Moore Chapter: Thrombolysis

Thrombolytic TherapyThrombolytic Therapy
for Vascular Diseasefor Vascular Disease
July 16, 2012July 16, 2012

HistoryHistory
 Morgagni (1761) noted blood forms clotsMorgagni (1761) noted blood forms clots
post-mortem, followed by reliqueficationpost-mortem, followed by reliquefication
 Dastre (1893) coined term “fibrinolysis” toDastre (1893) coined term “fibrinolysis” to
describe disappearance of fibrin from dogsdescribe disappearance of fibrin from dogs
who repeatedly hemorrhagedwho repeatedly hemorrhaged
 Morawitz (1906) noted post-mortem bloodMorawitz (1906) noted post-mortem blood
destroys fibrinogen and fibrin in normaldestroys fibrinogen and fibrin in normal
bloodblood

The Fibrinolytic SystemThe Fibrinolytic System
 Astrup (1958) proposed the concept ofAstrup (1958) proposed the concept of
“dynamic equilibrium”“dynamic equilibrium”
 Delicate balance of fibrinolysis and fibrinDelicate balance of fibrinolysis and fibrin
deposition throughout bodydeposition throughout body
 Limited activation of coagulation systemLimited activation of coagulation system
 Feedback loop to prevent systemicFeedback loop to prevent systemic
fibrinolysisfibrinolysis
 Inhibitors at activator levelInhibitors at activator level
 Specific inhibitors of plasminSpecific inhibitors of plasmin

 Final pathwayFinal pathway
 Plasminogen > PlasminPlasminogen > Plasmin
 PlasminogenPlasminogen
 Produced by liverProduced by liver
 Has a N and C terminalHas a N and C terminal
 4 types found in plasma4 types found in plasma
 Differences in N terminalDifferences in N terminal
 Degree of glycosylationDegree of glycosylation
 2 Main forms:2 Main forms:
 Glu-plasminogenGlu-plasminogen
 High concentrations found in plasmaHigh concentrations found in plasma
 Lys-plasminogenLys-plasminogen
 Converted through proteolysis of Glu-plasminogenConverted through proteolysis of Glu-plasminogen
 High affinity for fibrinHigh affinity for fibrin
 High concentrations found in thrombusHigh concentrations found in thrombus

 PlasminPlasmin
 Nonspecific proteaseNonspecific protease
 Targets factors V, VIII, vWF, kininogen,Targets factors V, VIII, vWF, kininogen,
prekallikrein, fibronectin, collagen, lamininprekallikrein, fibronectin, collagen, laminin

Fibrinolytic AgentsFibrinolytic Agents
 Indirect ActivatorsIndirect Activators
 Fibrinolysis without direct activity on plasminogenFibrinolysis without direct activity on plasminogen
 MOA variableMOA variable
 Unproven clinical valueUnproven clinical value
 Multiple agentsMultiple agents
 EpinephrineEpinephrine
 Nicotinic AcidNicotinic Acid
 DDAVP – clinically insignificant compared to its procoagulantDDAVP – clinically insignificant compared to its procoagulant
effectseffects
 Steroids (Stanozolol)**Steroids (Stanozolol)**
 Phenoformin**Phenoformin**

Direct Thrombolytic AgentsDirect Thrombolytic Agents
 First-Generation Thrombolytic DrugsFirst-Generation Thrombolytic Drugs
 Not Fibrin SpecificNot Fibrin Specific
 Plasminogen steal – activates circulating plasminogen,Plasminogen steal – activates circulating plasminogen,
paradoxical decrease of clot lysisparadoxical decrease of clot lysis
 Efficacy improved with administration of plasminogenEfficacy improved with administration of plasminogen
 Streptokinase, UrokinaseStreptokinase, Urokinase
 Second-Generation Thrombolytic DrugsSecond-Generation Thrombolytic Drugs
 Fibrin SpecificFibrin Specific
 Avoids Systemic Thrombolytic StateAvoids Systemic Thrombolytic State
 Tissue Plasminogen Activator, Pro-urokinaseTissue Plasminogen Activator, Pro-urokinase
 Third-Generation Thrombolytic DrugsThird-Generation Thrombolytic Drugs
 Reteplase, Tenecteplase, StaphylokinaseReteplase, Tenecteplase, Staphylokinase

