Anticoagulation in diagnostic and interventional procedure and monitoring and antiplatelet drugs

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Anticoagulation in diagnostic and interventional procedure and monitoring and antiplatelet drugs

  1. 1. Anticoagulation in Diagnostic andAnticoagulation in Diagnostic and Interventional Procedure andInterventional Procedure and Monitoring and Antiplatelet DrugsMonitoring and Antiplatelet Drugs..  Moderator: Prof R.V. PhadkeModerator: Prof R.V. Phadke  Presenter: Dr Deb K. BoruahPresenter: Dr Deb K. Boruah  2626thth November ’09November ’09
  2. 2. The Blood Clotting MechanismThe Blood Clotting Mechanism The three mechanisms of Blood Clotting are:The three mechanisms of Blood Clotting are:  Vascular SpasmVascular Spasm - The smooth muscle in blood vessel- The smooth muscle in blood vessel walls contracts immediately the blood vessel is broken. Thiswalls contracts immediately the blood vessel is broken. This response reduces blood loss for some time, while the otherresponse reduces blood loss for some time, while the other hemostatic mechanisms become active.hemostatic mechanisms become active.  Platelet Plug FormationPlatelet Plug Formation - When blood platelets- When blood platelets encounter a damaged blood vessel they form a "encounter a damaged blood vessel they form a "plateletplatelet plugplug" to help to close the gap in the broken blood vessel." to help to close the gap in the broken blood vessel. (The key stages of this process are called(The key stages of this process are called plateletplatelet adhesionadhesion,, platelet release reaction,platelet release reaction, andand plateletplatelet aggregationaggregation))
  3. 3.  Blood ClottingBlood Clotting (Coagulation)(Coagulation) --  Blood normally remains in its liquid state while it isBlood normally remains in its liquid state while it is within the blood vessels but when it leaves them thewithin the blood vessels but when it leaves them the blood may thicken and form a gel (coagulation).blood may thicken and form a gel (coagulation).  Blood clotting (technically "Blood clotting (technically "blood coagulationblood coagulation") is the") is the process by which (liquid) blood is transformed into aprocess by which (liquid) blood is transformed into a solid state.solid state.
  4. 4. • Interventional procedures Virchow’s Triad:
  5. 5. Mechanism of blood coagulationMechanism of blood coagulation
  6. 6. HemostasisHemostasis  involves a sequence of interactions of coagulation factorinvolves a sequence of interactions of coagulation factor interactions in two pathways called the intrinsic and extrinsicinteractions in two pathways called the intrinsic and extrinsic coagulation cascades .coagulation cascades .  The final common pathway involves the transformation ofThe final common pathway involves the transformation of prothrombin to thrombin by factor Xa.prothrombin to thrombin by factor Xa.  Thrombin (factor IIa) then serves to catalyze the activation ofThrombin (factor IIa) then serves to catalyze the activation of fibrinogen to fibrin, in addition to its role in feedback activationfibrinogen to fibrin, in addition to its role in feedback activation of several other clotting factors.of several other clotting factors.  UFH, LMWH, and fondaparinux( saccharides) all exert theirUFH, LMWH, and fondaparinux( saccharides) all exert their anticoagulant effect in a similar fashion, byanticoagulant effect in a similar fashion, by binding to andbinding to and activating antithrombinactivating antithrombin that then neutralizes selected coagulationthat then neutralizes selected coagulation factorsfactors..
  7. 7. Stages of blood coagulationStages of blood coagulation  Formation ofFormation of ProthrombinaseProthrombinase Prothrombinase can be formed in two ways, depending of which of twoProthrombinase can be formed in two ways, depending of which of two "systems" or "pathways" apply."systems" or "pathways" apply.  Intrinsic SystemIntrinsic System  This is initiated by liquid blood making contact with a foreign surface, i.e.This is initiated by liquid blood making contact with a foreign surface, i.e. something that is not part of the body;something that is not part of the body;  Extrinsic SystemExtrinsic System  This is initiated by liquid blood making contact with damaged tissue.This is initiated by liquid blood making contact with damaged tissue. Both the intrinsic and the extrinsic systems involve interactions betweenBoth the intrinsic and the extrinsic systems involve interactions between coagulation factorscoagulation factors..  2.2. ProthrombinProthrombin converted into the enzymeconverted into the enzyme ThrombinThrombin Prothrombinase (formed in stage 1.) converts prothrombin, which is a plasmaProthrombinase (formed in stage 1.) converts prothrombin, which is a plasma protein that is formed in the liver, into the enzymeprotein that is formed in the liver, into the enzyme thrombinthrombin..  3.3. FibrinogenFibrinogen (soluble) converted to(soluble) converted to FibrinFibrin (insoluble)(insoluble) In turn, thrombin converts fibrinogen into fibrin. Fibrin is insoluble andIn turn, thrombin converts fibrinogen into fibrin. Fibrin is insoluble and forms the threads that bind the clot.forms the threads that bind the clot.
  8. 8. BLOOD COAGULATION A sequence of reactions that are present in an inactive state in blood. Key is the conversion of the plasma protein fibrinogen to fibrin Intrinsic pathway Extrinsic pathway (activated by exposure of (activated by substances blood to damaged tissue) released from damaged tissue) Active factors X and V Prothrombin Thrombin Fibrinogen Fibrin Fibrin mesh inhibited by warfarin inhibited by heparin
  9. 9. Rationale for anticoagulant therapyRationale for anticoagulant therapy
  10. 10. PHARMACOLOGICAL AGENTSPHARMACOLOGICAL AGENTS
  11. 11. Pharmacologic AgentsPharmacologic Agents  AnticoagulantsAnticoagulants  Fibrinolytics (Agents for pharmacological recanalization)Fibrinolytics (Agents for pharmacological recanalization)  Anti platelet drugsAnti platelet drugs  Thrombin inhibitorThrombin inhibitor
  12. 12. ANTICOAGULANTSANTICOAGULANTS  Heparin and Low Molecular Weight HeparinsHeparin and Low Molecular Weight Heparins ((e.g. enoxaparin, dalteparin)e.g. enoxaparin, dalteparin) Oral anticoagulants:Oral anticoagulants:  Coumarin DerivatvesCoumarin Derivatves e.g. Warfarin,e.g. Warfarin, AcenocoumarolAcenocoumarol  Indandione DerivatvesIndandione Derivatves e.g. Phenindione,e.g. Phenindione, AnisindioneAnisindione
  13. 13. Thrombolytics:Thrombolytics: Plasminogen activators Fibrinolytics
  14. 14. Anti Platelet DrugsAnti Platelet Drugs Drug Mechanism UsesDrug Mechanism Uses AspirinAspirin Permanently inhibitsPermanently inhibits COX-1 and COX-2COX-1 and COX-2 CADCAD Stroke-TIAsStroke-TIAs NSAIDsNSAIDs Reversibly inhibitsReversibly inhibits COX-1COX-1 LimitedLimited DipyridamoleDipyridamole Inhibits PDE;Inhibits PDE; increases cAMPincreases cAMP TIAsTIAs ThenopyridinesThenopyridines (Ticlopidine(Ticlopidine Clopidegrel)Clopidegrel) Inhibits ADPInhibits ADP PlatAg;PlatAg; TIAs;StrokeTIAs;Stroke CAD; PVDCAD; PVD Abciximab (ReoPro)Abciximab (ReoPro) EptifibatideEptifibatide (Integrilin)(Integrilin) TirofibaTirofibann GP IIB/IIIA InhibitorsGP IIB/IIIA Inhibitors Stroke- TIAsStroke- TIAs
  15. 15.  Maintainance of patencyMaintainance of patency of vascular grafts, catheters,of vascular grafts, catheters, shunts, bypasses.shunts, bypasses.  Arterial thromboembolic diseaseArterial thromboembolic disease • Transient ischemic attacksTransient ischemic attacks • Stroke in evolutionStroke in evolution  Ischemic events occurs inIschemic events occurs in 1.3%1.3% of conventionalof conventional neuroangiographic procedures without Endovascularneuroangiographic procedures without Endovascular surgery.surgery. Indications for Antithrombotic Therapy inIndications for Antithrombotic Therapy in Diagnostics and Interventional ProceduresDiagnostics and Interventional Procedures
  16. 16. WHY TO MONITOR ANTICOAGULANT THERAPY?WHY TO MONITOR ANTICOAGULANT THERAPY?  Narrow therapeutic rangeNarrow therapeutic range  Can increase risk of bleedingCan increase risk of bleeding
  17. 17. Coagulation TestingCoagulation Testing  Monitoring therapyMonitoring therapy IntrinsicPathway Extrinsic Pathway Common Pathway CLOT Heparin CoumadinMonitor with ACT / aPTT Monitor with PT/INR Thrombolytics Monitor with TT / Fibrinogen
  18. 18. Monitoring ofMonitoring of Anti platelet drugsAnti platelet drugs  Bleeding timeBleeding time  Optical aggregometryOptical aggregometry  Point-of-care rapid platelet function assayPoint-of-care rapid platelet function assay
  19. 19. HeparinHeparin  Heterogeneous; 3,000-30,000 dalton in molecularHeterogeneous; 3,000-30,000 dalton in molecular weight.weight.  Average=15,000 d (~45monosaccharide chains)Average=15,000 d (~45monosaccharide chains)  AboutAbout 1/3 of dose binds to AT III and forms the1/3 of dose binds to AT III and forms the AT III:Heparin:Clotting Factor ComplexAT III:Heparin:Clotting Factor Complex  Complex binds to clotting factors of the intrinsic andComplex binds to clotting factors of the intrinsic and common pathway (Xa, IIa, IXa, XIa, XIIa, XIIIa)common pathway (Xa, IIa, IXa, XIa, XIIa, XIIIa) and inactivates themand inactivates them  Anticoagulant of choice in pregnancy (not crossesAnticoagulant of choice in pregnancy (not crosses placenta.)placenta.)
