Continuing Education Activity

May-Thurner syndrome is characterized by venous insufficiency, obstruction, or thrombosis from impaired venous return secondary to venous compression. The most common anatomical variant in patients with May-Thurner syndrome is compression of the left common iliac vein against the spine by the overlying right common iliac artery. Venous compression usually occurs between the aortic origination of the common iliac artery and the iliofemoral junction. The pulsations of the overriding artery compress the vein against the lower lumbar vertebrae, injure the venous endothelium, and promote the formation of endovenous fibrous bands or spurs. May-Thurner syndrome most commonly affects the left iliofemoral vein; alternate anatomical variations have been reported.

May-Thurner syndrome is an underdiagnosed cause of iliofemoral deep vein thrombosis, accounting for 2% to 5% of all deep vein thromboses. Iliofemoral venous thromboses can be extensive and, without proper diagnosis and treatment, have significant morbidity. Mortality from May-Thurner syndrome is usually due to concomitant pulmonary embolism. This activity reviews the etiology, epidemiology, pathophysiology, clinical presentation, diagnostic evaluation, and treatment of May-Thurner syndrome and highlights the role of the interprofessional team in improving outcomes for patients symptomatic of this vascular anatomical variant.

Objectives:

• Identify patients who may have May-Thurner syndrome based on their clinical history.

• Implement diagnostic strategies to screen patients with unprovoked iliofemoral deep venous thrombosis for May-Thurner syndrome.

• Apply best practices when treating patients with May-Thurner syndrome and iliofemoral deep venous thrombosis.

• Develop and effectively implement interprofessional team strategies to improve outcomes for patients with symptomatic May-Thurner syndrome.

Introduction

May-Thurner syndrome is the compression of the iliac vein against the lumbar spine by an overlying iliac artery, resulting in venous insufficiency, stenosis, and obstruction. While May-Thurner syndrome may be asymptomatic, typical symptoms include pain, swelling, and skin changes in the ipsilateral lower extremity. There are several variants of May-Thurner syndrome; the most common is compression of the left common iliac vein by the right common iliac artery. May-Thurner syndrome may be thrombotic or nonthrombotic but should be considered in all persons presenting with an iliofemoral deep venous thrombosis (DVT). 

Rudolf Virchow first reported compression of the left iliofemoral vein by the right common iliac artery in 1851 after cadaveric studies of patients with left iliofemoral thrombosis. However, it was not until 1957 that May and Thurner reported intraluminal fibrous bands within the left iliofemoral veins compressed by the right common iliac artery in 22% of 430 dissected cadavers; these bands were labeled "spurs," and the collection of findings was termed May-Thurner syndrome. Cockett and Thomas were the first to report May-Thurner syndrome in living patients.

Cadaveric and radiographic studies have reported a high prevalence of left iliofemoral vein compression by the right common iliac artery; the prevalence is so high that some consider the findings a normal anatomic variant.[1] Any symptoms that occur, however variable, all stem from the compressive effect of the artery on the vein. The vascular compression impedes venous return, induces endothelial injury, and may progress to thrombotic vascular occlusion. The stereotypical patient with May-Thurner syndrome is a young woman with the acute onset of left lower extremity swelling following stasis, surgery, or during the intrapartum or immediate postpartum periods.

While not all cases of May-Thurner syndrome result in DVT, up to two-thirds of iliofemoral DVTs demonstrate venous spurs.[1] DVT in this clinical context may present acutely, and the thrombus frequently propagates distally into the femoral and popliteal veins to create a sizeable thrombotic burden. Pulmonary embolism may accompany the DVT.[2]

The treatment goals in symptomatic May-Thurner syndrome are to reestablish venous flow, alleviate strictures and venous hypertension, and reduce the incidence of postthrombotic syndrome. Anticoagulation or catheter-directed therapy with mechanical lysis is always followed by vascular stenting due to the irreversible fibrotic nature of the syndrome.[2]

Etiology

May-Thurner syndrome is a symptomatic obstruction of the lower extremity venous system due to compression of a common iliac vein against the spine by the contralateral common iliac artery. Most frequently, the left common iliac vein is compressed by the right common iliac artery. However, right-sided and caval May-Thurner syndrome has been reported.[3][4] Pulsations of the overriding artery cause shear stress and endothelial changes in the vein, resulting in the formation of fibrous bands or spurs. Over time, the affected area forms a stricture, causing impaired venous return and, in some circumstances, DVT.