StreptokinaseStreptokinase
 Produced fromProduced from ββ-hemolytic streptococci-hemolytic streptococci
 Presence of circulating AbPresence of circulating Ab
 ComplicationsComplications
 FeverFever
 Allergic ReactionsAllergic Reactions
 TachyphylaxisTachyphylaxis
 MOAMOA
 Requires plasminogen as cofactorRequires plasminogen as cofactor
 Converts uncomplexed plasminogen to plasminConverts uncomplexed plasminogen to plasmin
 Precise control of thrombolysis difficultPrecise control of thrombolysis difficult
 Varied dose response per patientVaried dose response per patient
 2 separate half lifes: 16 and 83 minutes2 separate half lifes: 16 and 83 minutes
 Standardized dosagesStandardized dosages
 Bleeding complications in 15-20% of patientsBleeding complications in 15-20% of patients
 Only thrombolytic approved by FDA for arterial/venous thrombosisOnly thrombolytic approved by FDA for arterial/venous thrombosis
 Infrequently usedInfrequently used

UrokinaseUrokinase
 Produced by renal tubular cellsProduced by renal tubular cells
 Dose-dependent responseDose-dependent response
 Direct, specific plasminogen activatorDirect, specific plasminogen activator
 Lack of circulating antibodiesLack of circulating antibodies
 Febrile responses from interleukinsFebrile responses from interleukins
 Results similar to streptokinaseResults similar to streptokinase
 Bleeding in 5-10% of patientsBleeding in 5-10% of patients
 Significantly more expensiveSignificantly more expensive
 Taken off market from 1998-2002Taken off market from 1998-2002
 Deviated from FDA “good manufacturing guidelines”Deviated from FDA “good manufacturing guidelines”
 Approved for use in PEApproved for use in PE
 Half life 14 minutesHalf life 14 minutes

Tissue Plasminogen Activator (t-PA)Tissue Plasminogen Activator (t-PA)
 Originates from vascular endotheliumOriginates from vascular endothelium
 Tissue concentration correlates with vascularityTissue concentration correlates with vascularity
 SourcesSources
 Bowes melanoma cell lineBowes melanoma cell line
 Recombinant DNA technology (rt-PA)Recombinant DNA technology (rt-PA)
 MOAMOA
 Direct plasminogen activatorDirect plasminogen activator
 High affinity for thrombus-bound fibrinHigh affinity for thrombus-bound fibrin
 Inhibits platelet aggregation by inhibiting GpIb and vWFInhibits platelet aggregation by inhibiting GpIb and vWF
 Half life 4-7 minutesHalf life 4-7 minutes
 Recommended dosage 0.05 mg/kg/hrRecommended dosage 0.05 mg/kg/hr
 RCT failed to demonstrate significant difference inRCT failed to demonstrate significant difference in
efficacy from other agentsefficacy from other agents
 Similar rates of bleeding complicationsSimilar rates of bleeding complications

Pro-urokinase (Saruplase)Pro-urokinase (Saruplase)
 Recombinant urokinaseRecombinant urokinase
 MOAMOA
 Direct plasminogen activatorDirect plasminogen activator
 High affinity for Lys-plasminogenHigh affinity for Lys-plasminogen
 Most trials in acute MIMost trials in acute MI
 Higher incidence of intracranial hemorrhageHigher incidence of intracranial hemorrhage
 Prolonged half-lifeProlonged half-life
 Increased risk of bleedingIncreased risk of bleeding
 PROACT II StudyPROACT II Study
 10% (vs. 2% of control) intracranial hemorrhage with10% (vs. 2% of control) intracranial hemorrhage with
urokinase for acute ischemic strokeurokinase for acute ischemic stroke

ReteplaseReteplase
 Decreased endothelial bindingDecreased endothelial binding
 Increased circulating levelsIncreased circulating levels
 Decreased fibrin bindingDecreased fibrin binding
 Penetrates clot better with faster lysisPenetrates clot better with faster lysis
 Dependent on available plasminogenDependent on available plasminogen
 Less effective for large clot burden or old thrombusLess effective for large clot burden or old thrombus
 Half life of 14-18 minutesHalf life of 14-18 minutes
 Addition of GpIIB/IIIa inhibitors may increase efficacyAddition of GpIIB/IIIa inhibitors may increase efficacy
 INJECT and GUSTO III TrialsINJECT and GUSTO III Trials
 Compared reteplase to alteplase for MICompared reteplase to alteplase for MI
 Reteplase showed increased flow rates (thrombolysis)Reteplase showed increased flow rates (thrombolysis)
 No difference in mortalityNo difference in mortality

