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Diagnosis and Treatment of May-Thurner Syndrome

T he peculiar predilection for deep-vein throm-

bosis (DVT) to involve the left lower extremity

in humans has been long recognized in clini-

cal medicine. Virchow was the first in 1851 to ob-

serve that iliofemoral DVT was 5 times more likely

to occur in the left leg as compared to the right leg.

In 1908, McMurrich described the presence of stric-

tures in the common iliac vein, that were believed to

be responsible for the increased incidence of left-leg

DVT.1 May and Thurner’s discovery in 1957 of vas-

cular thickening in the left common iliac vein where

it was crossed and compressed by the right common

iliac artery, more than 100 years after Virchow’s find-

ings, definitively linked the vascular anomaly of fo-

cal segmental venous fibrosis or “venous spur,” to the

genesis of iliofemoral DVT. Their findings would

eventually be the germ of a clinical entity that would

become known by a multitude of names such as iliac

vein compression syndrome, May-Thurner syndrome

(MTS),2 Cockett’s syndrome3 or nonocclusive iliac

vein lesion. Left iliac vein compression from the con-

tralateral right common iliac artery, against the pos-

Manu Rajachandran, MD, FSVM; Robert M. Schainfeld, DOFrom Memorial Hospital, York, Pennsylvania, and Massachusetts General Hospital, Boston, Massachusetts.

ABSTRACT: In 1908, McMurrich described the presence of strictures in the common iliac vein

that were believed to be responsible for the increased incidence of left leg deep-vein thrombosis

(DVT). This syndrome would eventually become known as iliac vein compression syndrome or

May-Thurner, Cockett’s syndrome, or nonocclusive iliac vein lesion. Left iliac vein compression

from the contralateral right common iliac artery, against the posterior fifth lumbar vertebral body,

is estimated to comprise 49% to 62% of cases of left lower extremity disease. Although there is

some degree of iliac vein compression present as a normal anatomic variant in otherwise healthy

patients (>50% compression) in up to 25% of patients, those who experience DVT frequently have

anatomically abnormal veins with spur formation and are at high risk of developing recurrent DVT

and post-thrombotic syndrome. Herein we describe the presentation, diagnosis, and management

techniques for May-Thurner syndrome.

VASCULAR DISEASE MANAGEMENT 2014;11(11):E265-E273 Key words: deep vein thrombosis, anticoagulation, thrombolytic therapy,

thrombectomy, endovascular therapy

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terior fifth lumbar vertebral body is estimated to com-

prise 49% to 62% of cases of left lower extremity disease

(Figure 1). Although there is some degree of iliac vein

compression present as a normal anatomic variant in

otherwise healthy patients (>50% compression in up to

25% of patients), those who experience DVT frequent-

ly have anatomically abnormal veins with spur forma-

tion, and are at high risk of developing recurrent DVT

and post-thrombotic syndrome (PTS).4

The true clinical prevalence of MTS is unknown, but

it has been postulated to range in incidence from 18%

to 49%, in patients with left leg DVT. The syndrome

most commonly presents as an acute DVT. The clinical

incidence of DVT related to MTS, however, is quite

low, in the range of 2% to 3%. Patients can also present

with left lower extremity pain and swelling, or with

chronic venous insufficiency without thrombosis.

Possible mechanisms for the syndrome on the macro-

vascular level include vascular trauma to the vein from

repetitive compression from the overlying pulsating

artery, causing elastin and collagen deposition in the

iliac vein, which eventually leads to spur formation.

