May-Thurner syndrome

INTRODUCTION — May-Thurner syndrome (MTS) is an anatomically and pathologically variable condition leading to venous outflow obstruction because of extrinsic venous compression in the iliocaval venous territory. With partial venous obstruction, the condition can be asymptomatic, but progression with symptoms related to chronic venous hypertension or venous occlusion can occur, with or without venous thrombosis. It is important to keep this condition in mind whenever a patient presents acutely with lower extremity swelling or deep vein thrombosis (DVT), particularly in young females.

The approach to diagnosis and treatment depends upon whether venous thrombosis is present. When the diagnosis is highly suspected based upon clinical features or noninvasive vascular imaging, a definitive diagnosis is established using intravascular ultrasound (after removal of thrombus, if necessary). Minimally invasive treatment (angioplasty and stenting) of the venous lesion relieves outflow obstruction and provides immediate relief of symptoms with good long-term patency rates. For those with venous thrombosis, rates of post-thrombotic syndrome are reduced with endovascular treatment.

The clinical features, diagnosis, and management of MTS are reviewed here. General considerations for the diagnosis and management of venous thromboembolism are reviewed separately. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)" and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

ANATOMIC DEFINITION AND PATHOPHYSIOLOGY — MTS is defined as extrinsic venous compression by the arterial system against bony structures in the iliocaval territory. MTS is also referred to as iliocaval venous compression syndrome, iliac vein compression syndrome, Cockett's syndrome, and venous spur. The most common variant of MTS is due to compression of the left iliac vein between the overlying right common iliac artery and the fifth lumbar vertebrae, but others exist.

In the mid-19^th century, it was observed that deep vein thrombosis was five times more likely to occur in the left leg [1]. However, left iliac vein compression as a cause of isolated left lower extremity swelling was not described until 1908 and not fully understood until the mid-20^th century [2,3]. In approximately 22 percent of 430 cadavers, May and Thurner noted intraluminal thickening ("venous spurs"), which appeared to be directly and most commonly related to external compression of the left common iliac vein by the right common iliac artery against the fifth lumbar vertebra [3]. There are three histologic types of spurs: central, lateral, and fenestrated. The relationship between iliac vein compression and post-thrombotic syndrome was later illustrated by Cockett in 1967 [4].

The majority of cases follow the classic left-sided description, but other variants have been reported, such as right-sided MTS and compression of the inferior vena cava (IVC) by the right common iliac artery [5-9].

EPIDEMIOLOGY AND RISK FACTORS — The exact incidence and prevalence of those with MTS anatomy are unknown. Reported values depend upon the population studied but are likely underestimated given that most individuals do not have symptoms and require no treatment [10-13]. The prevalence of a hemodynamically significant lesion (ie, >50 percent iliac vein stenosis) was approximately 25 percent in a review of 50 abdominal computed tomography (CT) scans performed for abdominal pain but without suggestive left lower extremity symptoms [11]. The mean patient age was 50 years.

Among patients who present with a symptomatic lower extremity venous disorder, MTS has been estimated to be the etiology in 1 to 5 percent of patients [14-16]. Some retrospective reviews have reported higher rates [1,3,8,11,17-20]. In a small study of mechanical thrombectomy for proximal deep vein thrombosis, an underlying lesion responsible for the occlusion was uncovered in 59 percent (10 of 17 patients) [17].  

Risk factors — Risk factors for MTS are listed below and described in the table (table 1) [8,11,21-27]. These may be directly associated with MTS or may increase the likelihood that asymptomatic MTS will progress to symptomatic MTS.

●Female sex, particularly those who are postpartum, multiparous, or using oral contraceptives

●Scoliosis may predispose to MTS due to compression from the lower lumbar vertebra

●Dehydration

●Hypercoagulable disorders

●Cumulative radiation exposure

CLINICAL FEATURES — As noted above, the majority of individuals with MTS anatomy are asymptomatic, but progression of the venous lesion can occur, causing symptoms related to venous hypertension. Clinical presentations of symptomatic MTS include, but are not limited to, acute extremity pain and swelling, venous claudication, or chronic development of symptoms/signs of venous insufficiency (ie, edema, skin discoloration, or skin ulceration).

Female patients can also present with pelvic congestion syndrome related to underlying MTS [28].

The classic clinical presentation is that of a younger female in the second or third decade of life with chronic (≥4 to 6 weeks) left lower extremity swelling.

