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Acute DVT and Beyond: Acute DVT and Beyond: Endovascular ManagementEndovascular Management

Ryan Holthaus, MDRyan Holthaus, MDInterventional RadiologyInterventional Radiology

Mercy North Iowa Medical CenterMercy North Iowa Medical CenterRadiologists of North IowaRadiologists of North Iowa

Deep Vein ThrombosisDeep Vein Thrombosis

DVT is a major public health problemDVT is a major public health problemAdvances have streamlined anticoagulation therapyAdvances have streamlined anticoagulation therapyAcute symptoms and postthrombotic syndrome remain Acute symptoms and postthrombotic syndrome remain major causes of disability and societal burdenmajor causes of disability and societal burdenRestoration of venous patency has demonstrated a Restoration of venous patency has demonstrated a reduction in postthrombotic syndromereduction in postthrombotic syndromeCombination pharmacoCombination pharmaco--mechanical thrombolysis reduces mechanical thrombolysis reduces the costs, time, and complications associated with the costs, time, and complications associated with thrombolytic therapythrombolytic therapy

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DVT: Risk FactorsDVT: Risk Factors

Previous DVT/family history of Previous DVT/family history of DVT DVT Immobility, such as bed rest or Immobility, such as bed rest or sitting for long periods of time sitting for long periods of time Recent surgery Recent surgery Above the age of 40 Above the age of 40 Hormone therapy or oral Hormone therapy or oral contraceptives contraceptives Pregnancy or postPregnancy or post--partum partum Previous or current cancer Previous or current cancer Limb trauma and/or orthopedic Limb trauma and/or orthopedic procedures procedures Coagulation abnormalities Coagulation abnormalities Obesity Obesity

Diagnosed Cases

600,000

Silent PE1 Million

Estimated Cases2 Million

Death100,000

Estimated Cost of DVT/PE Care: $1.5 Billion/yearEstimated Cost of DVT/PE Care: $1.5 Billion/year11

DVT and PE DVT and PE A Significant A Significant National Health ProblemNational Health Problem

Post-Thrombotic Syndrome800,000

Pulmonary Hypertension

30,000

1. Goldhaber. . LancetLancet 1999; 353:13861999; 353:1386--13891389

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Post Thrombotic SyndromePost Thrombotic SyndromeChronic complication of DVTChronic complication of DVT4040--70% of DVT patients will develop PTS70% of DVT patients will develop PTS2525--35% of PTS patients will develop ulcers 35% of PTS patients will develop ulcers and skin deterioration.and skin deterioration.Approx. 6 million Americans have venous Approx. 6 million Americans have venous stasis skin changes and 500,000 have stasis skin changes and 500,000 have venous ulcers.venous ulcers.75% of DVT treatment cost is related to 75% of DVT treatment cost is related to PTSPTS

PostthromboticPostthrombotic SyndromeSyndrome

SignsSignsEdemaEdemaErythemaErythemaDermatitisDermatitisTelangectasiaTelangectasiaVaricose veinsVaricose veinsDependent Dependent cyanosiscyanosisHyperpigmentationHyperpigmentationUlcerUlcer

SymptomsSymptomsHeavinessHeaviness

CrampsCrampsPainPainParesthesiaParesthesiaSwellingSwellingItchingItching

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Pathophysiology of Postthrombotic SyndromePathophysiology of Postthrombotic Syndrome

Acute thrombus, inflammation, Acute thrombus, inflammation, and the process of vein and the process of vein recanalization cause valve recanalization cause valve dysfunctiondysfunction

Reflux and chronic obstruction Reflux and chronic obstruction cause venous hypertension cause venous hypertension which leads to edema, tissue which leads to edema, tissue hypoxia, or ulcerationhypoxia, or ulceration

Deep Venous Thrombosis Anthon J. Comerota, MD, FACS, RVT, Santiago Chahwan, MD, Conns Current Therapy, Editors: Robert E. Rakel, MD, Edward T Bope, MD, Submitted Dec 6, 2005

Kahn et al. Relationship between deep venous thrombosis and the postthrombotic syndrome. Arch Intern Med. 2004

Iliofemoral DVTIliofemoral DVT: : Post Thrombotic SyndromePost Thrombotic Syndrome90% of patients with iliofemoral DVT treated with 90% of patients with iliofemoral DVT treated with anticoagulation alone have symptoms of chronic venous anticoagulation alone have symptoms of chronic venous insufficiencyinsufficiency11

