Endovascular Intervention for Lower-Extremity Deep Venous Thrombosis

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Tuesday, 03/15/11 | 54053 reads
Author(s): 

Frank R. Arko, MD, M. Zachary Arko, Erin H. Murphy, MD

Deep venous thrombosis (DVT) is the third most common cardiovascular disease in the United States with 600,000 cases reported annually, resulting in more than 100,000 deaths.1,2 Clinical sequelae of DVT are significant in both the acute and chronic settings. Initial consequences include acute lower-extremity symptoms, risk of pulmonary emboli (PE) and death. Long-term consequences include recurrent DVT, lower-extremity venous hypertension, claudication, pain, swelling and ulceration, which can result in significant post-thrombotic morbidity.3–7 Traditionally, anticoagulation has been the mainstay for DVT therapy.8–12 While effective in preventing clot propagation and PE, clot resolution is slow, relying on the intrinsic fibrinolytic system.13,14 The prolonged venous obstruction prior to complete clot resolution may lead to permanent valvular damage, believed to be responsible for post-thrombotic symptoms and long-term morbidity after DVT treatment.13–16Multiple studies have now confirmed that early clot removal can preserve valve function and prevent much of the long-term morbidity associated with DVT. While multiple approaches have been proposed, the focus has shifted towards endovascular interventions for DVT. Thus far, the results are encouraging and far exceed those obtained with anticoagulation alone when used in the appropriate patient population. This paper will focus on the proper management of DVT, which requires prompt diagnosis, identification of patients who may benefit from more aggressive endovascular thrombus removal strategies and early implementation of appropriate treatment.

Diagnosis

Clinical manifestations. Clinical consequences of DVT differ in the acute and chronic settings. Acutely, patients present with symptoms of impaired venous return including unilateral lower-extremity pain, erythema and swelling. Physical examination may reveal tenderness, warmth and increased calf circumference of the affected limb when compared to the contralateral extremity. Patients may have palpable cords or evidence of superficial venous dilation, which may represent underlying obstruction in the venous system.3–7 Alternatively, patients with lower-extremity DVT may present with symptomatic PE manifested as dyspnea, cough, pleuritic chest pain, shock and even sudden death. Clinical signs include tachycardia, tachypnea, hypoxia, hypotension and cardiac arrest secondary to cardiac arrhythmia, most commonly pulseless electrical activity. Despite a common origin from DVT of the lower extremities, less than one-third of patients presenting with PE will have any clinical evidence of DVT at the time of presentation.4–8 In the chronic setting, patients with DVT may progress to develop symptoms of post-thrombotic syndrome. This syndrome may present months to years after initial diagnosis with lower-extremity venous hypertension, venous claudication, swelling, pain, discoloration and ulceration.13–16

Diagnostic imaging and hypercoagulable evaluation. While venography remains the gold standard for DVT diagnosis, this is both invasive and impractical as a standard diagnostic tool. Alternatively, lower-extremity duplex ultrasound can accurately diagnose DVT and is minimally invasive, low-risk, convenient and more cost-effective. Ultrasonographic evidence of DVT includes non-compressible or partially compressible venous segments, continuous venous flow patterns and the absence of normally phasic flow variation. The sensitivity and specificity of duplex ultrasonography in diagnosing proximal lower-extremity DVT is 95–97%, respectively.17,18 While the sensitivity and specificity drop to only 75% when used for the diagnosis of distal calf DVT, these patients may be screened with a repeat ultrasound in 5–7 days if clinical suspicion is high.12,17,18 Workup with a hypercoagulable panel has been suggested in patients < 50 years of age, an absence of additional risk factors for DVT, a family history of thromboembolic disorders, unusual thrombus location or recurrence of DVT. These patients should be screened for protein C or S deficiency, antithrombin deficiency, factor V Leiden, protein C resistance, prothrombin gene mutation 2021A and antiphospholipid antibody syndrome.12 Further, it mat be prudent to screen patients < 50 years of age presenting with left lower-extremity DVT for May-Thurner syndrome, a condition caused by compression of the left common iliac vein by the right common iliac artery against the fifth lumbar vertebra, which can predispose patients to DVT. Diagnosis of these conditions is important, as these patients may require additional treatment.19