Lower extremity swelling — Symptomatic patients typically present with pain and swelling of the left lower extremity, but right-sided and bilateral presentations have been reported [10,18]. (See 'Anatomic definition and pathophysiology' above.)

In the author's opinion, any ipsilateral limb swelling without evidence for deep vein thrombosis (DVT) should be evaluated for underlying MTS. Swelling usually involves the entire limb. With unilateral presentations, a size discrepancy between the limbs is usually noticeable. Over the course of the day, compression of venous outflow causes venous hypertension that escalates throughout the day, particularly after prolonged sitting or standing, causing significant limb swelling and tenderness. Lower extremity swelling may or may not be associated with venous thromboembolism (deep vein thrombosis, less commonly pulmonary embolism). (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity" and "Epidemiology and pathogenesis of acute pulmonary embolism in adults".)

Venous claudication — A significant number of patients (up to 85 percent) with MTS experience venous claudication [29-31]. This phenomenon is due to venous outflow obstruction. Venous claudication is defined as the presence of thigh/leg pain and tightness with exercise, which subsides with rest and/or elevation [4,32].

Patients with DVT with concurrent MTS may have a reduced risk of pulmonary embolism compared with those without MTS. A study examined 112 patients with DVT, two-thirds of whom had MTS. As expected, thrombotic events were higher in the MTS group (98.7 versus 48.5 percent; P <.001). Interestingly, pulmonary embolism was less common in the MTS group (50.6 versus 78.8 percent; P = .006) [33].

Other presentations — Patients can also present with recurrent superficial vein thrombosis or other symptoms and signs of moderate-to-severe chronic venous insufficiency (eg, hyperpigmentation [venous eczema], venous ulceration) (table 2). The physical examination and classification of symptoms of chronic venous disease are reviewed separately. (See "Clinical manifestations of lower extremity chronic venous disease" and "Classification of lower extremity chronic venous disorders" and "Superficial vein thrombosis and phlebitis of the lower extremity veins".)

Rare presentations — The following presentations are reported, but rare:

●MTS presenting with a ruptured iliac vein and retroperitoneal hematoma [34].

●Acquired MTS induced by an iliac artery stent or endovascular stent-graft [35,36]. In these cases, a left-sided presentation still predominates.

●MTS secondary to prostate enlargement [37].

●MTS presenting as cryptogenic stroke in patients with a patent foramen ovale [38,39].

●Pelvic congestion syndrome due to MTS.

DIAGNOSIS — The diagnosis of MTS may be suspected based upon clinical features and initial diagnostic testing in the patient with the lower extremity symptoms described above. Physicians need to keep a high index of suspicion for MTS, particularly when young females present with acute unilateral left limb swelling. (See 'Clinical features' above and 'Risk factors' above.)

A definitive diagnosis of MTS requires demonstration of the venous stenotic lesion in an appropriate anatomic location; however, the lesion may be obscured by overlying thrombus. Thus, the initial evaluation of the patient with lower extremity swelling first involves determining the clinical probability of deep vein thrombosis (DVT) (Wells score, D-dimer). Patients with moderate-to-high risk should undergo venous duplex ultrasound, which is the most reliable study to evaluate lower extremity swelling. Reported sensitivity and specificity of venous duplex ultrasound is 91 and 99 percent, respectively, for diagnosing proximal DVT using only venous compression criterion. Venous duplex ultrasound findings of iliocaval DVT include absence of variation of flow and narrowed iliac veins [40]. While venous duplex ultrasound is primarily used to rule out DVT (image 1), it is also used to evaluate venous reflux times. (See "Overview of iliocaval venous obstruction" and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

Approach to MTS diagnosis — Some have recommended routine evaluation of the suprainguinal venous outflow system for patients with proximal DVT, a history of DVT, or venous insufficiency to identify a possible venous stenotic lesion [21]. Others suggest limiting the evaluation to only those with the highest risk for MTS [25]. As noted above, the prevalence of MTS is increased in young females (20 to 40 years).

In general:

●For patients suspected of having MTS, but without the presence of concomitant DVT on initial studies, additional noninvasive venous imaging (reflux duplex ultrasound with or without computed tomographic [CT] or magnetic resonance [MR] venography) may be useful in selected group of patients. One review suggested that electrocardiogram (ECG)-gated MRI can demonstrate flow acceleration during systole, offering an important advantage over CT, which only provides anatomical images [41]. (See 'Noninvasive venous imaging' below.)