Following acute DVT, patients with combined obstruction and Following acute DVT, patients with combined obstruction and valvular incompetence suffer the most severe postvalvular incompetence suffer the most severe post--thrombotic thrombotic morbiditymorbidity

1.Akesson H, Brudin L, Dahlstron JA, et al. Venous Function assessed during a five year period after acute illeofemeral venous thrombosis treated with anticoagulation Eur J Vasc Surg 1990;4(1):43-48

2.Shull KC, Nicolaides AN, Fernandes E, et al, Significance of politeal reflux in relation to ambulatory venous pressure and ulceration. Arch of Surg. 1979;114:1304-1306

3. Johnson BF, Manzo RA, Bergelin RO, et al. relationship between changes in the Deep Venous system and the development of postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: a one to six year follow up. J Vascular. Surgery 1995; 21:307-313

During this short term follow up, 15% devoloped venous ulceration 1

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Therapeutic Goals of DVT Therapeutic Goals of DVT TreatmentTreatment

Prevent PEPrevent PEPrevent further thrombus propagationPrevent further thrombus propagationRelieve patient symptomsRelieve patient symptomsPrevent DVT recurrencePrevent DVT recurrenceMaintain valve competenceMaintain valve competencePrevent Post Thrombotic Syndrome (PTS)Prevent Post Thrombotic Syndrome (PTS)

Rationale for TreatmentRationale for Treatment Calf Vein ThrombosisCalf Vein Thrombosis: isolated calf vein thrombosis propagates up to 30% : isolated calf vein thrombosis propagates up to 30%

of casesof cases AntiAnti--coagulation is indicated in these patientscoagulation is indicated in these patients11..

Femoropopliteal Venous ThrombosisFemoropopliteal Venous Thrombosis: DVT involving the femoral and : DVT involving the femoral and popliteal veins is the most common presentationpopliteal veins is the most common presentation

all patients with proximal DVT should be treated with antiall patients with proximal DVT should be treated with anti--coagulationcoagulation22. .

Iliofemoral Venous ThrombosisIliofemoral Venous Thrombosis: the most extensive DVT is associated with : the most extensive DVT is associated with the most severe postthrombotic sequelaethe most severe postthrombotic sequelae33..

Early Thrombus Removal resulted in improved patency of Early Thrombus Removal resulted in improved patency of the iliofemoral venous system, Lower venous pressures, less the iliofemoral venous system, Lower venous pressures, less edema and fewer post thrombotic syndromesedema and fewer post thrombotic syndromes44..

1,2, 3, 4. .Catheter Based Interventions for Acute DVT, Anthony J Comerota, MD, FACS, Zakaria I. Assi M.D. Chapter 149, Vascular Surgery 6th edition, RB Rutherford Editor, Page 6

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DVT Treatment OptionsDVT Treatment Options

19501950s Anticoagulation onlys Anticoagulation only19801980s Systemic Thrombolysiss Systemic Thrombolysis19901990s Catheter Directed Thrombolysiss Catheter Directed ThrombolysisNOWNOW Pharmacomechanical ThrombolysisPharmacomechanical Thrombolysis

Anticoagulation TherapyAnticoagulation Therapy

Initial therapy of LMW or unfractionated heparinInitial therapy of LMW or unfractionated heparin

Long term oral warfarin sodium (3Long term oral warfarin sodium (3--6 months)6 months)

Anticoagulation is effective at prevention of fatal Anticoagulation is effective at prevention of fatal pulmonary embolism and has an acceptable bleeding pulmonary embolism and has an acceptable bleeding complication ratecomplication rate

FollowFollow--up ultrasound or other diagnostic assessments up ultrasound or other diagnostic assessments are not routineare not routine

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Anticoagulation TherapyAnticoagulation TherapyRelies on the patientRelies on the patients fibrinolytic system for s fibrinolytic system for thrombolysisthrombolysis

Only 6% of patients with acute iliofemoral DVT show Only 6% of patients with acute iliofemoral DVT show significant lysis within 10 dayssignificant lysis within 10 days

Anticoagulation does not directly resolve symptomsAnticoagulation does not directly resolve symptoms

Leg edema and pain usually subside over days to Leg edema and pain usually subside over days to weeks as lysis proceeds and collateral venous channels weeks as lysis proceeds and collateral venous channels developdevelop

