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.
Venous thromboembolic (VTE) disease is an important cause of pregnancy-related morbidity and mortality. Pulmonary embolism (PE) remains a leading cause of maternal death in the United States accounting for 10.5% of maternal mortality.1 The incidence of VTE events in pregnancy or the postpartum period is estimated at 1.72 to 2 per 1000 births—4 to 5 times higher than the expected incidence for nonpregnant women of the same age.2,3
The risk of VTE events in pregnancy is associated with the increasing incidence of obesity, heart disease, diabetes mellitus, advanced maternal age and cesarean delivery. A recent analysis of the 1994 to 2009 Nationwide Inpatient Sample reported the trends in venous thromboembolism among pregnancy-related hospitalization.4 The overall rate of hospitalizations for VTE events in pregnancy increased by 14% between 1994 to 1997 and 2006 to 2009 (1.74 to 1.99 per 1000 deliveries).4 Although the rate of deep venous thrombosis (DVT) hospitalization decreased from 1.42 to 1.26 per 1000 deliveries, the rate of hospitalization associated with PE (with or without DVT) increased by 128%. Among VTE-associated hospitalizations, increased prevalences of cesarean delivery (47.1 to 54.3%), diabetes mellitus (1.5–6.6% to 4.0–9.0%), heart disease (5.4–7.7% to 9.9–16.6%), hypertension (1.6–3.5% to 4.2–10.5%) and obesity (1.4–3.9% to 5.0–8.2%) were reported between 1994 to 1997 and 2006 to 2009.
Up to 50% of patients with DVT develop chronic symptoms, known as post-thrombotic syndrome (PTS).5 One of the least recognized risks for the development of DVT is iliac vein compression or the May–Thurner Syndrome (MTS). The prevalence of MTS is reported to be 18 to 49% in patients diagnosed with iliofemoral vein thrombosis;6 however, there is a paucity of obstetric literature related to this condition and its therapeutic options.7 We present three patients with MTS complicated by massive left lower extremity DVT managed with percutaneous pharmacomechanical thrombectomy during pregnancy.
A 28 year-old, para 0-0-5-0 presented at 18 2/7 weeks of gestation with left leg swelling, pain and inability to bear weight. A lower extremity ultrasound revealed occlusive thrombus extending from the left calf veins to the left common iliac vein. Chest computed tomography demonstrated bilateral segmental pulmonary emboli. Hematologic evaluation was negative for inherited thrombophilias. Given these findings, her unremitting lower extremity symptoms and risk for PTS, the patient was offered percutaneous pharmacomechanical thrombectomy.
In the vascular and interventional radiology angiography suite, a retrievable inferior vena cava (IVC) filter was placed in a suprarenal location to avoid compression by the gravid uterus. Percutaneous pharmacomechanical thrombectomy was performed to fragment and remove the lower extremity thrombus between two occlusion balloons using 20 mg of tissue plasminogen activator. The patient reported near complete resolution of lower extremity pain and was able to ambulate within 24 h post procedure. She was discharged 1 week after presentation on weight-based enoxoparin. At 36 weeks she was transitioned to unfractionated heparin. She delivered a female newborn weighing 3330 g with APGARs 8 at 1 min and 9 at 5 min at 39 and 3/7 weeks gestation by cesarean delivery due to arrest of dilation. Therapeutic enoxaparin was restarted postpartum. The newborn was discharged in good condition on day of life 4 from the newborn nursery.
Six weeks postpartum, MTS was confirmed by intravascular ultrasound and the patient underwent definitive stenting of her left common iliac vein stenosis and removal of the suprarenal IVC filter. Eight months after the initial thrombectomy procedure, the patient reported no lower extremity symptoms.
A 30 year-old nulliparous woman presented at 30 5/7 weeks of gestation with left thigh swelling and pain lasting 1 week following initiation of modified bed rest. Lower extremity ultrasound revealed an extensive occlusive thrombus extending from her left calf veins to the left external iliac vein. Hematologic work-up for inherited thrombophilias was negative.
