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Catheter Directed Thrombolysis 8Gan Dunnington M.D. Stanford Vascular Conference 9/12/05*Catheter Directed Thrombolysis    RBackground Patient selection Clinical Trials Techniques Adjuncts Future Directions Background  History First intravascular instillation 1955  Tillet First series 1965 -Cliffton Routinely utilized since  80 s Efficacy established by Berridge et al in 1991 Superiority of rt-PA, safety of catheter directed vs. systemicBZZ?Z?b8 . Background  Thrombolytic agents Plasminogen activators Cleave peptide bond to convert plasminogen to plasmin Plasminogen delivered into thrombus Lyses clot  breakdown of fibrinogen Protected from inhibitors v[?[? H  * [ Thrombolytics   Background  Thrombolytic Agents Streptokinase First described Derived from Streptococcus Antigenic potential  allergic reactions Must bind with plasmin or plasminogen to activate and be able to convert second plasminogen to plasmin :l d *  Background  Thrombolytic Agents Urokinase Derived from human urine, kidney cells Directly activates plasminogen Non-antigenic Recombinant form available Prourokinase Activated by plasmin to form urokinase Amplification Fibrin specific Preferentially binds fibrin bound plasminogen in thrombus Z ZoZ ZEZ:ZZ o E  :    ~  ; )   @   Background  Thrombolytic Agents Tissue plasminogen activator (t-PA) Naturally produced by endothelial cells Fibrin specific Has been bioengineered to lengthen half-life alteplase, reteplaseN$e$e Z  R   Background  Objectives of Catheter directed thrombolysis (CDT) Dissolve thrombus and restore perfusion Identify underlying lesion Allow for definitive correction >3ZdZZ3d l Background  Secondary benefits Urgent to elective Re-establish inflow/outflow for bypass Convert major operation to less extensive Avoid intimal injury from balloon thrombectomy Establish patency for inaccessible small vessels Reduce level of amputation(>}  :Patient selectionGood candidates Acute occlusion of relatively inaccessible vessels Wound complications Popliteal aneurysm acute thrombosis Acute thrombosis in proximal arteries Thrombosed SVG grafts (>1 yr old)&,W @  Patient selectionXPoor Candidates Acute embolus of large artery, easily accessible Acute post-op bypass thrombosis  modest ischemia Severe ischemia with limb viability imminently threatened&,i * ResultscRochester Trial Ouriel et al. 1994, single center, randomized 114 pts with acute ischemia (<7days) randomized Catheter directed thrombolysis (UK) vs operative revasc Equal limb salvage at 1 year (80%) Improved survival at 1 year of CDT (84% vs 58%) Related to periprocedural cardiopulmonary complications Equal 30 day mortality 70% success of thrombolysis^8S83^8S83: &  KD  ResultsSurgery vs Thrombolysis for Ischemic Lower Extremity trial (STILE) 393 pts randomized to surgery, rt-PA, or UK No consideration of duration of ischemia Halted at first data review Equivalent 30 day death (5%) and amputation (6) Significantly more morbidity with CDT (21%vs16%) CDT conveyed advantage for acute ischemia Operative intervention better for chronic ischemia No difference in safety/efficacy of urokinase vs rt-PA but shorter time to lysis with rt-PA (8 vs 16 hrs)CZqZZjZ qj>+ * $ResultsiSurgery vs Thrombolysis for Ischemic Lower Extremity trial (STILE) More bleeding complications with CDT Worse with lower fibrinogen or longer PTT Surgery better for native iliofem or fempop dz CDT better for acute graft ischemia Highest risk patients (diabetic, infrapop, critical ischemia) randomized to CDT had survival advantage at 1 yr (7% vs 32% mortality)CZ%Z*ZZ %*  ! 