  20. 20. Heparin and Low molecular weight heparinsHeparin and Low molecular weight heparins Structure and sequence O OH OH O COO O O CH2 OH NHSO3 OH _ _ O O CH2 OSO3 NHSO3 OH _ _ O OH OH O COO O O CH2OSO3 NHSO3 OH _ _ O OSO3 OH O COO O O CH2OSO3 NHCOCH3 OH _ _ _ _ _ O OH OH O COO 1 2 3 4 5 6 β-D-glucosamine α-L-iduronic acid β-D-glucuronic acid O O CH2OH NH2 OH 1 2 3 4 5 6 O OH OH O COO _ 1 2 3 4 5 6 polymeric structure of heparin
  21. 21. Anticoagulant Properties of HeparinAnticoagulant Properties of Heparin 1.1. Inhibits the thrombin-mediated conversion of fibrinogen toInhibits the thrombin-mediated conversion of fibrinogen to fibrinfibrin 2.2. Inhibits the aggregation of platelets by thrombin (prolongsInhibits the aggregation of platelets by thrombin (prolongs bleeding time)bleeding time) 3.3. Inhibits activation of fibrin stabilizing enzymeInhibits activation of fibrin stabilizing enzyme 4.4. Inhibits activated factors XII, XI, IX, X and IIInhibits activated factors XII, XI, IX, X and II  All available forms of heparin must be administeredAll available forms of heparin must be administered parenterally, since they are highly charged and rapidlyparenterally, since they are highly charged and rapidly hydrolyzed in the GI tract.hydrolyzed in the GI tract.  Heparin antagonist: Protamine sulfate (Heparin antagonist: Protamine sulfate (10mg for 1000 unit of10mg for 1000 unit of heparin)heparin)
  22. 22. Monitoring of heparinMonitoring of heparin  Subcutenous:Subcutenous: no monitoring requiredno monitoring required  Intravenous:Intravenous:  Partial thromboplastin time (P.T.T., normal value ~30sec)Partial thromboplastin time (P.T.T., normal value ~30sec)  Activated clotting time ( ACT normal value ~90-120sec)Activated clotting time ( ACT normal value ~90-120sec)  Daily or more frequent if PTT, ACT variesDaily or more frequent if PTT, ACT varies  MechanismMechanism – measures intrinsic pathway– measures intrinsic pathway  Therapeutic goalTherapeutic goal : 2-2.5 times normal control value .: 2-2.5 times normal control value .
  23. 23. ACT or aPTTACT or aPTT  Determine when to pull the femoral sheathDetermine when to pull the femoral sheath  Premature sheath pull can lead to bleeding.Premature sheath pull can lead to bleeding.  Delayed removal can increase time in ICU.Delayed removal can increase time in ICU.  Target setTarget set at each site.at each site.  ACT targets range from 150 – 220 secondsACT targets range from 150 – 220 seconds  aPTT targets range from 40 – 70 secondsaPTT targets range from 40 – 70 seconds
  24. 24. During neuroangiography-During neuroangiography-  Recommended therapeutic range of heparin in plasmaRecommended therapeutic range of heparin in plasma is 0.2-0.8 u/ml. ( corresponding to aPTT, ACT valuesis 0.2-0.8 u/ml. ( corresponding to aPTT, ACT values 1.5-2.5 times the baseline values)1.5-2.5 times the baseline values)  Dose : In diagnostic angiography bolus dose of 2500 iuDose : In diagnostic angiography bolus dose of 2500 iu is used followed by 1000 iu / hour.is used followed by 1000 iu / hour.  Bolus dose isBolus dose is 60 u/kg to maintain the therapeutic60 u/kg to maintain the therapeutic range.range. If procedure continues for more than 75 minutesIf procedure continues for more than 75 minutes additional dose is required ( half of the initial dose foradditional dose is required ( half of the initial dose for another 75 minutes)another 75 minutes) (AJNR 1994,15 : 51-54)
  25. 25. Mechanisms of HIT(Mechanisms of HIT( Heparin inducedHeparin induced ThrombocytopeniaThrombocytopenia))  Type 1:Type 1:  Fall in platelet count occurs within the first two days afterFall in platelet count occurs within the first two days after heparin initiation, often returns to normal with continuedheparin initiation, often returns to normal with continued heparin administration, and is of no clinical consequence.heparin administration, and is of no clinical consequence.  The mechanism of the thrombocytopenia is non-immune andThe mechanism of the thrombocytopenia is non-immune and appears to be due to a direct effect of heparin on plateletappears to be due to a direct effect of heparin on platelet activation.activation.  Type 2:Type 2:  Approximately 0.3 to 3 percent of patients receiving heparinApproximately 0.3 to 3 percent of patients receiving heparin develop an immune thrombocytopenia, mediated bydevelop an immune thrombocytopenia, mediated by antibodies to a heparin-platelet factor 4 complex.antibodies to a heparin-platelet factor 4 complex.
  26. 26. (AJNR 28:155-158, 2007)
  27. 27. Treatment of heparin-inducedTreatment of heparin-induced thrombocytopeniathrombocytopenia  When HIT is diagnosed, it is important to stop heparin,When HIT is diagnosed, it is important to stop heparin, mainly in type 2 and to avoid the use of LMWH.mainly in type 2 and to avoid the use of LMWH.  Because of the increased risk of thrombosis, however,Because of the increased risk of thrombosis, however, continuation of an anticoagulant must be considered.continuation of an anticoagulant must be considered.  The drugs currently approved for the treatment of HITThe drugs currently approved for the treatment of HIT in the United States are direct thrombin inhibitorsin the United States are direct thrombin inhibitors argatroban and lepirudin.argatroban and lepirudin.
  28. 28. WARFARIN: MECHANISM OF ACTIONWARFARIN: MECHANISM OF ACTION Inactive factors II, VII, IX, and X Proteins S and C Active factors II, VII, IX, and X Proteins S and C Vitamin K epoxide Vitamin K reduced WARFARIN Prevents the reduction of vitamin K, which is essential forPrevents the reduction of vitamin K, which is essential for activation of certain factorsactivation of certain factors Has no effect on previously formed thrombusHas no effect on previously formed thrombus Antagonist is Vit KAntagonist is Vit K
  29. 29. OPTIMIZING WARFARIN THERAPYOPTIMIZING WARFARIN THERAPY Use of large loading dose may lead to hemorrhage andUse of large loading dose may lead to hemorrhage and other complications.other complications.  Initial dose: 2-5 mg once dailyInitial dose: 2-5 mg once daily  Maintenance dose: 2-10 mg once dailyMaintenance dose: 2-10 mg once daily  If Immediate anticoagulation is requiredIf Immediate anticoagulation is required:: Heparin ISHeparin IS started along with loading dose of warfarin 10 mg.started along with loading dose of warfarin 10 mg. Heparin is usually discontinued after 4-5 days.Heparin is usually discontinued after 4-5 days. BeforeBefore discontinuing, INR should be in therapeutic range for 2discontinuing, INR should be in therapeutic range for 2 consecutive days.consecutive days.  Daily monitoring of INR until INR is in therapeuticDaily monitoring of INR until INR is in therapeutic range, then 3 times weekly for 1-2 weeks, then less oftenrange, then 3 times weekly for 1-2 weeks, then less often (every 4 to 6 weeks).(every 4 to 6 weeks).
  30. 30. OPTIMAL THERAPEUTIC RANGEOPTIMAL THERAPEUTIC RANGE IndicationIndication INRINR Prophylaxis of venousProphylaxis of venous thromboembolismthromboembolism 2.0-3.02.0-3.0 Treatment of venousTreatment of venous thromboembolismthromboembolism 2.0-3.02.0-3.0 Atrial fibrillationAtrial fibrillation 2.0-3.02.0-3.0 Mitral valve stenosisMitral valve stenosis 2.0-3.02.0-3.0 Heart valve replacementHeart valve replacement Bioprosthetic valveBioprosthetic valve Mechanical valveMechanical valve 2.0-3.02.0-3.0 2.5-3.52.5-3.5 Myocardial infarctionMyocardial infarction 2.0-3.02.0-3.0 2.5-3.52.5-3.5 (high risk patients)(high risk patients)
  31. 31. FACTORS INFLUENCING DOSE RESPONSEFACTORS INFLUENCING DOSE RESPONSE  Poor patient compliancePoor patient compliance  Concomitant medicationsConcomitant medications  Levels of dietary vitamin KLevels of dietary vitamin K  Alcohol Inaccurate lab testingAlcohol Inaccurate lab testing  Inaccurate lab testingInaccurate lab testing  Hepatic dysfunctionHepatic dysfunction  FeverFever
  32. 32. Contraindication for WarfarinContraindication for Warfarin::  Hypersensitivity to warfarinHypersensitivity to warfarin  Hemorrhagic tendencyHemorrhagic tendency  Condition with risk of hemorrhageCondition with risk of hemorrhage  Inadequate laboratory techniquesInadequate laboratory techniques  Protein C & S deficiencyProtein C & S deficiency  Vitamin K deficiencyVitamin K deficiency
  33. 33. SIDE EFFECTSSIDE EFFECTS  HemorrhageHemorrhage  Skin necrosisSkin necrosis  Purple toe syndromePurple toe syndrome  MicroembolizationMicroembolization  TeratogenecityTeratogenecity  Agranulocytosis, leukopenia,Agranulocytosis, leukopenia,  Diarrhoea,nausea, anorexia.Diarrhoea,nausea, anorexia.