Conventional Treatment

Anticoagulation remains the gold standard for treatment of lower-extremity DVT. This therapy is well suited for patients with isolated calf DVT who are at low risk of short- and long-term complications. Anticoagulation prevents clot propagation, PE and DVT recurrence, thereby reducing post-thrombotic morbidity and mortality. When contraindications to anticoagulation exist, patients with isolated calf DVT may also be managed with serial duplex ultrasound imaging. Patients who continue to have DVT isolated to the calf at 1 week will have less than a 1% risk of embolization, a 2% chance of recurrence and a low incidence of post-thrombotic syndrome.7–9 However, while anticoagulation also continues to be the most common treatment for patients with proximal DVT, this may be inadequate in a large number of patients. Clot resolution during anticoagulation therapy relies on the endogenous fibrinolytic pathways. This process is slow, particularly in patients with proximal DVT. When patients with proximal DVT underwent repeat venography 6 months after initiation of anticoagulation, complete clot lysis was seen in only 21%, incomplete lysis > 50% in 41%, incomplete lysis < 50% in 28% and extension of DVT in 7% of patients.13 Additionally, up to 50% of patients with proximal DVT treated with anticoagulation alone still have incompressible veins on follow-up duplex ultrasonography completed 1 year after initiation of treatment.14 Prolonged time from initial DVT development to venous recanalization may result in permanent valvular damage. As a direct consequence, patients may develop symptoms of post-thrombotic syndrome. Akesson demonstrated that during a 5-year follow-up of patients with iliofemoral DVT treated with anticoagulation alone, 95% developed venous hypertension, 90% had venous reflux, 15% had venous claudication and another 15% developed venous ulceration.15 Delis and colleagues confirmed these findings, demonstrating a 50% incidence of venous claudication and 15% with limited ambulation during a 5-year follow-up of patients with iliofemoral DVT treated with anticoagulation. This study further noted a poor quality of life reported by these patients following treatment.16

Early Thrombus Removal — Initial Strategies

Early clot removal strategies have been proposed for patients with proximal DVT to prevent valvular damage and symptoms of post-thrombotic syndrome. The first attempts at thrombus removal were reported by Fogarty and colleagues in 1966 by means of surgical embolectomy.20 This technique involved operative exposure of the femoral vein and balloon embolectomy of the proximal and distal veins. Improved venographic and clinical outcomes after surgical thrombectomy for proximal DVT have been reported compared to patients receiving anticoagulation alone. Plate and colleagues demonstrated normal venograms in 76%, 78% and 84% of patients post thrombectomy at 6 months, 5 years and 10 years, compared to only 35%, 50% and 41% of patients who received anticoagulation alone at the same time intervals.21–23 Furthermore, a reduced incidence of post-thrombotic symptoms was observed in the surgical thrombectomy cohort. The administration of systemic intravenous thrombolytic drugs demonstrated similar promising results without the need for operative exposure. When thrombus removal with lytic therapy was successful, valvular function was preserved and a reduced incidence of post-thrombotic syndrome was observed.24 While the results of surgical thrombectomy and systemic thrombolytic therapy illustrated the benefits of early thrombus removal in patients with proximal DVT, these therapies have not been widely utilized. Surgical thrombectomy is invasive, requiring operative exposure and risks damage to the venous endothelium and valves during embolectomy. The administration of systemic thrombolytics is associated with an unacceptably high rate of bleeding complications including retroperitoneal hemorrhage and intracranial hemorrhage. Further, complete clot resolution is not always achievable with either intervention. In fact, complete clot resolution after systemic thrombolytic administration was only achievable in 50% of patients with non-occlusive thrombus and 10% of patients with occlusive thrombus.24Nonetheless, these initial strategies have paved the route for the development of safer, more effective endovascular treatment strategies for thrombus removal in patients with proximal DVT.

