Diagnosis and Management of Iliac Vein Thrombosis in Pregnancy Resulting from May–Thurner Syndrome

PERINATAL/NEONATAL CASE PRESENTATION Diagnosis and management of iliac vein thrombosis in pregnancy resulting from May–Thurner Syndrome

CC DeStephano1, EF Werner1,2, BP Holly3 and ML Lessne3

One of the least recognized risks for the development of deep venous thrombosis (DVT) is iliac vein compression or the May–Thurner Syndrome (MTS), in which most often, the right common iliac artery compresses the subjacent left common iliac vein. We present three patients with MTS complicated by massive left lower extremity DVT managed with percutaneous pharmacomechanical thrombectomy during pregnancy. Although often not considered in obstetrics, percutaneous therapies to resolve extensive thrombosis should be considered in pregnant women, as they have the potential to improve symptoms and mitigate the risk of developing post-thrombotic syndrome.

Journal of Perinatology (2014) 34, 566–568; doi:10.1038/jp.2014.38

INTRODUCTION CASE 1 Venous thromboembolic (VTE) disease is an important cause of A 28 year-old, para 0-0-5-0 presented at 18 2/7 weeks of gestation pregnancy-related morbidity and mortality. Pulmonary embolism with left leg swelling, pain and inability to bear weight. A lower (PE) remains a leading cause of maternal death in the United extremity ultrasound revealed occlusive thrombus extending from States accounting for 10.5% of maternal mortality.1 The incidence the left calf veins to the left common iliac vein. Chest computed of VTE events in pregnancy or the postpartum period is estimated tomography demonstrated bilateral segmental pulmonary emboli. at 1.72 to 2 per 1000 births—4 to 5 times higher than the Hematologic evaluation was negative for inherited thrombophi- expected incidence for nonpregnant women of the same age.2,3 lias. Given these findings, her unremitting lower extremity The risk of VTE events in pregnancy is associated with the symptoms and risk for PTS, the patient was offered percutaneous increasing incidence of obesity, heart disease, diabetes mellitus, pharmacomechanical thrombectomy. advanced maternal age and cesarean delivery. A recent analysis In the vascular and interventional radiology angiography suite, a of the 1994 to 2009 Nationwide Inpatient Sample reported the retrievable inferior vena cava (IVC) filter was placed in a suprarenal trends in venous thromboembolism among pregnancy-related location to avoid compression by the gravid uterus. Percutaneous hospitalization.4 The overall rate of hospitalizations for VTE events pharmacomechanical thrombectomy was performed to fragment in pregnancy increased by 14% between 1994 to 1997 and 2006 and remove the lower extremity thrombus between two occlusion to 2009 (1.74 to 1.99 per 1000 deliveries).4 Although the rate of balloons using 20 mg of tissue plasminogen activator. The patient deep venous thrombosis (DVT) hospitalization decreased from reported near complete resolution of lower extremity pain and was 1.42 to 1.26 per 1000 deliveries, the rate of hospitalization able to ambulate within 24 h post procedure. She was discharged associated with PE (with or without DVT) increased by 128%. 1 week after presentation on weight-based enoxoparin. At 36 weeks Among VTE-associated hospitalizations, increased prevalences of she was transitioned to unfractionated heparin. She delivered a cesarean delivery (47.1 to 54.3%), diabetes mellitus (1.5–6.6% to female newborn weighing 3330 g with APGARs 8 at 1 min and 9 at 4.0–9.0%), heart disease (5.4–7.7% to 9.9–16.6%), hypertension 5 min at 39 and 3/7 weeks gestation by cesarean delivery due to (1.6–3.5% to 4.2–10.5%) and obesity (1.4–3.9% to 5.0–8.2%) were arrest of dilation. Therapeutic enoxaparin was restarted postpartum. reported between 1994 to 1997 and 2006 to 2009. The newborn was discharged in good condition on day of life 4 Up to 50% of patients with DVT develop chronic symptoms, from the newborn nursery. fi known as post-thrombotic syndrome (PTS).5 One of the least Six weeks postpartum, MTS was con rmed by intravascular fi recognized risks for the development of DVT is iliac vein ultrasound and the patient underwent de nitive stenting of her compression or the May–Thurner Syndrome (MTS). The prevalence left common iliac vein stenosis and removal of the suprarenal IVC fi of MTS is reported to be 18 to 49% in patients diagnosed with lter. Eight months after the initial thrombectomy procedure, the iliofemoral vein thrombosis;6 however, there is a paucity of patient reported no lower extremity symptoms. obstetric literature related to this condition and its therapeutic options.7 We present three patients with MTS complicated by CASE 2 massive left lower extremity DVT managed with percutaneous A 30 year-old nulliparous woman presented at 30 5/7 weeks of pharmacomechanical thrombectomy during pregnancy. gestation with left thigh swelling and pain lasting 1 week

1Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Department of Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, RI, USA and 3Division of Vascular and Interventional Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Correspondence: Dr CC DeStephano, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Phipps 279, 600 North Wolfe Street, Baltimore, MD 21287, USA. E-mail: [email protected] Received 6 November 2013; revised 4 January 2014; accepted 21 January 2014 Diagnosis and management of iliac vein thrombosis CC DeStephano et al 567

Figure 1. Intravascular ultrasound demonstrating a normal inferior vena cava (IVC) compared with a compressed left common iliac vein consistent with the May–Thurner Syndrome. following initiation of modified bed rest. Lower extremity plasminogen activator delivered locally within the thrombus. The ultrasound revealed an extensive occlusive thrombus extending patient reported improvement of left leg swelling and pain. from her left calf veins to the left external iliac vein. Hematologic She was discharged home on hospital day 8 on weight-based work-up for inherited thrombophilias was negative. unfractionated heparin. A retrievable suprarenal IVC filter was placed and left iliofemoral At 38 4/7 weeks gestation, she presented to labor and delivery. venous thrombectomy was performed requiring 12 mg of tissue She precipitously delivered a female newborn weighing 2990 g plasminogen activator administered locally within the thrombus with APGARs 9/9. She was restarted on weight-based enoxaparin between occlusion balloons. The patient was discharged home on postpartum and discharged home with her newborn on weight-based enoxaparin with no residual leg pain. Her post- postpartum day 2 in good condition. procedure course was complicated by partial rethrombosis and At 6 weeks postpartum, she underwent IVC filter removal and partial recurrence of leg pain and swelling; an anti-Xa level was stenting of the left common iliac vein after compression on shown to be subtherapeutic and the enoxaparin dose was intravascular ultrasound was confirmed. At that time she had no increased. At 36 weeks gestation, the patient was transitioned to recurrence of lower extremity symptoms. unfractionated heparin. She was induced at 37 6/7 weeks due to worsening leg pain and desire for definitive treatment. She delivered a male newborn weighing 2780 g with APGARs 9 at 1 min and 9 at 5 min vaginally without event. She was restarted on DISCUSSION weight-based enoxaparin postpartum. She was discharged with MTS is characterized by left, or much less commonly right, her newborn in good condition on postpartum day 2. common iliac vein compression between the right common iliac At 2 weeks postpartum, persistent compression of the left artery and the fifth lumbar vertebra. Traditionally, the syndrome is common iliac vein was confirmed by intravascular ultrasound , diagnosed in patients with symptoms of chronic leg swelling or compatible with MTS, and an iliac vein stent was placed. Nine DVT. Computed tomography, magnetic resonance imaging, months after her initial thrombectomy procedure, she reported venography or intravascular ultrasound demonstrate flattening mild pain with prolonged standing only, but could run miles of the iliac vein beneath the artery (Figure 1). Importantly, this without difficulty. anatomy can be found incidentally in asymptomatic patients. It is thought that MTS confers an anatomic predisposition to DVTs; vein compression results in endothelial damage and subsequent CASE 3 deposition of elastin and collagen spurs lead to sluggish venous An 18 year-old nulliparous woman with morbid obesity presented flow.8 When these at-risk individuals enter a hypercoagulable state to an outside hospital with dyspnea and left leg swelling, such as pregnancy, they often develop DVTs. tenderness and erythema. She was found to be pregnant at 35 The recommended treatment for thromboembolism in patients 1/7 weeks of gestation. Lower extremity ultrasound demonstrated without MTS consists of weight-based unfractionated heparin or occlusive thrombus extending from the left popliteal veins to the low-molecular weight heparin throughout pregnancy until at least left external iliac vein; chest computed tomography demonstrated 6 weeks postpartum. Despite anticoagulation, 42% of pregnancy- bilateral pulmonary emboli. Weight-based enoxaparin was related DVTs result in long-term PTS, which includes pain, swelling initiated and she was transferred to our institution for further or lower extremity ulceration.9 Of women with PTS, 16% reported management. their ‘health to be bad or very bad’ compared with 6% without After retievable suprarenal IVC filter placement, left iliofemoral PTS; 73% of women with PTS reported significantly more generali- venous thrombectomy was performed requiring 10 mg tissue zed pain versus 27% without PTS.9

