1. Joint Hospital Surgical Grand Round
Yolanda HY Chan
Kwong Wah Hospital

2. Management of Acute Iliofemoral DVT:
Why not Anticoagulation alone?
How do you usually treat a patient with acute DVT? Simple… Heparin and Warfarin.
I’d say that you are 90% correct, and I’m going to reveal the remaining 10% of the answer in the upcoming 10 minutes or so.

3. Deep Venous Thrombosis
Annual incidence
1.0 to 1.6 per 1,000 persons per year
Iliofemoral DVT
Complete / Partial thrombosis of iliac vein +/- common femoral vein
10 % of all DVT
Deep venous thrombosis is a common clinical condition with an overall annual incidence of 1 in 1000.
Iliofemoral DVT, which is defined as complete or partial thrombosis of iliac vein with or without common femoral vein, accounts for 10% of all DVT.
The post-thrombotic syndrome: The forgotten morbidity of deep venous thrombosis
Kahn SR
J Thromb Thrombolysis 21(1), 41-48,2006

4. Iliofemoral DVT Extrinsic compression of iliac vein (80 %)
May-Thurner syndrome
Tumour
Irradiation
Retroperioneal fibrosis
Extension of distal DVT
Idiopathic
80% of iliofemoral DVT have an underlying extrinsic iliac compression lesion, which include, most commonly, May-Thurner syndrome.
May-Thurner syndrome is a benign condition when the right common iliac artery compresses the left iliac vein against the spine and causes it to become narrowed and scarred.
Other causes include compression as a result of tumour, irradiation or retroperitoneal fibrosis.
Iliofemoral DVT can also be an extension of distal DVT, while the rest are idiopathic.

5. Management of Acute DVT
Compression therapy
+ Anticoagulation
Traditional therapy for acute iliofemoral DVT has been compression therapy together with systemic heparinization followed by Warfarin. It is efficient in reducing thrombus propagation and preventing pulmonary embolism but it fails to solve one big problem… the limb sequelae of DVT.

6. Management of Acute DVT
Post-thrombotic syndrome (PTS)
Phlegmasia
This poor patient who has history of DVT of right lower limb happens to suffer from another acute episode on the contralateral side.
She’s having quite severe phlegmasia, which literally means painful limb swelling. However, the really torturing fact is what she has been living with her other leg for the past few years – Post-thrombotic syndrome 6

7. Post-Thrombotic Syndrome
By definition, PTS is a syndrome and there is no one gold standard test for its diagnosis.
Patients with PTS complain of …
Signs on physical examination include …
PTS is a common and costly clinical condition that is, unfortunately, often under diagnosed, under appreciated, and understudied.
Relationship between deep venous thrombosis and the post-thrombotic syndrome
Kahn SR
Arch Intern Med.2004;164:17-26

8. Post-Thrombotic Syndrome
Despite adequate conventional therapy
Only 20 % of iliac vein completely recanalized
Every fourth patient with proximal DVT developed PTS
A prospective cohort study by Prandoni in 1996 followed up 355 patients for 8 years after acute DVT, and found that following adequate conventional treatment, only 20% of iliac vein completely recanalized, and approximately every fourth patient with proximal DVT of the lower limb develop PTS.
Ann Intern Med 1996;125:1-7

9. Post-Thrombotic Syndrome
Journal of Surgical Research
The Socioeconomic Effects of an Iliofemoral Venous Thrombosis
O'Donnell TF Jr, Browse NL, Burnand KG, Thomas ML
10 or more years after iliofemoral DVT, almost 90 % of patients were unable to work because of leg symptoms
PTS has a measurable adverse impact on quality of life. An early study in 1977 showed that 10 or more years after iliofemoral DVT, almost 90% of patients were disabled and unable to work because of leg symptoms.
J Surg Res 1977;22:

10. Rationale for Thrombus Removal
Early relief of thrombus
Eliminates luminal obstruction
Increases chance of preserving normal valve function
↓ Post-thrombotic morbidity
PTS evolves from persistent venous obstruction and venous insufficiency caused by inflammatory destruction of the venous valves.
Hence if thrombus is removed early, luminal obstruction is eliminated, and the chance of preserving normal valve function is increased; It reduces post-thrombotic morbidity and offers patients the best chance of a favorable outcome.