TenecteplaseTenecteplase
 TPA mutantTPA mutant
 High fibrin selectivityHigh fibrin selectivity
 Resistant to plasminogen activator inhibitorsResistant to plasminogen activator inhibitors
 Very effective in arterial thrombosis andVery effective in arterial thrombosis and
 Case series for peripheral arterial thrombolysisCase series for peripheral arterial thrombolysis
(48 patients)(48 patients)
 73% had complete lysis73% had complete lysis
 No deaths, bleeding, or embolic eventsNo deaths, bleeding, or embolic events
 Half life of 15-19 minutesHalf life of 15-19 minutes

StaphylokinaseStaphylokinase
 Plasminogen activator from S. aureusPlasminogen activator from S. aureus
 Activates thrombus bound plasminogenActivates thrombus bound plasminogen
 Minimal systemic effectsMinimal systemic effects
 Activity confined to thrombus through rapidActivity confined to thrombus through rapid
inactivation of circulating plasmininactivation of circulating plasmin
 High antigenicityHigh antigenicity

ImmunofibrinolysisImmunofibrinolysis
 Monoclonal anti-fibrin antibodies bondedMonoclonal anti-fibrin antibodies bonded
to urokinase or streptokinaseto urokinase or streptokinase
 Increased fibrin selectivityIncreased fibrin selectivity
 No cross-reactivity with fibrinogenNo cross-reactivity with fibrinogen
 Clinical application remains to beClinical application remains to be
determineddetermined

Summary of ThrombolyticsSummary of Thrombolytics
 Most experience with streptokinase,Most experience with streptokinase,
urokinase, and TPAurokinase, and TPA
 Streptokinase less desirable for peripheralStreptokinase less desirable for peripheral
thrombosis due to complex mechanismthrombosis due to complex mechanism
and dosingand dosing
 Similar rates of bleeding due to interactionSimilar rates of bleeding due to interaction
with hemostatic plugs in addition towith hemostatic plugs in addition to
pathological thrombuspathological thrombus
 Induction of systemic fibrinolysisInduction of systemic fibrinolysis

Thrombolytic AgentsThrombolytic Agents

Application of ThrombolyticsApplication of Thrombolytics
 SystemicSystemic
 Bleeding complications outweighBleeding complications outweigh
benefitsbenefits
 Intra-arterialIntra-arterial
 Prevention of systemic complicationsPrevention of systemic complications
 Useful for peripheral arterial and graftUseful for peripheral arterial and graft
occlusionocclusion
 Intra-operativeIntra-operative

Contraindications of SystemicContraindications of Systemic
ThrombolyticsThrombolytics

Indications for SystemicIndications for Systemic
 Pulmonary EmbolismPulmonary Embolism
 Deep Venous ThrombosisDeep Venous Thrombosis
 Axillary Vein ThrombosisAxillary Vein Thrombosis
 Superior Vena Cava ThrombosisSuperior Vena Cava Thrombosis

 Urokinase Pulmonary Embolism Trial – Phase IUrokinase Pulmonary Embolism Trial – Phase I
 Compared treatment with urokinase vs. heparinCompared treatment with urokinase vs. heparin
 Urokinase therapy resulted in accelerated resolution of PEUrokinase therapy resulted in accelerated resolution of PE
 No differences in mortality or recurrence ratesNo differences in mortality or recurrence rates
 Improved responseImproved response
 <50 yo<50 yo
 PE <48 hoursPE <48 hours
 Large embolusLarge embolus
 Cardiogenic ShockCardiogenic Shock
 7 yr F/U – Thrombolysis group had better preservation of normal pulmonary7 yr F/U – Thrombolysis group had better preservation of normal pulmonary
vasculature and higher pulmonary capillary blood volumesvasculature and higher pulmonary capillary blood volumes
 Urokinase Pulmonary Embolism Trial – Phase IUrokinase Pulmonary Embolism Trial – Phase I
 Compared treatment with 12h urokinase, 24h urokinase, and 24hCompared treatment with 12h urokinase, 24h urokinase, and 24h
streptokinasestreptokinase
 No difference in lytic resultsNo difference in lytic results
 No benefit to 24h urokinaseNo benefit to 24h urokinase

