CC BY 4.0 · TH Open 2020; 04(03): e189-e196
DOI: 10.1055/s-0040-1714694
Original Article

Clinical Outcomes of May–Thurner Syndrome in Pediatric Patients: A Single Institutional Experience

1   Division of Pediatric Hematology-Oncology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States
2   Special Coagulation Laboratory, Division of Hematopathology, Mayo Clinic, Rochester, Minnesota, United States
,
Amulya Nageswara Rao
1   Division of Pediatric Hematology-Oncology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States
,
Haraldur Bjarnason
3   Division of Vascular and Interventional Radiology, Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
,
Vilmarie Rodriguez
1   Division of Pediatric Hematology-Oncology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States
› Author Affiliations
 

Abstract

Introduction May–Thurner syndrome (MTS) is a vascular anatomic variant resulting in compression of the left common iliac vein by the right common iliac artery, affecting approximately 22% of the population. In adults, following acute deep vein thrombosis (DVT) of the iliofemoral veins, the incidence of postthrombotic syndrome (PTS) and recurrent DVT are high if treated with anticoagulation alone, warranting adjunctive treatment with thrombolysis and stent placement. However, there is paucity of literature documenting the course of treatment and associated outcomes in pediatric patients with MTS.

Methods A retrospective chart review of pediatric patients (≤ 18 years of age) with radiologic confirmation of MTS with or without DVT evaluated and/or treated at our institution from January 1, 2005 through December 31, 2015 was conducted.

Results Seventeen patients (4 male; 13 female) were identified. Median age was 15.4 years (range 8.8–17.1 years) with a median follow-up of 1.2 years (range 0.4–7.5 years). Thirteen (76.5%) patients presented with left lower extremity DVT. Management included catheter-directed thrombolysis (n = 5), systemic thrombolysis (n = 1), and mechanical thrombectomy (n = 1). Fifteen patients were treated with anticoagulation including two patients with endovascular stents without DVT. Median duration of anticoagulation was 6.3 months (range 3.2–18.7 months). Ten patients (59%) underwent stent placements.

Complete and partial thrombus resolution was noted in six patients each and no resolution in one patient. Four patients had recurrence/progression of thrombus (n = 3 with stents) at a median time of 29 days (range 12–495 days). No bleeding complications were observed. Clinically documented or self-reported PTS was noted in 8 patients (62%).

Conclusion There are no clear guidelines for MTS management in children and adolescents. In our cohort, thrombolysis, anticoagulation, or stent placements were not associated with bleeding risks, with recurrence/progression of DVT and signs and symptoms of PTS noted in 30 and 62%, respectively. Further studies are needed to determine a standardized treatment approach of the pediatric patient with MTS with or without thrombosis.


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Introduction

May–Thurner syndrome (MTS) also known as Cockett syndrome is an anatomic variant resulting in compression of the left iliac vein by the overlying right common iliac artery against the lumbar vertebrae. As the vessel is compressed, changes of chronic endothelial irritation including collagen deposition can develop over time with partial or complete occlusion of the vein. This anatomic variant associated with MTS is known to increase the incidence of left-sided lower extremity deep vein thrombosis (DVT).[1] [2] [3] [4] The true prevalence of MTS is unknown, but it is estimated to be associated in 18 to 49% of left leg DVT.[1] [2] Clinically, most patients present with acute DVT in the left lower extremity or progressively unilateral leg swelling and pain without an identifiable thrombosis; however, many patients may remain asymptomatic throughout their lifetime.[3] The clinical association of DVT and MTS is relatively low with a reported range of 2 to 3%.[5]

The main treatment goal of MTS associated with iliofemoral DVT is directed toward prevention of postthrombotic syndrome (PTS) (e.g., swelling secondary to venous insufficiency, pain, skin discoloration, and venous stasis skin ulceration). Anticoagulant therapy with unfractionated heparin (UFH), low molecular weight heparin (LMWH), with or without transition to warfarin, or direct-acting anticoagulants (e.g., rivaroxaban, apixaban) is the main treatment modality for patients presenting with acute DVT. Anticoagulation prevents thrombus propagation and/or pulmonary embolism (PE) but does not resolve the chronic venous occlusion secondary to thrombus or anatomic occlusion of the iliac vein secondary to compression by the overlying right iliac artery. Acute thrombosis associated with MTS has been historically treated with catheter-directed thrombolysis (CDT), mechanical thrombectomy (CDT in combination with mechanical thrombectomy is often referred to as pharmacomechanical thrombectomy [PMT]), percutaneous balloon angioplasty, and stenting.[5] [6] [7] [8] In adults with MTS and DVT, recurrence of thrombosis is more common in those patients treated with anticoagulation alone[9] than those treated with PMT. Most adults with DVT in the setting of MTS undergo stent placement[10] [11] whether in combination with PMT or later in association with venous recanalization of the chronic postthrombotic obstruction, angioplasty, and stent placement. However, few case reports and studies have reported the course of treatment and outcomes in pediatric patients with MTS.[12] [13] [14] There are currently no established standard treatment approaches in pediatric patients with MTS.