Early studies demonstrated that the formation of the fibrous bands and resulting stenosis is irreversible; once a thrombosis is treated and flow restored through a combination of pharmacologic, mechanical, and surgical interventions, the vein does not recanalize. Venous stenting is a mainstay of treatment.[5][6][3]

Epidemiology

The exact incidence and prevalence of May-Thurner syndrome are unknown; it is assumed the condition is underdiagnosed, as many patients are asymptomatic. Many patients with May-Thurner syndrome who develop pain and swelling of the ipsilateral lower extremity or have a DVT of the affected extremity demonstrate evidence of collateral venous circulation when imaged; the development of such venous collaterals indicates the syndrome's chronicity. DVT is more common in the left lower extremity in patients with May-Thurner syndrome, and left-sided iliofemoral DVT is considered a frequent late-stage presentation. Radiological studies of patients with a left lower extremity DVT reveal May-Thurner syndrome in 22% to 76%.[1] 

A systematic literature review reported that the incidence of May-Thurner syndrome in women is twice that of men. Women with symptomatic May-Thurner syndrome are commonly between 30 and 50 years of age and are more likely to present with a concurrent pulmonary embolism.[7] Men with May-Thurner syndrome are more likely to present with lower extremity pain and edema.

Pathophysiology

The chronic pulsatile stimulation from the overlying artery injures the venous endothelium; the characteristic response to injury in May-Thurner syndrome is the deposition of collagen and elastin and the formation of fibrous bands or spurs between the anterior and posterior walls of the vein. In conjunction with the ongoing external venous compression, these spurs lead to venous obstruction, stenosis, and, on occasion, DVT.

Many patients with May-Thurner syndrome remain asymptomatic due to venous collaterals that preserve flow in health. DVT most commonly occurs in the setting of May-Thurner anatomy when the additional risk factors of stasis, injury, or a prothrombotic state are present.[2]

Histopathology

The three histologic types of venous spurs in May-Thurner syndrome are central, lateral, and fenestrated.[8]

History and Physical

The clinical presentation of May-Thurner syndrome is highly variable. Some patients will demonstrate the gradual progression of venous insufficiency, while others may describe the acute onset of lower extremity pain and edema. The most common presentation of May-Thurner syndrome reported in the literature is a younger woman with left lower extremity swelling alleviated with rest and elevation. These symptoms may slowly progress to include dermal hyperpigmentation and ulceration. Contrarily, a patient may develop symptoms following surgery, during or shortly after pregnancy, or after starting oral contraceptives; the classic presentation in these scenarios is a painful and edematous left lower extremity. Rarely, patients of both genders may develop phlegmasia cerulea dolens or other limb-threatening processes.[9]

The pathologic changes from compression of the iliac vein may be subtle may go unrecognized secondary to functional collateral vasculature. Subtle symptoms include but are not limited to left lower extremity tightness that resolves during sleep, mild swelling, hyperpigmentation, telangiectasias, or venous ulceration; all are nonspecific for May-Thurner syndrome. Contrarily, these symptoms may present abruptly following an ineffective venous ablation procedure. Venous claudication is another symptom commonly reported by patients with May-Thurner syndrome.[1] 

The 3 stages of May-Thurner syndrome are: 

• Stage I: asymptomatic left iliac vein compression
• Stage II: formation of venous spurs
• Stage III: left lower extremity DVT.[10]

The diagnosis of May-Thurner syndrome requires a comprehensive physical examination and imaging. The physical examination should include a complete set of vital signs, a thorough cardiopulmonary examination, and an evaluation of both lower extremities.

Evaluation

Doppler ultrasonography is the preferred initial imaging modality and may reveal venous insufficiency or a distal thrombus. If no thrombus is found in the distal venous system, evaluation of the iliac and caval vessels is recommended. If ultrasonography proves suboptimal in assessing the proximal vessels, computed tomography (CT) or magnetic resonance (MR) venography is recommended.[11]

Doppler ultrasonography is noninvasive and readily available but is operator-dependent. While Doppler ultrasonography can measure venous flow, categorize the amount of reflux, measure vessel diameter, and assess for stenosis and obstruction, assessing the inferior vena cava and iliac veins may be limited by body habitus or impeding structures.[12]

