Deep Vein Thrombosis – A Case for Early Intervention Presentation by Dr. Hiranya A. Rajasinghe from Naples, Florida.

1. Deep Vein Thrombosis
A Case for Early Intervention
Hiranya A. Rajasinghe MD
Vascular and Endovascular
Surgery
Naples, Florida

2. Mainstream Rx
Clot removal is
not a part of
recommendation
for care
2004
Acute Venous Thromboembolism

3. Anticoagulation
Calf DVT
…. for everyone!
Femoral-popliteal
Iliofemoral
Do not recognize iliofemoral DVT
as a unique condition
…Change occurred in the 2008
guidelines…
Acute DVT

4. Where are We Going…
• Surgeon General’s “Call to Action”
– Joint Commission/NQF Mandates
• DVT/PE Risk Assessment Protocols 2008
– Prevention
– Intervention
• ACCP Recommendations Changing 2008
– Thrombolytic Therapy
• Iliofemoral
• SIR Recommendations
– Thrombolytic Therapy
• Iliofemoral

5. • This joint effort elevates the awareness of DVT
to a National healthcare level.
• This joint effort recognizes the need to
standardize the care of DVT patients and
measure outcomes.
• The American College of Chest Physicians
(ACCP) will publish the physician consensus on
patient treatment.
– It is changing its 2004 DVT treatment guidelines
• 2007 guidelines will include a thrombolysis recommendation
• 2007 guidelines will include a recommendation for
specifically treating iliofemoral DVT (CDT, PMT) (Comerota)
Why is this Information Important ?

6. 6
PE
600,000
Silent
PE
1 Million
DVT
2 Million
Death
200,000
Estimated Cost of VTE Care $1.5 Billion/yearEstimated Cost of VTE Care $1.5 Billion/year
VTE: A Public Health Problem
Estimated Annual Incidence
Post-
Thrombotic
Syndrome
800,000
Pulmonary
Hypertensio
n
30,000
Goldhaber.. LancetLancet 1999;353:1386-13891999;353:1386-1389

7. What is a DVT?
• Blood clot in a deep vein
• Blocks blood from returning
to heart
• Damages the valves and
vein wall
• Potentially grow or travel
VEIN

8. Virchow’s Triad
StasisStasis
Air Travel, Obesity,Air Travel, Obesity,
ImmobilityImmobility
Endothelial InjuryEndothelial Injury
Limb Trauma, Major SurgeryLimb Trauma, Major Surgery
HypercoagulabilityHypercoagulability
BCP, Cancer, HereditaryBCP, Cancer, Hereditary

9. DVT Risk Factors and
Symptoms
Risk Factors
• Immobility, such as bed rest or
sitting for long periods
• Previous DVT or family history
of DVT
• Recent surgery
• Above the age of 40
• Hormone therapy or oral
contraceptives
• Pregnancy or post-partum
• Previous or current cancer
• Limb trauma and/or orthopedic
procedures
• Coagulation abnormalities
• Obesity
Symptoms
• Pain
• Discoloration of the legs
• Calf or leg pain or tenderness
• Swelling of the leg or lower
limb
• Warm skin
• Surface veins become more
visible
• Leg fatigue

10. Economy Class Syndrome
• Flights over 4 hours
• Any prolonged trip in cramped conditions
• Immobility and dehydration
• Prevention:
– aspirin, fluids, avoid alcohol, frequent walks,
support stockings

11. Symptoms
• Commonly no symptoms!
• Pain
• Swelling
• Redness
• Palpable clot

12. Diagnosis
• Clinical: exam and
symptoms
• Venous duplex
• Magnetic
resonance
venography
• Blood test: Elevated D-dimer

13. DVT treatments
• MEDICAL
– Anticoagulation (blood thinning medications)
• IV Heparin (in hospital only)
• Low molecular weight heparin (given at home)
• Coumadin (by mouth)
– Support Stockings
– Elevation

14. Therapeutic Goals of DVT
Treatment
• Relieve Patient Symptoms
• Prevent Pulmonary Embolism
• Prevent Further Thrombus Propagation
• Prevent DVT Recurrence
• Maintain Valve Competence
• Prevent Postthrombotic Syndrome

15. Complications of DVT
• Pulmonary Embolus
• Post-DVT syndrome

16. Pulmonary Embolus
• Clot travels to lungs
• Blocks lung artery
• Frequently fatal
• Symptoms:
– chest pain
– shortness of breath
– or death

17. Vena Cava Interruption:
IVC Filters
Indications:
Prevent large emboli from
reaching the lungs
Contraindication for
anticoagulation therapy
Complications while receiving
anticoagulation therapy
High risk of mortality from
recurrent PE
Placement:
Below renal veins
Inserted via jugular or
femoral vein
May be easily removed