 FDA-Approved ThrombolyticsFDA-Approved Thrombolytics
 t-PA (100mg over 2hrs)t-PA (100mg over 2hrs)
 UrokinaseUrokinase
 IndicationsIndications
 Documented PEDocumented PE
 Evidence of Hemodynamic CompromiseEvidence of Hemodynamic Compromise
 No Absolute Contraindication to ThrombolysisNo Absolute Contraindication to Thrombolysis
 Anticoagulation Recommended forAnticoagulation Recommended for
Hemodynamically Stable PatientsHemodynamically Stable Patients

 GoalGoal
 Prevention of PEPrevention of PE
 Prevention of post-phlebitic syndromePrevention of post-phlebitic syndrome
 Anticoagulation ineffective therapyAnticoagulation ineffective therapy
Complete clotComplete clot
lysislysis
Normal valveNormal valve
function @ 6function @ 6
monthsmonths
PE/mortalityPE/mortality
BleedingBleeding
complicationcomplication
HeparinHeparin 4%4% 7%7% SameSame 4%4%
LyticsLytics 35%35% 50%50% SameSame 17%17%

 Efficacy of Mode of AdministrationEfficacy of Mode of Administration
 Pedal infusion: 20% successPedal infusion: 20% success
 Catheter directed: 83% success, complete lysis 33%Catheter directed: 83% success, complete lysis 33%
 No evidence of improved lysis with systemicNo evidence of improved lysis with systemic
administrationadministration

 Contraindications to ThrombolysisContraindications to Thrombolysis
 > 5 days old> 5 days old
 Post-op/post-partumPost-op/post-partum
 Trauma patientsTrauma patients
 Spinal injury/recent CVASpinal injury/recent CVA
 Recurrent DVTsRecurrent DVTs
 Already damaged valvesAlready damaged valves
 Distal ThrombusDistal Thrombus
 Little benefitLittle benefit

 Indications for ThrombolysisIndications for Thrombolysis
 No ContraindicationsNo Contraindications
 First IncidenceFirst Incidence
 Treatment Initiated < 5 Days of SymptomsTreatment Initiated < 5 Days of Symptoms
 Phlegmasia Cerulea DolensPhlegmasia Cerulea Dolens
 Massive ilio-femoral thrombus causing limb threateningMassive ilio-femoral thrombus causing limb threatening
venous outflow obstructionvenous outflow obstruction
 20-40% Mortality Rate20-40% Mortality Rate
 High Amputation RiskHigh Amputation Risk
 Venous thrombectomy burdened by re-thrombosisVenous thrombectomy burdened by re-thrombosis

 Axillary Vein ThrombosisAxillary Vein Thrombosis
 AKA Effort ThrombosisAKA Effort Thrombosis
 Younger PatientsYounger Patients
 Poor Resolution with AnticoagulationPoor Resolution with Anticoagulation
 Thrombolysis Indicated for Short SymptomThrombolysis Indicated for Short Symptom
DurationDuration
 Systemic and Local Infusion Equally EffectiveSystemic and Local Infusion Equally Effective
 Post-Treatment Evaluation for TOSPost-Treatment Evaluation for TOS
 Venography performed with Arm Abducted andVenography performed with Arm Abducted and
Externally RotatedExternally Rotated

 Superior Vena Cava ThrombosisSuperior Vena Cava Thrombosis
 Mediastinal Etiologies– Poor ResponseMediastinal Etiologies– Poor Response
 CancerCancer
 TraumaTrauma
 InfectionInfection
 Catheter-Induced ThrombosisCatheter-Induced Thrombosis
 Response Dependent on Duration of SymptomsResponse Dependent on Duration of Symptoms
 Idiopathic SVC Thrombosis (4%)Idiopathic SVC Thrombosis (4%)
 Good ResponseGood Response

Complications of Systemic TherapyComplications of Systemic Therapy
 Intracranial HemorrhageIntracranial Hemorrhage
 1% Incidence1% Incidence
 Time to Onset 3-36 hrsTime to Onset 3-36 hrs
 66% Mortality66% Mortality
 Risk FactorsRisk Factors
 Oral Anticoagulation Prior to AdmissionOral Anticoagulation Prior to Admission
 <70kg<70kg
 >65yo>65yo
 Higher doses of tPAHigher doses of tPA
 Protective Effect of Concomitant Beta-Blockade?Protective Effect of Concomitant Beta-Blockade?