Breddin HK et al. Effects of LMWH on thrombus regression and recurrent thomboembolism in patients with DVT. N Engl J Med. 2001

Thrombolytic Therapy for DVTThrombolytic Therapy for DVT

Immediate restoration of vein patencyImmediate restoration of vein patency

Rapid resolution of symptomsRapid resolution of symptoms

Preservation of valve functionPreservation of valve function Reduction in Recurrent DVT Reduction in Recurrent DVT Lower Likelihood of Postthrombotic SyndromeLower Likelihood of Postthrombotic Syndrome

Thrombolytic therapy is an adjunct to Thrombolytic therapy is an adjunct to anticoagulation, not a replacementanticoagulation, not a replacement

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Systemic Thrombolytic Therapy vs Systemic Thrombolytic Therapy vs Heparin AloneHeparin Alone

Long-Term Symptomatic Results (Follow-up 1.6 and 5 years)

0%

20%

40%

60%

80%

Severe Moderate None

Heparin Lysis with Streptokinase

Comerota A, Aldridge S. Semin Vasc Surg. 1992;5(2):76-81.

Catheter Directed ThrombolysisCatheter Directed Thrombolysis

Thrombolytic agent is delivered into Thrombolytic agent is delivered into thrombus using a drug infusion catheterthrombus using a drug infusion catheter

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National Venous Thrombolysis RegistryNational Venous Thrombolysis RegistryVenous Valve Function at 6 MonthsVenous Valve Function at 6 Months

62% of patients with

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Iliofemoral DVT: Conventional Therapy vs Iliofemoral DVT: Conventional Therapy vs Lysis and PTA/StentLysis and PTA/Stent

Short Term Patency and Symptom Resolution

0%

20%

40%

60%

80%

100%

Standard Therapy Lytic Therapy

30 Day Patency 6 Month Patency Long-term Symptom Resolution

AbuRahma et al. (Annals of Surgery, 2001)

Iliofemoral DVT: Conventional Therapy vs Iliofemoral DVT: Conventional Therapy vs Lysis and PTA/StentLysis and PTA/Stent

Iliofemoral Primary Patency

0%

20%

40%

60%

80%

100%

Standard Therapy Lytic Therapy

1 year 3 years 5 years

AbuRahma et al. (Annals of Surgery, 2001)

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PharmacoPharmaco--mechanical Thrombolysismechanical Thrombolysis

Combines thrombolytic infusion with Combines thrombolytic infusion with mechanical energymechanical energy

Maceration of thrombus increases the surface Maceration of thrombus increases the surface area for penetration of thrombolyticsarea for penetration of thrombolytics

Reduces total dose of thrombolyticReduces total dose of thrombolytic

Reduces procedure timeReduces procedure time

Reduces ICU admissionReduces ICU admission

PharmacoPharmaco--mechanical Thrombolysismechanical Thrombolysis

Pulse SprayPulse Spray

Power Pulse Power Pulse 11

Trellis Peripheral Infusion SystemTrellis Peripheral Infusion System

1 Jacob Cynamon, MD, et al. A New Method for Aggressive Management of Deep Vein Thrombosis: Retrospective Study of

the Power Pulse Technique J Vasc Interv Radiol 2006; 17:10431049

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Mechanical Thrombectomy DeviceMechanical Thrombectomy Device

Mechanical removal of thrombus

Powerful saline jets create a low pressure zone around the catheter tip that causes a vacuum effect. Thrombus is drawn into the catheter, where it is fragmented by the jets and then removed.

AngioJet Thrombectomy System

TRELLISTRELLIS--8 8 -- Isolated ThrombolysisIsolated Thrombolysis

Treatment area isolated within occluding balloons Treatment area isolated within occluding balloons Targeted delivery of thrombolytic agentTargeted delivery of thrombolytic agentMechanical dispersion of infused thrombolytic agentMechanical dispersion of infused thrombolytic agentAspiration of thrombolytic following treatmentAspiration of thrombolytic following treatment

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Venous thrombosis: AngioJetVenous thrombosis: AngioJet TherapyTherapy

CatheterCatheter--direct thrombolysis versus pharmacomechanical direct thrombolysis versus pharmacomechanical thrombectomy for treatment of symptomatic lower extremity thrombectomy for treatment of symptomatic lower extremity deep venous thrombosisdeep venous thrombosis