●For patients with extensive iliocaval DVT on initial studies, removal of the thrombus is necessary to uncover the stenotic venous lesion. However, it is important to note that most patients with proximal DVT do not have underlying undiagnosed MTS.

The following clinical features may be helpful for determining when to aggressively pursue the diagnosis of MTS, particularly among those at high risk for MTS (younger, female) and suspected DVT (particularly left-sided) [18,29] (see 'Risk factors' above):

●Pain or swelling of the entire limb (thigh and calf) or visible varicosities over the lower body wall, groin, or thigh on physical examination. These findings are suspicious for extensive proximal DVT.

●Dominance of venous claudication.

●Ongoing daily symptoms (especially if unilateral or unexplained) in spite of adequate treatment of DVT.

●Ipsilateral, recurrent, proximal DVT following cessation of treatment.

●Stigma of post-thrombotic syndrome – venous reflux, hyperpigmentation of the skin, chronic leg pain, phlebitis, lipodermatosclerosis, venous ulcers.

Noninvasive venous imaging — In the absence of thrombus, noninvasive vascular imaging can be used to identify the vascular lesion associated with MTS. Options include duplex ultrasound, CT venography, and MR venography.

Duplex ultrasound — Duplex ultrasound can identify iliac vein stenosis and allows dynamic evaluation of the status of the deep veins of the involved extremity. Although venous ultrasound has high sensitivity and specificity for the detection of proximal DVT using B-mode using compressibility criterion, the deep location of the proximal iliac vein along with other factors (eg, obesity, overlying gas) may limit ultrasound for making an accurate diagnosis of MTS [40,42].

We use the ultrasound parameters previously described to diagnose iliocaval stenosis, including poststenotic turbulence as indicated by the mosaic appearance (noisy signal), an abnormal Doppler signal at the area of stenosis, and sluggish and/or no spontaneous flow as well as very poor augmentation [43]. The contralateral vasculature serves as a control if inferior vena cava thrombosis/occlusion is not present.

The angle of insonation should be kept at <60°, and a 4 to 7 MHz linear array transducer is commonly used to evaluate the common femoral vein, while 2 to 3 MHz should be used to evaluate iliac and caval vessels. B-mode will help to compare vein diameter reduction at the smallest lumen area to that of normal vein diameter. Peak vein velocity (PVV) is measured in the poststenotic and compared to the prestenotic segment; a PVV gradient >2.0 is considered significant [43].

CT/MR venography — Cross-sectional imaging (eg, CT scan with venous phase, or MR venography) (image 2) is sensitive for estimating the location and degree of stenosis in nonthrombosed veins, identifying venous collaterals, and identifying other anatomic variations.

Both CT and MR venograms have >95 percent sensitivity and specificity for diagnosing MTS, but these imaging modalities require adequate technical protocols for imaging acquisition [44-48].

CT venography may be better at identifying more severely stenotic lesions and has the advantage of identifying other causes of extrinsic venous compression; however, a nondiagnostic test can result from technical issues such as suboptimal contrast opacification [45,49]. MR venography provides better imaging of the pelvic and spinal structures including lumbar vertebral degeneration, bulging or protruding intervertebral discs, osteophytes, or spondylolisthesis [44,50]. However, use of CT or MR venography may be limited because of cost. In the author's opinion, clinical presentations along with suggestive findings on venous duplex ultrasound are sufficient to pursue invasive venous imaging in most cases. However, if there is an anatomical concern that needs to be evaluated, this may best be performed using cross-sectional imaging.

Interestingly, a review of 268 patients with limb swelling using three-dimensional computed tomography venography (3D-CTV) to evaluate the prevalence of >50 percent venous compression found 92 patients were positive, and degree of compression correlated with clinical presentation (P = .017). Out of 92, 89 patients underwent venogram. Venogram for those with complete and partial inferior vena cava compression was negative in 33 and 50 percent, respectively. The study reported that 3D-CTV is more sensitive in detecting atypical compression in those with MTS [51].

Invasive venous imaging (venography, intravascular ultrasound)

Catheter-based venography — Catheter-based venography is warranted if there is a sufficient level of clinical suspicion for MTS in a patient with acute symptoms or if the patient has advanced clinical manifestations of chronic venous disease (CEAP [Clinical-Etiology-Anatomy-Pathophysiology] Clinical Class 4 to 6, or CEAP Class 3 with massive edema).