  34. 34. MONITORING OF WARFARIN THERAPYMONITORING OF WARFARIN THERAPY  Prothrombin timeProthrombin time  PT ratioPT ratio  INR (International Normalized Ratio)INR (International Normalized Ratio)
  35. 35. PROTHROMBIN TIME (PT)PROTHROMBIN TIME (PT)  Time required for blood to coagulate is called PTTime required for blood to coagulate is called PT ( normal value ~10sec)( normal value ~10sec)  Performed by adding a mixture of calcium andPerformed by adding a mixture of calcium and thromboplastin to citrated plasmathromboplastin to citrated plasma  As a control, a normal blood sample is testedAs a control, a normal blood sample is tested continuouslycontinuously  PT ratio (PTR) =PT ratio (PTR) = Patient’s PTPatient’s PT Control PTControl PT
  36. 36. PROBLEMS WITH PT/PTRPROBLEMS WITH PT/PTR  Thromboplastins are extracts from brain, lungThromboplastins are extracts from brain, lung or placenta of animalsor placenta of animals  Thromboplastins from various manufacturersThromboplastins from various manufacturers differ in their sensitivity to prolong PTdiffer in their sensitivity to prolong PT  May result in false control of anticoagulantMay result in false control of anticoagulant therapytherapy
  37. 37. INTERNATIONAL NORMALISED RATIO (INR)INTERNATIONAL NORMALISED RATIO (INR) International Normalized Ratio (INR):International Normalized Ratio (INR): a PT test with aa PT test with a formula based ratio to normalize the often variable sourceformula based ratio to normalize the often variable source of tissue factor (human, rabbit, recombinant).of tissue factor (human, rabbit, recombinant). INR = [PTINR = [PTptpt]] ISIISI [PT[PTRefRef]] PTPTptpt – prothrombin time of patient– prothrombin time of patient PTPTRefRef – prothrombin time of normal pooled sample– prothrombin time of normal pooled sample ISI – International Sensitivity IndexISI – International Sensitivity Index Warfarin is given orally and titrated to achieve an INR ofWarfarin is given orally and titrated to achieve an INR of typically 2.0 – 3.0typically 2.0 – 3.0
  38. 38. Heparin versus WarfarinHeparin versus Warfarin Drug Action Mechan- ism Moni- toring Effective Heparin Direct Inhibition of Thrombin ATIII cofactor APTT ACT Immediate Warfarin Decreases Production of factors Vitamin K PT Delay 3-5 days INR
  39. 39. Recanalization or Antegrade Reperfusion StrategiesRecanalization or Antegrade Reperfusion Strategies  Recanalization strategies focus on removing and/or dissolvingRecanalization strategies focus on removing and/or dissolving the occlusive thrombus to re-establish antegrade flow.the occlusive thrombus to re-establish antegrade flow. Strategies may be classified into 7 different categories on theStrategies may be classified into 7 different categories on the basis of their primary mechanism of action:basis of their primary mechanism of action: 1)1) IV and/or intraarterial thrombolysis (IAT),IV and/or intraarterial thrombolysis (IAT), 2) endovascular thrombectomy,2) endovascular thrombectomy, 3) endovascular thromboaspiration,3) endovascular thromboaspiration, 4) endovascular mechanical thrombus disruption or thromborrhexis,4) endovascular mechanical thrombus disruption or thromborrhexis, 5)5) transcranial or endovascular augmented fibrinolysis,transcranial or endovascular augmented fibrinolysis, 6) endovascular thrombus entrapment, and6) endovascular thrombus entrapment, and 7) temporary endovascular bypass.7) temporary endovascular bypass.
  40. 40. IAT in Acute Ischemic StrokeIAT in Acute Ischemic Stroke IAT advantages over IV thrombolysis.IAT advantages over IV thrombolysis.  Coaxial microcatheter techniques, the occluded intracranial vessel isCoaxial microcatheter techniques, the occluded intracranial vessel is directly accessible and the fibrinolytic agent can be infused directly into thedirectly accessible and the fibrinolytic agent can be infused directly into the thrombus.thrombus.  This permits a smaller dose of fibrinolytic agent to reach a higher localThis permits a smaller dose of fibrinolytic agent to reach a higher local concentration than that reached by systemic infusion.concentration than that reached by systemic infusion.  Allows more complete recanalization with lower total doses ofAllows more complete recanalization with lower total doses of thrombolytic.thrombolytic.  With the smaller dose, complications from systemic fibrinolytic effects,With the smaller dose, complications from systemic fibrinolytic effects, including intracranial hemorrhage (ICH), can theoretically be reduced.including intracranial hemorrhage (ICH), can theoretically be reduced.  Treatment window for endovascular techniques can be extended beyondTreatment window for endovascular techniques can be extended beyond the typical IV window of 3 hours.the typical IV window of 3 hours.  IA techniques have led to higher recanalization rates than IV thrombolysis.IA techniques have led to higher recanalization rates than IV thrombolysis.
  41. 41. Major disadvantagesMajor disadvantages  Relative complexity of the procedure, the level of requiredRelative complexity of the procedure, the level of required technical expertise and its relatively low availability,technical expertise and its relatively low availability,  Delays in initiating treatmentDelays in initiating treatment  InvasiveInvasive
  42. 42. Thrombolytics:Thrombolytics: Plasminogen activators Fibrinolytics
  43. 43. 1. Plasminogen Activators.1. Plasminogen Activators. drugs act by converting the inactive proenzyme, plasminogen into thedrugs act by converting the inactive proenzyme, plasminogen into the active enzyme, plasmin. Plasmin digests fibrinogen fibrin monomers andactive enzyme, plasmin. Plasmin digests fibrinogen fibrin monomers and cross-linked fibrin (as found in a thrombus) into fibrin degradationcross-linked fibrin (as found in a thrombus) into fibrin degradation products.products.  First-Generation Agents.First-Generation Agents.  StreptokinaseStreptokinase, a protein derived from group C ß-, a protein derived from group C ß- hemolytic streptococci, has a half-life of 16–90 minuteshemolytic streptococci, has a half-life of 16–90 minutes and low fibrin specificity. This drug proved to have aand low fibrin specificity. This drug proved to have a very narrow therapeutic window and significant rates ofvery narrow therapeutic window and significant rates of ICH and systemic hemorrhage18.ICH and systemic hemorrhage18.  UrokinaseUrokinase is a serine protease with a plasma half life ofis a serine protease with a plasma half life of 14 minutes and low fibrin specificity.14 minutes and low fibrin specificity.  The urokinase dose used in cerebral IAT has rangedThe urokinase dose used in cerebral IAT has ranged from 0.02 to 2 X106units.from 0.02 to 2 X106units.
  44. 44. Second-Generation Agents.Second-Generation Agents. Alteplase (rtPA)Alteplase (rtPA)  is a serineis a serine protease with a plasma half-life of 3.5 minutes andprotease with a plasma half-life of 3.5 minutes and a high degree of fibrin affinity and specificity.a high degree of fibrin affinity and specificity.  Dose used in cerebral IAT has ranged between 20 and 60 mg.Dose used in cerebral IAT has ranged between 20 and 60 mg.  Disadvantages of alteplase include its relatively short halflifeDisadvantages of alteplase include its relatively short halflife and limited penetration into the clot matrix because ofand limited penetration into the clot matrix because of strong binding with surface fibrin, which could delaystrong binding with surface fibrin, which could delay recanalization and increase the risk of recurrent occlusion.recanalization and increase the risk of recurrent occlusion. Prourokinase (r-prourokinase)Prourokinase (r-prourokinase)  is the proenzyme precursor of urokinase.is the proenzyme precursor of urokinase.  T1/2 of 7 minutes and high fibrin specificity.T1/2 of 7 minutes and high fibrin specificity.
  45. 45. Third-Generation AgentsThird-Generation Agents ReteplaseReteplase  is a structurally modifiedis a structurally modified form of alteplase, with a longerform of alteplase, with a longer half-life (15–18 minutes). In addition, it does not bind ashalf-life (15–18 minutes). In addition, it does not bind as highly to fibrin; unbound reteplase can thus theoreticallyhighly to fibrin; unbound reteplase can thus theoretically better penetrate the clot and potentiallybetter penetrate the clot and potentially improve in vivoimprove in vivo fibrinolytic activity.fibrinolytic activity. TenecteplaseTenecteplase  is another modified form of rtPA with a longer half-life (17is another modified form of rtPA with a longer half-life (17 minutes),minutes),  greater fibrin specificity, and greater resistance togreater fibrin specificity, and greater resistance to plasminogen activator inhibitor-1.plasminogen activator inhibitor-1.  IV tenecteplase in acute ischemic stroke suggest that the drugIV tenecteplase in acute ischemic stroke suggest that the drug is safe and promising.is safe and promising.
  46. 46. Newer plasminogen activatorNewer plasminogen activator DesmoteplaseDesmoteplase  is a genetically engineeredis a genetically engineered version of the clot-dissolving factor foundversion of the clot-dissolving factor found in the salivain the saliva of the vampire bat Desmodus rotundusof the vampire bat Desmodus rotundus..  moremore potent and more selective for fibrin-boundpotent and more selective for fibrin-bound plasminogen than any other known plasminogen activator.plasminogen than any other known plasminogen activator.  Unlike tissue plasminogen activator (tPA), desmoteplase isUnlike tissue plasminogen activator (tPA), desmoteplase is not activated by fibrinogen or -amyloid proteins, factors thatnot activated by fibrinogen or -amyloid proteins, factors that may exacerbate the risk for ICH.may exacerbate the risk for ICH.  The effect of IV administration of desmoteplase 3–9 hoursThe effect of IV administration of desmoteplase 3–9 hours after symptom onset in patients with stroke who present withafter symptom onset in patients with stroke who present with mismatch on MR imaging or CT perfusion .mismatch on MR imaging or CT perfusion .