The purpose of our study was to retrospectively review our institutional management of pediatric MTS with or without DVT, and outcomes including thrombus response, recurrence/progression of thrombus, stent failure, and development of PTS.


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Methods

This study was approved by the Mayo Clinic Institutional Review Board. Medical record data was abstracted for all pediatric patients (≤ 18 years of age) who presented for evaluation and/or treatment of MTS with or without DVT. The study period comprised from January 1, 2005 to December 31, 2015. Patient demographic data, baseline thrombosis risk factors (e.g., body mass index [BMI]), congenital or acquired thrombophilia, immobility, and oral contraceptive pill (OCP) use, were reviewed. Overweight was defined as a BMI ≥ 25 kg/m2 and obesity as a BMI ≥ 30 kg/m2.[15] Thrombophilia testing included antiphospholipid antibodies (i.e., lupus anticoagulant immunoglobulin [Ig] G, IgM, and anticardiolipin antibodies), activated protein C (APC) resistance with reflex gene sequencing for factor V Leiden if APC resistance abnormal, prothrombin G20210A mutation, antithrombin activity and antigen, protein C activity, free protein S, fibrinogen level, and fibrin D-dimer. Radiological techniques used for diagnosis of MTS and DVT, modality of treatment (e.g., catheter or systemic thrombolysis, thrombectomy, balloon angioplasty, stent placement), duration, and type of anticoagulation were also collected. Thrombosis outcomes were defined as complete resolution (no residual thrombus identified by ultrasound Doppler, magnetic resonance venography [MRV], or computed tomography venography [CTV], venography), partial resolution (residual thrombosis), and no resolution (complete occlusion of one or more affected left lower extremity veins). Recurrence and progression of DVT were defined as per guidelines developed by the Perinatal and Pediatric Haemostasis Subcommittee of the Scientific and Standardization Committee of International Society of Thrombosis and Haemostasis.[15]

Stent failure was defined as no demonstrable blood flow secondary to thrombosis or mechanical failure if no thrombosis. Signs and symptoms of PTS were reviewed from medical-clinical notes (e.g., pain, swelling, dilated blood vessels, varicosities, and skin ulceration). A previously developed and validated PTS survey instrument was mailed to patients with thrombosis.[16] [17]

Statistical Analyses

Standard statistical methods were used to summarize collected data: frequency and percent for categorical variables and mean, median, and range for ordinal or continuous variables. Analysis was performed using JMP software (JMP version 13, SAS Institute Inc, Cary, North Carolina, United States; 1989–2016). Comparative analysis among subgroups and significance of difference (two-tailed p-value < 0.05) were reported if sample size allowed analysis. Contingency analysis by Fisher's exact test was used for categorical comparisons and survival analysis was performed by Kaplan–Meier test.


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Results

Demographics

Seventeen patients (13 female) were identified. Median follow-up was 1.2 years (range 0.4–7.5 years) ([Table 1]). Fifteen patients identified as Caucasian, one patient each identified as African American and Hispanic. Median age at diagnosis of MTS was 15.4 years (range 8.8–17.1 years).

Table 1

Patient characteristics, management, and outcomes

Case ID

Gender/Age in years

Risk factors

Location extent thrombosis

Thrombolysis

Stenting

Anticoagulation

Recurrence/Progression (time)

Thrombosis outcomes (CR/PR/NR)

PTS/duration follow-up (y)

1

F/16.7

OCP

Inferior IVC/external and internal left iliac veins/common femoral extending popliteal and tibial veins

Catheter-directed Alteplase (0.5 mg/h, 1 mg/h)

Yes

UFH/LMWH/Warfarin/Clopidogrel

No

PR

No (5.6)

2

F/16.2

OCP

Left common iliac/common femoral, upper deep femoral to popliteal/PE

Catheter-directed Alteplase (0.5 mg/h)

Yes

UFH/Warfarin

LMWH recurrent occlusion stent

Yes (6 d)

PR

No (1.2)

3

F/15.5

Heterozygous factor V Leiden/immobility and OCP

Left iliofemoral to popliteal

None

Yes

UFH/Warfarin/Clopidogrel

No

PR

No (0.4)

4

F/15.2

OCP/ overweight (BMI 25.6)

Mid to distal left common iliac vein and external iliac vein

None

No

Warfarin/Clopidogrel

No

CR

Yes (0.9)

5

F/14.6

OCP

NA

None

No

None

No

NA

NA

6

M/14.5

None

Left common iliac vein through common femoral to popliteal

Catheter-directed Alteplase (0.5 mg/h, 0.75 mg/h)

No

LMWH/Warfarin

Yes (11 d)

PR

No (3.0)

7

M/17.1

Heterozygous factor V Leiden

Overweight (BMI 29.34)

Common femoral, superficial femoral to popliteal and proximal calf veins/PE

Systemic t-PA (0.03 mg/kg/h, 0.06 mg/kg/h)