Although less invasive imaging is useful for identifying thrombus and evaluating for other possible causes of venous compression, it is important to remember that an occlusive iliac vein lesion cannot be excluded with certainty using noninvasive assessments.

Catheter-based contrast venography, particularly with the added use of transvenous pressure measurements, has long been considered the gold-standard diagnostic test for MTS; however, because the study is invasive, it typically is not performed unless there is diagnostic uncertainty or treatment is expected. The other modalities described above are more frequently used initially to establish the diagnosis. Venography can provide insight toward chronicity of lesions as well as variable congenital features that may be associated, such as duplicated or rudimentary venous systems [52].

Contrast venography may fail to provide an accurate diagnosis, but a few steps can be taken to improve accuracy. Obtaining two or three projections during the injection phase is important since a "pancaked" vein (ie, externally compressed in the anteroposterior [AP] plane) will not exhibit diameter narrowing in the AP view [18]. Some clinicians feel that it is equally effective to perform hand-injection venography through the access sheath rather than using a power injector.

A specific diameter threshold defining a stenotic lesion has not been validated for the venous system. Although no study has identified what degree of stenosis will to lead to symptoms, some have suggested that relief of symptoms is more likely with correction of stenosis greater than 50 percent [53-55]. However, determining the degree of stenosis can be difficult. Veins are compliant and affected by factors (eg, volume status) that determine the degree of vein collapse or distention. Veins can also appear stenotic in one dimension when there is no decrease in the actual lumen surface area compared with more rounded segments of the vessel.

Invasive hemodynamic pressure measurements are a valuable adjunct for confirming the presence of the venous stenotic lesion associated with MTS. Simultaneous pressure measurements from both iliac veins can be obtained and compared; normally there should be no difference. An iliac vein pressure gradient more than 2 mmHg at rest is considered important when evaluating venous outflow stenosis [56]. A pullback method measuring the pressure in the lower inferior vena cava above the obstruction site and comparing it with the pressure obtained in the more distal iliac vein may be more accurate [43]. Again, there should be a pressure gradient between the two segments [30,43,56].

Intravascular ultrasound — When intravascular ultrasound is used to make a diagnosis, venography is not necessary. We regard intravascular ultrasound (IVUS) as the current venous imaging standard for establishing a diagnosis of MTS as well as a valuable adjunct for treatment. The sensitivity and specificity of IVUS for venous stenosis exceeds 98 percent [55,57-61]. IVUS shows the precise morphology of the "spur" and can be used to estimate the severity and distribution of pathology [43]. However, IVUS is invasive and is generally used in conjunction with venography at the time of anticipated intervention [18]. (See 'Approach to the patient' below and "Endovenous intervention for iliocaval venous obstruction".)

Since its inception and use over the last decade, IVUS has become an integral component of the treatment of MTS. IVUS is useful for determining vessel diameter, aiding accurate stent placement, ensuring full stent expansion, estimating the gain in cross-sectional area, and, with follow-up, identifying the severity of in-stent restenosis. (See 'Approach to the patient' below and "Endovenous intervention for iliocaval venous obstruction".)

IVUS emits high-frequency sound waves from the ultrasound transducer on the catheter, which provide the operator with a real-time intraoperative tool to examine the target vessel that is both sensitive and objective. At least two types of IVUS are available, mechanical and solid state (digital and rotational catheters). (See "Intravascular ultrasound, optical coherence tomography, and angioscopy of coronary circulation", section on 'Intravascular ultrasound'.)

IVUS catheters are specified by their maximal imaging diameter and transducer frequency. Catheters available for aortoiliac imaging that use a 0.035 inch wire platform include the Volcano (60 mm, 10 MHz), Opticross (30 mm, 15 MHz), and Sonicath (50 mm, 9 MHz).

Another uncommonly used tool is endovenous angioscopy. This will require a minimum of 9F introducer sheath that allows 8.5F videoscope insertion, usually with continuous saline irrigation to clear the visual area and to displace blood (10 mL/min to a maximum of 750 mL of saline). One study utilized angioscope Flex-XC, a 70-cm-long, 8.5F flexible videoscope providing a 1920 by 1080 pixel high-definition image. Researchers reported feasibility in chronic venous occlusion to differentiate between fibrosis versus thrombosis [62].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of MTS includes other causes of lower extremity swelling or pain, but since swelling associated with MTS is usually unilateral, the number of medical, nonvascular causes of lower extremity swelling that could be confused with MTS is limited. (See "Clinical manifestations and evaluation of edema in adults".)