Complications of Systemic TherapyComplications of Systemic Therapy
 Life-Threatening HemorrhageLife-Threatening Hemorrhage
 7-45% Incidence7-45% Incidence
 Risk FactorsRisk Factors
 Increased Number of Invasive Procedures during TherapyIncreased Number of Invasive Procedures during Therapy
 Increased Duration of TherapyIncreased Duration of Therapy
 Patients with Lower Fibrinogen LevelsPatients with Lower Fibrinogen Levels
 Bleeding Occurs During Lap Period btw Cessation ofBleeding Occurs During Lap Period btw Cessation of
Lysis and Initiation of HeparinLysis and Initiation of Heparin
 TreatmentTreatment
 FFPFFP
 CryoprecipitateCryoprecipitate

Application of Intra-arterialApplication of Intra-arterial
 Thrombosis after PTAThrombosis after PTA
 Native Vessel OcclusionNative Vessel Occlusion
 Acute Graft OcclusionAcute Graft Occlusion
 Lower Extremity IschemiaLower Extremity Ischemia
 Hemodialysis AccessHemodialysis Access
 Acute StrokeAcute Stroke

Patient Selection of Intra-arterialPatient Selection of Intra-arterial
 Low doses of thrombolytic administered close toLow doses of thrombolytic administered close to
thrombusthrombus
 Minimizes systemic effectsMinimizes systemic effects
 Dissolution of thrombus requires 12-72 hrs of therapyDissolution of thrombus requires 12-72 hrs of therapy
 Ensure viability of ischemic tissueEnsure viability of ischemic tissue
 Shouldn’t do in patients with neurologic demiseShouldn’t do in patients with neurologic demise
 IndicationsIndications
 High surgical risk of morbidity/mortalityHigh surgical risk of morbidity/mortality
 Poor surgical outcomePoor surgical outcome
 Multiple previous surgeriesMultiple previous surgeries
 Adjunct to surgeryAdjunct to surgery

Patient Selection of Intra-arterialPatient Selection of Intra-arterial
 <14 d of acute ischemia<14 d of acute ischemia
 71% successful lysis71% successful lysis
 Adjuntive procedures required in 72%Adjuntive procedures required in 72%
 Less likely in UELess likely in UE
 Equal response for prosthetic grafts (78%) andEqual response for prosthetic grafts (78%) and
native arteries (72%)native arteries (72%)
 Vein grafts lower response rates (53%)Vein grafts lower response rates (53%)
 Decreased response in diabeticsDecreased response in diabetics
 Predictors of successPredictors of success
 Passage through occlusionPassage through occlusion
 Placement of catheter within thrombusPlacement of catheter within thrombus

Contraindications to Intra-arterialContraindications to Intra-arterial

Indications for Intra-arterialIndications for Intra-arterial
 Thrombosis after PTAThrombosis after PTA
 InfrequentInfrequent
 Onset typically <24 hrs following PTAOnset typically <24 hrs following PTA
 80% Success rate80% Success rate
 Risk of bleeding and pseudoaneurysmRisk of bleeding and pseudoaneurysm
formationformation

 Determine the Mechanism of OcclusionDetermine the Mechanism of Occlusion
 More effective in peripheral embolization (80%) thanMore effective in peripheral embolization (80%) than
thrombotic occlusions (50-60%)thrombotic occlusions (50-60%)
 Embolization from Atrial FibrillationEmbolization from Atrial Fibrillation
 WellWell-organized componenets-organized componenets
 Poor response to lytic therapyPoor response to lytic therapy
 Surgical embolectomy for proximal A-fib occlusionSurgical embolectomy for proximal A-fib occlusion
 Thrombolysis for emboli from recent MIThrombolysis for emboli from recent MI
 Thrombotic Arterial OcclusionsThrombotic Arterial Occlusions
 Success (>50%)Success (>50%)
 Adjunctive procedures to maintain patencyAdjunctive procedures to maintain patency
 Less likely with resolution of large vessel occlusionsLess likely with resolution of large vessel occlusions