No

UFH/LMWH/Rivaroxaban

No

PR

Yes (1.2)

8

F/11.6

None

Left iliac vein

None

Yes

LMWH

No

CR

Yes (7.5)

9

F/16.4

Heterozygous factor V Leiden/Immobility/OCP

Left common iliac, femoral, deep femoral, and popliteal

Catheter-directed thrombolysis outside institution

Yes

LMWH/Warfarin

Yes (104 d)

NR

Yes (0.4)

10

M/8.8

None

NA

None

No

None

No

NA

NA

11

F/13.6

None

NA

None

Yes

Rivaroxaban

No

NA

NA

12

M/14.8

None

Left common and external iliac and femoral

None

No

ASA initially then LMWH/Warfarin after balloon venoplasty

No

PR

Yes (0.7)

13

F/14.6

Heterozygous factor V Leiden, protein C deficiency, and OCP

Left common and external iliac and common femoral

Mechanical thrombectomy-outside institution

Yes

LMWH/Warfarin

Yes (20 d)

CR

Yes (3.2)

14

F/15.4

Immobility and OCP

Obese (BMI 30.66)

Left external iliac/common femoral to popliteal/PE

Catheter-directed Alteplase (0.5 mg/h)

Yes

LMWH/Warfarin

No

CR

Yes (1.1)

15

F/16.5

None

NA

None

Yes

Heparin/LMWH/

Warfarin/Rivaroxaban and clopidogrel after Nutcracker repair

No

NA

NA

16

F/16.2

Immobility and OCP

Overweight (BMI 29.4)

Left external iliac and common femoral

None

Yes

LMWH/Warfarin/Rivaroxaban

No

CR

Yes (1.0)

17

F/16.8

Homozygous factor V Leiden/OCP

Obese (BMI 33.01)

Left common femoral to posterior tibial/PE

None

No

LMWH/Warfarin

No

CR

No (0.8)

Abbreviations: ASA, acetylsalicylic acid; BMI, body mass index; CR, complete resolution; DVT, deep vein thrombosis; LMWH, low molecular weight heparin; NA, not applicable; NR, no resolution; OCP, oral contraceptive pills; PE, pulmonary embolism; PR, partial resolution; PTS, postthrombotic syndrome; UFH, unfractionated heparin.



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Clinical Presentation

Pain and swelling were the most common presenting symptoms (n = 13, 76%). Thirteen patients presented with acute DVT of the left lower extremity (76%) while four were diagnosed with MTS without DVT (asymptomatic sibling of MTS patient [n = 1] and pain and/or swelling [n = 3]) ([Fig. 1]). Four patients were noted to have PE at the time of DVT diagnosis ([Table 1]).

Zoom Image
Fig. 1 Summary of patients with May–Thurner syndrome.

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Thrombotic Risk Factors

Comorbidities associated with risk for thrombosis such as increased BMI (≥ 25 kg/m2), immobility, OCP use, and thrombophilia were analyzed among patients with or without DVT ([Table 1]). The median BMI was 23.63 kg/m2 (range 18.32–33.01 kg/m2). The median BMI was similar at 23.81 kg/m2 when four patients without DVT were excluded (range 18.44–33.01 kg/m2). Thrombophilia testing was performed in only six patients. Five patients tested positive for factor V Leiden mutation (heterozygous = 4; homozygous = 1). Ten out of the 13 (76%) patients with DVT had one or more thrombosis risk factors such as inherited thrombophilia, immobility, increased BMI, and/or use of OCP. Increased BMI (n = 5), immobility (n = 4), and OCP use (n = 10) as risk factors for thrombosis were found to be nonsignificant (p-value 0.26, 0.52, and 0.25, respectively).


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Diagnostics

Radiological modalities used to establish the diagnosis of MTS with or without DVT included: ultrasound Doppler and venography (n = 7), ultrasound Doppler with MRV (n = 5), ultrasound Doppler and CTV (n = 4), and MRV only (n = 1).


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Management

Management in patients with or without DVT is summarized in [Table 1].

Initial treatment: Anticoagulation and Thrombolysis

Out of the 13 patients that presented with acute DVT, 6 (35%) were treated with thrombolysis in addition to systemic anticoagulation (catheter-directed = 5; systemic = 1) at a median of 1 day from DVT diagnosis (range 0–8 days). The median treatment duration was 2 days (range 1–4 days). One patient underwent PMT upon diagnosis of DVT at an outside institution 3 years prior to presentation. Overall, choice of anticoagulation therapy was variable and consisted of initial UFH or LMWH that were later transitioned to or continued on LMWH, warfarin, or direct oral anticoagulants such as rivaroxaban. Median duration of anticoagulation was 6.3 months (range 3.2–18.7 months). Antiplatelet agents such as clopidogrel and aspirin were used in some patients ([Table 1]). Anticoagulation with or without antiplatelet agents were used in patients without DVT who underwent placement of a stent or balloon angioplasty.