18. Caval Filters
• PERMANENT
• RETRIEVABLE

19. What We Know…
• Gold Standard
–Anticoagulation
• Heparin, Lovenox, Coumadin
–Compression Hose
• Long Term Results
–Anticoagulation
• Prevents Clot from Propagating
– Does not dissolve thrombus
• PE Prevention
– May Lead to Post Thrombotic Syndrome

20. Current Standard Therapy for DVT:
Anticoagulation Therapy
• Relies on the patient’s fibrinolytic system for
thrombolysis
– Veins have limited capacity to dissolve thrombus
– Only 6% of patients with acute proximal DVT show complete
lysis of thrombus within 10 days
– Recurrent thrombosis and postthrombotic syndrome have been
highly correlated to residual thrombus
• Anticoagulation does not directly resolve symptoms
– Leg edema, pain and difficulty ambulating associated with DVT
usually subside over days to weeks as collateral venous
channels develop
– Many patients continue to experience some degree of venous
obstructive symptoms, especially during exercise
Breddin HK et al. Effects of LMWH on thrombus regression and recurrent thomboembolsim in patients with DVT. N Engl J Med. 2001
Sherry S. Thrombolytic Therapy for Deep venous thrombosis. Semin Intervent Radiol 1985

21. Post-DVT Syndrome
• Reversed flow of blood
in veins
• Symptoms:
pain, swelling, ulceration
• 6-7 million patients with
venous stasis changes
• 500,000 patients with
leg ulcers yearly

22. Valvular Damage

23. Venous Blood Flow
• The Low pressure of the venous system
requires special adaptations to help return
blood to the heart.
• A complex system of venous valves, the
calf muscle pump, and the respiratory
pump all assist in returning blood to the
heart.
• Venous valves are one way valves of
hinge-like flaps formed by the Tunica
Intima
– Most abundant in the lower limbs where gravity
opposes flow.
– Prevent backflow as blood travels toward the
heart.

24. Calf muscle pump

25. Pathophysiology of
Postthrombotic Syndrome
• Acute thrombus, inflammation, and
the process of vein recanalization
cause valvular reflux
• Reflux and/or chronic obstruction
causes venous hypertension which
leads to edema, tissue hypoxia, or
ulceration
• Clinical studies suggest that reflux
in proximal veins is associated with
the manifestation of Postthrombotic
Syndrome
Kahn et al. Relationship between deep
venous thrombosis and the
postthrombotic syndrome. Arch Intern
Med. 2004

27. Postthrombotic Syndrome (PTS)
• 29-47% of DVT patients
eventually develop PTS
(Prandoni, Brandjes, Kahn)*
• 25-33% of Patients with PTS will
develop severe symptoms such
as ulcers and skin deterioration
(Kahn)
• 75% of the cost of Treating DVT
is related to PTS (Kahn,
Berqvist)
• 6% of home care clientele and
18% of expenditures are related
to PTS (Kahn)
Frequency of PTS with
symptomatic DVT (Prandoni)
Follow up Incidence
1 Year 17%
2 Years 23%
5 Years 28%
8 Years 29%
Frequency of PTS with
symptomatic DVT (Brandjes)
5 years 47%
Frequency of PTS with
symptomatic DVT (Ginsberg)
1 Year 27%

28. Postthrombotic Syndrome
Signs & Symptoms
Signs
• Edema
• Stasis
• Dermatitis
• Redness
• Dependent Cyanosis
• Varicose Veins
• Venous dilation
• Open Ulcer
• Hyperpigmentation
• Healed Ulcer
Symptoms
• Heaviness
• Cramps
• Pain
• Paresthesia
• Swelling
• Bursting Pain
• Itching

29. Long-Term Follow-Up
• 59 patients with iliofemoral DVT
• Conventional anticoagulation
• Followed 5 years
Anticoagulation
Iliofemoral DVT
Akesson H,
Eur J Vasc Surg 1990
Delis K T et al
Ann Surg 2004;239(1):116

30. Parameter @ 5 yrs %
Calf muscle dysfunction 50%
Ambulatory venous hypertension 95%
Venous insufficiency 90%
Venous claudication 15% -45%
Venous ulceration 15%
Limited ambulation 15%
Reduced QOL nearly all
Anticoagulation
Iliofemoral DVT
Akesson H,
Eur J Vasc Surg 1990
Delis K T et al
Ann Surg 2004;239(1):116

31. Risk of Recurrence
1,149 Symptomatic DVT Rx’ed
with Anticoagulation
Iliofemoral DVT
Overall recurrence @ 3 mos – 5.1%
Femoral vein thrombosis – 5.3%
Iliofemoral DVT – 11.8%
Douketis JD et al
Am J Med 2001;110:515
Results
Risk for Recurrence
Factor Odds Ratio
Iliofemoral DVT 2.4
Cancer 2.6

