Introduction
Venous thromboembolic disease (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is morbid, expensive, and potentially fatal. It ranks as the third most common cardiovascular disease, and consumes significant health care dollars. Over the past several decades, the management of DVT and PE for many patients has been altered by the introduction of catheter-based therapies. Considerable data has been generated for these techniques during this time, although randomized trials are few. This chapter is divided into two sections, one discussing lower extremity DVT and the second describing the interventional management of pulmonary embolism. The DVT section will review epidemiology, medical management, the post-thrombotic syndrome and its prevention, and both the conservative and interventional management of established post-thrombotic syndrome. Section 2 will discuss the epidemiology, categorization, and escalation options for acute pulmonary embolism, with a focus on the evolving role of catheter-based techniques.
Section 1: Lower Extremity Deep Vein Thrombosis
Acute Deep Vein Thrombosis
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 ( ). 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 ( ).
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.
Endovascular Thrombus Removal Techniques
Catheter-based therapies have evolved considerably over the past two decades to minimize complications and maximize efficacy and patient comfort. Under the umbrella of endovascular thrombus removal is the following: catheter-directed thrombolysis (CDT), percutaneous mechanical thrombectomy (PMT), and pharmacomechanical catheter-directed thrombolysis (PCDT). The procedural details of these variant techniques and their results are discussed below.
CDT refers to the placement of a multi-sidehole infusion catheter into the thrombus with subsequent infusion of a lytic drug over a period of time. Access is gained most commonly into the popliteal vein under ultrasound guidance. After a guidewire and catheter traverse the clot, venography is performed to delineate thrombus extent. Next, an appropriately sized multi-sidehole infusion catheter is positioned within the clot, and an infusion is begun at a rate of 50 to 100 cc/hour of recombinant tissue plasminogen activator (rt-PA, maximum 1 mg/hr), reteplase (0.25-0.5 U/hr), or tenecteplase (0.25 mg/hr). It should be noted that none of these are FDA approved for DVT lysis. Infusion on average lasts between 6 and 24 hours, after which the patient is brought back to the interventional suite for repeat venography. If an underlying obstructive lesion is identified in the deep pelvic veins, it is commonly stented to reduce the incidence of recurrent thrombosis and improve outflow and symptomatology.
In a multicenter registry conducted in the late 1990s, the major bleeding rate from CDT was found to be 11%. Since then, limiting the hourly rt-PA dose, reducing the heparin to “subtherapeutic” levels (e.g., partial thromboplastin time 1.2-1.7 times control), and routinely using ultrasound guidance have reduced the major bleed rate to 2% to 4%. Ultrasound-assisted thrombolysis has emerged relatively recently to theoretically speed the time to lysis and improve lytic drug efficacy; however, the technology is yet unproven in its ability to do either of these compared with standard infusion, and further studies are needed.
Percutaneous mechanical thrombectomy refers to clot removal from the venous lumen. The rationale is that partial thrombus reduction with a mechanical device will create a flow channel and increase the surface area for endogenous thrombolysis. Through either a 7 or 8 Fr catheter or using a specialized device, thrombus is aspirated from the obstructed vein. Results have been fairly disappointing without the addition of a thrombolytic agent, and clot manipulation carries the risk of embolism and valvular damage.
Pharmacomechanical catheter-directed thrombolysis (PCDT) ( Figure 26-3 ) is a combination of the above techniques that uses both mechanical methods and lytic drugs to achieve thrombus reduction. The mechanical portion both reduces thrombus burden and achieves faster and more robust intrathrombus dispersion of the lytic drug, while the lytic component reduces the risk of embolism and results in more complete lysis. First-generation PCDT is the serial use of CDT and PMT, in which one of the techniques is used first, and the second is used subsequently. Either method requires two separate sessions with an infusion of lytic drug in between. First-generation PCDT has been shown to reduce the dose of lytic drug required, reduce hospitalization length, and cost. More recently, PCDT has evolved to include techniques that enable very rapid drug dispersion, often permitting single-session DVT treatment. Two such methods include the “power-pulse” technique using the AngioJet (Bayer Healthcare) and “isolated thrombolysis” with the Trellis (Covidien). With the Angiojet in “power-pulse” mode, the diluted thrombolytic is forcefully injected into the thrombus and allowed to dwell for 20 to 30 minutes. The setting is then switched to “aspiration,” and the catheter is run along the length of the thrombus to remove thrombus fragments. The Trellis consists of a multi-sidehole catheter flanked by two balloons that isolate the thrombus. A rotating wire is introduced coaxially that macerates and distributes lytic throughout the thrombus. At the end of the infusion, thrombus aspiration can be accomplished through the device itself or a separate aspiration catheter. Approximately 50% of patients can be treated in this manner without a subsequent period of lytic infusion.