11. Thrombus Removal in Acute DVT
Until the late 1970s, interventional treatment for iliofemoral DVT was confined to surgical thrombectomy, which requires general anaesthesia, surgical incision, a prolonged recovery period, and most of the time, creation of a temporary arteriovenous fistula.
In the 1970’s, early thrombolytic agents such as urokinase and streptokinase were tried in an attempt to accelerate clot dissolution.
Although systemic lytic therapy is associated with better outcomes than anticoagulation alone, absolute failure rates are high, most likely due to inadequate penetration of thrombus by the lytic agent.
Because of the disappointing results, others have adapted an aggressive regional approach… catheter-directed thrombolysis.

12. Catheter-directed Thrombolysis
In this approach, catheters with multiple side-holes were directed into the clotted veins from a puncture of the ipsilateral popliteal vein, contralateral femoral vein or from the right internal jugular vein. A lytic agent, usually tPA, was then infused into the thrombus over a period of hours or sometimes days, until lysis was achieved.
An underlying cause, such as a venous stenosis, was often found, and it could be dilated with balloon angioplasty and stented.

13. Catheter-directed Thrombolysis
Accelerates thrombolysis
Lessens overall dose of lytic agent
Reduces duration of infusion
(CDT)
CDT accelerates thrombolysis, reduces the overall dose and duration of the infusion of lytic agent; therefore, it is reasonable to expect that complications will be reduced compared with systemic lytic therapy.

14. Catheter-directed Thrombolysis
A mural thrombus extends to the IVC
After 24 hours of catheter-directed thrombolysis, patency of the femoral and iliac veins was restored
with no residual thrombus in the IVC

15. Extensive iliofemoral DVT Acute onset of symptoms within 14 days
Group 1
(33)
Heparin (5 to 7 days)
Warfarin (6 months)
Group 2
(18)
Catheter-directed thrombolysis
+/- Angioplasty & Stenting
A case control trial in 2001 included 51 consecutive patients with extensive iliofemoral DVT of acute onset within 14 days. Patients choose between two modalities: conventional therapy with heparin and warfarin or, lytic therapy with or without percutaneous transluminal angioplasty and stenting.
Ann Surg 2001;233:

16. This table shows that the primary iliofemoral venous patency rates were significantly higher in Group 2 with aggressive treatment than in Group 1. Long-term symptom resolution was also achieved in a much higher proportion of patients.
Ann Surg 2001;233:

17. Pharmacomechanical Thrombolysis
Power-Pulse Angiojet
And here comes the invention of some new toys… for what we call pharmacomechanical thrombolysis.
This Angiojet device uses high-velocity saline jets to create a localised, low-pressure zone at the catheter tip for thrombus aspiration, breakup, and extraction, and treatment times have usually been under 24 hours from start to finish.

18. Pharmacomechanical Thrombolysis
There is another similar tool called Trellis-8 device. This catheter isolates a segment of thrombosed vein, injects thrombolytic agent directly into the clot, and the “stirs” the mixture with a rotating wire like a blender. The clot is then aspirated, the catheter moved to a new segment, and the process repeated.
Trellis-8 device

19. Pharmacomechanical Thrombolysis
A recent paper has documented a significant increase in success, dramatically shorter treatment times, and reduced cost when compared to conventional catheter-directed techniques.

20. Conclusion
Patients with iliofemoral DVT are at high risk of post-thrombotic syndrome
Early thrombus removal minimizes PTS
Catheter-directed thrombolysis can reduce acute symptoms and prevent PTS
Pharmacomechanical thrombolysis has the benefit of shortening treatment time
Patients with iliofemoral DVT are at particularly high risk for PTS and late disability
Treatment strategies that feature early thrombus removal may prevent PTS, while stand-alone anticoagulant therapy fails to do so.
CDT has great potential to prevent PTS and offers distinct advantages compared with surgical thrombectomy, systemic thrombolysis, and anticoagulation alone
Pharmacomechanical thrombolysis has the additional benefit of shortening treatment time

21. Management of Acute DVT
This is a suggested treatment protocol for acute iliofemoral DVT:
Immediate anticoagulation is a must, with compression therapy.
After diagnosis is confirmed and extent of DVT delineated with contrast CT scan, patients who are physically active should be seriously considered for thrombus removal.
If there is no contraindications to thrombolysis, CDT or pharmacomechanical thrombolysis is suggested.
And the underlying venous stenosis can be corrected with balloon angioplasty or stenting.
Gloviczki P, Wakefield TW, Comerota A, et al
Handbook of venous disorders: Guidelines of the American venous forum

22. Thank You
PTS leads to significant quality of life impairment and socioeconomic costs. As technology continues to improve, many more patients could be spared their otherwise certain post-thrombotic morbidity
With just one gentle reminder: Treatment of acute iliofemoral DVT does not equal to anticoagulation alone.