32. Time after Initial DVT, mo
CumulativeProportionof
PatientswithRecurrentVTE
Hazard ratio 2.9 with
residual thrombus
P = 0.001
Residual Venous Thrombus
Recurrent DVT
Prandoni, P et al
Ann Intern Med 2002;137:955
Residual thrombus predictive
of recurrent DVT

33. Increasing evidence…
• Early thrombus resolution is associated
with improved outcome!
(especially iliofemoral DVT)
…and…
• Without thrombus removal, risk of
recurrence is increased
Acute DVT

34. Early Intervention =
Reduction of Postthrombotic
Syndrome
• Early thrombus removal may decrease the risk of valvular
insufficiency, thereby decreasing the risk developing
postthrombotic syndrome. 1–4
– Rapidly remove clot
– Restore venous flow
– Preserve valvular function
– Identify and treat the cause of the thrombosis
• Valve function is preserved with rapid successful lytic therapy3
• Venous thrombectomy shows significant benefit vs
anticoagulation in randomized trials1,4
1. Plate et al. J Vasc Surg. 1984;1:867–876.
2. Meissner et al. J Vasc Surg. 1993;18:596–602.
3. Jeffrey et al. Proc 2nd Intl Vasc Sympos. 1989; London Abstract S20–3.
4. Plate et al. Eur J Vasc Surg. 1990;4:483–489.

35. Thrombolytic Therapy for DVT
• Thrombolytic agent is delivered into thrombus using
a drug infusion catheter
• Immediate restoration of Vein Patency
• Immediate Resolution of Patient Symptoms
• Preservation of Valve Function
– Reduction in Recurrent DVT
– Lower Likelihood of Postthrombotic Syndrome
Thrombolytic therapy is an
adjunctive therapy to
anticoagulation, not a replacement

39. 1100
Patency @ 1 yrPatency @ 1 yr
IliacIliac
FemoralFemoral
63%63%
40%40%
64%64%
47%47%
78%78%
------------
Iliac Stent: Patency @ 1 yrIliac Stent: Patency @ 1 yr
++ StentStent
-- StentStent
54%54%
75%75%
74%74%
53%53%
89%89%
71%71%
Initial SuccessInitial Success
IliacIliac
FemoralFemoral
79%79%
63%63%
40%40%
83%83%
64%64%
47%47%
84%84%
78%78%
------------
Bjarnason ‘97Bjarnason ‘97
(n=77)(n=77)
Mewissen ‘99Mewissen ‘99
(n=287)(n=287)
Comerota ‘01Comerota ‘01
(n=58)(n=58)
Mewissen et alMewissen et al
RadiolRadiol 19991999
Bjarnason H et alBjarnason H et al
JVIRJVIR 19971997
Comerota et alComerota et al
PhlebologyPhlebology 20012001
Contemporary Series: Bleeding Complications
Iliofemoral DVT – CD Thrombolysis

40. Fatal PEFatal PE
Death 2Death 2°°
LysisLysis
0%0%
0%0%
0.2%0.2%
0.4%0.4%
0%0%
0%0% (? 2%)(? 2%)
Bjarnason ‘97Bjarnason ‘97
(n=77)(n=77)
Mewissen ‘99Mewissen ‘99
(n=287)(n=287)
Comerota ‘01Comerota ‘01
(n=58)(n=58)
Bleeding complications < 5%
in reports since 2001
Bleeding complications < 5%
in reports since 2001
Contemporary Series: Bleeding Complications
Iliofemoral DVT – CD Thrombolysis
Mewissen et alMewissen et al
RadiolRadiol 19991999
Bjarnason H et alBjarnason H et al
JVIRJVIR 19971997
Comerota et alComerota et al
PhlebologyPhlebology 20012001
Pulm EmbPulm Emb 1%1% 1%1% 0%0%
Major BleedMajor Bleed 5%5% 11%11% 9%9%
IC BleedIC Bleed 0%0% <1%<1% 0%0%

42. • Trellis 8 clinical results
O’Sullivan JVIR 2007; 18:715-724
• 19 Oncology patients with above knee DVT treated with Trellis with
one year follow up.
• 96% of limbs showed Grade III and Grade II thrombus removal
immediately post procedure
• Primary assisted patency rate of 100% at 30 days post procedure
• Valvular function was maintained in 82% of treated lower extremities
(one year follow up)
• Systemic thrombolysis was absent in patients tested for serum
fibrinogen levels or fibrin degradation products
• All patients had an adjunctive procedure (PTV and/or venous
stenting)