A retrievable suprarenal IVC filter was placed and left iliofemoral venous thrombectomy was performed requiring 12 mg of tissue plasminogen activator administered locally within the thrombus between occlusion balloons. The patient was discharged home on weight-based enoxaparin with no residual leg pain. Her post-procedure course was complicated by partial rethrombosis and partial recurrence of leg pain and swelling; an anti-Xa level was shown to be subtherapeutic and the enoxaparin dose was increased. At 36 weeks gestation, the patient was transitioned to 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 weight-based enoxaparin postpartum. She was discharged with her newborn in good condition on postpartum day 2.
At 2 weeks postpartum, persistent compression of the left common iliac vein was confirmed by intravascular ultrasound , compatible with MTS, and an iliac vein stent was placed. Nine months after her initial thrombectomy procedure, she reported mild pain with prolonged standing only, but could run miles without difficulty.
An 18 year-old nulliparous woman with morbid obesity presented to an outside hospital with dyspnea and left leg swelling, tenderness and erythema. She was found to be pregnant at 35 1/7 weeks of gestation. Lower extremity ultrasound demonstrated occlusive thrombus extending from the left popliteal veins to the left external iliac vein; chest computed tomography demonstrated bilateral pulmonary emboli. Weight-based enoxaparin was initiated and she was transferred to our institution for further management.
After retievable suprarenal IVC filter placement, left iliofemoral venous thrombectomy was performed requiring 10 mg tissue plasminogen activator delivered locally within the thrombus. The patient reported improvement of left leg swelling and pain. She was discharged home on hospital day 8 on weight-based unfractionated heparin.
At 38 4/7 weeks gestation, she presented to labor and delivery. She precipitously delivered a female newborn weighing 2990 g with APGARs 9/9. She was restarted on weight-based enoxaparin postpartum and discharged home with her newborn on postpartum day 2 in good condition.
At 6 weeks postpartum, she underwent IVC filter removal and stenting of the left common iliac vein after compression on intravascular ultrasound was confirmed. At that time she had no recurrence of lower extremity symptoms.
MTS is characterized by left, or much less commonly right, common iliac vein compression between the right common iliac artery and the fifth lumbar vertebra. Traditionally, the syndrome is diagnosed in patients with symptoms of chronic leg swelling or DVT. Computed tomography, magnetic resonance imaging, venography or intravascular ultrasound demonstrate flattening of the iliac vein beneath the artery (Figure 1). Importantly, this 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 deposition of elastin and collagen spurs lead to sluggish venous flow.8 When these at-risk individuals enter a hypercoagulable state such as pregnancy, they often develop DVTs.
The recommended treatment for thromboembolism in patients without MTS consists of weight-based unfractionated heparin or low-molecular weight heparin throughout pregnancy until at least 6 weeks postpartum. Despite anticoagulation, 42% of pregnancy-related DVTs result in long-term PTS, which includes pain, swelling or lower extremity ulceration.9 Of women with PTS, 16% reported their ‘health to be bad or very bad’ compared with 6% without PTS; 73% of women with PTS reported significantly more generalized pain versus 27% without PTS.9
In non-pregnant patients, catheter-directed thrombolysis requiring infusion of thrombolytics typically over 1 to 3 days has shown improved outcomes in patients with DVT.5 A Cochrane Review examining thrombolysis versus anticoagulation for acute DVT reported complete clot lysis was more likely (risk ratio (RR)=4.14, 95% confidence interval (CI) 1.22 to 14.01) and the development of PTS was less likely (RR=0.66, 95% CI 0.47 to 0.94) in the thrombolysis group.5 A more recent review of the treatment of acute iliofemoral DVT showed that catheter-directed pharmacologic thrombolysis decreased the incidence of PTS and venous obstruction compared with systemic anticoagulation (RR=0.19, 95% CI 0.07 to 0.48).10