23. Risks of CDT Major bleeding 8 % Pulmonary embolism
Intracranial bleeding %
Pulmonary embolism
Symptomatic %
Fatal %
Definition of CDT-related major bleeding is defined as intracranial bleeding or any bleeding severe enough to result in death, surgery, cessation of therapy, or blood transfusion
In a pooled analysis of 19 published studies involving 1.46 patients with acute DVT treated with adjunctive CDT…
These frequencies do not appear to exceed those in DVT cohorts treated with anticoagulation alone. Hence, there is no evidence to support a contention that PE prevention would be adversely affected by the use of adjunctive CDT
Society of interventional radiology position statement: Treatment of acute iliofemoral deep vein thrombosis with use of adjunctive catheter-directed intrathrombus thrombolysis
Vedantham S, Millward SF, Cardella JF, et al
J Vasc Interv Radiol 2006;17:

24. Indications for Intervention
Post-thrombotic syndrome
- Ambulatory
- Reasonable life expectancy
- Proximal thrombosis
Phlegmasia
- Severe symptoms
- Limb-threatening
Patients with limited clot burden do not justify the risks and expense of this form of treatment. Nor do the many patients with extensive DVT in association with late-stage cancer, who generally do not live long enough to benefit from a reduced incidence of PTS.
Indications for thrombolysis in deep venous thrombosis
Gogalniceanu P, Johnston CJ, Khalid U, et al
Eur J Vasc Endovasc Surg 2009 Aug;38(2):192/198 24

25. Post-Thrombotic Syndrome
Relationship between deep venous thrombosis and the post-thrombotic syndrome
Kahn SR
Arch Intern Med.2004;164:17-26

26. Predictive factors of PTS
Ipsilateral recurrence of DVT
Iliofemoral location
Old age
Obesity
Failure of prompt recovery from acute symptoms
Insufficient oral anticoagulant therapy
Post-thrombotic syndrome: Prevalence, prognostication and need for progress
Prandoni P, Kahn SR
Br J Haematol 2009;145(3):

27. Contraindications to CDT
Bleeding disorders
Active internal bleeding
Recent GI bleeding or CVA
Recent major surgery (< 10 days)
Severe hypertension
Metastatic malignancy with CNS involvement
Iliofemoral deep vein thrombosis: Conventional therapy versus lysis and percutaneous transluminal angioplasty and stenting
AbuRahma AF, Perkins SE, Wulu JT, et al
Ann Surg 2001;233:

28. Catheter-directed Thrombolysis
After thrombolytic therapy, flow was restored within the small and chronically diseased iliac vein; however there was a large residual thrombus in the common iliac vein
The common iliac vein was treated with a balloon-expandable stent to compress the residual thrombus, and the external iliac and distal common femoral veins were treated with a self-expanding stent
Final subtraction venogram shows complete restoration of iliac vein flow and no residual filling defects 28

29. Management of Acute DVT
Anticoagulation
Lessen propagation of thrombus
Prevent pulmonary embolism
Thrombus removal
Provide early symptom relief
Minimize PTS
The common mistakes is for clinicians to treat all DVT patients with anticoagulation only, and belatedly refer those who complain of severe pain and swelling during follow-up for consideration of thrombolysis or thrombectomy – too late for them to achieve their goals.

30. Post-Thrombotic Syndrome
The average cost of treating PTS was US $ 4,700
PTS is a costly chronic condition too. In a Swedish study in 1997, the average overall direct medical cost of treating late complications of DVT was $ 4700, or approximately 75% of the cost of treatment of the primary DVT.
Ann Intern Med 1997;126(6):

31. Catheter-directed Thrombolysis
Numerous reports have been published over the years supporting favorable outcomes of catheter-directed thrombolysis for acute DVT.
Three of the larger reports demonstrate approximately an 80% success rate… 31

32. Catheter-directed Thrombolysis
… and a high percentage of asymptomatic patients at nearly one-year follow-up.
Despite its good results, the infusion requires monitoring in an ICU setting, with frequent trips to the imaging suite to check progress. Infusions of 2 or 3 days have been common. 32