Endovascular Management of DVT

Endovascular intervention for DVT should be considered in all patients with proximal lower-extremity DVT and a reasonable life expectancy. While multiple techniques and devices are available for endovascular DVT intervention, the majority of available treatment options may be separated by mechanism of action and include catheter-directed thrombolysis, ultrasound accelerated thrombolysis and percutaneous mechanical thrombectomy. Figure 1 demonstrates the pre- and post-operative images of a patient treated with the Trellis device. Percutaneous access for endovascular interventions is most often achieved in the vein distal to the occluded segment. For isolated iliac DVT, an ipsilateral common femoral puncture is most appropriate. Alternatively, a retrograde approach from the contralateral femoral vein may be used for isolated iliac and femoral vein DVT. More commonly, however, patients present with more extensive iliofemoral or iliofemoral popliteal thrombosis, in which case access is best obtained from the ipsilateral popliteal vein while the patient is positioned prone. Ultrasound guidance should be considered for access of the popliteal or tibial veins and for any access obtained while the patient is fully anticoagulated. Further, a micropucture technique with a 22-gauge needle and 0.014-inch guidewire may minimize bleeding complications and vessel wall trauma. Following initial access, the thrombus is crossed with a guidewire to facilitate catheter or device positioning. The use of retrievable inferior vena caval (IVC) filters during catheter-directed thrombolysis (CDT) or percutaneous mechanical thrombectomy (PMT) may be prudent for prevention of periprocedural pulmonary embolization as clot is disrupted.25–43 In an animal model, IVC filters were shown to decrease the incidence of angiographically diagnosed PE after mechanical thrombolysis of DVT.26 Further, Thery et al have demonstrated that 31% of patients (41/132) undergoing thrombolysis for lower-extremity DVT after placement of retrievable IVC filters had significant thrombus in the filter at the end of the procedure. More importantly, no patients in this study suffered a PE.27 A subsequent study confirmed these results, demonstrating a 40% incidence of thrombus debris in implanted filters following mechanical thrombectomy.28 It is our standard practice, and recommendation, to use retrievable IVC filters prior to thrombolysis or mechanical thrombectomy.29 In over 100 patients treated at our institution with IVC filters, mechanical thrombectomy and catheter-directed thrombolysis, there have been no occurrences of symptomatic PE, no filter-related complications and all IVC filters have been successfully removed when they have been placed. Other authors have reported similar success with IVC filters in this setting.29,30 Filters placed prior to CDT or PMT should be placed in standard fashion below the renal veins. In addition, access for filter deployment should be planned such that the endovenous delivery route is free of thrombus. Often, filters may be placed from the contralateral femoral vein in a percutaneous fashion. Extension of DVT into the IVC, however, may require filter placement from the internal jugular vein to avoid thrombus disruption during placement. Timing of filter retrieval is largely a matter of surgeon preference. It is generally accepted that filters may be removed at the end of the procedure if the completion venogram reveals no substantial clot burden. However, filter thrombus or persistent post-procedural contraindications to anticoagulation mandate longer filter indwell times.19,29,30In our experience, these filters may be removed without complications at a later date.

Endovascular Treatment Options

Catheter-directed thrombolysis (CDT). Catheter-directed thrombolysis allows infusion of thrombolytics directly into the venous thrombosis, limiting systemic drug exposure. Thrombolytic agents used with CDT include: urokinase (ImaRx Therapeutics, Tucson, Arizona), tissue plasminogen activator (tPA) (Activase, Genentech, South San Francisco, California), recombinant tissue plasminogen activator (r-tPA) (Retavase, PDL BioPharma, Fremont, California) or tenecteplase (Genentech). Most commonly, patients treated with CDT undergo percutaneous access in the operating room and initial venography to determine the extent of thrombus. A small infusion catheter is placed just proximal to the location of thrombus and is secured in place externally. Patients are monitored in the intensive care unit (ICU) and thrombolytics are slowly administered through the catheter. The patient undergoes repeat venography in the operating room to assess clot lysis once every 24 hours until complete lysis is achieved. This option has proven effective in proximal DVT resulting in early clot resolution, prevention of PE, prevention of recurrent DVT, preservation of valve function and improved quality of life compared to treatment with isolated anticoagulation. Results have demonstrated 60–90% clot resolution in proximal DVT,31–34 with the degree of clot removal correlating directly with improvements in long-term patency and a reduced incidence of post-thrombotic syndrome.34 Unfortunately, this therapy is still associated with significant bleeding complications in 11–43% of patients.31–37 Ouriel et al demonstrated insertion-site bleeding in 22–44%, transfusion requirements in 12–22% and intracranial hemorrhage in 0.6–3% of patients undergoing CDT with urokinase and r-tPA, respectively.37 Further limitations to the widespread use of this technique include prolonged lytic infusion times of 36–72 hours, prolonged ICU stay and expensive drug costs.31–37