With the advent of newer endovascular devices, many patients can be treated in a single pharmacomechanical thrombectomy session without overnight infusion of tissue plasminogen activator. The procedure offers pregnant women immediate symptom relief and mitigates risks. If imaging reveals iliac vein compression, then stent placement either at the time of initial procedure or in the postpartum setting can aid in resolving obstructive physiology 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 clot removal was achieved in 70% of catheter-directed thrombolysis cases and 75% of pharmacomechanical thrombectomy cases.11 However, patients in the catheter-directed thrombolysis group required significantly more procedures, longer intensive care unit stays, longer hospital lengths of stay and higher costs as compared with the pharmacomechanical thrombectomy group.11 Important to the pregnant patient, thrombolytic doses and duration of subsequent thrombolytic infusions are often less with pharmacomechanical thrombectomy compared with cathether-directed thrombolysis.12
Catheter-directed thrombolysis and pharmacomechanical thrombectomy have traditionally been avoided in cases of pregnancy-related DVT owing to concerns for thombolytic-related bleeding and fetal radiation exposure. As thrombolysis is most effective for acute thrombosis, delaying the procedure until delivery may not be feasible to achieve maximal clot clearance. A recent report demonstrates that surgical or cathether-directed thrombolysis of DVTs during pregnancy can be successful.13 However, open surgical thrombectomy or overnight thrombolytic infusion with the need for repeated fluoroscopic procedures carries serious risks.
As with any endovascular procedure, the risk of blood vessel injury is present during thrombolysis. However, thrombosis itself results in damage to the vein and valves. If left untreated, this damage can result in valvular incompetence, deep venous reflux and in many cases venous obstruction. Historically, the main concern with catheter-directed thrombolysis is major and catastrophic intracranial hemorrhage, which has been reported in ~11 and 1% of patients, respectively.14 A major advantage of pharmacomechanical thrombectomy is the ability to minimize and possibly obviate thrombolytic infusion thereby decreasing the risk for maternal hemorrhage.12
Ionizing radiation has been linked with fetal teratogenesis, miscarriage and mental and growth retardation depending on the gestational age of the fetus at the time of exposure and the absorbed radiation dose. As iliac vein thrombosis necessitates imaging of the pelvis, fetal parts receive more radiation than they would if other body parts are imaged. Therefore, employing the ALARA (as low as reasonably achievable) principle of radiation safety is paramount during these procedures. These practices include imaging only during essential portions of the procedure, relying on low-dose fluoroscopy rather than digital subtraction angiography, and careful shielding and coning of the radiation beam.15 Dose-dependent, predictable risks of radiation (nonstochastic risks) include miscarriage, mental retardation, congenital malformations and growth restriction. These risks are thought not to occur below a threshold dose of 2 rem.16 Stochastic risks, such as childhood leukemia, are less predictable with no threshold dose defined. Mathematical models can estimate the percentage increase in risk from fetal radiation exposure. For example, in some studies with fetal radiation exposure related to maternal occupational exposure of 500 mrem, the risk of childhood cancer or congenital defects is increased by 0.05%.16 It must be emphasized that the risks of fetal radiation, regardless of their magnitude, must be carefully balanced against the risks to the pregnant patient if the intervention is avoided.
The cases presented in this study add to the literature and demonstrate that MTS should be considered in pregnant patients with extensive left lower extremity DVT. Although endovascular procedures during pregnancy carry risks of maternal and fetal injury and should be performed in carefully selected patients by physicians with expertise, percutaneous therapies to reduce or resolve extensive thrombosis and relieve the venous compression should be considered in pregnancy-related DVT given the potential for improved symptoms and decreased risk of PTS.
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The authors declare no conflict of interest.
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DeStephano, C., Werner, E., Holly, B. et al. Diagnosis and management of iliac vein thrombosis in pregnancy resulting from May–Thurner Syndrome. J Perinatol 34, 566–568 (2014). https://doi.org/10.1038/jp.2014.38
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