CT venography has greater than 95% sensitivity and specificity to detect iliac vein compression and can visualize stenosis, collaterals, and DVT. CT venography can exclude other causes of iliac vein compression, such as lymphadenopathy, malignancy, and hematoma.[13] However, CT venography cannot incorporate the volume status of the patient and may overestimate the degree of venous compression in a dehydrated patient. Maneuvers can be employed during CT venography to overcome any false appearance of May-Thurner syndrome.[10] CT venography must be avoided in pregnancy and used cautiously in those with renal insufficiency. MR venography is comparable to CT venography but offers better delineation of structures and is acceptable during pregnancy. However, an isolated MR venography evaluation may be insufficient to diagnose May-Thurner syndrome effectively; compression of the common iliac vein can be intermittent and variable.[14] MR venography is more expensive and less readily available than either Doppler ultrasonography or CT venography.[14]

Intravascular ultrasonography has largely replaced the catheter venography studies historically employed when noninvasive diagnosis was inconclusive; contrast agents, radiation exposure, prolonged procedure times, and bleeding risks render catheter venography a suboptimal diagnostic modality. Intravascular ultrasound has greater than 98% sensitivity for iliac vein compression and can characterize the location and severity of fibrosis, stenosis, and thrombus.[15] Intravascular ultrasonography is capable of precise measurements and is performed when preparing for stent placement, visualizing guidewires during recanalization, and confirming stent placement. Additionally, intravascular ultrasonography is the only imaging modality capable of identifying and quantifying subtle vessel changes.[16] Intravascular ultrasonography provides information regarding thrombus chronicity, facilitating treatment decisions, including pursuing clot lysis.[11] Intravascular ultrasonography does not require contrast agents but is invasive, not widely available, and cannot provide information about surrounding anatomical structures.

Treatment / Management

The clinical presentation and the presence of a thrombus dictate the treatment of May-Thurner syndrome. Angioplasty and venous stenting are indicated in patients with nonthrombotic May-Thurner syndrome; patients with minimal symptoms are treated with conservative measures such as compression and elevation of the affected extremity, counseling regarding prothrombotic risks, and close follow-up. Anticoagulation or antiplatelet therapy is recommended for patients with May-Thurner syndrome, a confirmed thrombus, and an acceptable anticoagulation risk profile.[17] Delaying initiation of anticoagulation is associated with an increased risk of life-threatening pulmonary embolism (PE).[18]

Anticoagulation for patients with May-Thurner syndrome is characterized by the initiation of unfractionated heparin, followed by low-molecular-weight heparin or fondaparinux as a bridge to warfarin or novel oral anticoagulants.[19][20][21][22] A multicenter randomized trial demonstrated the safety of rivaroxaban in patients with iliofemoral vein thrombosis; 50% of studied patients were diagnosed with May-Thurner syndrome.[22] Although the difference in major bleeding events did not reach statistical significance, the risk of bleeding was lower in the rivaroxaban group compared to the warfarin group.[22] 

Anticoagulation alone is insufficient therapy for patients with thrombosis of the iliofemoral vein secondary to May-Thurner syndrome. The Catheter-Directed Venous Thrombolysis (CaVenT) trial and a subgroup analysis of the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Vatheter-Directed Thrombolysis (ATTRACT) trial demonstrated that catheter-directed thrombolysis with anticoagulation is superior to anticoagulation alone.[23][24] Berger et al were the first to report the safety and efficacy of vascular stenting in May-Thurner syndrome.[25] Multiple studies have demonstrated that vascular angioplasty without stenting is insufficient in patients with May-Thurner syndrome due to irreversible venous stenosis.[26][27][28] The Society of Interventional Radiology guidelines and the Society of Vascular Surgery recommend iliac venous stenting for external iliac vein compression.[29][30] 

Open thrombectomy followed by angioplasty and stenting is reserved for those patients with contraindications to lytic therapy.[15][31] Absolute contraindications to catheter-directed pharmacologic thrombolysis include active bleeding, cerebral infarction, head trauma within the past 3 months, and the presence of intracranial tumor, aneurysm, or vascular malformation.[32] Additionally, patients undergoing planned procedures such as neurologic or ocular intervention should not be offered catheter-directed pharmacologic intervention.[32] Relative contraindications to catheter-directed pharmacologic thrombolysis include pregnancy, thrombophlebitis, major trauma or surgery in the preceding 10 days, a gastrointestinal bleed within the past 3 months, chronic blood pressure readings greater than 180 mmHg systolic or 110 mmHg diastolic, severe renal or hepatic disease, hemorrhagic diabetic retinopathy, or bleeding diathesis.[33] 