The differential diagnosis of leg pain that may or may not be associated with lower extremity swelling or deep vein thrombosis is presented separately. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Differential diagnosis'.)

DVT without extrinsic venous compression — As noted above, the majority of patients with acute or chronic venous disease do not have external venous compression as a cause of limb swelling or deep vein thrombosis. Our approach to distinguishing between the patients is outlined above. (See 'Approach to MTS diagnosis' above and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

Other causes of iliac vein compression — Other causes of iliac vein compression include the following:

●Pelvic mass, which may be due to tumor, abscess or phlegmon, or hematoma

●Uterine enlargement from fibroids, cancer, or pregnancy, and also pelvic masses

●Aortoiliac aneurysm

●Retroperitoneal fibrosis

●Osteophyte

The patient's medical history is likely to point to one of these as a cause of iliac vein compression as a source for lower extremity swelling. Ultrasound or cross-sectional imaging, or other studies as appropriate, should provide the correct diagnosis.

Other vascular causes of extremity swelling — Unilateral lower extremity swelling is also a feature of venous insufficiency that is not due to iliac vein compression and also of unilateral peripheral lymphedema. However, it is essential for clinicians to regard the venous system of the lower extremity as a continuous unit. For patients presenting with symptoms and signs of severe venous reflux of both axial and nonaxial venous systems including deep venous reflux, iliac vein compression should be considered as a possible etiology. (See "Overview of lower extremity chronic venous disease" and "Clinical features and diagnosis of peripheral lymphedema".)

TREATMENT — Based on observational studies, for patients with moderate-to-severe symptoms and a demonstrable significant venous stenosis associated with MTS, we suggest endovenous treatment rather than conservative management. Relief of the venous outflow obstruction results in immediate symptom relief and reduces the incidence of post-thrombotic syndrome. (See 'Efficacy of endovenous therapy' below.)

Approach to the patient — The treatment of MTS depends upon whether deep vein thrombosis (DVT) is present (algorithm 1). (See 'Approach to MTS diagnosis' above.)

Nonthrombotic MTS with no or mild symptoms — In the absence of DVT, for patients with no or only mild symptoms (CEAP [Clinical-Etiology-Anatomy-Pathophysiology] 1 through 3), treatment is conservative; compression stockings are usually sufficient for relieving symptoms.

Nonthrombotic MTS with moderate-to-severe symptoms — For advanced nonthrombotic MTS with symptoms/signs of advanced chronic venous insufficiency (eg, limb swelling, pain, and skin discoloration [CEAP 4 through 6]), treatment is targeted toward reducing the severity of the stenotic venous lesion using angioplasty and stenting of the affected segment. Angioplasty of the venous stenotic lesion alone is not sufficient and is associated with high recurrence rates [63]. Stenting is not universally agreed upon, and recurrence rates may depend on stent type used [64]. Thus, we use self-expanding stents with post-stenting balloon dilation to fully expand the stent. We agree with others that extending the stent into the inferior vena cava (IVC) has no negative impact [53]. Angioplasty and stenting of MTS lesions also decreases the recurrence rate of superficial reflux following ablation therapies [65]. (See "Endovenous intervention for iliocaval venous obstruction".)

Thrombotic MTS, no contraindications to lytic therapy — If MTS is strongly suspected in a patient with venous thromboembolism (VTE), treatment begins with full therapeutic anticoagulation, if not contraindicated. Subsequent treatment is aimed at decreasing the volume of thrombus using catheter-directed thrombolysis or pharmacomechanical thrombolysis, evaluating for underlying intrinsic venous stenosis using intravascular ultrasound (IVUS), and, if present, angioplasty and stenting of the diseased iliocaval segment. The appropriate expertise and institutional resources must be available to provide this intervention. Where this is not available, an alternative strategy may be anticoagulation with interval follow-up vascular imaging; however, medical treatment with anticoagulation alone is associated with suboptimal outcomes in those with MTS. With successful treatment of MTS, rates of post-thrombotic syndrome are less than 10 percent. Without treatment, post-thrombotic syndrome is estimated to occur in 80 to 90 percent. (See "Post-thrombotic (postphlebitic) syndrome" and 'Endovascular techniques' below and "Endovenous intervention for iliocaval venous obstruction".)