May and Thurner, in their initial study of 430 cadav-

ers, found obstructive lesions in 22% of left common

iliac veins and observed 3 different histologic types

of spurs, including a lateral spur, a central spur, and

a web of multiple fenestrations, which they termed

partial obliteration.2

CLINICAL PRESENTATION Clinical features of MTS include a female predomi-

nance, with two common variants in presentation. The

classic acute presentation is a woman between 20 and

40 years of age presenting with a DVT either associated

with a plausible explanation or identifiable risk factor

(i.e., provoked), or unprovoked, without a discernible

etiology. Without definitive treatment, chronic limb

swelling, recurrent DVT, and venous claudication may

develop. The less common chronic presentation involves

progressive pain, unilateral left leg swelling, varicose veins

and venous ulcers without antecedent acute thrombo-

sis. Many patients with May-Thurner anatomy remain

entirely asymptomatic throughout their adult life. Rare

cases of right common iliac vein compression have also

been described, usually in patients with left-sided infe-

rior vena cava.5,6 A thorough history and physical exam

is mandatory in young patients presenting with unilat-

eral lower-extremity edema. A concurrent evaluation

for thrombophilia is required in these cases, because up

to 67% of patients with iliofemoral DVT or MTS can

manifest some variant of thrombophilia.7

Figure 1. Severe narrowing of left common iliac vein from overlying right common iliac artery (arrow), on coronal magnetic resonance venography, consistent with May-Thurner syndrome or nonocclusive iliac vein lesion.

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In patients presenting with signs or symptoms of MTS,

the diagnosis may be made by a variety of methods. Du-

plex ultrasonography has long been the initial screening

exam for lower-extremity DVT due in part to its por-

tability and ease of use. Lensing et al in 1989 observed

a sensitivity and specificity of 91% and 99% respectively

for the detection of proximal DVT with B-mode ultra-

sound, using the single criterion of vein compressibility.8

Noninvasive testing may be employed in supporting the

diagnosis of iliofemoral DVT, with findings on duplex

ultrasonography consisting of narrowing of the iliac

vein at the level of the artery, abnormal Doppler flow

below the level of compression and absent variation of

flow within the common femoral vein when patient

inhales and exhales.9

The gold standard for diagnosis of MTS historically has

been contrast venography. This invasive study can delin-

eate the location and extent of thrombosis, help differ-

entiate between acuity and chronicity of the occlusion,

and aid in the detection of truncal venous malformations

of the femoral vein, such as duplication of the femoral

vein, which can occur in up to 12% of patients and is

usually bilateral in distribution. Venography has also

helped identify up to 3 common angiographic patterns

in MTS. These include focal stenosis or collateralized

short-segment occlusion of the left common iliac vein,

acute iliofemoral venous thrombosis with the underly-

ing lesion being revealed after successful thrombolysis,

and chronic isolated thrombosis of the left common

and external iliac veins with collaterals arising from the

common femoral vein.10

Venography entails inserting a catheter directly into

the adjacent veins, and administering a contrast agent

or dye into the vein, which may show compression of

the iliac vein with spur or web formation. CT venog-

raphy11 and magnetic resonance (MR) venography12 are

two newer, minimally invasive modalities that may be

used to evaluate the iliac veins. The advantage of both of

these technologies is that they may detect occult pelvic

masses and other causes for extrinsic venous compression

as well as provide important information about venous

architecture and extent of thrombus.

The sensitivity and specificity of MR venography ap-

proached that of invasive venography for the detection

of iliofemoral thrombosis, in one prospective study.13 In

cases where a therapeutic intervention appears indicated,

intravascular ultrasonography (IVUS) has been exten-

sively relied on for the diagnosis and documentation

of iliac vein stenosis and dynamic compression and to

facilitate in planning of stent procedure.14

TREATMENT May-Thurner syndrome should be treated only when

it is symptomatic. The treatment of MTS in the setting

of iliofemoral DVT is aimed at preventing the sequelae

of veno-occlusive disease including PTS, venous clau-

dication, venous stasis ulceration, and chronic venous

insufficiency arising from damage to venous valve ar-

chitecture. Anticoagulant therapy, such as intravenous

heparin or low molecular weight heparin, which are ad-

ministered subcutaneously, with an eventual transition

to warfarin or coumadin, is the mainstay of treatment for

patients with acute DVT. This pharmacologic regimen

prevents thrombus propagation and cephalad extension

into the pulmonary artery but does little to dissolve any

existing chronic clot. It is therefore inadequate to treat

the long-term sequelae of iliofemoral DVT associated

with MTS, as mentioned previously. Definitive therapy

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of symptomatic MTS usually requires revascularization

to relieve venous hypertension. Endovascular recana-

lization can be achieved by a multitude of modalities.