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Endovascular Stenting

Ten patients (59%) had stent placement at a median of 3.5 days (range 0–376 days) in those following DVT diagnosis (n = 8) ([Table 2]). In two patients without DVT, the stents were placed at 767 and 1,117 days (2.1 and 3.1 years) from the diagnosis of MTS, respectively. Stent failure occurred in 5 patients (50%) at a median of 1.7 months (range 0.3–72 months): 1 due to growth-related stent migration from compression site, 1 due to stent narrowing, and 3 due to thrombosis leading to stent replacement. All 5 patients underwent interventional stent recanalization procedure, of which 4 remained patent while 1 remained occluded. Proportion of stent survival at last follow-up was 90% (9 of 10 stents) with a median follow-up of 1.1 years (range 0.2–6.5 years). There was no association between stent size (diameter of 14 mm vs. > 14 mm) and stent failure (p = 0.52)

Table 2

Summary of endovascular stenting and patency rates

Case ID

Thrombosis

Time to stent placement from MTS diagnosis in days (in years)

Stent location

Type of stent (number)

Stent size

Time to stent failure in days (in years)

Additional stent

(location)

Stent patency at last follow-up

Duration from MTS diagnosis in months (in years)

1

Yes

4

CIV

ProtégéTM1

14 mm × 80 mm

NA

Patent

67 (5.6)

EIV extending into CFV

ProtégéTM2

14 mm × 80 mm, 14 mm × 40 mm

2

Yes

0

CIV

WallstentTM1

14 mm[a]

9

Protégé™ (CIV)

Patent

14.3 (1.2)

EIV extending into CFV

WallstentTM2

14 mm[a], 12 mm[a]

3

Yes

0

CIV

WallstentTM1

18 mm × 60 mm

NA

Patent

4.5

8

Yes

337

CIV

ProtégéTM1

14 mm × 60 mm

2190 (6 y)

Wallstent™ (IVC)

Patent

89.6 (7.5)

9

Yes

1

CIV

WallstentTM2

14 mm × 60 mm, 14 mm × 40 mm

112

Not placed

Occluded (CIV, EIV)

5.3

EIV extending into CFV

ProtégéTM2

14 mm × 80 mm, 14 mm × 80 mm

11

No

1117 (3.1 y)

CIV

WallstentTM1

16 mm × 60 mm

NA

Patent

36.7 (3.1)

EIV

WallstentTM1

16 mm × 60 mm

13

Yes

0

CIV, EIV, and CFV

Unknown

Unknown

31

Type unknown

Patent

38.1 (3.2)

14

Yes

1

CIV

WallstentTM1

16 mm × 60 mm

NA

Patent

13.4 (1.1)

15

No

767 (2.1 years)

CIV

WallstentTM1

16 mm × 40 mm

51

Not placed

Patent

26.9 (2.2)

16

Yes

287

CIV

WallstentTM2

14 mm × 60 mm, 14 mm × 40 mm

NA

Patent

12

EIV

ProtégéTM2

14 mm × 80 mm, 14 mm × 80 mm

Abbreviations: CIV, left common iliac vein; CFV, left common femoral vein; EIV, left external iliac vein; IVC, inferior vena cava; MTS, May–Thurner syndrome; NA, not applicable.


Note: Protégé™ [Medtronic, Minneapolis, Minnesota, United States]; Wallstent™ [Boston Scientific, Marlborough, Massachusetts, United States].


a Stent length information not available.



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Outcomes

Complete resolution of thrombus was noted in 6 (46%) patients, partial resolution in 6 (46%), and no response in 1 (8%). Four patients (31%) had recurrence/progression of thrombus (n = 3 with stents) at a median time of 29 days (range 12–495 days). No bleeding complications were observed. One patient had progression of DVT 11 days from diagnosis; CDT was initiated with partial resolution of the thrombosis; no stent was placed due to multiple collateral vessels. The role of thrombolysis therapy and its potential role for the prevention of recurrent thrombosis was analyzed and found to be nonsignificant (p = 1.0). Neither degree of thrombosis clearance (complete vs. partial or no resolution) nor stent implantation (stent vs. no stent) were found to be associated with thrombosis recurrence (p = 0.26 and p = 1.0, respectively).

On reviewing patients charts for signs and symptoms of PTS such as swelling, pain, skin discoloration, varicosities, skin ulceration, and claudication, five patients were noted to have had signs and symptoms consistent with PTS at the time of last follow-up. Only 4 patients responded to the mailed PTS survey that confirmed PTS documentation in 1 patient and an additional 3 patients reported PTS symptoms (mild PTS = 1; moderate PTS = 3) resulting in a total of 8 (62%) patients with PTS following DVT at a median follow-up of 16 months (range 9.6–89.8 months). Of the 8 patients with DVT that had stent placements, 5 (63%) patients had clinically documented and/or self-reported PTS at a median follow-up of 17 months (range 4.9–89.8 months). The degree of DVT clearance (complete vs. partial or no resolution), use of thrombolysis, and stent placement were not found to be significantly associated with development of PTS (p = 1.0, 0.10, and 0.62, respectively).


