Interventional Management of Lower Extremity Deep Vein Thrombosis and Pulmonary Embolism

Epidemiology and Pulmonary Embolus Prevention

It is estimated that 350,000 to 600,000 acute symptomatic DVTs are diagnosed per year in the United States, out of which up to 250,000 are a new diagnosis in the lower extremity. Given the 100,000 to 180,000 individuals who die of pulmonary embolism, the treatment for DVT has traditionally focused on the prevention of PE through anticoagulation. Since the focus of this chapter is the interventional management of VTE, an in-depth discussion of anticoagulation will not be provided here. Briefly, the majority of patients will be initiated on a parenteral regimen (e.g., unfractionated heparin, a low-molecular-weight heparin [LMWH], fondaparinux) and transitioned to an oral vitamin K antagonist (warfarin) for a minimum of 3 months, with the duration of therapy based on multiple factors, the most important being the presence or absence of reversible provoking factors. Patients with active cancer appear to derive the most benefit from extended LMWH therapy. Recently, the oral factor X inhibitor rivaroxaban was FDA approved for the treatment of VTE, and it has gained traction given its convenience and apparent equal efficacy compared with warfarin. If rivaroxaban is used, antecedent heparin therapy is not needed. However, rivaroxaban does not yet have an antidote, which can be problematic should bleeding occur, and the longitudinal experience physicians have had with warfarin for many years is lacking.

IVC Filters

When anticoagulation is contraindicated or fails, inferior vena cava (IVC) filters are frequently inserted to prevent large thrombi from traveling to the lungs. These two scenarios are relative indications for filter placement per societal guidelines. Filters may also be placed in the setting of a hemodynamically significant pulmonary embolus in a patient with limited cardiopulmonary reserve who would poorly tolerate additional emboli. The placement of IVC filters for perioperative prophylaxis in patients who are deemed to be at high risk for VTE (e.g., patients with prior history of VTE who will be immobilized after surgery for a prolonged period) is controversial at present, with little substantiating data for or against. While filters are effective at preventing pulmonary embolism, they may be associated with a number of complications, including perforation, migration, fracture, and caval thrombosis/stenosis. The PREPIC (Prevention du Risque d’Embolie Pulmonaire par Interruption Cave) study from the late 1990s indicated that in DVT patients who can be anticoagulated, filters reduce the rate of PE but increase the rate of DVT, resulting in a similar rate of VTE to patients not receiving filters. Thus, insertion of a filter should be performed only after a thorough evaluation of the short-term and long-term risks and benefits. Moreover, when IVC filtration is no longer indicated, every effort should be made to remove the filter if safe to do so.

IVC filters may be retrievable or permanent. No data adequately compares the merits of one versus the other, but retrievable filters are being more frequently placed because of the potential ability to remove them at a later date and thus avoid some of the complications listed above. When selecting a retrievable filter brand, consideration of (1) the time window for planned retrieval and (2) the filter's track record in terms of extent of use and documented migrations/fractures/embolizations is worthwhile. Several new designs are entering the market in an attempt to overcome some of the complications associated with retrievable filters, but no formal recommendation can be made based on current data ( Video 26-1 ). The insertion can be performed via the internal jugular vein, common femoral vein, or arm vein (brachial, basilic, or cephalic) if the delivery sheath is low profile. Care must be taken to ensure the appropriate orientation of the device if the same kit is used for a jugular or femoral insertion. Especially in the absence of prior cross-sectional imaging, venography prior to insertion provides some valuable information. The size of the cava, position of the renal veins, presence of caval thrombus, caval duplication, and variant anatomy such as a circumaortic renal vein can all be detected. If possible, venography should be performed from the left common iliac vein, as a duplicated cava can be detected most commonly from this position. Megacava is defined as a diameter greater than 28 mm; this finding is rare, and it is important to rule out a flattened cava by performing cavography at multiple obliquities. If one is found, only filters capable of filling the entire diameter, such as a bird's nest filter, should be deployed. If standard caval anatomy and size are present, the filter should be deployed inferior to the renal vein insertions to avoid trapped clot from propagating into the renal veins. In the event of caval duplication, two filters may be necessary ( Figure 26-1 ). A circumaortic renal vein may require a suprarenal filter, given that it can act as a bypass circuit if the filter is inserted below its more cranial insertion. Post-deployment venography ensures proper positioning and may be useful for later retrieval.

As mentioned previously, given the later complications of IVC filters, the need for filtration should be reassessed at periodic time points after insertion if a retrievable filter was used; the optimal time frame for removal is within 4 to 6 weeks of placement. With time, filters can become embedded in the wall of the cava and more difficult to extract. At the time of retrieval, venography should be performed to exclude significant clot within the filter. In the absence of this, retrieval may proceed. A ubiquitous feature of currently available retrievable filters is a “hook” at the top or bottom that can be engaged with a snare. The venous access site (femoral vs. jugular) depends on filter design; however, most filters have the hook at the cranial aspect, necessitating a jugular approach. Once the snare grasps the hook, an appropriately sized sheath (typically between 10 and 12 Fr) can be advanced over the filter to collapse it, and the filter is then pulled through the sheath out the body ( Video 26-2 ).

