Catheter Directed Thrombolysis

for Iliofemoral Deep Vein Thrombosis

Devang Butani, MD, and David L. Waldman, MD, PhD

he annual incidence of clinically recognized acute deep

venous thrombosis (DVT) in the United States is estimated to be between 116,000 and 250,000.1 This risk increases with age, immobility, hypercoagulable states, oral
contraceptives, the postsurgical and postpartum periods, and
after trauma. The most feared complication, pulmonary embolus (PE), occurs in about 10% of cases. The most common
and costly complication, however, is chronic venous insufficiency (true postphlebitic syndrome). Greater than 90% of
symptomatic PE originates from the leg veins.2 Conventional
treatment is simple anticoagulation, the goals of which are to
prevent propagation of clot, relieve local symptoms, and prevent PE. Anticoagulation does not, however, physically remove the thrombus, only prevent propagation and embolization. Physical clot removal is associated with improved
long-term outcome. Surgical removal is associated with very
high recurrence rates, and is rarely performed. With the advent of catheter-based therapy, however, results are much
better, and in cases where the benefit is expected to exceed
the risk, aggressive endoluminal removal of thrombus should
be considered.

Treatment Options
Once DVT is confirmed by imaging (usually sonographic
evaluation) a typical, clinically stable, patient is medically
treated with anticoagulation. Catheter-directed thrombolysis
should be considered, however, for young patients at risk for
postphlebitic chronic venous problems, patients with possible May-Thurner syndrome (a reversible cause), patients
with severe local symptoms, and patients with overwhelming
symptomatic outflow obstruction and limb threat (phlegmasia) (Fig 1). Postphlebitic syndrome is debilitating and occurs
very late, often not becoming symptomatic for up to 10 to 15
years after the original DVT; aggressive therapy to remove
clot is the best way to preserve valvular function, which will
reduce the chances and severity of postphlebitic syndrome.
Phlegmasia, by definition, requires aggressive and urgent in-

Department of Imaging Sciences, University of Rochester Medical Center,

Rochester, NY.
Address reprint requests to Devang Butani, MD, Department of Imaging
Sciences, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642. E-mail: Devang_Butani@urmc.rochester.edu

1524-153X/08/$-see front matter Published by Elsevier Inc.

doi:10.1053/j.optechgensurg.2008.09.001

tervention to decrease compartment pressures and resolve

ischemia. Thrombolysis accomplishes these goals very well.
Factors limiting widespread use of percutaneous therapy
are lack of prospective, randomized data, safety concerns of
thrombolytic agents versus anticoagulation, cost of inpatient
catheter directed therapy versus outpatient anticoagulation,
lack of awareness by primary care physicians that these techniques exist, and lack of an accepted reporting system and
clinical benefit endpoint.3 Because postphlebitic syndrome is
such a late complication randomized clinical trials are difficult to perform, although the long-term financial impact and
quality if life in patients with established postphlebitic syndrome are poor.

Patient Selection
As described above, certain patients can be anticipated to
have unusual benefit from active thrombolysis. These include those with significant iliofemoral clot burden and acute
phlegmasia (symptom onset less than 10 days), young patients, and patients with May May-Thurner syndrome. Eligibility for thrombolytic therapy and subsequent anticoagulation requires, in general, absence of active bleeding, absence
of stroke within the past 12 months, no recent intracranial or
intraspinal surgery, and absence of pregnancy or coagulopathy. Patients need to be otherwise reasonably healthy and
have a near-normal life expectancy (as the major benefit lies
in the future). Patients with DVT related to diffuse malignancy or malignant obstruction are not ideal candidates. Patients who are already anticoagulated usually undergo emergent correction before thrombolysis. IVC filters are placed
only if potentially embolic thrombus (free floating) is identified in the iliac vein or IVC, or if the patient has an unequivocal new major thrombus despite adequate anticoagulation.

Procedure
Prior imaging studies are reviewed to evaluate the extent of
the DVT. Before thrombolysis, CBC with platelets, BUN, creatinine, and eGFR are obtained, the patients history and
physical examination are reviewed, and informed consent is
obtained.
A very critical point is that thrombolysis is catheter-directed; that is, delivered within the clot itself, not adminis143

D. Butani and D.L. Waldman

144

Figure 1 It is probably still fair to say that conventional anticoagulation remains the default treatment for most patients
with deep vein thrombosis (DVT), although it is not accurate to call this the gold standard. Aggressive physical
removal of clot burden has the advantage of yielding better long-term outcome, although adds the drawbacks of the risk
of vessel access and thrombolytic administration along with significant financial and logistical burdens. Conservative
therapy consists of acute heparinization, either via intravenous unfractionated heparin infusion or subcutaneous
administration of low-molecular weight heparin. The latter can be administered as an outpatient with equivalent safety
and efficacy; hospitalization is rarely required today. Either way, warfarin is administered to a goal INR of approximately 2. Current recommendations are to treat for 6 months for a first episode, lifetime if a second has occurred.
As described above, certain patients can be anticipated to have unusual benefit from active clot removal. These
include young patients (lower short-term risk and a greater lifespan to accrue long-term benefit), patients with potential
May-Thurner syndrome (a correctable cause of DVT), and those with enough clot burden to cause unusually severe
symptoms (either very severe local pain or true phlegmasia). Eligibility for thrombolytic therapy and subsequent
anticoagulation requires, in general, absence of active bleeding, absence of stroke within the past 12 months, no recent
intracranial or intraspinal surgery, and absence of pregnancy or coagulopathy; patients need to be otherwise reasonably
healthy and have a near-normal life expectancy (as the major benefit lies in the future) and patients with DVT related
to diffuse malignancy or malignant obstruction are not ideal candidates.

