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Catheter Directed Thrombolysis

for Iliofemoral Deep Vein ThrombosisDevang Butani, MD, and David L. Waldman, MD, PhD

The annual incidence of clinically recognized acute deepvenous thrombosis (DVT) in the United States is esti-mated to be between 116,000 and 250,000.1 This risk in-

creases with age, immobility, hypercoagulable states, oral

contraceptives, the postsurgical and postpartum periods, and

after trauma. The most feared complication, pulmonary em-bolus (PE), occurs in about 10% of cases. The most common

and costly complication, however, is chronic venous insuffi-

ciency (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 pre-vent PE. Anticoagulation does not, however, physically re-

move the thrombus, only prevent propagation and emboli-

zation. Physical clot removal is associated with improvedlong-term outcome. Surgical removal is associated with very

high recurrence rates, and is rarely performed. With the ad-vent 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 shouldbe considered.

Treatment Options

Once DVT is confirmed by imaging (usually sonographic

evaluation) a typical, clinically stable, patient is medically

treated with anticoagulation. Catheter-directed thrombolysisshould be considered, however, for young patients at risk for

postphlebitic chronic venous problems, patients with possi-ble May-Thurner syndrome (a reversible cause), patients

with severe local symptoms, and patients with overwhelming

symptomatic outflow obstruction and limb threat (phlegma-sia) (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 removeclot 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-

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 inpatientcatheter directed therapy versus outpatient anticoagulation,

lack of awareness by primary care physicians that these tech-niques exist, and lack of an accepted reporting system and

clinical benefit endpoint.3 Because postphlebitic syndrome issuch a late complication randomized clinical trials are diffi-cult to perform, although the long-term financial impact andquality if life in patients with established postphlebitic syn-drome are poor.

Patient Selection

As described above, certain patients can be anticipated tohave unusual benefit from active thrombolysis. These in-clude those with significant iliofemoral clot burden and acute

phlegmasia (symptom onset less than 10 days), young pa-tients, and patients with May May-Thurner syndrome. Eligi-bility for thrombolytic therapy and subsequent anticoagula-

tion requires, in general, absence of active bleeding, absenceof stroke within the past 12 months, no recent intracranial orintraspinal surgery, and absence of pregnancy or coagulopa-

thy. Patients need to be otherwise reasonably healthy andhave a near-normal life expectancy (as the major benefit liesin the future). Patients with DVT related to diffuse malig-

nancy or malignant obstruction are not ideal candidates. Pa-tients who are already anticoagulated usually undergo emer-gent correction before thrombolysis. IVC filters are placed

only if potentially embolic thrombus (“free floating”) is iden-tified in the iliac vein or IVC, or if the patient has an unequiv-ocal 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, cre-atinine, and eGFR are obtained, the patient’s history andphysical examination are reviewed, and informed consent is

obtained. A very critical point is that thrombolysis is “catheter-di-

rected”; that is, delivered within the clot itself, not adminis-

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 Ave-

nue, Rochester, NY 14642. E-mail: [email protected]

1431524-153X/08/$-see front matter Published by Elsevier Inc.

doi:10.1053/j.optechgensurg.2008.09.001

mailto:[email protected]:[email protected]



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) andthe popliteal vein is accessed using ultrasound (Fig 2). Asmall amount of contrast is injected to evaluate thrombosisand secure sheath access obtained. An angled hydrophiliccatheter andhydrophilic wire areused to navigate the throm-

bus 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 isdetermined, a suitable infusion catheter is selected based onthe length of the thrombus, with the goal being to bathe theentire thrombus with thrombolytic drug. At our institution, Alteplase (rt-PA; Genentech, San Francisco, CA) is mostcommonly used at a rate of 0.5 mg/hr, with concurrent sys-

temic heparin at 800 U/hr (Fig 3).