  47. 47. 3. Defibrinogenating/Fibrinogenolytic Agents.3. Defibrinogenating/Fibrinogenolytic Agents. AncrodAncrod(Viprinex)(Viprinex)  isis the purified fraction of the Malayan pit viper venom.the purified fraction of the Malayan pit viper venom.  It acts by directly cleaving and inactivating fibrinogen andIt acts by directly cleaving and inactivating fibrinogen and thus indirectly promoting anticoagulation.thus indirectly promoting anticoagulation.  The reduction in the blood levels of fibrinogen also leads toThe reduction in the blood levels of fibrinogen also leads to a reduced blood viscosity, which may improve blood flow toa reduced blood viscosity, which may improve blood flow to the affected areas of the brain.the affected areas of the brain.  In the Stroke Treatment with Ancrod Trial, 500 patients withIn the Stroke Treatment with Ancrod Trial, 500 patients with stroke presenting within 3 hours of symptom onset werestroke presenting within 3 hours of symptom onset were randomized to receive ancrod (randomized to receive ancrod (n 248) or a placebo (n 252).n 248) or a placebo (n 252). Good outcome (BarthelGood outcome (Barthel Index, 95–100 at 3 months) wasIndex, 95–100 at 3 months) was achieved in 42.21% and 34.4% of the patients respectively .achieved in 42.21% and 34.4% of the patients respectively .
  48. 48. 2. Direct Fibrinolytics.2. Direct Fibrinolytics. Microplasmin (Microplasmin (ThromboGenics, Heverlee, Belgium)ThromboGenics, Heverlee, Belgium)  is a truncated form of plasmin that is more resistant to theis a truncated form of plasmin that is more resistant to the effects of antiplasmin.effects of antiplasmin.  microplasmin can be used upto 4–12 hours after stroke onset.microplasmin can be used upto 4–12 hours after stroke onset.  There was no evidence of increased bleeding risk withThere was no evidence of increased bleeding risk with microplasmin.microplasmin. Alfimeprase (Nuvelo, San Carlos, Calif)Alfimeprase (Nuvelo, San Carlos, Calif)  is a recombinant truncated form of fibrolase, a fibrinolytic zinc metalloproteinaseis a recombinant truncated form of fibrolase, a fibrinolytic zinc metalloproteinase isolated from the venom of the southern copperhead snake.isolated from the venom of the southern copperhead snake.  It degrades fibrin directly and achieves thrombolysisIt degrades fibrin directly and achieves thrombolysis independent of plasmin formation.independent of plasmin formation.  its thrombolytic activity appears to be localized to the site ofits thrombolytic activity appears to be localized to the site of delivery. These properties should theoretically result in fasterdelivery. These properties should theoretically result in faster recanalization and lower hemorrhagic conversion riskrecanalization and lower hemorrhagic conversion risk..
  49. 49. Anti-fibrinolyticsAnti-fibrinolytics to limit fibrinolytic activityto limit fibrinolytic activity  εε-aminocaproic acid (EACA):-aminocaproic acid (EACA): competitively inhibitscompetitively inhibits plasminogen and plasminogen activators fromplasminogen and plasminogen activators from binding to fibrinbinding to fibrin  alpha2-antiplasminalpha2-antiplasmin: a serine protease inhibitor that: a serine protease inhibitor that neutralizes any free circulating plasmin.neutralizes any free circulating plasmin.  Plasminogen activator inhibitor-1Plasminogen activator inhibitor-1: a serine protease: a serine protease inhibitor that inhibits tissue-type plasminogeninhibitor that inhibits tissue-type plasminogen activator.activator.
  50. 50. Glycoprotein (GP) IIb/IIIa antagonistsGlycoprotein (GP) IIb/IIIa antagonists,,  such as ReoPro (abciximab), Integrilin (eptifibatide), orsuch as ReoPro (abciximab), Integrilin (eptifibatide), or Aggrastat (tirofiban) in ischemic stroke remainsAggrastat (tirofiban) in ischemic stroke remains investigational. Deshmukh et al38 reported 21 patients withinvestigational. Deshmukh et al38 reported 21 patients with large-vessel occlusion refractory to IAT with rtPA who werelarge-vessel occlusion refractory to IAT with rtPA who were treated with IV and/or IA abciximab, eptifibatide, ortreated with IV and/or IA abciximab, eptifibatide, or tirofiban.tirofiban.
  51. 51. IA Mechanical Approaches in Acute Ischemic StrokeIA Mechanical Approaches in Acute Ischemic Stroke Mechanical strategies have several advantagesMechanical strategies have several advantages  First, they lessen and may even preclude the use of chemicalFirst, they lessen and may even preclude the use of chemical thrombolytics, in this manner very likely reducing the risk of ICH.thrombolytics, in this manner very likely reducing the risk of ICH.  Second, by avoiding the use of chemical thrombolytics, it is possibleSecond, by avoiding the use of chemical thrombolytics, it is possible to extend the treatment window beyond the limit of 6–8 hours.to extend the treatment window beyond the limit of 6–8 hours.  Third, mechanically fragmenting a clot increases the surface areaThird, mechanically fragmenting a clot increases the surface area accessible to fibrinolytic agents and allows inflow of freshaccessible to fibrinolytic agents and allows inflow of fresh plasminogen, which, in turn, may increase the speed of thrombolysis.plasminogen, which, in turn, may increase the speed of thrombolysis.  Finally, clot-retrieval devices may provide faster recanalization .Finally, clot-retrieval devices may provide faster recanalization .
  52. 52. The disadvantages of the mechanical approachesThe disadvantages of the mechanical approaches  technical difficulty of navigating mechanical devices into thetechnical difficulty of navigating mechanical devices into the intracranial circulation, excessive trauma to the vasculatureintracranial circulation, excessive trauma to the vasculature (potentially leading to vasospasm, vessel dissection,(potentially leading to vasospasm, vessel dissection, perforation, or rupture),perforation, or rupture),  fragmented thrombus causing distal embolization intofragmented thrombus causing distal embolization into previously unaffected territories.previously unaffected territories. Nevertheless, the advantages of mechanical stroke therapyNevertheless, the advantages of mechanical stroke therapy appear to significantly outweigh its disadvantages and risks.appear to significantly outweigh its disadvantages and risks.
  53. 53. Contraindications to Thrombolytic agentsContraindications to Thrombolytic agents  Recent thoracic, abdominal, or intracranial surgeryRecent thoracic, abdominal, or intracranial surgery  Recent haemorrhagic CVA, Head injury, or neoplasmRecent haemorrhagic CVA, Head injury, or neoplasm  Bleeding ulcerBleeding ulcer  Anticipated invasive procedures (arterial punctures,Anticipated invasive procedures (arterial punctures, biopsies)biopsies)  Concurrent hemostatic dysfunctionConcurrent hemostatic dysfunction
  54. 54. Monitoring of thrombolytic therapyMonitoring of thrombolytic therapy  Thrombin time: Measures the availability of functional fibrinogen Normal thrombin time is 10-14 sec Prolonged when fibrinogen level is below 75-100 mg/dl
  55. 55. Half Life of ThrombolyticsHalf Life of Thrombolytics:: Agent Administration Half Life Streptokinase IA 60-80min Urokinase IA,IV 9-12min rTPA IA,IV 6min Abciximab(Reopro) IA,IV 12hour Aspirin PO,IV 15-20min Heparin IV,SC 60min Coumadin PO 1.5-2.5 days
  56. 56. Anti Platelet DrugsAnti Platelet Drugs DrugDrug MechanismMechanism UsesUses AspirinAspirin Permanently inhibitsPermanently inhibits COX-1 and COX-2COX-1 and COX-2 CADCAD Stroke-TIAsStroke-TIAs NSAIDsNSAIDs Reversibly inhibitsReversibly inhibits COX-1COX-1 LimitedLimited DipyridamoleDipyridamole Inhibits PDE; increasesInhibits PDE; increases cAMPcAMP TIAsTIAs ThenopyridinesThenopyridines (Ticlopidine(Ticlopidine ClopidrgrelClopidrgrel)) Inhibits ADPInhibits ADP PlatAg;PlatAg; TIAs;StrokeTIAs;Stroke CAD; PVDCAD; PVD Abciximab (ReoPro)Abciximab (ReoPro) Eptifibatide (Integrilin)Eptifibatide (Integrilin) TirofibanTirofiban GP IIB/IIIA InhibitorsGP IIB/IIIA Inhibitors Stroke- TIAsStroke- TIAs
  57. 57. MonitoringMonitoring  Bleeding timeBleeding time  Optical aggregometryOptical aggregometry  Point-of-care rapid platelet function assayPoint-of-care rapid platelet function assay
  58. 58. Bleeding timeBleeding time Requires a skin incision (usually made on the ear lobe or forearm, ofRequires a skin incision (usually made on the ear lobe or forearm, of a depth that results in disruption of capillary loops and small vessels)a depth that results in disruption of capillary loops and small vessels) AdvantagesAdvantages  Universally availableUniversally available  Relatively simple techniquesRelatively simple techniques  Can be performed bedsideCan be performed bedside DisadvantagesDisadvantages  Insensitive, inaccurate, non-specific techniqueInsensitive, inaccurate, non-specific technique  Poorly reproducible (as depends on multiple variables)Poorly reproducible (as depends on multiple variables)
  59. 59. Optical aggregometryOptical aggregometry  Gold standard assay for platelet functionGold standard assay for platelet function  Agonist induced aggregation is measuredAgonist induced aggregation is measured  Different agonist are available for different agentsDifferent agonist are available for different agents  However, require unique expertise and are not universallyHowever, require unique expertise and are not universally available.available.  Aspirin measured with ADP or AA(>70% aggregation s/oAspirin measured with ADP or AA(>70% aggregation s/o resistance)resistance)  Clopidogrel( ADP > 90% aggregation means resistance)Clopidogrel( ADP > 90% aggregation means resistance)
  60. 60. Point-of-care rapid platelet function assayPoint-of-care rapid platelet function assay  Can be performed bed sideCan be performed bed side  Different assay devices with different agonist areDifferent assay devices with different agonist are used for each of different antiplatelet agentsused for each of different antiplatelet agents For Aspirin AA is used (result is reported as aspirin reaction units [ARU]For Aspirin AA is used (result is reported as aspirin reaction units [ARU] ARU> 550 indicates non-responsiveness)ARU> 550 indicates non-responsiveness) Verify IIb/IIIa assay device uses TRAP as agonist for Abciximab andVerify IIb/IIIa assay device uses TRAP as agonist for Abciximab and TirofibanTirofiban
  61. 61. Practical Applications related toPractical Applications related to specific Neurovascular interventionsspecific Neurovascular interventions
  62. 62. Acute ischemic StrokeAcute ischemic Stroke  When an artery occludes, neurons are affected differently,When an artery occludes, neurons are affected differently, depending upon the amount of residual blood flow.depending upon the amount of residual blood flow.  Normal cerebral blood flow is greater than 50 mL/100 mg/min.Normal cerebral blood flow is greater than 50 mL/100 mg/min.  Once blood flow decreases to less than 20 mL/100 mg/min,Once blood flow decreases to less than 20 mL/100 mg/min, infarction occurs.infarction occurs.  If blood flow decreases to less than 10 mL/100 mg/min,If blood flow decreases to less than 10 mL/100 mg/min, irreversible neuronal death occurs rapidly.irreversible neuronal death occurs rapidly.  Blood flow between 11 and 20 mL/100 mg/min is thought toBlood flow between 11 and 20 mL/100 mg/min is thought to represent the ischemic penumbra , an area where the cells arerepresent the ischemic penumbra , an area where the cells are functionally silent because of ischemia, but are still able to recoverfunctionally silent because of ischemia, but are still able to recover if blood flow is restored.if blood flow is restored.  Many acute stroke therapies are targeted toward restoring flow orMany acute stroke therapies are targeted toward restoring flow or function to the ischemic penumbra.function to the ischemic penumbra.