Ultrasound-accelerated thrombolysis — EKOS EndoWave. The EKOS EndoWave (EKOS Corporation, Bothell, Washington) uses low-power, high-frequency ultrasound (2 MHz) in combination with catheter-directed thrombolysis to achieve clot disruption (Figure 2). Ultrasound waves generated by the unit do not directly macerate the clot, but rather create microstreams that increase thrombus permeability via alteration of fibrin composition. Increased permeability results in augmented lytic dispersion within the thrombus.38–40 In fact, a 65% increase in the number of fibrin strands exposed to thrombolytic drugs has been demonstrated to occur with a 44% ultrasound-mediated reduction in the diameter of fibrin strands.39 This translates to increased thrombus uptake of r-tPA by 48%, 84% and 89% at 1, 2, and 4 hours, respectively.40 Further, the ultrasound waves penetrate past valves, allowing for thrombus removal behind the valves that may be inaccessible with other PMT devices. The device consists of an infusion/aspiration catheter, an ultrasound core wire and a drive unit. The catheter, available in treatment lengths of 6–50 cm, contains a central lumen that accommodates the 0.035-inch ultrasound core wire and normal saline infusate used for central cooling. In a triangular distribution around the central lumen are three separate infusion channels containing microinfusion pores for drug delivery and thermocouples to monitor changes in temperature and flow patterns. The ultrasound core wire has transducers (2.2 MHz) located at 1-centimeter intervals. When the drive unit is activated, ultrasound waves are delivered to the core wire and transmitted through the catheter, penetrating thrombus and allowing lytic dispersion. Access is obtained with a 6 Fr introducer sheath and the lesion is crossed with a 0.35-inch guidewire. The catheter is positioned such that the treatment zone extends through the length of the thrombosed venous segment. After positioning, the guidewire is exchanged for the ultrasound core wire. The three separate drug infusion lumens are primed with unfractionated heparin. The control unit is activated and delivers ultrasound energy via the core wire while the thrombolytic agent of choice is administered through micropores located throughout the length of the treatment zone on each of the three catheters. Normal saline is infused through the central lumen continuously during the procedure to dissipate heat production. The drive unit automatically adjusts power according to changing vessel conditions, reducing power as flow is restored. The procedure is continued until complete lysis is achieved. Early evaluation of the EKOS EndoWave system in 53 patients, including 32 patients with lower-extremity DVT, demonstrated > 90% clot lysis in 70% of patients and at least partial thrombus resolution in 91%. Importantly, at least partial lysis was achieved in 96% of acute DVT cases (< 14 days), 100% of subacute DVT (15–28 days) and 77.8% of chronic (> 28 days) and acute or chronic DVT cases. Median lytic infusion time was 22 hours and bleeding complications were low (3.8%). Furthermore, median infusion times and median total drug dosages administered were lower with ultrasound-mediated thrombolysis compared to standard CDT when using urokinase, tPA, or r-tPA. The median dosages and infusion times were similar for CDT and ultrasound-mediated thrombolysis when tenecteplase was used.41The EKOS EndoWave system is used and functions in the same manner as the EndoWave system, however, the company is promoting faster clot lysis with this newer device.

Percutaneous Mechanical Thrombectomy

Percutaneous mechanical thrombectomy offers the benefit of early thrombus removal, while limiting thrombolytic dosages and bleeding complications. PMT additionally offers a treatment option for patients with absolute contraindications for lytic therapy as the AngioJet (Medrad, Inc., Warrendale, Pennsylvania), a PMT device discussed below, is the only device that can be used without the addition of lytics. PMT has further been shown to be more cost-effective than alternative treatment regimens when considering the lower thrombolytic dosages administered, the decreased length of ICU stay compared to CDT42 and the decreased long-term morbidity from post-thrombotic syndrome compared to traditional anticoagulation.