Peter H. Lin, MD, Wei Zhou, MD, Alan Dardik, MD, Firas Mussa, MDPeter H. Lin, MD, Wei Zhou, MD, Alan Dardik, MD, Firas Mussa, MD,,Panos Kougias, MD, Nasim Hedayati, MD, Joseph J. Naoum, MD,Panos Kougias, MD, Nasim Hedayati, MD, Joseph J. Naoum, MD,Hosam El Sayed, MD, Eric K. Peden, MD, Tam T. Huynh, MD Hosam El Sayed, MD, Eric K. Peden, MD, Tam T. Huynh, MD

The American Journal of Surgery vol.192, number 6, Dec. 2006The American Journal of Surgery vol.192, number 6, Dec. 2006

Conclusions:PMT with adjunctive thrombolytic therapy is an effective treatment modality in patients with significant DVT. When compared to CDT, this treatment provides similar treatment success with reduced ICU, total hospital length of stay and hospital costs.

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56.6

30.3

6.72.95 3.42 2.5

0

10

20

30

40

50

60

Tx duration hr Uk Dose (million U) Number of Venograms CDT Alone CDT & PMT

Catheter Directed Thrombolysis Alone Versus Pharmacomechanical Thrombolysis

SourceKim et al,Journal of Vascular and Interventional RadiologyVol.17,7,July 2006

$10,127

$5,128

$0

$2,000

$4,000

$6,000

$8,000

$10,000

$12,000

CDT Alone CDT & PMT

Dollars per treatment

CDT Alone CDT & PMT

SourceKim et al,Journal of Vascular and Interventional RadiologyVol.17,7,July 2006

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Venous thrombosis: AngioJetVenous thrombosis: AngioJetTherapyTherapy

ComplicationsComplications CDT Alone CDT Alone (26 Limbs)(26 Limbs)

CDT & PMTCDT & PMT(19 Limbs)(19 Limbs)

Major BleedingMajor Bleeding 2 (7.7)2 (7.7) 1 (5.3)1 (5.3)Minor Bleeding Minor Bleeding 1 (3.8)1 (3.8) 00Pulmonary Pulmonary embolism embolism

1 (3.8)1 (3.8) 1(5.3) 1(5.3)

SourceKim et al,Journal of Vascular and Interventional RadiologyVol.17,7,July 2006

Venous thrombosis: AngioJetVenous thrombosis: AngioJet TherapyTherapy

4.6

0.6

8.4

2.4

0

1

2

3

4

5

6

7

8

9

Mean ICU Stay (days) Overall Hosp Length Of Stay(days)

Hospital Stay & Associated Costs

Catheter Directed Lytics Pharmacomechanical Thrombectomy

Total Hospital Cost

PMT $47,742 + $19,247

CDL $85,301 + $24,832P Value

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Trellis Cost Compared to Catheter Directed Trellis Cost Compared to Catheter Directed Thrombolysis for DVTThrombolysis for DVT

Trellis CDTCost of Thrombolytic Therapy 529$ 3,666$ Device Cost 1,800 270Bleeding Costs 0 238Room Time 325 650ICU Costs 400 1,200Total 3,054$ 6,024$

Hilleman, Daniel Creighton University: Clinical and economic Evaluation of the TrellisInfusion System for Deep vein thrombosis: a preliminary analysis.

CFV DVT

46 y/o 46 y/o woman woman with 2 day h/o painful, with 2 day h/o painful, cyanotic and swollen left legcyanotic and swollen left leg

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Thrombolysis reveals chronic left common iliac vein stenosis, May-Thurner synd.

S/p stent

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17 yo male with acute LLE DVT17 yo male with acute LLE DVT

PharmacoPharmaco--Mechanical Mechanical ThrombolysisThrombolysis

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After 6hrs of additional After 6hrs of additional thrombolysis and CIV stentingthrombolysis and CIV stenting

33 yo woman with LLE DVT33 yo woman with LLE DVT

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After PharmacoAfter Pharmaco--Mechanical Mechanical Thrombolysis and StentingThrombolysis and Stenting

Clinical Improvement After Clinical Improvement After ThrombolysisThrombolysis

Swelling caused by iliofemoral DVT

1 day following thrombolysis procedure

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62 yo woman before/after PMT 62 yo woman before/after PMT and Stentingand Stenting

Current Standard Therapy for Current Standard Therapy for DVT: AnticoagulationDVT: Anticoagulation