  63. 63. Therapeutic window in management of acuteTherapeutic window in management of acute Ischemic Stroke:Ischemic Stroke: The early diagnosis of ischemic stroke is critical to the with only aThe early diagnosis of ischemic stroke is critical to the with only a narrow therapeutic window in the first few hours following strokenarrow therapeutic window in the first few hours following stroke ictus.ictus.  Diagnosis in the first 3 hours postictus provides the opportunity forDiagnosis in the first 3 hours postictus provides the opportunity for intravenous or intraarterial thrombolysis and intra-arterial clotintravenous or intraarterial thrombolysis and intra-arterial clot mechanical treatment which improve the outcome .mechanical treatment which improve the outcome .  Diagnosis in the time period between 3 and 6 hours provides anDiagnosis in the time period between 3 and 6 hours provides an opportunity for intra-arterial thrombolysis and mechanical treatment.opportunity for intra-arterial thrombolysis and mechanical treatment.  Involvement of the posterior circulation, especially the basilar artery,Involvement of the posterior circulation, especially the basilar artery, is treated by some regardless of time of onset or up until 12 to 24is treated by some regardless of time of onset or up until 12 to 24 hours in some practices. This is related to the potentially highhours in some practices. This is related to the potentially high mortality and morbidity associated with basilar artery thrombosis.mortality and morbidity associated with basilar artery thrombosis.
  64. 64. Infarct evaluation on angiographyInfarct evaluation on angiography (CT angiography and catheter angiography)(CT angiography and catheter angiography) CTA is an excellent first-line examination for evaluation ofCTA is an excellent first-line examination for evaluation of the head and neck arteries.the head and neck arteries.  In comparison with catheter angiography, what it givesIn comparison with catheter angiography, what it gives up in resolution and dynamic properties it makes up forup in resolution and dynamic properties it makes up for with rapid acquisition of a 3-D dataset and the potentialwith rapid acquisition of a 3-D dataset and the potential for assessment of whole-brain perfusion and betterfor assessment of whole-brain perfusion and better parenchymal evaluation.parenchymal evaluation.  Moreover, CTA illustrates not only arterial stenosis orMoreover, CTA illustrates not only arterial stenosis or occlusion, but also the vessel wall. This factor is mostocclusion, but also the vessel wall. This factor is most important for evaluation of intramural dissection andimportant for evaluation of intramural dissection and thrombosed aneurysms, which may both complicatethrombosed aneurysms, which may both complicate evaluation of stroke patients.evaluation of stroke patients.
  65. 65. Early angiographic signs of strokesEarly angiographic signs of strokes both CTA and DSAboth CTA and DSA  Vessel occlusion or cutoff related toVessel occlusion or cutoff related to thromboembolithromboemboli  aneurysmsaneurysms  arterial dissectionarterial dissection  Meniscus or flattened shape to clot (recent) versusMeniscus or flattened shape to clot (recent) versus reverse meniscus (older)reverse meniscus (older)  tram track (nonocclusive or recanalized clot)tram track (nonocclusive or recanalized clot)  delayed (antegrade) flow (manifest as decreaseddelayed (antegrade) flow (manifest as decreased whole-brain perfusion on CTA)whole-brain perfusion on CTA)  retrograde collateral flowretrograde collateral flow
  66. 66. Non-occlusive left MCA thrombus on 3-D imaging performed from CTA source data and was confirmed at catheter angiography
  67. 67.  Therapy to be started within a 6-hr time toTherapy to be started within a 6-hr time to treatment (TTT) window (while in case of IV.treatment (TTT) window (while in case of IV. thrombolysis therapy to be started with in 3hrs)thrombolysis therapy to be started with in 3hrs)  Exclusion criteriaExclusion criteria  Rapidly improving neurologic deficit orRapidly improving neurologic deficit or  Sustained blood pressure of >180/100Sustained blood pressure of >180/100  Hemorrhage is detected on CTHemorrhage is detected on CT  Infarct involving > more than 1/3 rd territory ofInfarct involving > more than 1/3 rd territory of MCA.MCA.  MRA/DWI-Perfusion mismatch< 20%MRA/DWI-Perfusion mismatch< 20%  Definite hypodensity on CTDefinite hypodensity on CT Intra-arterial Thrombolysis
  68. 68. Fibrinolytics + AntiplateletsFibrinolytics + Antiplatelets  PlasminogenPlasminogenactivators through fibrinolysis exposes free thrombinactivators through fibrinolysis exposes free thrombin and paradoxically stimulatesand paradoxically stimulatesplatelet aggregation which leads toplatelet aggregation which leads to formation of aformation of aplatelet thrombus ("white clot").platelet thrombus ("white clot").  This new thrombus is relatively resistant to fibrinolyticsThis new thrombus is relatively resistant to fibrinolytics  So new regimen in case of acute stroke isSo new regimen in case of acute stroke is  fibrinolytics + antiplatelet drugsfibrinolytics + antiplatelet drugs  rtPA + IIb/IIIa inhibitors( tirofiban, abciximab) orrtPA + IIb/IIIa inhibitors( tirofiban, abciximab) or  Urokinase + IIb/IIIa inhibitors( tirofiban,Urokinase + IIb/IIIa inhibitors( tirofiban, abciximab)abciximab)
  69. 69. Intra-arterial Thrombolysis  Tirofiban (0.4 µg/kg/min bolus for 3 min followed by 0.125Tirofiban (0.4 µg/kg/min bolus for 3 min followed by 0.125 ug/kg/min)ug/kg/min) ++ Heparin (2000–3000 IU bolus followed by 1000 IU/hourHeparin (2000–3000 IU bolus followed by 1000 IU/hour infusioninfusion with ACT maintained b/w 200-300) throughout the interventional procedurewith ACT maintained b/w 200-300) throughout the interventional procedure and for 24–48 hours thereafter when there is neither intraprocedural bleeding norand for 24–48 hours thereafter when there is neither intraprocedural bleeding nor suspicion of increased risk of bleeding.suspicion of increased risk of bleeding.  Maximum dose of UrokinaseMaximum dose of Urokinase  Anterior circulation stroke - 500,000 IU (mean, 400,000 IU; range, 300,000–Anterior circulation stroke - 500,000 IU (mean, 400,000 IU; range, 300,000– 500,000 IU)500,000 IU)  Posterior circulation stroke -1,000,000 IU (mean, 837,000 IU; range, 300,000–Posterior circulation stroke -1,000,000 IU (mean, 837,000 IU; range, 300,000– 1,000,000 IU)1,000,000 IU) American Journal of NeuroradiologyAmerican Journal of Neuroradiology 26:2595-2601, 200526:2595-2601, 2005
  70. 70. Intravenous ThrombolysisIntravenous Thrombolysis  The first method to restore cerebral perfusion isThe first method to restore cerebral perfusion is clot lysis, with the goal of re-establishing bloodclot lysis, with the goal of re-establishing blood flow to the affected tissue.flow to the affected tissue.  IV thrombolysis rt-PA is the only FDA-IV thrombolysis rt-PA is the only FDA- approved treatment for AIS.approved treatment for AIS.  Fibrinolysis is enhanced powerfully by rt-PA.Fibrinolysis is enhanced powerfully by rt-PA.