AngioJet Rheolytic Thrombectomy System — Pulse Power Spray Technique. The AngioJet catheter system is comprised of a single-use catheter, a single-use pump set and a drive unit. The catheter, which is available in working lengths of 60, 100 and 120 cm, contains a central lumen for infusate and a larger lumen encompassing the central channel, the guidewire and aspirate from the thrombus. The drive unit generates 10,000 psi of pulsatile infusion flow, which is released from the catheter in retrograde-directed high-velocity saline jets. These jets create a localized low-pressure zone (Bernoulli’s principle) at the catheter tip, macerating thrombus and redirecting flow and debris into outflow channels directed behind the catheter tip for aspiration and removal. Access for the AngioJet system requires a 6 Fr introducer sheath. The AngioJet catheter is then advanced over a 0.035 inch guidewire through the thrombus load (Figure 3). While this system was originally intended for use without adjunctive thrombolytics, it has been demonstrated that the addition of lytics to the infusion solution results in decreased treatment time and improved results. We recommend that thrombolytics be routinely used except when contraindicated, as is our practice. While thrombolytic choice and dose will vary dependent upon surgeon preference, we have experienced good results using 10 mg of tenecteplase in 50 ml of sodium chloride infusing solution.29 With the aspiration port clamped, infusate is released into the thrombosed venous segment during a slow pullback of the catheter, effectively lacing the clot with thrombolytic drug. After 10 minutes the aspiration function of the catheter is turned on. The catheter is then advanced through the thrombosed segment a second time, removing macerated thrombus through the aspiration ports as the catheter is advanced. This process may be repeated if there is remaining thrombus burden at the end of the first pass. Alternatively, as is often our preference, the patient may then undergo catheter-directed thrombolysis in the ICU overnight and return to the operating room the following day for re-evaluation with venography and possible repeat thrombectomy or venous stenting if indicated. Success in thrombus removal, restoration of venous patency and preservation of valvular function have been demonstrated with the use of the AngioJet pulse-power spray technique. While Kasirajan reported only 24% of patients had > 90% clot resolution, 35% had 50–90% resolution and 41% had < 50% resolution,43 improved results have been demonstrated with the addition of lytics to the infusate as discussed above. Bush et al reported complete thrombus resolution in 65% of patients, with at least partial resolution seen in all of the remaining patients.30 Lin et al demonstrated that PMT with the AngioJet system was at least as effective as CDT in treating lower-extremity DVT. They showed complete clot lysis in 75% of patients treated with AngioJet versus 70% in patients treated with CDT (p = NS), with similar patency rates at 1-year follow-up of 64% and 68%, respectively. Additionally, they demonstrated a reduced ICU stay, hospital length of stay and reduced costs in the PMT cohort.42 In our series we demonstrated a 90% venous patency restoration and maintenance of venous valvular function in 88% of patients at a mean follow-up of 6 months.29 This therapy is associated with a low incidence of hemorrhagic complications. Isolated case reports of pancreatitis resulting from massive hemolysis with use of the AngioJet system have been reported but appear to be rare occurrences.44