Initial therapy of LMW heparin or unfractionated Initial therapy of LMW heparin or unfractionated heparinheparinLong term oral warfarin Long term oral warfarin -- three to six months three to six months Anticoagulation is effective at prevention of fatal Anticoagulation is effective at prevention of fatal pulmonary embolism and has an acceptable bleeding pulmonary embolism and has an acceptable bleeding complication ratecomplication rate However, this strategy relies on the patientHowever, this strategy relies on the patients fibrinolytic s fibrinolytic

system for thrombolysissystem for thrombolysis Veins have Veins have limitedlimited capacity to dissolve thrombuscapacity to dissolve thrombus22

2. Comerota et al; Iliofemoral Venous Thrombosis; J Vasc Surg 2007; 46:1065-1076

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Anticoagulation AloneAnticoagulation Alone

does prevent clot propagation.does prevent clot propagation.does reduce risk of pulmonary embolism.does reduce risk of pulmonary embolism.does does notnot resolve clot.resolve clot.does does notnot prevent valvular damage.prevent valvular damage.does does notnot prevent venous hypertension.prevent venous hypertension.does does notnot prevent Postprevent Post--Thrombotic Syndrome.Thrombotic Syndrome.does does notnot rapidly resolve symptoms.rapidly resolve symptoms.is not enough.is not enough.

The Paradigm Has ShiftedThe Paradigm Has Shifted

Anticoagulation alone is not enoughAnticoagulation alone is not enough22 Thrombolysis is now recognized by national guiding Thrombolysis is now recognized by national guiding

organizations as a valid interventional approach to organizations as a valid interventional approach to treating DVTtreating DVT

NQF/Joint Commission requires that hospitals have an NQF/Joint Commission requires that hospitals have an evidenceevidence--based thrombolysis protocolbased thrombolysis protocol88

ACCP ACCP ssuggests the use of Pharmacomechanical uggests the use of Pharmacomechanical ThrombolysisThrombolysis99

New Guidelines must be considered when modifying New Guidelines must be considered when modifying DVT treatment protocolsDVT treatment protocols

8. National Quality Forum.National Voluntary Consensus Standards for Prevention and Care of Venous Thromboembolism: Policy, Preferred Practices, and Initial Performance Measures. 2008

9. Kearon et al. Antithrombotic Therapy for Venous Thromboembolic Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2008; 133:454-545

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ACCP Suggests the Use of ACCP Suggests the Use of Pharmacomechanical ThrombolysisPharmacomechanical Thrombolysis

June 2008 Clinical Practice GuidelinesJune 2008 Clinical Practice Guidelines1010 In selected patients with extensive acute proximal In selected patients with extensive acute proximal

DVTDVTwe suggest that catheterwe suggest that catheter--directed thrombolysis directed thrombolysis may be usedmay be used

We suggest pharmacomechanical thrombolysis (e.g., We suggest pharmacomechanical thrombolysis (e.g., with inclusion of thrombus fragmentation and/or with inclusion of thrombus fragmentation and/or aspiration) in preference to catheteraspiration) in preference to catheter--directed directed thrombolysis alonethrombolysis alone

10. Hirsh, Jack, Guyatt, Gordon, Albers, Gregory, Harrington, Robert, Schunemann, Holger. Executive Summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2008: 133; 71-109, Section 1.9

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Treatment FlowTreatment Flow

Patient diagnosed with iliofemoral DVTPatient diagnosed with iliofemoral DVT Begin anticoagulation regimenBegin anticoagulation regimen Consult to DVT interventionalistConsult to DVT interventionalist Perform pharmacomechanical Perform pharmacomechanical

thrombolysis when indicatedthrombolysis when indicated Release on anticoagulation therapy as Release on anticoagulation therapy as

indicatedindicated

ConclusionsConclusions

Acute symptoms of DVT and postAcute symptoms of DVT and post--thrombotic thrombotic syndrome are major causes of disabilitysyndrome are major causes of disabilityAnticoagulation has limited capacity to prevent Anticoagulation has limited capacity to prevent postpost--thrombotic syndromethrombotic syndromeEarly restoration of vein patency improves acute Early restoration of vein patency improves acute symptoms and decreases frequency of symptoms and decreases frequency of postthrombotic syndromepostthrombotic syndromeLytic therapy leads to more reliable and rapid Lytic therapy leads to more reliable and rapid relief of venous obstructionrelief of venous obstruction

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ConclusionsConclusions

Best results with acute DVT (