidewire penetration Intrathrombus infusion (saturate thrombus with plasminogen activator) Pulse-spray-bolus dose initially Pharmacomechanical techniques Correct proximal venous lesions (CFV and above) Maximize inflow to lysed proximal veins Persist to remove maximal thrombus Augment lysis with IPC
Extensive DVT Treated with Once Daily Intra-Clot Injection of rt-pa Study 20 patients: 1 st onset DVT 7 iliofemoral 13 extensive fem-pop Ages 18-79 years 50mg rt-pa/leg/day maximum 0.5-1.0mg per cm of thrombus 4 fr catheter left in vein Bedrest X 2hrs then ambulate IPC while in bed IV-UFH to 50-70 sec Endpoint: antegrade flow Chang R et al Radiology 2008; 246(2):619
Extensive DVT Treated with Once Daily Intra-Clot Injection of rt-pa Results 20 patients: 1 st onset DVT 80% antegrade flow (100% in IFDVT) 90% symptom free 40% PE at baseline (asympt) 15% PE during Rx (asympt) No major bleed Follow-up 3.4 years (mean) No PTS No recurrence Chang R et al Radiology 2008; 246(2):619
Extensive DVT Treated with Once Daily Intra-Clot Injection of rt-pa Pharmacokinetic Changes Chang R et al Radiology 2008; 246(2):619