1. Catheter-Based Treatment of DVT: Who & When?
Karun Sharma, MD, PhD
Interventional Radiology
Children’s National Medical Center
Sheikh Zayed Institute for Pediatric Surgical Innovation

2. Karun Sharma, MD, PhD
I have no relevant financial relationships

3. Overview DVT and standard therapy Catheter Directed Treatment Who ?
When ?
Why ?
Phlegmasia cerulea dolens: Rare – all venous return from LE occluded, painful, swollen and cyanotic, comprimised arterial inflow, emergency, venous gangrene, massive PE and death

4. Virchow’s Triad: Cumulative Risk Factors
Surgery
Prior DVT
Central venous access
Cancer chemotherapy
or radiotherapy
Estrogen use
Cancer
Family history
IBD
Nephrotic syndrome
Blood transfusions
Thrombophilia
Risk factors for Venous thromboembolic disease which included DVT and PE – red is more PEDS. Cumulative risk and that hospitalized patients usually have multiple risk factors.
Age >40 years
Immobilization MI
CHF
Paralysis
Anatomic Abnormality
5. Geerts et al. Chest. 2004;126(suppl):338S-400S.

5. DVT Treatment Options Pharmacological Options: Endovascular Options:
Anticoagulants (STANDARD DVT TREATMENT):
Unfractionated Heparin (UFH)
Low Molecular Weight Heparins (LMWH) - Enoxaparin
Direct thrombin inhibitors - Bivalirudin, Lepirudin, Argatroban
Vitamin K antagonists - Warfarin
Newer, more specific agents – Fondaparinux and Ximelagatran
Thrombolytics (systemic): FDA approved for MI, Stroke and PE
Streptokinase
Urokinase
tPA
Endovascular Options:
IVC Filtration
Catheter Directed Thrombolysis
Catheter Based Pharmacomechanical Thrombolysis

6. Catheter Based DVT Treatment Options
tPA infusion + Device for local delivery
Multisidehole infusion catheter
Trellis – Balloons to localize tPA and wire to fragment thrombus – aspiration port
Angiojet – Rheolytic device for tPA delivery, microfragmentation of thrombus and concurrent aspiration
Ekos – US to “soften” thrombus and allow better tPA binding

7. WHO to treat with catheter based treatment?
Phlegmasia
May-Thurner Syndrome
Iliofemoral DVT in healthy patients
Worsening symptoms despite anticoagulation
Phlegmasia cerulea dolens: Rare – all venous return from LE occluded, painful, swollen and cyanotic, comprimised arterial inflow, emergency, venous gangrene, massive PE and death

8. WHO: Phlegmasia Cerulea Dolens
Rare – all venous return from LE occluded
painful, swollen and cyanotic
comprimised arterial inflow
emergency
venous gangrene, massive PE and death

9. WHO: May Thurner Anatomy
AKA left iliac vein compression syndrome
Anatomic constriction of L CIV by R CIA
Repetitive trauma leading to venous injury

10. WHO else ? Iliofemoral DVT in healthy, active patients
Patients with lack of symptomatic improvement or worsening despite therapeutic anticoagulation
When ?
– Acute DVT (< 14 days, ? up to 21 days)
Why ?
To prevent PTS
Iliofemoral DVT Accounts for 20% of lower extremity DVT
Etiologies:
propagation of femoro-popliteal DVT (10-20%), pelvic mass, May Thurner syndrome
Unique: relatively resistant to anticoagulation, rarely completely recanalize, more frequently results in post thrombotic syndrome

11. Post Thrombotic Syndrome (PTS)
Anticoagulants do not quickly eliminate thrombus % of patients with proximal DVT who are on therapeutic anticoagulation and use compression stockings develop PTS
Valvular Damage from residual thrombus
Valvulur Reflux in deep and superficial systems
Venous hypertension
Edema, tissue hypoxia and calf pump dysfunction
Pruritis, Stasis dermatitis
Chronic, debilitating leg pain and swelling
Skin ulceration

12. WHO should be treated with catheter based treatment?
Catheter based DVT treatment is commonly performed but…
Not endorsed by the American College of Chest Physicians (ACCP) guidelines; lack of strong evidence
Many supportive retrospective, non-randomized studies
CaVENT - Enden et al. Lancet 2012
ATTRACT (results expected in 2015)
American Society of Hematology (ASH)
Society of Interventional Radiology (SIR)
CaVenT (Norway) - Catheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis--the CaVenT study
first randomized trial to evaluate CDT in preventing PTS, CDT vs. anti - coagulation and compression stockings, PTS decreased by 24% in CDT group, Patency of iliac veins increased in CDT group at 6 months.
ATTRACT (US – on going) = randomized trial, phase 3, open label, pharmacomechanical CDT vs. anticoagulation, results pending. Stratification…IF vs. FP
ATTRACT : ACUTE VENOUS THROMBOSIS: THROMBUS REMOVAL WITH ADJUNCTIVE CATHETER-DIRECTED THROMBOLYSIS