The Post-Thrombotic Syndrome

The traditional view of treating DVT with anticoagulation to prevent pulmonary embolism needs modification because of the growing awareness of the post-thrombotic syndrome (PTS). In spite of anticoagulation, ~40% of individuals suffering an acute symptomatic DVT experience some version of this disease. PTS is a constellation of chronic symptoms and signs in the affected limb that includes daily pain, swelling, aching, paresthesia, fatigue, and heaviness that worsen as the day progresses and in the standing position. Severe manifestations include stasis dermatitis, venous claudication, and ulceration ( Figure 26-2 ). The post-thrombotic syndrome has been shown to adversely affect quality of life and self-perception, and the individual and societal costs (both direct medical and indirect loss of work) are significant. Thus, any strategy that can prevent or reduce the severity of PTS needs to be examined.

The development of PTS following a proximal DVT is thought to be secondary to a combination of obstruction and valvular damage. While incompletely understood, the pathogenesis is related to an inflammatory leukocytic infiltration and cytokine release in response to acute thrombus that ultimately results in clot organization and wall thickening in the event of incomplete thrombus clearance. The narrowed lumen causes outflow obstruction, and in combination with damaged valves, results in venous hypertension and dilation of more peripheral uninvolved deep and superficial veins. Ultimately, the venous hypertension and reflux cause edema, calf pump dysfunction, tissue hypoxia, subcutaneous fibrosis, and ulceration.

Several factors have been identified that place a patient at higher risk for developing the post-thrombotic syndrome. These include recurrent ipsilateral DVT (2.6-fold increased risk), subtherapeutic anticoagulation (2.5-fold increased risk), and iliofemoral (iliac and/or common femoral vein) DVT (50% incidence of PTS). Minor risk factors include advanced age, obesity, and female gender. The main lesson is that a patient presenting with an iliofemoral DVT needs to receive meticulous anticoagulation therapy and monitoring to prevent recurrent DVT and PTS. It should be noted, however, that even with this approach, the rate of PTS in this population is unacceptably high.

Preventing the Post-Thrombotic Syndrome: Beyond Anticoagulation

Until recently, elastic compression stockings (ECS) were considered standard of care in the prevention of PTS, given two randomized single-center studies that demonstrated a reduction in PTS with their daily use. However, the recently completed placebo-controlled, double-blind, randomized controlled multicenter SOX trial, which was more than twice as large as the two previous studies combined, demonstrated an equally high rate of PTS in the ECS group as the “sham” stocking group. Thus, the best evidence suggests that ECS therapy does not prevent PTS and the recommendation to use compression stockings will likely come under scrutiny. However, a case-by-case approach may be appropriate to control PTS symptoms during long-term follow-up—if stockings provide symptomatic relief and there are no contraindications (e.g., peripheral arterial disease, skin hypersensitivity), the patient may certainly use them.

Given the high incidence of PTS following a symptomatic proximal DVT in spite of therapeutic anticoagulation, thromboreductive strategies, ranging from systemic thrombolysis to surgical embolectomy to catheter-directed techniques, have been trialled. These more aggressive strategies are predicated on the “open-vein” theory, which maintains that restoring patency to a thrombosed vein makes that vein less susceptible to re-thrombosis, reflux, and the pathophysiologic process leading to post-thrombotic syndrome. There is significant evidence to support the open-vein theory. Prandoni et al. noted higher 2-year rates of PTS in patients who had residual thrombus at 6 months. Hull et al. found a strong correlation between the amount of residual thrombus and recurrent VTE, which, as stated above, correlates with higher rates of PTS. Taking the lessons of small studies examining systemic thrombolysis and surgical embolectomy, aggressive thrombus clearance resulted in lower rates of PTS (albeit at the cost of higher morbidity and bleeding rates).

From these experiences, catheter-directed therapy has emerged with the possibility of offering comparable or greater efficacy with less morbidity and bleeding. This approach allows for intra-thrombus injection of lytic to allow for greater clot penetration. The rationale stems from studies that have demonstrated that nonocclusive thrombi are much more likely to be lysed than occlusive thrombi when systemic thrombolytics are administered. In essence, when the lytic drug is capable of reaching thrombus, it has a greater likelihood of lysing it. In contrast to directed intravenous lytic infusion (placing a catheter peripheral to a thrombus and infusing a lytic drug), image-guided catheter-directed intra-thrombus infusion has shown greater efficacy and safety.