45. Pharmaco-Mechanical Thrombolysis
• Combines thrombolytic infusion with mechanical
energy
• Increases the surface area penetration of
thrombolytics
• Dissolves and macerates thrombus
• Reduces the thrombolytic dose
• Reduces the time of thrombolytic infusion
• Reduces or eliminates patient time in the ICU

46. Patient Selection
 Patient with an expected long-term survival
 Massive DVT or iliofemoral thrombophlebitis
 Iliofemoral DVT
 Multiple segment DVT
 Patients who are symptomatic despite
anticoagulation
 Acute clot diagnosis: <14 DAYS

47. Isolated Thrombolysis Catheter –
Design and Components
Balloon Inflation &
Thrombolytic Infusion Ports
8Fr Multi-Lumen
Catheter
Oscillation
Drive Unit
Isolated Treatment Zone
Combination of Mechanical Motion & Drug Infusion
• Single-Setting Thrombolysis
• Targeted delivery of thrombolytic
agents
• Treatment area isolated within
occluding balloons
• Mechanical dispersion of infused
thrombolytic agents
• Aspiration following treatment
Aspiration Port

48. Isolated Thrombolysis Catheter -
Thrombus Removal
Aspiration allows removal of residual vessel content
• Post-Operative Care:
– Monitor Puncture Site and Dressings
– Begin Standard Anti-Coagulation Therapy
– Observe Patient for 4-8 Hours, Depending on Physician Orders

49. Isolated Thrombolysis Catheter –
Efficacy
• Mechanical “agitation” created by the drive wire
– Combines mechanical action and thrombolytic infusion
– Greater drug dispersion
• Note: It may be important to treat thrombus as soon as possible
– Ease of thrombus removal may decrease over time as clot ages.

50. Isolated Thrombolysis Catheter
Potential for Improved Safety
Isolated treatment zone: Created by 2 Occlusion
Balloons
Potential for lower lytic utilization
Reduced treatment time
Procedure Time
Dosage
(t-PA)
Catheter
Directed
Thrombolysis
2-6
days
0.5mg/hr
(24mg / 2
days)
Isolated
Thrombolysis
2 hours
3-5mg
(per
segment)

51. Isolated Thrombolysis Catheter –
TRELLIS Venograms
Full occlusion in common femoral through iliac veinsFull occlusion in common femoral through iliac veins
Patency restored throughout treated areasPatency restored throughout treated areas

52. Isolated Thrombolysis Catheter
Symptom Relief
Pain and swelling caused by
iliofemoral DVT
Reduced swelling following
Isolated Thrombolysis

53. May Thurner Syndrome
(Iliac Vein Compression)

54. Iliofemoral Vein Thrombus
Case Study
Iliac/Femoral Vein withIliac/Femoral Vein with
Acute on ChronicAcute on Chronic
ThrombusThrombus
Iliac Vein Subacute ThrombusIliac Vein Subacute Thrombus
Final FilmFinal Film

55. DVT also occurs in the arm
Thoracic outlet syndrome
Paget Schroeder syndrome
Chronic catheterization
Dialysis access
Trauma

56. Subclavian DVT
Case Study
BeforeBefore AfterAfter

57. Subclavian Thrombus Removed

58. Isolated Thrombolysis Catheter -
Benefits For All
• Isolated Thrombolysis:
– Pharmaco-Mechanical system aids in rapid thrombus removal
– Restores vessel patency
– Minimizes drug exposure
• Patient:
– More immediate symptomatic relief
– Decreased risk of Post-Thrombotic Disease (PTS)
– Potential for NO ICU Stay and overall shorter length of stay
– Single setting treatment of DVT
• Physician & Staff:
– 1.5 to 2 hour procedure
– Easier post-up care
– Elimination of repeat venograms
• Hospital:
– Decreased Procedural Costs:
• $2,000-$3,000 Per DVT Patient
– Decreased ICU Costs
• $4,000-12,000 Savings per DVT Patient

59. The Evolution of DVT Treatment

60. DVT Management Strategy
Anticoagulation/Lysis Risk Assessment*
PMT
Temporary
IVC Filter Anticoagulation
IVC and/or Iliofemoral Femoral/Popliteal Isolated Calf
Symptomatic Asymptomatic
Unstable Thrombus?
Compression Hose
Anticoagulation
Follow-up
Compression Hose
Consider Hypercoagulability Work-up
Yes
No
Follow-up
Lytic Contraindications? Isolated PMT*
Correct Underlying Stenosis

61. Therapeutic Goals of DVT
Treatment
Relieve Patient Symptoms
Prevent Pulmonary Embolism
Prevent Further Thrombus Propagation
Prevent DVT Recurrence
Maintain Valve Competence
Prevent Postthrombotic Syndrome

62. Early Intervention =
Quality of Life Improvement