Acute MTS is most effectively treated with catheter-di-

rected thrombolysis (CDT), mechanical thrombectomy

(MT), and adjunctive percutaneous balloon venoplasty

and stenting. This is usually best accomplished by an-

tegrade percutaneous access with ultrasound guidance

of the ipsilateral popliteal vein, with the patient in the

prone position. This approach allows treatment of the

occluded venous segment in the direction of flow, and

minimizes catheter-related damage to the venous valves,

as opposed to a contralateral retrograde approach or

ipsilateral antegrade common femoral vein puncture.

Because less than 1% of iliofemoral venous thrombosis

is solely confined to the iliac venous segment, the more

distal popliteal vein access route enhances the ability to

access and lyse thrombus in the common femoral venous

segment, thus improving overall technical success rates.15

Other venous access points have included the small sa-

phenous vein, with catheter insertion into the popliteal

vein past the sapheno-popliteal junction, and in certain

instances, the posterior tibial vein. Traditional therapy

involved catheter-directed thrombolysis often up to 48

hours or longer, followed by balloon angioplasty of the

underlying outflow lesion, usually found at the level

of the confluence of the common iliac vein with the

inferior vena cava (IVC).

Recently developed treatment paradigms have sought

to shorten the recanalization process by acceleration of

thrombolysis of the venous occlusion. The added benefit

of this method is the reduction in bleeding risk, due

to a lower dose of infused lytic agent, along with the

shorter duration of exposure to lytic therapy. Endovas-

cular therapy with CDT and/or percutaneous MT refers

to a heterogeneous group of devices used to fragment,

ablate, or extract intravascular thrombus in an effort

to produce more rapid and efficacious lysis.16 PMT has

a number of advantages over CDT alone, including

more rapid restoration of flow in situations where limb

viability is compromised. This therapy is most likely

to be successful when thrombus is acute (<14 days old)

and much less effective when the clot is chronic (>4

weeks old).17 Lytic drugs include alteplase, tenecteplase,

reteplase, streptokinase, and urokinase. None, however,

have specific FDA approval for use in DVT.

Vedantham et al, using a variety of thrombolytic

agents and MT devices, employed CDT with adjunc-

tive thrombectomy to treat 28 symptomatic limbs in 22

patients with MTS. They achieved procedural success in

82% of limbs treated, with a major bleeding rate of 14%.

Mean infusion time was approximately 17 hours, and

mean per-limb total dosages of lytic agent were lower

than in previously reported studies of DVT thromboly-

sis. Serial venographic analysis in this study revealed

inefficient thrombus removal using MT alone and far

more substantial thrombus removal when using both

CDT and MT.18 Typical thrombolytic protocols now

incorporate both CDT and MT in synergistic fashion

to facilitate venous recanalization.

A number of mechanical thrombectomy catheters

with different mechanisms of action are commercially

available. These include the Trellis device (Covidien),

which uses a sinusoidal nitinol wire to mechanically

disintegrate thrombus while lytic agent is infused be-

tween proximal and distal occlusion balloons, and the

Angiojet rheolytic thrombectomy catheter (Boston Sci-

entific), which can be used in the pulse spray mode to

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deliver lytic agent directly into the clot, and then in the