  71. 71. Intravenous rTPAIntravenous rTPA administration protocol.administration protocol.  Total dose of rt-PA: 0.9 mg/kg (maximum dose 90 mg)Total dose of rt-PA: 0.9 mg/kg (maximum dose 90 mg)  Give 10% as initial IV bolusGive 10% as initial IV bolus  Infuse remainder over 1 hourInfuse remainder over 1 hour  Admit patient to an ICU or stroke unit for monitoringAdmit patient to an ICU or stroke unit for monitoring  Neurologic assessments: every 15 minutes duringNeurologic assessments: every 15 minutes during infusion, then every 30 minutes for next 6 hours, theninfusion, then every 30 minutes for next 6 hours, then every hour until 24hours after treatment.every hour until 24hours after treatment.
  72. 72. Favorable Outcome vs Treatment Time with IV rTPAFavorable Outcome vs Treatment Time with IV rTPA Protocol limit = 3 hrs ? Benefit ~ 4.5 hrs
  73. 73. Thromboembolism During coilingThromboembolism During coiling  Most feared and frequent complicationMost feared and frequent complication  Reported incidence - Approx. 7%Reported incidence - Approx. 7%  SourcesSourcesof Thromboembolism areof Thromboembolism are - Clots at the aneurysmal neck during or immediately- Clots at the aneurysmal neck during or immediatelyafterafter embolizationembolization - Thrombus forming on catheters during- Thrombus forming on catheters duringprocedures.procedures. - Stenosis of an adjacent artery d/t coil mass- Stenosis of an adjacent artery d/t coil mass or herniationor herniation - Migration of intraaneurysmal- Migration of intraaneurysmalthrombus during coil placement.thrombus during coil placement. - Slow flow d/t vasospasm- Slow flow d/t vasospasm - Rare and unlikely causes are hypercoagulable- Rare and unlikely causes are hypercoagulablestate such asstate such as antiphospholipid antibody syndrome or due to HIT.antiphospholipid antibody syndrome or due to HIT.  Occur more often with wide-necked aneurysms (d/t increasedOccur more often with wide-necked aneurysms (d/t increased exposed surface area of thrombogenic coil material)exposed surface area of thrombogenic coil material)
  74. 74. Current regimen of endovascular managementCurrent regimen of endovascular management  TheThe glycoprotein IIb/IIIa antagonist tirofibanglycoprotein IIb/IIIa antagonist tirofiban (0.4 µg/kg/min bolus(0.4 µg/kg/min bolus for 30 minutes followed by infusion of 0.125 ug/kg/min until thefor 30 minutes followed by infusion of 0.125 ug/kg/min until the thrombus dissolved)thrombus dissolved)  Intraarterial thrombolysis withIntraarterial thrombolysis with urokinase or r- TPAurokinase or r- TPA  increase of intravenous (IV) heparin (measured by ACT).increase of intravenous (IV) heparin (measured by ACT).  Intravenous aspirin.Intravenous aspirin. Coil-related platelet aggregation (white clot) is unlikely to respond toCoil-related platelet aggregation (white clot) is unlikely to respond to fibrinolytics but has a high risk of hemorrhage. (In ISAT), all 5fibrinolytics but has a high risk of hemorrhage. (In ISAT), all 5 patients who had received thrombolytic therapy with tPA to treat apatients who had received thrombolytic therapy with tPA to treat a thromboembolic complication after endovascular treatment rebleedthromboembolic complication after endovascular treatment rebleed and all of these patients died)and all of these patients died)
  75. 75. IntracranialIntracranial StentingStenting  Metallic foreign body such as stent will accumulate thrombus in theMetallic foreign body such as stent will accumulate thrombus in the absence of platelet inhibition.absence of platelet inhibition.  Antiplatelet drugs are important to prevent peri or post-Antiplatelet drugs are important to prevent peri or post- interventional thromboembolic events.interventional thromboembolic events.  Optimal treatment regimens has not been determined but usually:Optimal treatment regimens has not been determined but usually:  Aspirin(250mg/d)+Clopidogrel(75mg/d) – for 3 days pre-procedureAspirin(250mg/d)+Clopidogrel(75mg/d) – for 3 days pre-procedure OrOr  Bolus Clopidogrel(225mg)+Aspirin(250mg) orally- 1day before procedureBolus Clopidogrel(225mg)+Aspirin(250mg) orally- 1day before procedure With these additional dose of Aspirin(250mg)+Clopidogrel(75mg) – on morning of procedureWith these additional dose of Aspirin(250mg)+Clopidogrel(75mg) – on morning of procedure If need to use stent is not pre-planned thanIf need to use stent is not pre-planned than Abciximab ( glycoprotein IIb/IIIa inhibitor) is used (0.25 ug/kgAbciximab ( glycoprotein IIb/IIIa inhibitor) is used (0.25 ug/kg I.V.bolus followedI.V.bolus followed by I.V. infusion of 0.125ug/kg/min for 12 hours)by I.V. infusion of 0.125ug/kg/min for 12 hours) Glycoprotein IIb/IIIa inhibitor are not used routinely during elective stentingGlycoprotein IIb/IIIa inhibitor are not used routinely during elective stenting procedure d/t increased risk of ICH,procedure d/t increased risk of ICH,
  76. 76. Carotid StentingCarotid Stenting  Pre-procedure:Pre-procedure: Double Antiplatelet therapy is routinely given beginning at least 3Double Antiplatelet therapy is routinely given beginning at least 3 days before the proceduredays before the procedure Aspirin 325mg/d+Clopidogrel 75mg/dAspirin 325mg/d+Clopidogrel 75mg/d  During procedure:During procedure: Heparin is given with target clotting time of 250-300secHeparin is given with target clotting time of 250-300sec  Post-procedure:Post-procedure: Aspirin 325mg is continued indefinitely andAspirin 325mg is continued indefinitely and Clopidogrel 75mg/d for at least 6 weeks.Clopidogrel 75mg/d for at least 6 weeks.
  77. 77. Inclusion criteria: for Local ThrombolysisInclusion criteria: for Local Thrombolysis:: a)a) Patients in severe clinical grade on admission withPatients in severe clinical grade on admission with evidence of dural venous sinus thrombosis andevidence of dural venous sinus thrombosis and restrictive venous outflow on cerebral angiogram;restrictive venous outflow on cerebral angiogram; b)b) Patients in clinical grade 3 worsening on heparinPatients in clinical grade 3 worsening on heparin therapy. Restriction to venous outflow was definedtherapy. Restriction to venous outflow was defined as an increase in brain circulation time > 12 s, delayas an increase in brain circulation time > 12 s, delay in the drainage of cortical veins with cortical veinsin the drainage of cortical veins with cortical veins hanging in space.hanging in space. Treatment Options for Venous Thrombosis:
  78. 78. CT Grading for Venous Thrombosis:CT Grading for Venous Thrombosis:  Grade I: no parenchymal change (hyperdenseGrade I: no parenchymal change (hyperdense sinuses, cortical veins, empty delta sign);sinuses, cortical veins, empty delta sign);  Grade II: non hemorrhagic venous infarct withoutGrade II: non hemorrhagic venous infarct without mass effect;mass effect;  Grade III: non-hemorrhagic infarct with mass effect;Grade III: non-hemorrhagic infarct with mass effect;  Grade IV: hemorrhagic venous infarct (maxGrade IV: hemorrhagic venous infarct (max diameter < 3 cm) with no mass effect;diameter < 3 cm) with no mass effect;  Grade V: hemorrhagic venous infarct (max diameterGrade V: hemorrhagic venous infarct (max diameter > 3 cm) with mass effect.> 3 cm) with mass effect.
  79. 79. Local Thrombolysis:Local Thrombolysis:  Femoral /Jugular access was secured and a guiding catheter wasFemoral /Jugular access was secured and a guiding catheter was placed in the jugular bulb.placed in the jugular bulb. Mechanical clot macerationMechanical clot maceration was donewas done with the guidewire following which a microcatheter (waswith the guidewire following which a microcatheter (was navigated and placed in the thrombosed segment of sinusnavigated and placed in the thrombosed segment of sinus confirmed on a selective venogram .confirmed on a selective venogram .  Urokinase infusion ; Bolus dose of 2-6 lacs followed by 60,000Urokinase infusion ; Bolus dose of 2-6 lacs followed by 60,000 to 100,000 units per hour along with periodic check venogram .to 100,000 units per hour along with periodic check venogram . Along with maintenance systemic infusion of Heparin.Along with maintenance systemic infusion of Heparin. OtherOther agents such as streptokinase, altepase or rTPAagents such as streptokinase, altepase or rTPA can be also used.can be also used.  After thrombolysis patient should subjected to oralAfter thrombolysis patient should subjected to oral anticoagulation for six months.anticoagulation for six months.