Patient Selection ( Table 26-1 )
The decision of whether to proceed with thrombolysis is based on a risk-benefit analysis, where the risk is primarily bleeding. Acute limb-threat, caval thrombus, and thrombus extension/worsening symptoms in spite of adequate anticoagulation have lower thresholds for intervention to minimize short-term mortality and morbidity from the thrombus itself. If none of these is present, the decision to lyse is normally based upon the desire to prevent PTS and alleviate severe symptoms of the acute DVT, if present. Thus, a patient with a reasonable life expectancy, low likelihood of bleeding, and an iliofemoral DVT (which, as stated above, has the strongest association with PTS) is a good candidate for intervention. A young, healthy, and active individual may elect to undergo thrombolysis in the setting of a highly symptomatic femoropopliteal DVT, although the outcomes of lytic therapy in this patient subgroup have not been separately reported.
| DVT PRESENTATION | Bleeding Risk | ||
|---|---|---|---|
| LOW | MODERATE | HIGH | |
| Proximal DVT with limb threat | Yes | Yes | Possibly, with surgical consultation |
| IVC thrombus | Yes | Yes | No |
| DVT symptom progression or thrombus progression on anticoagulation | Yes | Possibly | No |
| Iliofemoral DVT to prevent PTS | Usually yes | No | No |
Outcomes and Data ( Table 26-2 )
Numerous studies have been performed on outcomes associated with endovascular thrombus removal that show improved PTS and venous patency rates. It should be noted that significant methodological flaws exist for each, however, including small sample size, lack of randomization, single-center experience, and lack of objective measures of PTS. Comerota et al. conducted a multicenter registry and found improved rates of PTS and quality of life in the treated group. AbuRahma et al. performed a nonrandomized comparison of treated and untreated groups and found better 5-year symptoms and venous patency. Elsharawy et al. conducted a single-center randomized trial that showed higher venous patency rates and less reflux in the catheter-treated group.
| STUDY | DESIGN | OUTCOME |
|---|---|---|
| Comerota (2000) | Multicenter registry | Reduction in PTS, improved physical functioning |
| AbuRahma (2001) | Prospective nonrandomized | Improved patency and freedom from symptoms |
| Elsharawy (2002) | Randomized single-center | Higher return to normal venous function |
| CaVenT (2012) | Multicenter randomized trial | Significant improvement in 2 year rate of PTS |
| ATTRACT (ongoing) | Multicenter randomized trial | Pending |
Most recently, the multicenter randomized controlled CaVenT study (Long-Term Outcome After Additional Catheter-Directed Thrombolysis Versus Standard Treatment for Acute Iliofemoral Deep Vein Thrombosis) was completed in Norway and showed a 26% relative risk reduction in those who received CDT. This study was limited by its modest sample size (n = 189) and the use of an older technique (CDT). The ongoing NIH-sponsored ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) seeks to definitively answer the primary question of whether PCDT should be a first-line therapy for the treatment of symptomatic proximal DVT to prevent PTS.
Chronic Deep Vein Thrombosis
Chronic venous insufficiency is costly and morbid, with venous ulcers alone costing $3 billion per year and resulting in the loss of 2 million working days per year. Historical data suggest that PTS accounts for at least ~12% of chronic venous insufficiency cases. As alluded to in the previous section, incomplete thrombus clearance and organization result in endothelialized channels that partially recanalize the vein. The robustness of this recanalization and collateral formation determines whether the patient will develop PTS. Most patients present with mild-moderate PTS, while a minority present with severe PTS/ulcer formation.
Patient Workup
Pertinent data to gather include a history of VTE, trauma, IVC filter placement, dialysis catheter placement, a family history of VTE, or malignancy. The duration and severity of symptoms should also be documented; a sudden exacerbation may represent an acute thrombotic episode. Recording an objective measurement of disease severity with a Villalta score and/or a CEAP score establishes a baseline ( Table 26-3 ). A photograph of the affected limb(s) and calf and thigh circumferences can be added to the baseline assessment. Understanding the anatomic extent of the post-thrombotic veins is essential for treatment planning; Doppler sonography can assess up to the peripheral external iliac vein, but visualizing pelvic veins and the IVC requires cross-sectional imaging (magnetic resonance venography or computed tomography, Figure 26-4 ).
| “C” or “Clinical” Definition of CEAP Classification |
|
| Villalta Scale * |
|
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