aspiration mode to remove thrombus. Other devices

that have historically been used for thrombus removal

are the Oasis device (Boston Scientific), the Trerotola

percutaneous thrombectomy device (Teleflex), and the

Amplatz thrombectomy device (Microvena). Recent

experience with the EKOS Endowave system, which

uses ultrasound-accelerated catheter-directed throm-

bolysis to treat iliofemoral DVT, has also been favor-

able.19 This device uses ultrasound to thin and expand

the fibrin component of the thrombus, thus exposing

plasminogen receptor sites to increase the efficacy of the

thrombolytic agent; the device does not mechanically

remove clot. A pilot study of the device in 12 patients

with iliofemoral DVT, using either rtPA and urokinase

as lytic agents, resulted in a technical success rate of 85%

(complete clot lysis), with minimal major bleeding, and

no instances of pulmonary embolism. Routine IVC

filter placement was not performed in this study.20

Once the occluded iliac vein is rendered patent by the

modalities described above, in cases of suspected iliac

vein compression, contrast venography with adjunctive

IVUS are complementary tools to confirm the diagno-

sis and guide therapy (Figure 2). It is “de rigeur” to

perform balloon venoplasty of the underlying outflow

obstruction followed by stenting of the segment in or-

der to ensure long-term success. These measures not

only prevent early venous reocclusion but also improve

primary patency rates to 70% to 80% in the first year

following treatment. The degree of lysis also has been

found to be a major predictor of early and long-term

patency. More complete clearance of thrombus yields

venous patency rates in excess of 75% in most studies,

whereas incomplete lysis (>50% remaining residual

clot) leads to poor (<40%) patency.15 Stenting relieves

the mechanical obstruction in the common iliac vein,

offers definitive immediate technical success, and im-

proves long-term vessel patency. A large self-expanding

Figure 2. Iliocaval venogram after percutaneous mechanical thrombectomy (A). Venoplasty of occluded left common iliac vein (CIV) presumed due to iliac vein compression (May-Thurner). Note inferior vena cava (IVC) filter deployed after retinal hemorrhage during tPA (B). Wallstent (Boston Scientific) deployed in IVC/CIV confluence restoring patent iliac vein (C).

A B C

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stent (12 mm to 16 mm in diameter) is deployed across

the stenosis and extended into the IVC. It is gener-

ally oversized slightly to the diameter of the common

iliac vein, and is allowed to “mushroom” up into the

IVC, just above the iliocaval junction, so that anchor-

ing is secure and the risk of stent migration reduced.

Intravascular ultrasound can also be helpful in these

instances, to size the stent appropriately to the dimen-

sions of the vessel and to select the optimal length of

stent that will allow secure anchoring at the iliocaval

junction. Intravascular ultrasound can also delineate

the adequacy of a balloon percutaneous transluminal

angioplasty result, quantify the presence of residual

thrombus within the treated segment of vein with

greater clarity than venography, and help assess the

need for further thrombus removal. Once the outflow

obstruction is treated, thrombolysis may be continued

for an additional 24 to 48 hours for optimal clot reso-

lution. In some studies of acute DVT with underlying

MTS, primary 2-year stent patency rates for primary

and secondary iliac vein compression approach 95%

to 100%.21,22

Percutaneous MT with CDT and venous stenting pro-

vides optimal benefit in young and functionally intact

patients who have acute (<14 day) presentation of ex-

tensive proximal (IVC or iliofemoral vein) thrombus, or

in patients with phlegmasia cerulea dolens. The optimal

window for lysis is somewhat controversial, but existing

data suggest that lytic therapy should be initiated within

10 days to 21 days of acute symptom onset. Older clot has

significant heterogeneity of composition, with chronic

thrombus interspersed with acute or subacute throm-

bus, and would likely be more resistant to thrombolytic

therapy. Venous stenting has been used to successfully

treat iliac vein obstruction, of various causes, including

post-thrombotic occlusion, iliac vein compression, and

obstruction from malignancies. Patients with chronic

iliac vein obstruction from extrinsic compression fare

better when treated with stenting as compared to those

patients who have occlusive venous disease (Figure 3).

Figure 3. Venogram of severely stenotic iliac vein in 40-year-old female with significant edema and varicose veins of left thigh and calf. Retrograde filling of internal iliac vein with pelvic collaterals and ascending lumbar vein is seen (A). Percutaneous transluminal angioplasty (PTA) of iliac vein (B). Post-PTA venography with significant residual stenosis due to elastic recoil (C). Venogram following successful revascularization of iliac vein with Wallstent (Boston Scientific) (D).