 Popliteal Artery Occlusion with Distal ClotPopliteal Artery Occlusion with Distal Clot
Propagation or EmboliPropagation or Emboli
 Poor surgical resultPoor surgical result
 Amputation risk – 40%Amputation risk – 40%
 Moderate IschemiaModerate Ischemia
 Trial of Lytic TherapyTrial of Lytic Therapy
 Severe IschemiaSevere Ischemia
 Surgical Exploration with Intraoperative Intra-arterial LysisSurgical Exploration with Intraoperative Intra-arterial Lysis
 Renal Artery OcclusionRenal Artery Occlusion
 Acute Mesenteric Artery OcclusionAcute Mesenteric Artery Occlusion
 Acute Surgical Intervention w Change in Clinical StatusAcute Surgical Intervention w Change in Clinical Status

 Acute Graft OcclusionAcute Graft Occlusion
 Prosthetic GraftsProsthetic Grafts
 Unsuccessful Non-Operative ManagementUnsuccessful Non-Operative Management
 Adjunct to convert urgent surgical therapy to elective revisionAdjunct to convert urgent surgical therapy to elective revision
 Thrombectomy treatment of choiceThrombectomy treatment of choice
 Autogenous Vein GraftsAutogenous Vein Grafts
 75% success if thrombosis <14 days old75% success if thrombosis <14 days old
 Poor ResponsePoor Response
 Long graftsLong grafts
 Low flow graftsLow flow grafts
 Early graft failure (<1 year old)Early graft failure (<1 year old)

 STILE (Surgery vs. Thrombolytics for Ischemia of LE)STILE (Surgery vs. Thrombolytics for Ischemia of LE)
 393 pts with native arterial or graft occlusion393 pts with native arterial or graft occlusion
 tPA 0.05 mg/kg/hr for 12 hourstPA 0.05 mg/kg/hr for 12 hours oror urokinase (250K bolus,urokinase (250K bolus,
then 4000 u/min for 4 hour, then 2000 u/min for up to 36 hrs)then 4000 u/min for 4 hour, then 2000 u/min for up to 36 hrs)
 Thrombolysis GroupThrombolysis Group
 Failure to pass catheter in 28% of patients (Treatment Failure)Failure to pass catheter in 28% of patients (Treatment Failure)
 Acute Ischemia (<14 days)Acute Ischemia (<14 days)
 Lower amputation and shorter hospital staysLower amputation and shorter hospital stays
 55% had a reduction in surgical procedure55% had a reduction in surgical procedure
 Surgery GroupSurgery Group
 Chronic Ischemia (>14 days)Chronic Ischemia (>14 days)
 Less recurrent ischemia, lower amputation ratesLess recurrent ischemia, lower amputation rates

 STILE ConclusionsSTILE Conclusions
 Surgery was safer and more effective in patients withSurgery was safer and more effective in patients with
symptoms < 6 months duration, >14 dayssymptoms < 6 months duration, >14 days
 Lytics showed improved amputation free survival inLytics showed improved amputation free survival in
patients with <14 days of ischemiapatients with <14 days of ischemia
 No difference in outcome for tPA vs. urokinaseNo difference in outcome for tPA vs. urokinase

 RCT of 114 limb threatening ischemic patients of <7RCT of 114 limb threatening ischemic patients of <7
days durationdays duration
 Thrombolytics vs. SurgeryThrombolytics vs. Surgery
 Similar limb salvage rates (12 months - 82%)Similar limb salvage rates (12 months - 82%)
 Survival improved in lytic group (84% vs. 58%)Survival improved in lytic group (84% vs. 58%)
 Surgery Group – High Cardiopulmonary ComplicationsSurgery Group – High Cardiopulmonary Complications
 Lytics slightly more expensive ($15,672 vs. $12,253)Lytics slightly more expensive ($15,672 vs. $12,253)