tered systemically. The patient is placed prone on the table

(another critical point as it results in a reversed image;
physicians involved in these cases must be aware of this) and
the popliteal vein is accessed using ultrasound (Fig 2). A
small amount of contrast is injected to evaluate thrombosis
and secure sheath access obtained. An angled hydrophilic
catheter and hydrophilic wire are used to navigate the thrombus and gain access to the inferior IVC. The inferior IVC is

examined to evaluate the superior extent of the thrombus.

Once the inferior and superior extent of the thrombus is
determined, a suitable infusion catheter is selected based on
the length of the thrombus, with the goal being to bathe the
entire thrombus with thrombolytic drug. At our institution,
Alteplase (rt-PA; Genentech, San Francisco, CA) is most
commonly used at a rate of 0.5 mg/hr, with concurrent systemic heparin at 800 U/hr (Fig 3).

Thrombolysis for iliofemoral DVT

Figure 2 DVT is diagnosed/confirmed using duplex ultrasound (B-mode imaging of the area along with Doppler flow
detection). Acute thrombosis is not usually echogenic; the B-mode image itself is often normal. The vessels are located
and compression applied. A patient without DVT will have a very easily compressible vein, whereas the adjacent artery
will not compress without unusual pressure. A patient with acute thrombosis, however, will show lack of compression
of the vein, even if the thrombus cannot be directly visualized.
A very critical point is that thrombolysis must be catheter-directed; that is, delivered within the clot itself, not
administered systemically. The patient is placed prone on the table (another critical point as it results in a reversed
image; physicians involved in these cases must be aware of this) and the popliteal vein is accessed using ultrasound. A
small amount of contrast is injected to evaluate thrombosis and secure sheath access obtained. Access is at times
problematic as liquid blood is usually not aspirated; entrance into the vein depends on good ultrasonic visualization
along with experience and feel. An angled hydrophilic catheter and hydrophilic wire are used to navigate the
thrombus and gain access to the inferior IVC. The wire should pass easily and follow the expected track of the vein. Note
the situation at the iliac confluence; the RIGHT iliac artery passes over (anterior to) the LEFT iliac vein, often producing
extrinsic compression and secondary LEFT sided iliofemoral DVT (May-Thurner syndrome). IVC filters are placed only
if potentially embolic (free floating) thrombus is identified in the iliac vein or IVC, or if the patient has an unequivocal
new major thrombus despite adequate anticoagulation. v. vein.

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D. Butani and D.L. Waldman

Figure 3 Again, note that the patient is placed prone on the procedure table. After proper access, sheath placement, and wire
passage into the inferior vena cava (IVC), the IVC is examined radiographically to evaluate the superior extent of the thrombus.
Once the inferior and superior extent of the thrombus is determined, a suitable infusion catheter is selected based on the length of
the thrombus, with the goal being to bathe the entire thrombus with thrombolytic drug. At our institution, Alteplase (rt-PA;
Genentech, San Francisco, CA) is most commonly used at a rate of 0.5 mg/hr, with concurrent systemic heparin at 800 U/hr. After
thrombus debunking the catheter and sheath are secured and patient monitored overnight. It is important that the patient be placed
on a floor with appropriately trained staff, to ensure regular monitoring for abnormal bleeding and maintenance of the catheter and
sheath, although ICU care is not typically needed as this is a venous problem with low-pressure vessels being involved. The patient
is brought back for evaluation in 24 h and the interval change guides further treatment.
If complete resolution of thrombus is seen and no underlying stenosis found, no further intervention is needed. If complete
resolution of thrombus is seen but underlying iliac vein disease is present (almost always extrinsic compression of the left iliac vein
by the overlying right iliac artery; May-Thurner syndrome), angioplasty followed by stent placement yields excellent results. If the
thrombus has resolved but underlying femoral vein disease is present, angioplasty is performed but stenting avoided. Finally, if only
partial resolution is seen, infusion therapy continues. This can be supplemented with further mechanical intervention and/or
repositioning of the catheter if needed. These patients are re-evaluted by venography at appropriate intervals for a maximum of three
infusion periods and/or 48 h total treatment.