A B C D

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This is reflected in the 6-year follow-up results for

iliofemoral venous stenting, with cumulative patency

rates of 79% to 100% for nonthrombotic vessels, as

compared to 57% to 86% in individuals with throm-

botic occlusive disease.23 Complementing these excel-

lent technical and patency rates, recently published

series report laudable clinical outcomes with reduced

pain, swelling and improved quality of life in those

patients who underwent venous stenting.24

For those patients with chronic iliofemoral venous

occlusion, thrombolytic therapy can be omitted in

favor of direct recanalization with balloon venoplasty

and stenting. In those cases that remain recalcitrant

to MT and CDT, surgical intervention should be

considered. This usually involves operative venous

thrombectomy and creation of a temporary arteriove-

nous fistula to prevent recurrent thrombosis, usually

between the saphenous vein and superficial femoral

artery, and this was historically the only intervention

available for treatment of patients with iliofemoral

obstruction prior to the introduction of balloon veno-

plasty. Compared to anticoagulation alone, operative

intervention is associated with reduced leg swelling

and ulceration with sustained long-term patency rates

of 65% to 85% in the long term.25 Owing to reduced

procedural morbidity or complications, endovascular

approaches are recommended as first-line treatment

in most patients, but in those individuals deemed at

high-risk for bleeding with thrombolytic therapy, sur-

gery may be considered where appropriate expertise

and resources are available.

COMPLICATIONSComplications have been reported after stent

implantation, which include bleeding at site of venous

access, and more serious complications such as intra-

abdominal and retroperitoneal bleeding. A recent re-

view of 16 retrospective case series of CDT with MT

for DVT reported transfusion rates ranging between

4.2% and 14% in 130 patients.26 The most potentially

devastating bleeding complication is intracranial hem-

orrhage, which is quite rare at 0.2%, and pulmonary

embolism in 1%. These complications are more of-

ten observed with the use of adjunctive thrombolytic

therapy. Stent thrombosis is a rare complication, and

was observed more frequently in thrombosed (10%)

vs nonoccluded veins (1%).24

FOLLOW-UP Patients are usually placed on a short-term regi-

men of enteric-coated aspirin (81 mg to 325 mg) and

clopidogrel (75 mg daily) for at least 4 weeks to 6

weeks post intervention to prevent stent thrombosis.

Anticoagulation with warfarin is initiated in patients

who present with acute DVT and MTS and is con-

tinued for a specified duration based on established

clinical criteria (3 months to 6 months). Aspirin or

clopidogrel may be continued as the sole antiplatelet

agent indefinitely after the 4-week to 6-week time

period for dual antiplatelet therapy has elapsed. In

patients with documented thrombophilia, long-term

anticoagulation with warfarin may be considered. Pa-

tients are followed clinically and with periodic duplex

venous ultrasound exams of the iliofemoral venous

stented segment to assess for long-term patency. Re-

peat venography and IVUS study are reserved for those

patients with persistent, recurrent, or new signs and

symptoms suggesting venous occlusion or thrombosis.

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CONCLUSION Iliac vein compression is a source of significant risk and

morbidity and appears to be relatively underdiagnosed.

It should be considered as a possible cause of unexplained

left-leg DVT or when persistent swelling and pain exist

in the left limb. Venous balloon angioplasty and stent-

ing appears to be a safe, simple, and efficient method

to treat iliofemoral vein obstruction or narrowing from

compression. Because patients with chronic venous dis-

ease are young and have excellent life expectancy and a

favorable prognosis, venous stenting must be offered to

maintain clinical improvement and high rates of patency

in the long term. The chronic effects of stents in the ve-

nous system remain largely unknown, and as such several

more years of monitoring the efficacy and safety of this

therapy is required in all patients with veno-occlusive

disease due to May-Thurner syndrome. n

Editor’s note: Disclosure: The authors have completed

and returned the ICMJE Form for Disclosure of Potential

Conflicts of Interest. The authors report no financial relation-

ships or conflicts of interest regarding the content herein.

Manuscript submitted July 15, 2013; provisional acceptance

given October 3, 2013; final version accepted May 12, 2014.

Address for correspondence: Manu Rajachandran MD,

FSVM, Memorial Hospital, 325 South Belmont Street,

York, PA 17405. Email: stentdoc63@yahoo.com.

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