Thrombotic MTS with contraindications to lytic therapy — For patients suspected to have MTS but who have contraindications to lytic therapy, endovascular mechanical thrombectomy can be used. Options include:

●Rheolytic thrombectomy – Rheolytic thrombectomy injects high-velocity saline using Bernoulli principle to break up and aspirate clot (eg, Angiojet-Zelante [8 Fr], Angiojet-Solent [6 Fr]) [66]. Devices are placed over a 0.035 inch wire.

●Rotational thrombectomy – Rotational thrombectomy macerates thrombus using a rotating sinusoidal wire (eg, Cleaner-XT [6 Fr] and Cleaner-15 [7 Fr]) [67]. No guidewire is needed.

●Suction thrombectomy – For suction thrombectomy, a steerable delivery catheter provides a high-velocity vacuum suction to aspirate thrombus (eg, Indigo Penumbra; 4, 6, and 8 Fr) or 13-F ClotTriever funnel sheath with catheter 13 to 25 mm (Inari). These catheters can offer lytic free clot retrieval in one session [68].

Open surgery is primarily indicated for failure of endovascular therapy, given the morbidity associated with operative dissection, and overall worse results for surgery [69-71]. An open cut-down via a common femoral venotomy can be used to evacuate gross thrombus [52,53,72]. The open surgical approach can also include dissection of the iliac vein from the overlying iliac artery, open thrombectomy, and possible patch angioplasty of the left iliac vein, possibly adding adjunctive procedures, such as an arteriovenous fistula to enhance flow in the diseased vein [63]. For an occluded iliac vein, surgical bypass options include cross-femoral venous bypass (Palma-Dale procedure) [73], femorofemoral or ilioiliac prosthetic bypass, and femorocaval and aortic elevation [31,74-76]. An arteriovenous fistula is often created to assist long-term patency of the bypass grafts or reconstructed veins, and the fistula is ligated in six weeks.

Following successful intervention for symptomatic MTS, we prescribe knee- or thigh-high compression stockings (30 to 40 mmHg). For patients with DVT, therapeutic anticoagulation should be continued using similar dosing, monitoring, and duration per venous thromboembolism (VTE) guidelines [52,77]. Following stenting, concurrent antiplatelet therapy is reasonable, provided bleeding risk is low [78-80]. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Patients at low risk of bleeding'.)

Complications of endovascular therapy include jailing the contralateral common iliac vein, which can lead to thrombosis, rupture of the iliac vein, migration or displacement of stent, and erosion of stent into overlying artery.

Efficacy of endovenous therapy — Prior to refinement of endovenous techniques, thrombotic lesions were treated with anticoagulation or open surgical thrombectomy with dismal results. There was no standard therapy for nonthrombotic MTS [81,82]. Advancements in minimally invasive techniques and devices have been instrumental in providing the means to treat iliofemoral stenotic lesions and for decreasing the long-term consequences of venous outflow obstruction. Early studies confirmed the feasibility of left iliac vein angioplasty/stenting [83]. Subsequent case reports and retrospective reviews have consistently showed the safety and high patency rates of endovascular intervention of iliac vein stenosis, even for cases with challenging anatomy [22,84-92]. For MTS that presents in a delayed manner, improved outcomes with intervention including less pain, less swelling, and improved quality of life have also been demonstrated [59,93-95].

Most studies addressing thrombolysis in patients with DVT are not stratified based upon patient risk for MTS or its diagnosis [17,66,86,87,96-110]. For patients with acute DVT, guidelines from the American College of Chest Physicians (ACCP) and American Heart Association (AHA) do not support routine thrombolytic therapy, given the risk of adverse events [77,78,111]. This is appropriate, as most patients, even those with proximal DVT, do not have MTS. As discussed above, it is reasonable to pursue a diagnosis and treatment of MTS in those at high risk. (See 'Approach to MTS diagnosis' above.)

In systematic reviews of studies evaluating treatment of extensive iliofemoral thrombosis [112-115], catheter-directed thrombolysis compared with anticoagulation alone appears to be associated with more complete thrombus resolution and reduced risk for post-thrombotic syndrome (PTS).