Trellis-8 Infusion System — Pharmacomechanical Thrombectomy. The Trellis-8 infusion system (Bacchus Vascular, Inc., Santa Clara, California) incorporates the use of both chemical thrombolysis and mechanical thrombectomy (Figure 4). The Trellis device consists of a single-use catheter, a dispersion wire and an integral drive unit. The catheter contains proximal and distal occlusion balloons that allow infusion of thrombolytics to an isolated segment of thrombosed vein. Catheters are available in lengths of 80 or 120 cm, with varied distances between occlusion balloons allowing treatment of 10, 15, or 30 cm venous segments. Catheter selection will depend on the location and length of the thrombosed segment determined on initial venography, with the goal of minimizing treatment length of the non-thrombosed vein. The drive unit is attached to the sinusoidal dispersion wire, which creates catheter oscillatation at 500–3,500 rpm, causing dispersion of lytics within the thrombus load and mechanical clot disruption. Aspiration of thrombus debris and lytic remaining in the isolated segment completes treatment of the isolated venous segment. Access for the Trellis-8 infusion system requires an 8 Fr introducer sheath. A 0.35 inch glidewire is used to cross the thrombosed venous segment and the Trellis-8 catheter is advanced over the glidewire. With proximal and distal balloons inflated, 5–10 mg of lytics are infused within the thrombus. After 10 minutes, the dispersion wire is inserted into the catheter. Catheter vibration between the occlusion balloons aids in clot maceratation and increases the thrombus surface area exposed to the lytics. The dispersion wire may further be advanced and retracted once per minute during the treatment interval to further assure mixing of the lytics with the thrombus. After 5–15 minutes, the distal balloon is deflated and the catheter aspirated via a side port to remove macerated thrombus and a substantial portion of the remaining lytics. The proximal balloon is left inflated during aspiration to prevent embolization of clot. After aspiration, with both balloons deflated, the system may be removed or advanced into adjacent thrombosed segments, repeating the procedure until the thrombus load is resolved. Hilleman et al reported success with the Trellis-8 infusion system for the treatment of proximal lower-extremity DVT in 135 patients. They demonstrated superior clot lysis with the Trellis-8 compared to conventional catheter-directed thrombolysis, with 93% achieving grade II (50–99% clot resolution) or III lysis (100% clot resolution) versus 79%, respectively. They additionally demonstrated that pharmacomechanical lysis required a lower lytic dose, was more cost-effective and was associated with significantly lower rates of hemorrhage (0% vs. 8.5%; p < 0.001).45 Arko et al further demonstrated that 80% of patients experienced complete clot resolution with this technique in a single setting, with venous patency maintained in 88% of patients treated with this device at a mean follow-up period of 6 months.29 O’Sullivan demonstrated grade II or III lysis in 96% of patients in a single setting, with 100% assisted primary patency at 30 days.46

Adjunctive Endovascular Procedures

Use of multiple PMT devices or adjunctive CDT. Recalcitrant thrombus after initial treatment with PMT may require further therapy. While small residual thrombus may respond to venous angioplasty and stenting, as discussed in the text to follow, larger amounts of residual thrombus may require the use of a second PMT device or overnight catheter-directed thrombolysis.19,29,30,38 Use of an adjunctive device or CDT should not be regarded as a failure of the first device, but rather as complementary procedures.38 The initial device achieves significant clot burden reduction, paving an easier path for the second intervention. Use of a second PMT device can be performed in the same setting, often with lower doses of thrombolytics.19,29 Alternatively, overnight CDT therapy may be sufficient to eliminate residual thrombus after clot debulking with PMT.19,29,30 This significantly reduces the time required for effective CDT and thereby reduces the associated bleeding risks with this treatment modality.19,29,30Patients should then undergo a second evaluation with intravascular ultrasound and/or completion venography to evaluate vessel conditions.

Adjunctive Venoplasty and Stenting

Post-treatment evaluation of the venous segment may reveal areas of venous compression, stenosis or recalcitrant thrombus in > 90% of patients.19,29,30 May-Thurner anatomy is the most common anatomic variant found on completion imaging during the treatment of proximal DVT (Figure 5). This syndrome is characterized by compression of the left common iliac vein by the right common iliac artery against the fifth lumbar vertebra, resulting in venous compression, development of venous scar tissue and eventually venous stenosis. This condition then predisposes the patient to left iliofemoral DVT.47,48 With anticoagulation alone, untreated iliac vein obstruction prevents vessel recanalization in 70–80% of patients and clot propagation may continue in up to 40% of cases.49,50 Further, patients with iliofemoral DVT and untreated May-Thurner anatomy experience an increased risk of recurrent DVT and universally experience symptoms of post-thrombotic syndrome during follow-up.5,51 Adequate treatment of anatomic compression, stenosis or persistent small thrombus after CDT or PMT requires angioplasty and stenting.52–60 Patel et al demonstrated 100% symptom resolution in May-Thurner syndrome and acute DVT treated with early thrombus removal and venous stenting. They further demonstrated preservation of valvular function in all patients on follow-up ultrasonography.56 Additionally, we have reported on the use of PMT and iliac vein stenting in 12 women with May-Thurner syndrome, demonstrating 100% intraoperative clot resolution and 100% primary stent patency with follow-up out to 45 months. All patients have had complete symptom resolution and there were no occurrences of post-thrombotic syndrome.19