Thrombolysis for iliofemoral DVT

Figure 4 Mechanical thrombolysis refers to the technique of

physical, usually real-time removal of thrombus (as opposed
to allowing lytic drugs to break
up clot). These techniques can
be used before beginning chemical thrombolysis or during treatment, as choice of technique, experience, and individual findings
suggest. The two most common
techniques are the Angiojet (Possis Medical, Minneapolis, MN)
and the Arrow-Trerotola PTD (Arrow International, Reading, PA).
The Arrow-Terotola PTD device
acts as an eggbeater to physically
macerate clot in the area shown;
the macerated clot, ideally of very
small particulate size, will pass
centrally and be taken care of by
the lungs. By contrast, the Angiojet physically removes clot by
means of the Venturi effect produced by a jet of high-velocity
crystalloid solution. Treatment
area for the Angiojet is obviously
less than the Terotola device, but
this technique carries with it the
advantage of physically removing
the thrombus rather than sending
it proximally within the body.
Although experience is less
with this device, the Trellis device (Bacchus, Santa Clara, CA)
potentially combines the benefits of both. This device consists
of two balloons with a rotating sine-wave-shaped catheter
and infusion/aspiration ports
between them. After the balloons are inflated, treatment is
instituted in 10-min increments,
with infusion of 5 mg or so of t-PA
and adjustment of the nodes of rotation during this interval. After
this, the macerated, t-PA infused
debris are aspirated and the catheter repositioned and the process
repeated. This device has the
theoretical benefit of very rapid
treatment of the entire lesion in
one sitting; if residual thrombus is
present t-PA can then be infused
per protocol above for a short period of time, but usually thrombus
removal is complete.

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D. Butani and D.L. Waldman

148
Mechanical thrombolyisis can also be used, usually before
beginning chemical thrombolysis. The two most common
techniques are the Angiojet (Possis Medical, Minneapolis,
MN) and the Arrow-Trerotola PTD (Arrow International,
Reading, PA). These devices are used to decrease clot burden
before beginning pharmaceutical lysis. Additional techniques include the combination of Angiojet and pulse spray
infusion of rTPA4 and use of the rotating Trellis device (Bacchus, Santa Clara, CA) with aspiration of macerated, t-PA
infused debris after treatment (Fig 4).
After thrombus debunking the catheter and sheath are
secured and patient monitored overnight. It is important that
the patient be placed on a floor with appropriately trained
staff, to ensure regular monitoring for abnormal bleeding and
maintenance of the catheter and sheath, although ICU care is
not typically needed as this is a venous problem with lowpressure vessels being involved. The patient is brought back
for evaluation in 24 h and the interval change guides further
treatment.
If complete resolution of thrombus is seen and no underlying stenosis found, no further intervention is needed. If
complete resolution of thrombus is seen but underlying iliac
vein disease is present (almost always extrinsic compression
of the left iliac vein by the overlying right iliac artery; MayThurner syndrome), angioplasty followed by stent placement
yields excellent results (Fig 3). If the thrombus has resolved
but underlying femoral vein disease is present, angioplasty
is performed but stenting avoided. Finally, if only partial
resolution is seen, infusion therapy continues. This can be
supplemented with further mechanical intervention and/
or repositioning of the catheter if needed. These patients
are re-evaluted by venography at appropriate intervals for
a maximum of three infusion periods and/or 48 h total
treatment.
All patients are anticoagulated for at least 6 months after
thrombolysis, typically on heparin as a bridge to oral warfa-

rin, with a goal INR 2 to 3. Patients with iliac stents are placed
on 6 weeks of clopidogrel as well. Imaging follow-up includes baseline Doppler ultrasound followed by re-imaging
at 6 and 12 months. For iliac stenting, the Stanford study has
shown a 1 year patency rate 90%.5

Conclusions
Anticoagulation alone (heparin followed by oral warfarin) is
firmly ingrained as the treatment for DVT in medical education and practice. Catheter-directed thrombolysis has the
major advantage of actively and quickly removing clot (as
well as identifying an underlying lesion causing the problem)
but requires logistically complex, expensive, and somewhat
risky treatment regimens, and is thus currently reserved for
patients who present with limb threat (phlegmasia), locally
symptomatic disease, or those who are young and healthy.
Various infusion regimens and novel protocols, some involving combinations of mechanical thrombectomy and infusion
thrombolysis, are in use. Well-designed, prospective, randomized data, along with appropriate treatment regimens are
needed to modify the treatment of DVT.

References
1. Anderson FA, Wheeler HB, Goldberg RJ, et al: A population based perspective of the hospital incidence and case fatality rates of deep vein
thrombosis and pulmonary embolism. Arch Intern Med 151:933-938,
1991
2. Plate G, Ohlin P, Eklof B: Pulmonary embolism in acute ileofemoral
venous thrombosis. Br J Surg 72:912-915, 1985
3. Semba CP, Razavi MK, Kee ST, et al: Thrombolysis for lower extremity
deep venous thrombosis. Tech Vasc & Int Rad 7:68-78, 2004
4. Mohsen Sharifi, MD, Mahshid Mehdipour, David Skloven, et al: Case
study and review: Power-pulse spray and angiojet thrombectomy in
massive inferior vena cava and bilateral lower extremity deep venous
thrombosis. Vascular Disease Management 5:62-65, 2008
5. OSullivan GO, Semba CP, Bittner CA, et al: Endovascular management
of iliac vein compression (May-Thurner) syndrome. J Vasc Intervent
Radiol 11:823-836, 2000