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Discussion

Compression of the left iliac vein by the overriding right iliac artery, also known as MTS, can result in left iliofemoral thrombosis in approximately 50 to 60% of patients as a result of intraluminal spurs from compression.[4] [18] Similar to other pediatric series, a female preponderance was noted (M:F ratio 1:3.3). Other precipitating factors such as immobility, inherited thrombophilia, surgery, hormonal therapy, and pregnancy were also noted.[4] [19] [20] [21] In our review, 77% of patients with MTS and DVT had one or more thrombosis risk factors such as inherited thrombophilia, immobility, and/or use of OCPs.

Several radiological imaging modalities are useful in establishing the diagnosis of MTS. Ultrasound Doppler is usually the first and fastest method used to diagnose DVT.[22] However, this radiological technique cannot identify the anatomic compression of the left iliac vein reliably and cannot demonstrate the venous spurs caused by chronic compression. To accurately diagnose MTS, other cross-sectional imaging modalities such as CTV or angiography, magnetic resonance angiography, and/or venography are used for detailed visualization of the pelvic vasculature and anatomy.[23] [24] [25]

Anticoagulation is the first-line treatment used to prevent clot extension and occurrence of PE. However, anticoagulation alone neither corrects the anatomic compression of the left iliac vein nor results in clot dissolution. Surgical thrombectomy was considered a treatment option before PMT and stent placements became more commonly used.[26] [27] Despite the different surgical techniques, similar primary and secondary patency have been reported at 5 years (42 and 59%, respectively).[28] Due to advances in endovascular techniques, MTS patients rarely have to undergo open vascular surgical procedures.[4] [8] [10] [19] [29] In adults, catheter-directed PMT with or without stent placement in addition to anticoagulation are considered the standard treatment for MTS with acute thrombosis with patency rates reported at 79 to 100% at 2 years.[11] [29] [30] [31] [32] To date, pediatric (≤ 18 years of age) literature consist primarily of case reports and limited case series, of which the largest series include Goldenberg et al,[12] Murphy et al,[33] and Goldman et al[14] that studied 6 (prospective), 5 (prospective), and 10 (retrospective) cases, respectively. In these reports, all patients presenting with thrombotic MTS received anticoagulation with catheter-directed mechanical or pharmacomechanical thrombolysis followed by endovascular stent placement. Murphy et al and Goldman et al[14] reported primary patency rates of 100% at the end of procedure and 79% at 12 months, respectively, while Goldman et al[14] reported secondary patency rate of 100% at 12 months and 89% at 36 months, as defined by the Society of Interventional Radiology.[34] Primary and secondary patency rates in the 6 patients in Goldenberg study were 40 and 20% at 12 and 24 months, respectively.[12] [14] In our series, only 59% patients (10/17) had stent placements. Five stent failures were noted due to thrombosis or mechanical failure. Patency was restored in 3 patients with additional stent placements (n = 3) and CDT (n = 1). A primary patency rate of 62% at 12 months ([Fig. 2A]), with secondary patency rate of 88% at last follow-up ([Fig. 2B]) were observed. The limited sample size precluded definitive comparisons of outcomes based on thrombolytic therapy.

Zoom Image
Fig. 2 Stent patency. (A) Primary patency. (B) Secondary patency.

The role of congenital or acquired thrombophilia as a risk factor for thrombosis recurrence in MTS is inconsistent in the pediatric and adult literature.[12] [14] [35] Goldman et al reported a single patient in their cohort of patients with MTS, with loss of secondary stent patency due to congenital thrombophilia and poor adherence to anticoagulation.[14] Goldenberg et al reported 2 recurrent thromboses out of 6 patients with MTS to have associated hypercoagulability.[12] In contrast to the pediatric literature, a large retrospective analysis by Neglén et al in 870 adult patients did not show an increased risk for stent thrombosis in association with thrombophilia.[35] In our series, of the 5 patients with congenital thrombophilic risk factor, only 2 experienced recurrence/progression of thrombosis ([Table 1]) at a median follow-up of 16.8 months (range 4.9–41.4 months); however, the generalizability of these findings is limited to the lack of uniform testing for hypercoagulability disorders in these patients (only 6 patients were tested).

Regardless for treatment modalities, these patients are at risk of developing PTS that is usually associated with swelling, pain, signs of venous insufficiency with dilated blood vessels, varicosities, skin changes, and potential for stasis ulceration in the long term, especially with recurrence of DVT or chronic venous insufficiency.[36] In one study, among adult patients with iliofemoral DVT who were managed with anticoagulation alone, 71% had leg swelling and 18% skin ulcerations at 10 years of follow-up.[37] In our study, signs and symptoms of PTS were clinically documented in 8 of the 13 patients who sustained a DVT; however, the grading severity could not be analyzed due to nonstandardized screening practices and documentation. A previously validated PTS survey tool was sent to all patients who experienced a DVT in the setting of PTS; however, this was met with a poor survey response rate (30.7%). Among patients with stent placement, 63% had clinically documented and/or self-reported PTS. With the exception of Murphy et al reporting 0% PTS symptoms in their cohort at last follow-up, our results are comparable to PTS rates reported by Goldman et al at 60% and Goldenberg et al at 75% of evaluable patients at last follow-up.