Figure 1 It is probably still fair to saythat conventionalanticoagulation remains the“default” treatmentfor mostpatientswith deep vein thrombosis (DVT), although it is not accurate to call this the “gold standard.” Aggressive physical

removal of clot burdenhas theadvantage of yielding betterlong-term outcome, although adds thedrawbacks of theriskof 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 subcutaneousadministration of low-molecular weight heparin. The latter canbe administered as an outpatient with equivalent safety

and efficacy; hospitalization is rarely required today. Either way, warfarin is administered to a goal INR of approxi-

mately 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 youngpatients (lower short-term riskand a greater lifespan to accruelong-term benefit), patients with potentialMay-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 subsequentanticoagulation requires, in general, absence of active bleeding, absence of stroke within thepast 12 months, no recent

intracranialor intraspinal surgery, andabsence of pregnancyor coagulopathy; patients need to be otherwise reasonablyhealthy 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.

144 D. Butani and D.L. Waldman



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 locatedand 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 compressionof 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, notadministered 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. Asmall 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 visualizationalong with experience and “feel.” An angled hydrophilic catheter and hydrophilic wire are used to navigate the

thrombus andgain accessto theinferiorIVC. Thewire should pass easilyand followthe expected track of thevein.Note

thesituation at theiliac confluence; theRIGHTiliac arterypassesover (anterior to) theLEFT iliac vein, often producingextrinsic compression andsecondary LEFT sided iliofemoral DVT(May-Thurnersyndrome). IVCfilters areplaced only

if potentially embolic(“free floating”) thrombus is identifiedin theiliac vein or IVC, or if thepatient hasan unequivocalnew major thrombus despite adequate anticoagulation. v. vein.

Thrombolysis for iliofemoral DVT 145



Figure 3 Again, note that the patient is placed prone on theprocedure table.After properaccess, sheathplacement, andwire

passage into the inferior vena cava (IVC), the IVC is examined radiographically to evaluate the superior extent of the thrombus.Once theinferior andsuperior extent of thethrombus is determined, a suitableinfusion catheter is selected basedon thelengthof

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 commonlyused ata rate of0.5mg/hr,with concurrentsystemicheparinat 800 U/hr.After

thrombusdebunkingthecatheterandsheathare securedand patientmonitoredovernight.It is important that thepatientbeplacedona floorwithappropriatelytrainedstaff,toensureregularmonitoring forabnormal bleedingand maintenanceof thecatheterand

sheath,althoughICUcareis nottypicallyneededasthis isa venousproblemwithlow-pressure vesselsbeinginvolved.Thepatientis brought back forevaluation 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 completeresolution of thrombusis seenbut underlyingiliacveindisease ispresent (almost always extrinsiccompression of the left iliacvein

by theoverlying right iliac artery;May-Thurnersyndrome), angioplasty followedby stent placement yields excellent results. If the

thrombushasresolvedbutunderlyingfemoralvein diseaseispresent, angioplastyis performedbutstentingavoided.Finally, ifonlypartial resolution is seen, infusion therapy continues. This can be supplemented with further mechanical intervention and/or

repositioningofthecatheterifneeded.Thesepatientsarere-evalutedbyvenographyatappropriateintervalsfor amaximumof threeinfusion periodsand/or 48h total treatment.




Figure 4 Mechanical thromboly-sis refers to the technique of

physical, usually “real-time” re-moval of thrombus (as opposed

to allowing lytic drugs to break

up clot). These techniques canbe used beforebeginningchem-

ical thrombolysis or during treat-ment, as choice of technique, ex-

perience, and individual findingssuggest. The two most common

techniques are the Angiojet (Pos-sis Medical, Minneapolis, MN)

andtheArrow-TrerotolaPTD (Ar-

row International, Reading, PA).The Arrow-Terotola PTD device

acts asan“eggbeater”to physically

macerate clot in the area shown;the macerated clot, ideally of verysmall particulate size, will pass

centrally and be taken care of by

the lungs. By contrast, the Angio- jet physically removes clot by

means of the Venturi effect pro-duced by a jet of high-velocity

crystalloid solution. Treatmentarea for the Angiojet is obviously

less than the Terotola device, butthis technique carries with it the

advantage of physically removing

thethrombus rather than sending

it proximally withinthe body. Although experience is lesswith this device, the Trellis de-