Follow-up After Endovascular DVT Management

Patients should be anticoagulated post procedure with unfractionated heparin or low-molecular-weight heparin and transitioned to oral warfarin for 6 months (goal international normalized ratio 2.0–3.0). Patients with recurrent DVT or hypercoagulable disorders may require a longer duration of anticoagulation and consultation with primary care physicians is recommended. Patients with venous stents require lifelong aspirin therapy. Follow-up with duplex ultrasonography is also recommended at 1- and 6-month intervals and yearly thereafter (Figure 6).

Conclusions

Endovascular options are more effective in reducing long-term morbidity after proximal DVT when compared to anticoagulation alone. These options should be considered for all patients with proximal lower-extremity DVT and a reasonable life expectancy. Percutaneous mechanical thrombectomy is at least as effective as catheter-directed thrombolysis, with reduced ICU and hospital stays and decreased overall costs. Further, use of a second PMT device or adjunctive CDT may provide optimal results. Venous angioplasty and stenting may be required to treat recalcitrant thrombus or anatomic causes of DVT. With widespread implementation of these advanced treatment options for DVT, we can achieve a significant reduction in long-term morbidity after proximal DVT.

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36. AbuRahma AF, Pekins SE, Wulu JT, Ng HK. Iliofemoral deep vein thrombosis: conventional therapy versus lysis and percutaneous transluminal angioplasty and stenting. Ann Surg 2001;233:752–760.

37. Ouiel K, Grey B, Clair DG, Olin J. Complications associated with the use of urokinase and recombinant tissue plasminogen activator for catheter directed peripheral aterial and venous thrombolysis. J Vasc Interven Radiol 2000;11:295–298.

38. McLafferty RB. Endovascular management of deep venous thrombosis. Perspect Vasc Surg Endovasc Ther 2008;20:87–91.

39. Braaten JV, Goss RA, Francis CW. Ultrasound reversibly disaggregates fibrin fibers. Thromb Haemost 1997;78:1063–1068.

40. Francis CW, Blinc A, Lee S, Cox C. Ultrasound accelerates transport of recombinant tissue plasminogen activator into clots. Ultrasound Med Biol 1995;21:419–424.

41. Parikh S, Motarjeme A, McNamara T, et al. Ultrasound-accelerated thrombolysis for the treatment of deep vein thrombosis: initial clinical experience. J Vasc Interv Radiol 2008;19:521–528.

42. Lin PH, Zhou W, Dardick A, et al. Catheter-direct thrombolysis versus pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis. Am J Surg 2006;192:782–788.

43. Kasirajan K, Grey B, Ouriel K. Percutaneous AngioJet thrombectomy in the management of extensive deep venous thrombosis. J Vasc Interv Radiol 2001;12:179–185.

44. Piercy KT, Ayerdi J, Geary RL, et al. Acute pancreatitis: A complication associated with rheolytic mechanical thrombectomy of deep venous thrombosis. J Vasc Surg 2006;44:1110–1113.

45. Hillman DE, Pharm D, Razavi MK. Clinical and economic evaluation of the Trellis-8 infusion catheter for deep vein thrombosis. J Vasc Interv Radiol 2008;19:377–383.

46. O’Sullivan GJ, Lohan DG, Gough N, et al. Pharmacomechanical thrombectomy of acute deep vein thrombosis with the Trellis-8 isolated thrombolysis catheter. J Vasc Interv Radiol 2007;715–724.

47. May R, Thurner J. The cause of predominately sinistral occurence of thrombosis of the pelvic veins. Angiology 1957;8:419–427.

48. Kim D, Orron DE, Porter DH (eds.). Venographic anatomy, technique and interpretation. In: Peripheral Vascular Imaging and Intervention. St Louis: Mosby-Year Book. 1992, pp.269–349.

49. Krupski WC, Bass A, Dilley RB, et al. Propagation of deep venous thrombosis identified by duplex ultrasonography. J Vasc Surg 1990;12:467–475.