Although our study reports the largest pediatric cohort with MTS and real-life experience, we acknowledge several limitations that include retrospective study design, small sample size, heterogeneous treatment strategies, nonstandardized management and documentation, and recall bias. The clinical decision for CDT versus systemic thrombolysis, angioplasty, or stent placement, was at the discretion of the treating physician that incorporated patients' preferences as well. Due to nonstandardized screening methods during clinical documentation of PTS and poor response rate of the mailed-out survey, this study may underestimate the prevalence and severity of PTS.

In summary, MTS should be considered in adolescents with left iliofemoral thrombosis. CDT should be considered early on following diagnosis. For those patients who underwent anticoagulation with or without thrombolysis, no bleeding or procedural complications were observed. The decision algorithm for placement of endovascular stents in adolescents that have achieved full growth is not well established. Our institutional practice for stent placement takes into account the degree of vascular occlusion, resolution with anticoagulation and/or thrombolysis or thrombectomy, and vascular evidence of chronicity (e.g., presence of surrounding collateral vessels), to maximize the chances of successful endovascular stenting and prevent recurrent thrombosis or mechanical failure. Our study emphasizes the need of prospective multi-institutional collaborative efforts to study MTS in children and adolescents to establish standardized guidelines for diagnosis, management including anticoagulation, endovascular approach, and monitoring DVT-related sequelae to optimize long-term outcomes.


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Conflict of Interest

None declared.

Authors' Contributions

All authors have contributed significantly to this study and preparation of the manuscript. All authors have reviewed and approved the manuscript.


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  • 13 Raffini L, Raybagkar D, Cahill AM, Kaye R, Blumenstein M, Manno C. May-Thurner syndrome (iliac vein compression) and thrombosis in adolescents. Pediatr Blood Cancer 2006; 47 (06) 834-838
  • 14 Goldman RE, Arendt VA, Kothary N. , et al. Endovascular management of May-Thurner syndrome in adolescents: a single-center experience. J Vasc Interv Radiol 2017; 28 (01) 71-77
  • 15 Mitchell LG, Goldenberg NA, Male C, Kenet G, Monagle P, Nowak-Göttl U. ; Perinatal and Paediatric Haemostasis Subcommittee of the SSC of the ISTH. Definition of clinical efficacy and safety outcomes for clinical trials in deep venous thrombosis and pulmonary embolism in children. J Thromb Haemost 2011; 9 (09) 1856-1858
  • 16 Kumar R, Rodriguez V, Matsumoto JM. , et al. Development and initial validation of a questionnaire to diagnose the presence and severity of post-thrombotic syndrome in children. Pediatr Blood Cancer 2012; 58 (04) 643-644
  • 17 Kumar R, Rodriguez V, Matsumoto JM. , et al. Health-related quality of life in children and young adults with post-thrombotic syndrome: results from a cross-sectional study. Pediatr Blood Cancer 2014; 61 (03) 546-551
  • 18 Steinberg JB, Jacocks MA. May-Thurner syndrome: a previously unreported variant. Ann Vasc Surg 1993; 7 (06) 577-581