Surgical resection of the involved venous segment is rarely performed and is reserved for patients who fail endovascular procedures. Surgical approaches include saphenofemoral crossover bypass, cross-pelvic venous bypass, femoro-femoral prosthetic bypass, femoro-caval bypass, ilio-ilial prosthetic bypass, and aortic elevation.[34]

Differential Diagnosis

Iliac vein compression may be due to underlying malignancy, lymphadenopathy, hematoma, or cellulitis.[35][36] Anatomic variants or disease processes that may compress the iliac vein include uterine leiomyoma, aortoiliac aneurysm, retroperitoneal fibrosis, and osteophytes.[37][38] Any person presenting with an iliofemoral thrombus of uncertain etiology should undergo an evaluation for thrombophilia and appropriate cancer screening. 

Prognosis

May-Thurner syndrome remains asymptomatic in most patients. Multiple cadaveric studies have demonstrated a much higher prevalence than is accounted for by symptomatic patients. With timely diagnosis of symptomatic patients and alleviation of mechanical compression, most patients with May-Thurner syndrome can maintain a high quality of life. It is important to continue intermittent surveillance to address symptom progression. Close clinical follow-up is recommended to mitigate thrombotic recurrence and optimize quality of life.[2]

Complications

Postthrombotic syndrome is a common complication of symptomatic May-Thurner syndrome; the rate of postthrombotic syndrome can be reduced to less than 10% with comprehensive therapeutic interventions.[39] Postthrombotic syndrome is a complication of DVT of any etiology and is marked by chronic pain, edema, and ulceration of the affected limb. Risk factors for postthrombotic syndrome include an extensive thrombotic burden, residual thrombus following thrombolysis, obesity, and thrombus recurrence. Comerota et al demonstrated that residual thrombosis after catheter-based thrombolysis is positively associated with the development of postthrombotic syndrome.[40][41] Mechanical or pharmacological thrombolysis may reduce the risk of postthrombotic syndrome; patients may benefit from knee- or thigh-high compression stockings in addition to a prescribed exercise regimen.[40][42][34]

Consultations

Personnel typically involved in the care of patients with May-Thurner syndrome include:

• Interventional radiologists
• Vascular surgeons
• Wound care specialists
• Hematologists.

Deterrence and Patient Education

Patients with May-Thurner syndrome must be counseled about the signs and symptoms of thrombosis and the need to seek care when symptoms present. Long-term follow-up is recommended to identify any progression in symptoms. Affected persons should be encouraged to practice compression and elevation of the affected extremity. Patients treated with anticoagulant therapy must be educated about the inherent bleeding risks and instructed to seek immediate care during periods of uncontrolled or extensive bleeding.[43]

Pearls and Other Issues

The symptoms of May-Thurner syndrome may be subtle until they are quite advanced. Thrombotic events often occur coincident with the development of a prothrombotic risk factor such as stasis, endothelial injury, or pregnancy. The prompt initiation of anticoagulant therapy minimizes the risk of postthrombotic syndrome, the risk of which is significantly increased by residual thrombus following thrombolysis and stenting. 

Enhancing Healthcare Team Outcomes

Identifying patients with May-Thurner syndrome is the critical step to reducing morbidity mortality. Diagnosing May-Thurner syndrome requires a high index of clinical suspicion and a collaborative approach among healthcare professionals to ensure timely and appropriate testing and improved outcomes.

Primary care practitioners, emergency department providers, radiologists, interventional specialists, vascular surgeons, nurses, pharmacists, physical therapists, and wound care specialists must possess the clinical knowledge and skills to diagnose May-Thurner syndrome and manage its sequelae. Expertise with noninvasive and invasive diagnostic modalities, including advanced endovascular techniques, is required. 

Coordinated care teams help with timely diagnosis and intervention, as well as improving long-term outcomes and overall quality of life. Patient education regarding daily practices, medication, and warning signs and symptoms is crucial to mitigating morbidity from May-Thurner syndrome. Interprofessional communication is important for patient care and informed decision-making and leads to the best outcomes for affected persons.