© 2014 Nature America, Inc. Journal of Perinatology (2014), 566 – 568 Diagnosis and management of iliac vein thrombosis CC DeStephano et al 568 In non-pregnant patients, catheter-directed thrombolysis to occur below a threshold dose of 2 rem.16 Stochastic risks, such requiring infusion of thrombolytics typically over 1 to 3 days has as childhood leukemia, are less predictable with no threshold dose shown improved outcomes in patients with DVT.5 A Cochrane defined. Mathematical models can estimate the percentage Review examining thrombolysis versus anticoagulation for acute increase in risk from fetal radiation exposure. For example, in DVT reported complete clot lysis was more likely (risk ratio some studies with fetal radiation exposure related to maternal (RR) = 4.14, 95% confidence interval (CI) 1.22 to 14.01) and the occupational exposure of 500 mrem, the risk of childhood development of PTS was less likely (RR = 0.66, 95% CI 0.47 to 0.94) cancer or congenital defects is increased by 0.05%.16 It must be in the thrombolysis group.5 A more recent review of the treatment emphasized that the risks of fetal radiation, regardless of their of acute iliofemoral DVT showed that catheter-directed pharma- magnitude, must be carefully balanced against the risks to the cologic thrombolysis decreased the incidence of PTS and venous pregnant patient if the intervention is avoided. obstruction compared with systemic anticoagulation (RR = 0.19, The cases presented in this study add to the literature and 95% CI 0.07 to 0.48).10 demonstrate that MTS should be considered in pregnant patients With the advent of newer endovascular devices, many patients with extensive left lower extremity DVT. Although endovascular can be treated in a single pharmacomechanical thrombectomy procedures during pregnancy carry risks of maternal and fetal session without overnight infusion of tissue plasminogen activa- injury and should be performed in carefully selected patients by tor. The procedure offers pregnant women immediate symptom physicians with expertise, percutaneous therapies to reduce or relief and mitigates risks. If imaging reveals iliac vein compression, resolve extensive thrombosis and relieve the venous compression then stent placement either at the time of initial procedure or in should be considered in pregnancy-related DVT given the poten- the postpartum setting can aid in resolving obstructive physiology tial for improved symptoms and decreased risk of PTS. and risk of DVT recurrence. Studies comparing catheter-directed thrombolysis with pharmacomechanical thrombectomy demonstrate their efficacy to be similar. In one study of 93 patients, total CONFLICT OF INTEREST clot removal was achieved in 70% of catheter-directed thrombo- The authors declare no conflict of interest. lysis cases and 75% of pharmacomechanical thrombectomy cases.11 However, patients in the catheter-directed thrombolysis group required significantly more procedures, longer intensive REFERENCES care unit stays, longer hospital lengths of stay and higher costs as compared with the pharmacomechanical thrombectomy group.11 1 Berg CJ, Callaghan WM, Syverson C, Henderson Z. Pregnancy-related mortality in the United States, 1998 to 2005. Obstet Gynecol 2010; 116: 1302–1309. Important to the pregnant patient, thrombolytic doses and 2 Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ 3rd. 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