  • 19 Oguzkurt L, Tercan F, Ozkan U, Gulcan O. Iliac vein compression syndrome: outcome of endovascular treatment with long-term follow-up. Eur J Radiol 2008; 68 (03) 487-492
  • 20 Hassell DR, Reifsteck JE, Harshfield DL, Ferris EJ. Unilateral left leg edema: a variation of the May-Thurner syndrome. Cardiovasc Intervent Radiol 1987; 10 (02) 89-91
  • 21 Abboud G, Midulla M, Lions C. , et al. “Right-sided” May-Thurner syndrome. Cardiovasc Intervent Radiol 2010; 33 (05) 1056-1059
  • 22 Ahmed HK, Hagspiel KD. Intravascular ultrasonographic findings in May-Thurner syndrome (iliac vein compression syndrome). J Ultrasound Med 2001; 20 (03) 251-256
  • 23 Chung JW, Yoon CJ, Jung SI. , et al. Acute iliofemoral deep vein thrombosis: evaluation of underlying anatomic abnormalities by spiral CT venography. J Vasc Interv Radiol 2004; 15 (03) 249-256
  • 24 Oguzkurt L, Tercan F, Pourbagher MA, Kizilkilic O, Turkoz R, Boyvat F. Computed tomography findings in 10 cases of iliac vein compression (May-Thurner) syndrome. Eur J Radiol 2005; 55 (03) 421-425
  • 25 Gurel K, Gurel S, Karavas E, Buharalıoglu Y, Daglar B. Direct contrast-enhanced MR venography in the diagnosis of May-Thurner syndrome. Eur J Radiol 2011; 80 (02) 533-536
  • 26 Jost CJ, Gloviczki P, Cherry Jr KJ. , et al. Surgical reconstruction of iliofemoral veins and the inferior vena cava for nonmalignant occlusive disease. J Vasc Surg 2001; 33 (02) 320-327 , discussion 327–328
  • 27 Plate G, Einarsson E, Ohlin P, Jensen R, Qvarfordt P, Eklöf B. Thrombectomy with temporary arteriovenous fistula: the treatment of choice in acute iliofemoral venous thrombosis. J Vasc Surg 1984; 1 (06) 867-876
  • 28 Garg N, Gloviczki P, Karimi KM. , et al. Factors affecting outcome of open and hybrid reconstructions for nonmalignant obstruction of iliofemoral veins and inferior vena cava. J Vasc Surg 2011; 53 (02) 383-393
  • 29 Heijmen RH, Bollen TL, Duyndam DAC, Overtoom TT, Van Den Berg JC, Moll FL. Endovascular venous stenting in May-Thurner syndrome. J Cardiovasc Surg (Torino) 2001; 42 (01) 83-87
  • 30 Bjarnason H, Kruse JR, Asinger DA. , et al. Iliofemoral deep venous thrombosis: safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy. J Vasc Interv Radiol 1997; 8 (03) 405-418
  • 31 Verhaeghe R, Stockx L, Lacroix H, Vermylen J, Baert AL. Catheter-directed lysis of iliofemoral vein thrombosis with use of rt-PA. Eur Radiol 1997; 7 (07) 996-1001
  • 32 Hurst DR, Forauer AR, Bloom JR, Greenfield LJ, Wakefield TW, Williams DM. Diagnosis and endovascular treatment of iliocaval compression syndrome. J Vasc Surg 2001; 34 (01) 106-113
  • 33 Murphy EH, Davis CM, Journeycake JM, DeMuth RP, Arko FR. Symptomatic ileofemoral DVT after onset of oral contraceptive use in women with previously undiagnosed May-Thurner Syndrome. J Vasc Surg 2009; 49 (03) 697-703
  • 34 Vedantham S, Grassi CJ, Ferral H. , et al; Technology Assessment Committee of the Society of Interventional Radiology. Reporting standards for endovascular treatment of lower extremity deep vein thrombosis. J Vasc Interv Radiol 2009; 20 (07) S391-S408
  • 35 Neglén P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg 2007; 46 (05) 979-990
  • 36 Manco-Johnson MJ. Postthrombotic syndrome in children. Acta Haematol 2006; 115 (3-4): 207-213
  • 37 Plate G, Eklöf B, Norgren L, Ohlin P, Dahlström JA. Venous thrombectomy for iliofemoral vein thrombosis--10-year results of a prospective randomised study. Eur J Vasc Endovasc Surg 1997; 14 (05) 367-374