7  Results   Thromboysis Or Peripheral Arterial Surgery for acute ischemia (TOPAS) 544 pts randomized to primary surgery vs. UK Amputation free survival comparable at 1yr (68%) Fewer major surgeries for CDT patients Worse bleeding complications for CDT patientsF-  "-$ )   ResultsPConsistent findings from STILE and TOPAS 1-year mortality for acute limb ischemia 10-20% Treatment of occluded grafts better outcome than treatment of native arteries Risk of bleeding higher with CDT Worse in proportion to induced coagulopathy Risk of intracranial bleed 1-2% with CDT CDT patients require fewer open surgical proceduresV),]),]>I   H Results (comparing CDT agents) PURPOSE Trial (Recombinant prourokinase vs. urokinase) Bleeding dose dependent Rate of in-hospital amputation or death worsened for distal embolization during CDT Rt-PA vs Urokinase for fem-pop dz Mahler et al. Integrated mechanical techniques Rt-PA better for pure lysis Results better with mechanical techniques as adjunct C/w STILE trial Dosing iniquity Better lysis with higher dose, bolus dosing7ZlZ0ZrZ Z,Z7l0r  ,  V    0]  Techniques  Consensus Document for CDT in lower limb arterial occlusion - 1998 Guide wire traversal test Higher success if can traverse entire occluded vessel  thrombus lacing Higher success with intrathrombus bolusL^6(^6( Techniques  ~ pulsed spray  forceful injection Increased working surface area Once antegrade flow established, no benefit to additional pulsed spray vs infusion Greenberg et al  in vitro model with PTFE comparing pulsed spray vs continuous infusion Time to reperfusion less, more complete with infusion, more emboli than infusionF$ZZQZ$Q>H 8Ke  Techniques  wPercutaneous mechanical thrombectomy Device dependent High risk patients not candidates for thrombolysis Adjunct to CDT&%S%S6  7 Adjuncts  Platelet inhibitors ASA Plavix GIIbIIIa inhibitors Abciximab  fewer embolic episodes Heparin Worsens bleeding if given systemically No benefit if subtherapeutic Intra-arterial use might lessen bleeding risk and deliver more beneficial dose ZZ#ZZZZ#  > VPIntra-operative CDTHigh degree of residual thrombus after balloon thrombectomy Bolus and or infusion of thrombolytics is effective 20-30 min Isolated limb perfusion technique Extra-corporeal pumpN<5 7<5 7,/  PSummaryCDT is good first line therapy for appropriate patients CDT increases bleeding risk 2% intracranial hemorrhage Acute limb ischemia is associated with significant morbidity/mortality Further device and agent investigation needed Intraoperative therapy can be valuable adjunct to surgeryXTZZZ  >>W  a+ References:  1. Comerota Anthony. Intra-Arterial Catheter Directed Thrombolysis. Vascular Surgery. Rutherford. 2. Oriel K. Current Status of Thrombolysis for Peripheral Arterial Occlusive Disease. Ann Vasc Surg; 2002:16:797-804. 3. Sarac T, Hilleman D, Arko F, et al. Clincal and economic evaluation of the trellis thrombectomy device for arterial occlusions: preliminary analysis. Soc for Vasc Surg; 2004:39: 556-9. 4. Working Party. Thrombolysis in the management of lower limb peripheral arterial occlusion  a consensus Document. Am J Cardiol. 1998; 81: 207-18. 5. Marty B, Wicky S Ris H. Success of thrombolysis as a predictor of outcome in acute thrombosis of popliteal aneurysms. J Vasc Surg. 2002; 35: 487-93.: + @ 0   ' ? & \" 1    0` ` ̙33` 333MMM` ff3333f` f` f` 3>?" dd@,|?" dd@   " @ ` n?" dd@   @@``PR    @ ` ` p>> 0((    6 P  T Click to edit Master title style! !  0   RClick to edit Master text styles Second level Third level Fourth level Fifth level!     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"2 0Catheter Directed ."System"-@Times New Roman-. 2 0Y Thrombolysis.-@Times New Roman-. 2 K0Gan Dunnington .-@Times New Roman-.  2 KbM.D..-@Times New Roman-. 12 V%Stanford Vascular Conference.-@Times New Roman-. 2 `E9/12/05.-՜.+,0`    On-screen ShowHome Times New RomanDefault Design!Catheter Directed Thrombolysis Catheter Directed Thrombolysis Background BackgroundThrombolytics Background Background Background Background BackgroundPatient selectionPatient selectionResultsResultsResults Results ResultsResults (comparing CDT agents) Techniques Techniques Techniques AdjunctsIntra-operative CDTSummary References:  Fonts UsedDesign Template Slide Titles(_:0Jason T. Lee, MDJason T. Lee, MD  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./012345678:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|~Root EntrydO)PicturesqCurrent UserSummaryInformation(}%PowerPoint Document(9^DocumentSummaryInformation8