  80. 80. Low-molecular-weight heparinLow-molecular-weight heparin  PharmacologyPharmacology LMWH, as its name suggests, is a glycosaminoglycan that is approximatelyLMWH, as its name suggests, is a glycosaminoglycan that is approximately one third the molecular weight of UFH. It is derived from UFH through variousone third the molecular weight of UFH. It is derived from UFH through various depolymerization processes. LMWH binds to antithrombin, which in turndepolymerization processes. LMWH binds to antithrombin, which in turn Neutralizes actors Xa and IIa. Because LMWH lacks many of the longer chainsNeutralizes actors Xa and IIa. Because LMWH lacks many of the longer chains required for binding to thrombin, it has less ability to neutralize thrombinrequired for binding to thrombin, it has less ability to neutralize thrombin relativeto its ability to neutralize factor Xa LMWH also has less nonspecificrelativeto its ability to neutralize factor Xa LMWH also has less nonspecific binding to other proteins. There is greater bioavailability with more predictablebinding to other proteins. There is greater bioavailability with more predictable pharmacokinetics that eliminates the need for monitoring. The smaller size alsopharmacokinetics that eliminates the need for monitoring. The smaller size also allows for enhanced subcutaneous absorption when compared with UFH.allows for enhanced subcutaneous absorption when compared with UFH.
  81. 81.  Three LMWH preparations are currentlyThree LMWH preparations are currently approved for use in the United States: (1)approved for use in the United States: (1) enoxaparin, (2) dalteparin, and (3) tinzaparin.enoxaparin, (2) dalteparin, and (3) tinzaparin.  They are all administered subcutaneously atThey are all administered subcutaneously at intervals of either once or twice daily for bothintervals of either once or twice daily for both prophylaxis and treatment doses.prophylaxis and treatment doses.
  82. 82. Few Experiences ofFew Experiences of ThrombolysisThrombolysis
  83. 83.  Vickey, 25 Yrs male patient presented with 12Vickey, 25 Yrs male patient presented with 12thth day H/O severe headache with right sidedday H/O severe headache with right sided hemiplegia.hemiplegia.  MRI shows thrombosis of the superior sagittal ,MRI shows thrombosis of the superior sagittal , left transverse, left sigmoid sinuses and corticalleft transverse, left sigmoid sinuses and cortical veins in the fronto-parietal regions with e/oveins in the fronto-parietal regions with e/o haemorrhagic infarct in the left cerebralhaemorrhagic infarct in the left cerebral hemisphere with mass effect( Grade –V).hemisphere with mass effect( Grade –V).
  84. 84.  Sashi Srivastava, 64 yrs /FSashi Srivastava, 64 yrs /F  In a follow up case of MRD with infra-renalIn a follow up case of MRD with infra-renal aortic abdominal and bilateral renal arteryaortic abdominal and bilateral renal artery thrombosis, renal angiogram shows fillingthrombosis, renal angiogram shows filling defects in the right Renal artery .defects in the right Renal artery .  Initially Renal angioplasty was done. FollowingInitially Renal angioplasty was done. Following angioplasty few thrombi are seem to extendsangioplasty few thrombi are seem to extends into the segmental branches and causinginto the segmental branches and causing blockage. So Thrombolysis was plane to dissolveblockage. So Thrombolysis was plane to dissolve the run-out thrombi with urokinase.the run-out thrombi with urokinase.
  85. 85.  Rakesh ,34yrs/MRakesh ,34yrs/M  Left SFA pseudoaneurysm with Covered stentLeft SFA pseudoaneurysm with Covered stent placement.placement.  Pre operative antiplatelets with post procedurePre operative antiplatelets with post procedure heparin, Tirofiban followed by aspirin andheparin, Tirofiban followed by aspirin and clopidogrel were used.clopidogrel were used.
  86. 86.  IAT may be a treatment option for selected patients.IAT may be a treatment option for selected patients.  Possible selection criteria includePossible selection criteria include  presentation between 3 and 6 hours from symptom onset,presentation between 3 and 6 hours from symptom onset,  major cerebral artery occlusion,major cerebral artery occlusion,  severe neurologic deficits,severe neurologic deficits,  high risk of systemic hemorrhage with IV rt-PA (eg, recent surgery).high risk of systemic hemorrhage with IV rt-PA (eg, recent surgery).  The MERCI (Mechanical Embolus Removal in Cerebral Ischemia)The MERCI (Mechanical Embolus Removal in Cerebral Ischemia) retrievalretrieval  system .system .  Has been FDA-approved for recanalizing acutely occluded cerebralHas been FDA-approved for recanalizing acutely occluded cerebral arteries.arteries.  In the Multi-MERCI study, patients who did not improve immediatelyIn the Multi-MERCI study, patients who did not improve immediately after IV rt-PA underwent mechanical embolectomy within 8 hours ofafter IV rt-PA underwent mechanical embolectomy within 8 hours of symptom onset.symptom onset.  Partial or complete recanalization occurred in 74% of patients,Partial or complete recanalization occurred in 74% of patients,  with a symptomatic intracerebral hemorrhage (sICH) rate of 6.7% .with a symptomatic intracerebral hemorrhage (sICH) rate of 6.7% .  Mechanical embolectomy with the MERCI retriever may be a feasible andMechanical embolectomy with the MERCI retriever may be a feasible and safe option for patients after IV rt-PA.safe option for patients after IV rt-PA.
  87. 87.  Penumbra stroke systemPenumbra stroke system  This device combines two methods of clot extraction,This device combines two methods of clot extraction, aspiration and mechanical extraction.aspiration and mechanical extraction.  First the clot is aspirated; then a thrombus removal ringFirst the clot is aspirated; then a thrombus removal ring can be used if necessary to remove remaining clot.can be used if necessary to remove remaining clot.  successful recanalizing 82%successful recanalizing 82%  Bridging therapy.Bridging therapy.  0.6 mg/kg IV rt-PA followed by IAT with IA rt-PA (up0.6 mg/kg IV rt-PA followed by IAT with IA rt-PA (up to 20 mg)to 20 mg)  achieved a higher recanalization rateachieved a higher recanalization rate
  88. 88. Criteria for thrombolysis with rTPACriteria for thrombolysis with rTPA  Inclusion criteriaInclusion criteria  Clinical signs and symptoms consistent with ischemic strokeClinical signs and symptoms consistent with ischemic stroke  Patient last seen normal within 3 hoursPatient last seen normal within 3 hours  Measurable neurologic deficitMeasurable neurologic deficit  Exclusion criteriaExclusion criteria  Any hemorrhage on neuroimaging (CT or MRI)Any hemorrhage on neuroimaging (CT or MRI)  Symptoms suggestive of subarachnoid hemorrhageSymptoms suggestive of subarachnoid hemorrhage  Seizure at stroke onset that is thought to contribute to neurologicSeizure at stroke onset that is thought to contribute to neurologic deficitdeficit  Hypodensity greater than one third cerebral hemisphere on CTHypodensity greater than one third cerebral hemisphere on CT  SBP greater than 185 mm Hg or DBP greater than 110 mm HgSBP greater than 185 mm Hg or DBP greater than 110 mm Hg  International normalized ratio (INR) greater than 1.7International normalized ratio (INR) greater than 1.7
  89. 89. Ischemic Stroke Treatment –Ischemic Stroke Treatment – 20062006  IV tissue plasminogen activator (tPA)IV tissue plasminogen activator (tPA)  –– Only FDA-approved acute stroke drugOnly FDA-approved acute stroke drug  –– 3 hour treatment window3 hour treatment window  MERCI - Concentric clot retrieval deviceMERCI - Concentric clot retrieval device  –– Rescue therapy - approved 2004Rescue therapy - approved 2004  –– Device approval (not outcomes-based)Device approval (not outcomes-based)  Off label approachesOff label approaches  –– IV tPA after 3 hoursIV tPA after 3 hours  –– IV-IA tPA sequential strategiesIV-IA tPA sequential strategies  –– IA tPA, clot angioplasty / fragmentationIA tPA, clot angioplasty / fragmentation  –– Ultrasound-assisted tPA lysisUltrasound-assisted tPA lysis
  90. 90. rt-PA Trials: NINDSrt-PA Trials: NINDS  Acute stroke - 624 patients.Acute stroke - 624 patients.  Treat within 3 hrs.Treat within 3 hrs.  Intravenous 0.9 mg/kg rt-PA vs placebo.Intravenous 0.9 mg/kg rt-PA vs placebo.  Hemorrhage: 6.4% tPA; 0.6% placebo.Hemorrhage: 6.4% tPA; 0.6% placebo.  Neurologic recovery better with tPA: 30% moreNeurologic recovery better with tPA: 30% more like to have minimal or no disability.like to have minimal or no disability. First proven / approved treatment for strokeFirst proven / approved treatment for stroke
  91. 91. Limitations of tPALimitations of tPA  Only 4% of acute strokes receive tPAOnly 4% of acute strokes receive tPA (Kleindorfer et al, Stroke 2004; 35: e27-e29)(Kleindorfer et al, Stroke 2004; 35: e27-e29)  Only 22% of patients present within 3 hoursOnly 22% of patients present within 3 hours 􀂃􀂃 51% of these ineligible due to51% of these ineligible due to  •• Mild severityMild severity  •• Medical or surgical historyMedical or surgical history  •• Blood testsBlood tests  Sustained recanalization only 13%Sustained recanalization only 13% (Alexandrov et al, NEJM 2004; 351: 2170-8)(Alexandrov et al, NEJM 2004; 351: 2170-8)  Concern for hemorrhageConcern for hemorrhage  tPA potentiates apoptotic injurytPA potentiates apoptotic injury (Liu et al, Nature Med 2004; 10:1379-83)(Liu et al, Nature Med 2004; 10:1379-83)
  92. 92. PROACT II IA Lysis TrialPROACT II IA Lysis Trial Baseline 24 hours 8 days Baseline 60 minutes 120 minutes 9mg IA Prourokinase
  93. 93. Desmoteplase Trials: DEDAS / DIASDesmoteplase Trials: DEDAS / DIAS Trial Overview:Trial Overview:  Double blind, randomized, placebo controlled trialsDouble blind, randomized, placebo controlled trials  IV delivery, 3-9 hour time windowIV delivery, 3-9 hour time window  Plasminogen activator – fromPlasminogen activator – from vampire bat salivavampire bat saliva  Selection based on PWI-DWI MismatchSelection based on PWI-DWI Mismatch MRI Inclusion:MRI Inclusion:  PWI defect at least 2 cm AND ~20% larger than DWIPWI defect at least 2 cm AND ~20% larger than DWI  PWI should be obvious, even visible on raw imagesPWI should be obvious, even visible on raw images MRI Exclusion:MRI Exclusion:  DWI > 1/3 MCADWI > 1/3 MCA  MRA: ICA occlusionMRA: ICA occlusion