Address for correspondence

Deepti M. Warad, MD
Division of Pediatric Hematology-Oncology, Department of Pediatric and Adolescent Medicine, Mayo Clinic
200 First Street SW, Rochester, MN 55905
United States   

Publication History

Received: 30 April 2020

Accepted: 25 June 2020

Article published online:
20 August 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

Georg Thieme Verlag KG
Stuttgart · New York

  • References

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  • 11 Patel NH, Stookey KR, Ketcham DB, Cragg AH. Endovascular management of acute extensive iliofemoral deep venous thrombosis caused by May-Thurner syndrome. J Vasc Interv Radiol 2000; 11 (10) 1297-1302
  • 12 Goldenberg NA, Branchford B, Wang M, Ray Jr C, Durham JD, Manco-Johnson MJ. Percutaneous mechanical and pharmacomechanical thrombolysis for occlusive deep vein thrombosis of the proximal limb in adolescent subjects: findings from an institution-based prospective inception cohort study of pediatric venous thromboembolism. J Vasc Interv Radiol 2011; 22 (02) 121-132
  • 13 Raffini L, Raybagkar D, Cahill AM, Kaye R, Blumenstein M, Manno C. May-Thurner syndrome (iliac vein compression) and thrombosis in adolescents. Pediatr Blood Cancer 2006; 47 (06) 834-838
  • 14 Goldman RE, Arendt VA, Kothary N. , et al. Endovascular management of May-Thurner syndrome in adolescents: a single-center experience. J Vasc Interv Radiol 2017; 28 (01) 71-77
  • 15 Mitchell LG, Goldenberg NA, Male C, Kenet G, Monagle P, Nowak-Göttl U. ; Perinatal and Paediatric Haemostasis Subcommittee of the SSC of the ISTH. Definition of clinical efficacy and safety outcomes for clinical trials in deep venous thrombosis and pulmonary embolism in children. J Thromb Haemost 2011; 9 (09) 1856-1858
  • 16 Kumar R, Rodriguez V, Matsumoto JM. , et al. Development and initial validation of a questionnaire to diagnose the presence and severity of post-thrombotic syndrome in children. Pediatr Blood Cancer 2012; 58 (04) 643-644
  • 17 Kumar R, Rodriguez V, Matsumoto JM. , et al. Health-related quality of life in children and young adults with post-thrombotic syndrome: results from a cross-sectional study. Pediatr Blood Cancer 2014; 61 (03) 546-551
  • 18 Steinberg JB, Jacocks MA. May-Thurner syndrome: a previously unreported variant. Ann Vasc Surg 1993; 7 (06) 577-581
  • 19 Oguzkurt L, Tercan F, Ozkan U, Gulcan O. Iliac vein compression syndrome: outcome of endovascular treatment with long-term follow-up. Eur J Radiol 2008; 68 (03) 487-492
  • 20 Hassell DR, Reifsteck JE, Harshfield DL, Ferris EJ. Unilateral left leg edema: a variation of the May-Thurner syndrome. Cardiovasc Intervent Radiol 1987; 10 (02) 89-91
  • 21 Abboud G, Midulla M, Lions C. , et al. “Right-sided” May-Thurner syndrome. Cardiovasc Intervent Radiol 2010; 33 (05) 1056-1059
  • 22 Ahmed HK, Hagspiel KD. Intravascular ultrasonographic findings in May-Thurner syndrome (iliac vein compression syndrome). J Ultrasound Med 2001; 20 (03) 251-256
  • 23 Chung JW, Yoon CJ, Jung SI. , et al. Acute iliofemoral deep vein thrombosis: evaluation of underlying anatomic abnormalities by spiral CT venography. J Vasc Interv Radiol 2004; 15 (03) 249-256
  • 24 Oguzkurt L, Tercan F, Pourbagher MA, Kizilkilic O, Turkoz R, Boyvat F. Computed tomography findings in 10 cases of iliac vein compression (May-Thurner) syndrome. Eur J Radiol 2005; 55 (03) 421-425
  • 25 Gurel K, Gurel S, Karavas E, Buharalıoglu Y, Daglar B. Direct contrast-enhanced MR venography in the diagnosis of May-Thurner syndrome. Eur J Radiol 2011; 80 (02) 533-536
  • 26 Jost CJ, Gloviczki P, Cherry Jr KJ. , et al. Surgical reconstruction of iliofemoral veins and the inferior vena cava for nonmalignant occlusive disease. J Vasc Surg 2001; 33 (02) 320-327 , discussion 327–328
  • 27 Plate G, Einarsson E, Ohlin P, Jensen R, Qvarfordt P, Eklöf B. Thrombectomy with temporary arteriovenous fistula: the treatment of choice in acute iliofemoral venous thrombosis. J Vasc Surg 1984; 1 (06) 867-876
  • 28 Garg N, Gloviczki P, Karimi KM. , et al. Factors affecting outcome of open and hybrid reconstructions for nonmalignant obstruction of iliofemoral veins and inferior vena cava. J Vasc Surg 2011; 53 (02) 383-393
  • 29 Heijmen RH, Bollen TL, Duyndam DAC, Overtoom TT, Van Den Berg JC, Moll FL. Endovascular venous stenting in May-Thurner syndrome. J Cardiovasc Surg (Torino) 2001; 42 (01) 83-87
  • 30 Bjarnason H, Kruse JR, Asinger DA. , et al. Iliofemoral deep venous thrombosis: safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy. J Vasc Interv Radiol 1997; 8 (03) 405-418
  • 31 Verhaeghe R, Stockx L, Lacroix H, Vermylen J, Baert AL. Catheter-directed lysis of iliofemoral vein thrombosis with use of rt-PA. Eur Radiol 1997; 7 (07) 996-1001
  • 32 Hurst DR, Forauer AR, Bloom JR, Greenfield LJ, Wakefield TW, Williams DM. Diagnosis and endovascular treatment of iliocaval compression syndrome. J Vasc Surg 2001; 34 (01) 106-113
  • 33 Murphy EH, Davis CM, Journeycake JM, DeMuth RP, Arko FR. Symptomatic ileofemoral DVT after onset of oral contraceptive use in women with previously undiagnosed May-Thurner Syndrome. J Vasc Surg 2009; 49 (03) 697-703
  • 34 Vedantham S, Grassi CJ, Ferral H. , et al; Technology Assessment Committee of the Society of Interventional Radiology. Reporting standards for endovascular treatment of lower extremity deep vein thrombosis. J Vasc Interv Radiol 2009; 20 (07) S391-S408
  • 35 Neglén P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg 2007; 46 (05) 979-990
  • 36 Manco-Johnson MJ. Postthrombotic syndrome in children. Acta Haematol 2006; 115 (3-4): 207-213
  • 37 Plate G, Eklöf B, Norgren L, Ohlin P, Dahlström JA. Venous thrombectomy for iliofemoral vein thrombosis--10-year results of a prospective randomised study. Eur J Vasc Endovasc Surg 1997; 14 (05) 367-374

Zoom Image
Fig. 1 Summary of patients with May–Thurner syndrome.
Zoom Image
Fig. 2 Stent patency. (A) Primary patency. (B) Secondary patency.