●In the largest multicenter trial, the Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial, pharmacomechanical catheter-directed thrombolysis plus standard therapy was compared with standard therapy alone for treatment of DVT [116,117]. The main limitation of ATTRACT is a lack of accurate definitions for the duration of DVT in patients. Overall, the two-year data supported the use of standard therapy/anticoagulation alone [118,119]. Catheter-directed thrombolysis did not reduce the incidence of PTS and was associated with an increased risk of bleeding. Among those with iliofemoral DVT, catheter-directed thrombolysis reduced early DVT symptoms as well as PTS severity. It was less effective in older patients (≥65 years).

●In a multicenter study from Norway, 209 patients with iliofemoral vein thrombosis were assigned to catheter-directed thrombolysis or standard therapy [120-122]. In the thrombolysis group, angioplasty or stenting was left to the discretion of the operator and was performed in 39 of 90 patients. Iliofemoral patency after six months was higher in the thrombolysis group compared with standard therapy (65.9 versus 47.4 percent). There were 20 bleeding complications in the thrombolysis group, which included three major and five clinically relevant bleeds. At 24 months, the rate of PTS was significantly reduced for those treated with thrombolysis compared with standard therapy (41.1 versus 55.6 percent; absolute risk reduction of 14.4 percent [95% CI 0.2-27.9], number needed to treat 7 [95% CI 4-502]) [120,123,124].

●In a smaller trial, 74 patients with residual stenosis after thrombolysis were randomly assigned to stenting or no stenting [105]. Primary patency at one year was improved for the stenting group (86.0 versus 54.8 percent) with an associated reduction in CEAP category (1.61±0.21 versus 0.69±0.23) and quality-of-life measures (venous clinical severity scale [VCSS] (calculator 1)): 7.57±0.27 versus 0.69±0.23; Chronic Venous Insufficiency Quality of Life Questionnaire [CIVIQ] score: 22.7±3.0 versus 39.3±6.7).

In observational studies, following catheter-directed thrombolysis in selected patients shown to have MTS, primary patency following angioplasty and stenting ranges from 61 to 92 percent at one year, with secondary patency rates as high as 98 percent [22,84-92,125]. In an older study comparing stenting versus no stenting in patients identified with a venous spur following removal of thrombus, the rate of rethrombosis was lower for stenting compared with anticoagulation alone (13 versus 73 percent; 1 of 8 versus 16 of 22 patients) [63].

For patients presenting with chronic limb or pelvic symptoms from MTS without acute DVT, angioplasty and stenting are also clinically successful for the majority of patients [126]. A retrospective review included 982 chronic obstructive lesions that were stented using intravascular ultrasound (IVUS) [53]. The one-year primary and secondary patency rates were 50 and 81 percent, respectively. In another series of 304 limbs with symptomatic chronic venous occlusion (142 non- and 162 post-thrombotic), patients were stented without thrombolysis [127]. Primary and secondary patency rates at 24 months were 71 and 97 percent, respectively. The resolution of symptoms mirrored the patency of the stented vein. The patency of nonthrombotic legs was superior to those with post-thrombotic disease (90 versus 70 percent).

Still, it is important to note that in a small study of 12 female patients with MTS, isolated endovascular treatment of MTS without embolization of gonadal vein was less successful for those with concurrent pelvic congestion syndrome (16.6 versus 83.4 percent) [128].

For patients with severe venous reflux in both the superficial and deep venous systems, it has been postulated that ablation of the superficial venous system may also be useful for treatment. In a retrospective review of 207 patients with MTS and superficial venous reflux, 121 patients were successfully treated with stent placement combined with endovenous laser ablation (EVLA) [65]. The remaining 86 patients, who were treated with EVLA for superficial venous reflux alone, served as a control group. The rate of technical success was 100 percent. The mean follow-up period was 70.4 months. The four-year primary patency rate was 93.3 percent. The incidence of pain, edema, and ulceration was decreased significantly in the stent plus EVLA group. However, there was a high rate of reflux recurrence in the control group. The authors concluded that stent placement is an effective and durable treatment for MTS combined with symptomatic reflux disease and results in a high level of long-term patency and significant relief of pain, edema, and ulceration.

Endovascular techniques — Endovascular techniques for treating iliocaval obstruction, including MTS, are reviewed separately. (See "Endovenous intervention for iliocaval venous obstruction".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism" and "Society guideline links: Chronic venous disorders".)

SUMMARY AND RECOMMENDATIONS

●May-Thurner Syndrome – May-Thurner syndrome (MTS) is defined as extrinsic venous compression by the arterial system against bony structures in the iliocaval venous territory, most commonly of the left common iliac vein by the right common iliac artery. With partial obstruction, the condition can be asymptomatic, but progression to symptomatic extensive deep vein thrombosis (DVT) can occur. The majority of cases are left-sided, but other variants exist. (See 'Anatomic definition and pathophysiology' above.)

