Abstract

Introduction : May-Thurner syndrome (MTS) is a condition in which the right iliac artery compresses the left iliac vein, predisposing affected individuals to venous outflow obstruction and deep vein thrombosis (DVT). Despite the frequency of this anatomic variant, found in 20-25% of adults, not everyone with this variant will develop a DVT. Adults with MTS are treated with catheter-directed thrombolysis (CDT), anticoagulation, and often iliac vein stent placement. There is no standard of care established for pediatric MTS patients. The aims of this study are to 1) describe risk factors, clinical factors, and outcomes (complications of CDT, recurrence rate, post-thrombotic syndrome) in a pediatric MTS cohort and 2) determine what factors are associated with thrombus resolution, recurrence, and development of post-thrombotic syndrome (PTS).

Methods : A retrospective cohort of children (0-21 years) diagnosed with MTS and DVT were identified between January 1, 2012 and July 15, 2017. MTS was confirmed by CT venogram, MR venogram, intravascular ultrasound, and/or conventional endovascular venography. Patient demographic, clinical, and thrombophilic risk factors, clinical outcomes (resolution, recurrence, PTS using modified Villalta scale), and bleeding complications were abstracted from review of the electronic medical record. Bleeding complications were defined by ISTH definitions for pediatric trials. Student's t test, Wilcoxon rank sum test, Chi square test and logistic regression analysis were used for statistical analysis (SAS v9.4, Cary, NC, USA).

Results : The cohort was comprised of 23 subjects, 65% of them female (n=15), with a median age at presentation of 16.1 years (9.9-19.7 years). The median follow-up time was 505 days. The most frequent risk factor was thrombophilia (n=10), which included Factor V Leiden mutation (n=6), antithrombin deficiency (n=3), protein S deficiency (n=3), lupus anticoagulant (n=3), prothrombin gene mutation (n=1), protein C deficiency (n=1), or more than one thrombophilia (n=3). Other risk factors included hormone therapy (n=8), obesity (n=7), family history of DVT (n=6), immobility (n=5), central line (n=2), lupus (n=1), pregnancy (n=1), trauma (n=1), surgery (n=1), nephrotic syndrome (n=1), and retroperitoneal fibrosis (n=1). One subject had no risk factor, while 14 (61%) had multiple risk factors. Among the subjects, 78% underwent CDT (n=18) and 83% had stent placement (n=19). The remaining subjects will have future stent placement. Following CDT, there were no major bleeding complications (1 minor and 1 clinically relevant non-major bleeding complication). Other complications included pain (n=8), hemolysis (n=7), hemoglobinuria (n=2), hypofibrinogenemia requiring cryoprecipitate infusion (n=2), and transient increase in creatinine (n=1). Primary patency, defined as >90% patency of vessel diameter in the first week after CDT, was achieved in 91% (n=21). Thrombosis resolution was seen in 91% (n=21) of the cohort. Anticoagulant treatment prescribed included enoxaparin (65%), rivaroxaban (30%) and warfarin (26%). In univariate analyses, the only factor associated with thrombus resolution was primary patency (p=0.0012). DVT recurred in 13% (n=3), with a median time of 32 days off anticoagulation. The only factor associated with recurrence was antithrombin deficiency (p=0.048). Ten subjects (43%) had no evidence of PTS and 13 had mild PTS (57%). There were no significant factors associated with the development of PTS.

Conclusions : To our knowledge, this is the largest retrospective cohort of pediatric subjects with MTS and DVT. Underlying thrombophilia was the most common risk factor found, suggesting that patients diagnosed with MTS warrant thrombophilia evaluation. Bleeding complications associated with CDT were minimal and non-bleeding complications were transient, demonstrating that CDT is safe in the pediatric population. Efficacy of CDT in this population is supported by the finding that primary patency is an important factor for thrombosis resolution. Lastly, thrombosis recurrence was not uncommon (13%) and was likely to occur soon after stopping anticoagulation. These findings demonstrate that multicenter studies are needed in children with MTS to evaluate the efficacy of CDT to achieve thrombus resolution, and that evaluation of thrombophilic risk factors should be considered.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.