vice (Bacchus, Santa Clara, CA)potentially combines the bene-

fits of both. This device consistsof two balloons with a rotat-

ing “sine-wave”-shaped catheter

and infusion/aspiration portsbetween them. After the bal-

loons are inflated, treatment isinstituted in 10-min increments,

withinfusion of5 mgor soof t-PAandadjustmentofthenodesof ro-

tation during this interval. After

this, the macerated, t-PA infuseddebris are aspirated and the cath-

eter repositioned and the processrepeated. This device has the

theoretical benefit of very rapidtreatment of the entire lesion in

onesitting;if residualthrombus ispresent t-PA can then be infused

per protocol above for a short pe-riodof time,butusuallythrombus

removal is complete.

Thrombolysis for iliofemoral DVT 147



Mechanical thrombolyisis can also be used, usually beforebeginning chemical thrombolysis. The two most commontechniques are the Angiojet (Possis Medical, Minneapolis,MN) and the Arrow-Trerotola PTD (Arrow International,Reading, PA). These devices are used to decrease clot burdenbefore beginning pharmaceutical lysis. Additional tech-

niques include the combination of Angiojet and pulse sprayinfusion of rTPA4 and use of the rotating Trellis device (Bac-chus, Santa Clara, CA) with aspiration of macerated, t-PAinfused debris after treatment (Fig 4).

After thrombus debunking the catheter and sheath aresecured andpatient monitoredovernight. It is important thatthe patient be placed on a floor with appropriately trainedstaff, to ensureregular monitoring forabnormalbleeding andmaintenance of the catheter and sheath, although ICU care isnot typically needed as this is a venous problem with low-pressure vessels being involved. The patient is brought backfor evaluation in 24 h and the interval change guides furthertreatment.

If complete resolution of thrombus is seen and no under-

lying stenosis found, no further intervention is needed. If complete resolution of thrombus is seen but underlying iliacvein disease is present (almost always extrinsic compressionof the left iliac vein by the overlying right iliac artery; May-Thurner syndrome),angioplasty followed by stent placementyields excellent results (Fig 3). If the thrombus has resolvedbut underlying femoral vein disease is present, angioplastyis performed but stenting avoided. Finally, if only partialresolution is seen, infusion therapy continues. This can besupplemented with further mechanical intervention and/ or repositioning of the catheter if needed. These patientsare re-evaluted by venography at appropriate intervals fora maximum of three infusion periods and/or 48 h total

treatment. All patients are anticoagulated for at least 6 months afterthrombolysis, typically on heparin as a bridge to oral warfa-

rin,witha goal INR 2 to 3.Patientswithiliac stents are placedon 6 weeks of clopidogrel as well. Imaging follow-up in-cludes baseline Doppler ultrasound followed by re-imagingat 6 and 12 months. For iliac stenting, the Stanford study hasshown a 1 year patency rate 90%.5

Conclusions Anticoagulation alone (heparin followed by oral warfarin) isfirmly ingrained as the treatment for DVT in medical educa-tion and practice. Catheter-directed thrombolysis has themajor advantage of actively and quickly removing clot (aswell as identifying an underlying lesion causing theproblem)but requires logistically complex, expensive, and somewhatrisky treatment regimens, and is thus currently reserved forpatients who present with limb threat (phlegmasia), locallysymptomatic disease, or those who are young and healthy. Various infusion regimens and novel protocols, some involv-ing combinations of mechanical thrombectomy and infusionthrombolysis, are in use. Well-designed, prospective, ran-

domized data, alongwithappropriate treatment regimensareneeded to modify the treatment of DVT.

References1. Anderson FA, Wheeler HB, Goldberg RJ, et al: A population based per-

spective 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. O’Sullivan GO, Semba CP, Bittner CA, et al: Endovascular managementof iliac vein compression (May-Thurner) syndrome. J Vasc Intervent

Radiol 11:823-836, 2000


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