13. Data? Primary patency 63-90% at one year post CDT
Most data from non randomized trials and registries
CaVenT (Norway)
first randomized trial to evaluate CDT in preventing PTS
CDT vs. anti - coagulation and compression stockings
Patency of iliac veins increased in CDT group at 6 months
PTS decreased by 24% in CDT group
ATTRACT (US – on going)
Randomized, multicenter, phase 3 trial (n=692)
pharmacomechanical CDT vs. anticoagulation and compression
results expected in 2015
Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis (ATTRACT)
Am Heart J. 2007 Nov;154(5): Epub 2007 Sep 6.
Catheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis--the CaVenT study

14. Standard therapy only (n = 99)
Long-Term Outcome After Additional Catheter-Directed Thrombolysis versus Standard Treatment for Acute Iliofemoral Deep Vein Thrombosis (The CaVenT Study): A Randomised Controlled Trial
Outcome
Additional CDT
(n = 90)
Standard therapy only (n = 99)
p-value n
% (95% CI)
PTS after 6 mo 27
30.3 ( ) 32
32.2 ( )
0.77
PTS after 24 mo 37
41.1 ( ) 55
55.6 ( )
0.047
Iliofemoral patency after 6 mo* 58
65.9 ( ) 45
47.4 ( )
0.012
PTS is defined as a Villalta score ≥5.
p-values stated are from an unadjusted Chi-square test.
Absolute risk reduction of long-term endpoint PTS at 24 months of follow-up in CDT versus standard therapy: 14.4% (95% CI 4-502).
Enden T et al. Lancet 2012;379(9810):31-8.

15. Standard treatment (n = 108)
Adverse Events (AEs)
AEs
Additional CDT (n = 101)
Standard treatment (n = 108)
Bleeding complications
Major bleeding complications
Clinically relevant bleeding complications 20 3 5
Deaths NR
Pulmonary embolisms
Cerebral hemorrhages
Nonbleeding complications 4
Recurrent VTE at 24 mo 10 18
Enden T et al. Lancet 2012;379(9810):31-8.

16. Author Conclusions
Additional CDT improved the clinically relevant long-term outcome after iliofemoral DVT by decreasing PTS compared to conventional therapy.
The CaVenT study demonstrates that additional CDT should be considered as treatment for patients with a high proximal DVT and low risk of bleeding.
Enden T et al. Lancet 2012;379(9810):31-8.

17. Contraindications to Catheter-Directed Thrombolysis
Absolute Contraindications
Active internal bleeding or disseminated intravascular coagulation
Recent cerebrovascular event (including transient ischemic attacks), neurosurgery (intracranial, spinal), or intracranial trauma ( < 3 months)
Absolute contraindication to anticoagulation
Strong Relative Contraindications
Recent cardiopulmonary resuscitation, major surgery, obstetrical delivery, organ biopsy, or major trauma ( <10 days)
Intracranial tumor, other intracranial lesion, or seizure disorder
Uncontrolled hypertension: systolic > 180 mm Hg, diastolic > 110 mm Hg
Recent major gastrointestinal bleeding (< 3 months)
Serious allergic or other reaction to thrombolytic agent, anticoagulant, or contrast media (not controlled by steroid/antihistamine pretreatment)
Severe thrombocytopenia
Known right-to-left cardiac or pulmonary shunt or left heart thrombus
Massive PE with hemodynamic compromise
Suspicion for infected venous thrombus
Other Relative Contraindications
Renal failure (serum creatinine 2.0 mg/dL)
Pregnancy or lactation
Severe hepatic dysfunction
Bacterial endocarditis
Diabetic hemorrhagic retinopathy

18. Take Home Points: Who ? When ?
Phlegmasia cerulea dolens
May-Thurner syndrome
Healthy, active patients with low bleeding risk and symptomatic proximal DVT (Iliofemoral)
Patients with proximal DVT and persistent or worsening symptoms despite therapeutic anticoagulation
When ?
– Acute DVT (< 14 days, maybe up to 21 days)
Iliofemoral DVT is often refractory to standard anticoagulation and associated with higher rates of PTS which can be debilitating

19. Thank You Children's National Medical Center kvsharma@cnmc.org
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20. PTS After 24 Months in Patients with Iliofemoral Patency or Insufficient Recanalization After 6 Months
Outcome
Regained iliofemoral patency (n = 103)
Insufficient recanalization (n = 80)
p-value n
% (95% CI)
PTS after 24 mo 38
36.9 ( ) 49
61.3 ( )
0.001
Absolute gain in short-term endpoint iliofemoral patency after 6 months in CDT versus standard therapy group: 18.5% (95% CI 4.2–31.8).
Absolute risk reduction in the frequency of PTS after 24 months in patency versus insufficient recanalization: 24.4% (95% CI 9.8–37.6).
Enden T et al. Lancet 2012;379(9810):31-8.

21. Initial imaging: CT