●Epidemiology – The prevalence of MTS is unknown for certain and is likely underestimated, largely because most individuals with this anatomic anomaly remain asymptomatic. Among symptomatic patients, MTS has been estimated to be the underlying etiology in 2 to 5 percent of patients. (See 'Epidemiology and risk factors' above.)

●Risk factors – Risk factors for MTS include female sex, particularly those who are postpartum, multiparous, or using oral contraceptives; individuals with spinal abnormalities; or prior aortoiliac vascular stent placement (acquired form of MTS). The development of symptomatic MTS may be more likely in the face of dehydration or hypercoagulable states. (See 'Epidemiology and risk factors' above.)

●Clinical features – Patients can present acutely with extremity pain and swelling, with venous claudication, or with chronic development of symptoms/signs of venous insufficiency. The classic clinical presentation is that of a younger female in the second or third decade of life presenting acutely with left lower extremity swelling that involves the entire limb. (See 'Clinical features' above.)

●Diagnosis – A diagnosis of MTS may be suspected based upon clinical features and initial diagnostic testing, typically duplex ultrasound. A definitive diagnosis requires demonstration of the stenotic or occlusive venous lesion on vascular imaging (see 'Approach to MTS diagnosis' above):

•For patients suspected of having MTS but without venous thrombosis, advanced noninvasive venous imaging (computed tomographic or magnetic resonance venography) should be obtained first to make the diagnosis prior to invasive diagnostic testing and intervention.

•For patients who present with DVT, a presumptive clinical diagnosis of MTS can be made based on risk factors and characteristic clinical features that are highly suggestive of MTS (eg, young age, female, left-sided extensive acute or recurrent DVT). The definitive diagnosis is established with invasive venous imaging after removal of the thrombus.

●Vascular imaging – Advanced noninvasive venous imaging can suggest a diagnosis of MTS with reasonable accuracy. However, to definitively establish a diagnosis of MTS, we prefer to use intravascular ultrasound (IVUS). IVUS is highly sensitive and specific and also shows the precise morphology of the "spur" and degree of stenosis. IVUS requires insertion of the transducer directly into the vein and is generally used in conjunction with catheter-based venography at the time of anticipated intervention. (See 'Intravascular ultrasound' above.)

●Endovascular treatment – The treatment of MTS depends upon the presence of symptoms and their severity and whether DVT is present (see 'Approach to the patient' above and 'Efficacy of endovenous therapy' above):

•No symptoms – For patients identified with MTS anatomy who lack symptoms, no treatment is needed.

•Mild symptoms – For mildly symptomatic MTS in the absence of DVT, we suggest conservative management rather than intervention (Grade 2C). Compression stockings are usually sufficient to manage mild symptoms.

•Moderate-to-severe symptoms

-In the absence of DVT, treatment of MTS is targeted toward reducing the severity of the chronic venous stenosis/occlusion. We suggest angioplasty and stenting of the affected segment, rather than angioplasty alone (Grade 2C). Angioplasty alone is associated with recurrent stenosis.

-For suspected MTS in a patient with DVT, we suggest catheter-directed thrombolysis or pharmacomechanical thrombolysis in addition to anticoagulation rather than anticoagulation alone (Grade 2C). This uncovers the lesion and confirms the diagnosis. Catheter-directed thrombolysis appears to be associated with more complete thrombus resolution and reduced risk for post-thrombotic syndrome. If venous stenosis is confirmed, subsequent management is the same as in patients with moderate-to-severe symptomatic MTS without DVT (ie, angioplasty and stenting).

-Following angioplasty and stenting for symptomatic MTS, we prescribe knee- or thigh-high compression stockings (30 to 40 mmHg) and antiplatelet therapy (provided bleeding risk is low). For patients with DVT, anticoagulation is continued per venous thromboembolism guidelines.

●Surgical treatment – Open surgical treatment (open venous angioplasty, venous bypass) is associated with worse outcomes compared with percutaneous angioplasty/stenting and is rarely needed to manage MTS. However, if thrombolysis is contraindicated, an open cut-down via a common femoral venotomy can be used to evacuate thrombus to uncover the lesion prior to percutaneous angioplasty and stenting. (See 'Approach to the patient' above.)