 Hemodialysis AccessHemodialysis Access
 Short onset of signsShort onset of signs
 Successful in 87%Successful in 87%
 Most require revision of venous anastamosisMost require revision of venous anastamosis

 Acute StrokeAcute Stroke
 Must be administered within 3 hrs of onsetMust be administered within 3 hrs of onset
 PROACT IIPROACT II
 Superior response of intra-arterial urokinase (67%)Superior response of intra-arterial urokinase (67%)
vs. heaprin (18%)vs. heaprin (18%)
 10% risk of ICH10% risk of ICH

Technique of Intra-arterialTechnique of Intra-arterial
 Arterial PunctureArterial Puncture
 Avoid sites distal to lesionAvoid sites distal to lesion
 Avoid sites where bleeding causes morbidityAvoid sites where bleeding causes morbidity
 Axillary, translumbar, etc.Axillary, translumbar, etc.
 Below SFA – ipsilateral antegradeBelow SFA – ipsilateral antegrade
 Above SFA – contralateralAbove SFA – contralateral
 Upper Extremity - transfemoralUpper Extremity - transfemoral
 Place catheter through clotPlace catheter through clot
 If unsuccessful, avoid branches between catheter and lesionIf unsuccessful, avoid branches between catheter and lesion
 High doseHigh dose
 Short Length of TimeShort Length of Time
 Bleeding related to duration of treatmentBleeding related to duration of treatment
 Should not infuse for > 96 hoursShould not infuse for > 96 hours

 Begin TPA at 0.5-1 mg/hourBegin TPA at 0.5-1 mg/hour
 25-50 cc/hour of 10mg/500cc NS25-50 cc/hour of 10mg/500cc NS
 Obtain baseline fibrinogen, PTT, and FSPObtain baseline fibrinogen, PTT, and FSP
 Repeat in 12 hours then dailyRepeat in 12 hours then daily
 Expect fibrinogen to drop, FSP to be +, and PTTExpect fibrinogen to drop, FSP to be +, and PTT
prolonged in 50% (suggests lytic state)prolonged in 50% (suggests lytic state)
 No specific parameters correlate with bleedingNo specific parameters correlate with bleeding
 Fibrinogen <150 carries 4-fold increase in bleedingFibrinogen <150 carries 4-fold increase in bleeding
 FSP > 400 carries 2.5-fold increase in bleedingFSP > 400 carries 2.5-fold increase in bleeding
 If no progress made and no evidence ofIf no progress made and no evidence of
bleeding, can increase dosage to 1+ mg/hourbleeding, can increase dosage to 1+ mg/hour

 Heparin administrationHeparin administration
 Recommended to prevent peri-catheter thrombosisRecommended to prevent peri-catheter thrombosis
 Aim for PTT 1.5-2x normalAim for PTT 1.5-2x normal
 Attempt to run through sheath in affected limbAttempt to run through sheath in affected limb
 Usually run at 500-1000 unit/hourUsually run at 500-1000 unit/hour
 PTT should not exceed 60 secPTT should not exceed 60 sec
 If surgery required, give FFP to normalizeIf surgery required, give FFP to normalize
fibrinogen levelfibrinogen level

Indications for IntraoperativeIndications for Intraoperative
 30% of embolectomies are incomplete30% of embolectomies are incomplete
 Residual intravascular defects seen onResidual intravascular defects seen on
completion angiographycompletion angiography
 Further mechanical manipulation increasesFurther mechanical manipulation increases
thrombogenicitythrombogenicity
 AdvantagesAdvantages
 Bulk of thrombus removed, less lysis neededBulk of thrombus removed, less lysis needed
 Employment of higher concentrations ofEmployment of higher concentrations of
thrombolyticthrombolytic

Indications for IntraoperativeIndications for Intraoperative
 Multiple trials with streptokinase andMultiple trials with streptokinase and
urokinaseurokinase
 Few bleeding complicationsFew bleeding complications
 Improved outflow in 61-76%Improved outflow in 61-76%
 tPA not studied, but would be ideal giventPA not studied, but would be ideal given
its selectivity for fibrin and short half lifeits selectivity for fibrin and short half life

Moore Chapter: Thrombolysis

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Notes de l'éditeur