  94. 94. Desmoteplase – DIAS ResultsDesmoteplase – DIAS Results
  95. 95. Mechanical Thrombolysis devicesMechanical Thrombolysis devices  mechanical thrombolysis potentially extends the treatment window because they actmechanical thrombolysis potentially extends the treatment window because they act promptly at the site of the thrombus.promptly at the site of the thrombus.  The devices can retrieve large clots that pharmaceutical agents may not successfullyThe devices can retrieve large clots that pharmaceutical agents may not successfully lyse.lyse.  Patients treated with IV tPA may be considered for treatment of residual clot withPatients treated with IV tPA may be considered for treatment of residual clot with some of these devices.some of these devices.  suction-creating saline jets,suction-creating saline jets,  laser energy, ultrasound,laser energy, ultrasound,  a corkscrew apparatus to treat strokes.a corkscrew apparatus to treat strokes. The AngioJet systemThe AngioJet system  uses saline jets that are directed back into the catheter to create a low-pressure zoneuses saline jets that are directed back into the catheter to create a low-pressure zone around the catheter tip, inducing suction .around the catheter tip, inducing suction .  The clot is pulled into the exhaust lumen and removed from the vessel. Although USThe clot is pulled into the exhaust lumen and removed from the vessel. Although US Food and Drug Administration (FDA) has approved this device for use inFood and Drug Administration (FDA) has approved this device for use in arteriovenous dialysis grafts and fistulae and for the treatment of coronary arteries,arteriovenous dialysis grafts and fistulae and for the treatment of coronary arteries, saphenous vein grafts, and peripheral vessels, clinical trials for the treatment of acutesaphenous vein grafts, and peripheral vessels, clinical trials for the treatment of acute stroke are no longer in progress.stroke are no longer in progress. Most devices are used in cerebral vessels that 2-5 mm
  96. 96. The Latis laser deviceThe Latis laser device  used laser energy to ablate clots.used laser energy to ablate clots.  Arteries 2-5 mm in diameter could be treated, includingArteries 2-5 mm in diameter could be treated, including the ICA, M1 or M2 branch of the MCA, A1 branch ofthe ICA, M1 or M2 branch of the MCA, A1 branch of the anterior cerebral artery (ACA), basilar artery,the anterior cerebral artery (ACA), basilar artery, posterior cerebral artery (PCA), and vertebralposterior cerebral artery (PCA), and vertebral  Patients could receive treatment as late as 8 hours afterPatients could receive treatment as late as 8 hours after symptom onset in the anterior circulation and within 24symptom onset in the anterior circulation and within 24 hours in the posterior circulation.hours in the posterior circulation.
  97. 97. Endovascular Photo AcousticEndovascular Photo Acoustic Recanalization (EPAR)Recanalization (EPAR)  A laser power source generated energy for the system.A laser power source generated energy for the system.  The energy was delivered by means of fiberoptics to the tip ofThe energy was delivered by means of fiberoptics to the tip of the catheter at the treatment site.the catheter at the treatment site.  Absorption of laser light by darkly pigmented materials (ie, theAbsorption of laser light by darkly pigmented materials (ie, the clot) occurred inside the 1-mm catheter tipclot) occurred inside the 1-mm catheter tip  the system was designed to minimize scattering of laser light.the system was designed to minimize scattering of laser light.  Absorption converted photo energy to acoustic energy, whichAbsorption converted photo energy to acoustic energy, which then emulsified the clot inside the catheter tipthen emulsified the clot inside the catheter tip
  98. 98. EKOS ultrasound( the UltrasoundEKOS ultrasound( the Ultrasound Thrombolytic Infusion Catheter)Thrombolytic Infusion Catheter)  combines the use of a distal ultrasound transducer with infusion of acombines the use of a distal ultrasound transducer with infusion of a thrombolytic agent through the microcatheter.thrombolytic agent through the microcatheter.  Ultrasound changes the structure of the clot to temporarily increase itsUltrasound changes the structure of the clot to temporarily increase its permeability while providing an acoustic pressure gradient to move the drugpermeability while providing an acoustic pressure gradient to move the drug into the clot to speed its dissolution.into the clot to speed its dissolution.  The EKOS catheter is placed in the proximal portion of the clot.The EKOS catheter is placed in the proximal portion of the clot.  After a 2-mg bolus of tPA was injected through the catheter,After a 2-mg bolus of tPA was injected through the catheter,  the patient received a continuous infusion of IA tPA 0.3 mg/min to athe patient received a continuous infusion of IA tPA 0.3 mg/min to a maximum of 20 mg and simultaneous ultrasound transmission for as long asmaximum of 20 mg and simultaneous ultrasound transmission for as long as 60 minutes.60 minutes.  One patient was treated with a total of 4 units of recombinant reteplaseOne patient was treated with a total of 4 units of recombinant reteplase (Retavase) hand-injected over 60 minutes.(Retavase) hand-injected over 60 minutes.
  99. 99. Penumbra systemPenumbra system  The Penumbra system (Penumbra, Inc.) provides a dual approach to clotThe Penumbra system (Penumbra, Inc.) provides a dual approach to clot extraction, using aspiration followed by clot retrieval with a "ring" device, ifextraction, using aspiration followed by clot retrieval with a "ring" device, if needed.needed. Mechanical Embolus Removal in Cerebral Ischemia (MERCI)Mechanical Embolus Removal in Cerebral Ischemia (MERCI)  a corkscrew-like apparatus, "to remove blood clots from the brain in patientsa corkscrew-like apparatus, "to remove blood clots from the brain in patients experiencing an ischemic stroke" .experiencing an ischemic stroke" .  The corkscrew itself resides in the catheter tip, which shields it from the wallThe corkscrew itself resides in the catheter tip, which shields it from the wall of the vessel until it is ready to be burrowed into the clot. Once lodged in theof the vessel until it is ready to be burrowed into the clot. Once lodged in the clot, the device and clot are withdrawn from the vesselclot, the device and clot are withdrawn from the vessel Snarelike devicesSnarelike devices Snares, such as the Neuronet snare (Guidant Endovascular, Santa Clara, CA),Snares, such as the Neuronet snare (Guidant Endovascular, Santa Clara, CA), have been developed specifically for use in the treatment of strokes.have been developed specifically for use in the treatment of strokes. These devices are simple in design and do not require the clot to be amenableThese devices are simple in design and do not require the clot to be amenable to emulsification.to emulsification.
  100. 100. X-Sizer deviceX-Sizer device  a device with small, moving blades at the catheter tip.a device with small, moving blades at the catheter tip.  This device, the X-Sizer device (EndiCor Medical, San Clemente,This device, the X-Sizer device (EndiCor Medical, San Clemente, CA), can be used to excise the thrombus and aspirate it.CA), can be used to excise the thrombus and aspirate it.  The device was being evaluated in randomized studies ofThe device was being evaluated in randomized studies of coronary vessels and in a registry of patients with acutecoronary vessels and in a registry of patients with acute myocardial infarction.myocardial infarction.  Although the manufacturer had modified the device for use inAlthough the manufacturer had modified the device for use in cerebral vessels, a safety and feasibility study was indefinitelycerebral vessels, a safety and feasibility study was indefinitely suspended after only 1 patient was treated with the device insuspended after only 1 patient was treated with the device in Europe.Europe.
  101. 101. Suction thrombectomySuction thrombectomy  This method of mechanical thrombolysis is one of the simplest.This method of mechanical thrombolysis is one of the simplest.  In this readily available technique, suction is applied with a syringe to removeIn this readily available technique, suction is applied with a syringe to remove thrombus in the ICA.thrombus in the ICA.  It requires no other devices.It requires no other devices.  A catheter with a large inner diameter (Brite Tip; Cordis Corporation, Miami,A catheter with a large inner diameter (Brite Tip; Cordis Corporation, Miami, FL) was placed in the symptomatic vessel and navigated over a guidewire intoFL) was placed in the symptomatic vessel and navigated over a guidewire into the thrombus.the thrombus.  A 60-mL syringe was used to aspirate the thrombus.A 60-mL syringe was used to aspirate the thrombus.  Each patient required angioplasty and stenting of carotid bifurcation stenosisEach patient required angioplasty and stenting of carotid bifurcation stenosis and received daily aspirin and ticlopidine after the procedure. Noand received daily aspirin and ticlopidine after the procedure. No complications occurred.complications occurred.
  102. 102. Summary: Acute Stroke ImagingSummary: Acute Stroke Imaging  PhysiologyPhysiology: importance collaterals: importance collaterals ––Growing role for perfusion assessmentGrowing role for perfusion assessment  tPAtPA: guidelines & limitations: guidelines & limitations  Signs on CT & MRSigns on CT & MR: follow physiology: follow physiology  Stroke trialsStroke trials: PWI-DWI mismatch: PWI-DWI mismatch ––Treat based on physiology, not timeTreat based on physiology, not time  ProtocolsProtocols: should be fast and comprehensive: should be fast and comprehensive

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