50. Cockett FB, Thomas ML, Negus D. Iliac vein compression. Its relation to iliofemoral thrombosis and the post-thrombotic syndrome. Br Med J 1967;2:14–19.

51. Calnan J, Kountz S, Pentecost B, et al. Venous obstruction in the aetiology of lymphoedema praecox. Br Med J 1964;2:221–226.

52. O’Sullivan GJ, Semba CP, Bittner CA, et al. Endovascular management of iliac vein compression (May-Thurner) syndrome. J Vasc Interv Radiol 2000;11:823–836.

53. Kwak HS, Han YM, Lee YS, et al. Stents in common iliac vein obstruction with acute ipsilateral deep venous thrombosis: Early and late results. J Vasc Interv Radiol 2005;16:815–822.

54. AbuRahma AF, Perkins SE, Wulu JT, Ng HK. Iliofemoral deep vein thrombosis: conventional therapy versus lysis and percutaneous transluminal angioplasty and stenting. Ann Surg 2001;233:752–760.

55. Nazarian GK, Bjarnarson H, Dietz CA, et al. Iliofemoral venous stenosis: Effectiveness of treatment with metallic endovascular stents. Radiology 1996;200:193–199.

56. Patel NH, Stookey KR, Ketcham DB, Cragg AH. Endovascular management of acute extensive iliofemoral deep venous thrombosis caused by May-Thurner syndrome. J Vasc Interv Radiol 2000;11:1297–1302.

57. Hollis K, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: Long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg 2007;46:979–990.

58. Hartung O, Benmiloud F, Barthelemy P, et al. Late results of surgical venous thrombectomy with iliocaval stenting. J Vasc Surg 2008:47:381–387.

59. Schwarzbach MH, Schumacher H, Bockler D, et al. Surgical thrombectomy followed by intraoperative endovascular reconstruction for symptomatic ilio-femoral venous thrombosis. Eur J Vasc Surg 2005;29:58–66.

60. Husmann MJ, Heller G, Kalka C, et al. Stenting of common iliac vein obstructions combined with regional thrombolysis and thrombectomy in acute deep venous thrombosis. Eur J Vasc and Endovasc Surg 2007;34:87–91.

_________________________________________________________________

From the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas. The authors report no conflicts of interest regarding the content herein. Address for correspondence: Frank R. Arko, MD, Associate Professor, Division of Vascular and Endovascular Surgery, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas. E-mail: Frank.Arko@utsouthwestern.edu

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Endovascular Intervention for Lower-Extremity Deep Venous Thrombosis

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Tuesday, 03/15/11 | 54053 reads
Author(s): 

Frank R. Arko, MD, M. Zachary Arko, Erin H. Murphy, MD

Deep venous thrombosis (DVT) is the third most common cardiovascular disease in the United States with 600,000 cases reported annually, resulting in more than 100,000 deaths.1,2 Clinical sequelae of DVT are significant in both the acute and chronic settings. Initial consequences include acute lower-extremity symptoms, risk of pulmonary emboli (PE) and death. Long-term consequences include recurrent DVT, lower-extremity venous hypertension, claudication, pain, swelling and ulceration, which can result in significant post-thrombotic morbidity.3–7 Traditionally, anticoagulation has been the mainstay for DVT therapy.8–12 While effective in preventing clot propagation and PE, clot resolution is slow, relying on the intrinsic fibrinolytic system.13,14 The prolonged venous obstruction prior to complete clot resolution may lead to permanent valvular damage, believed to be responsible for post-thrombotic symptoms and long-term morbidity after DVT treatment.13–16Multiple studies have now confirmed that early clot removal can preserve valve function and prevent much of the long-term morbidity associated with DVT. While multiple approaches have been proposed, the focus has shifted towards endovascular interventions for DVT. Thus far, the results are encouraging and far exceed those obtained with anticoagulation alone when used in the appropriate patient population. This paper will focus on the proper management of DVT, which requires prompt diagnosis, identification of patients who may benefit from more aggressive endovascular thrombus removal strategies and early implementation of appropriate treatment.

Diagnosis

Clinical manifestations. Clinical consequences of DVT differ in the acute and chronic settings. Acutely, patients present with symptoms of impaired venous return including unilateral lower-extremity pain, erythema and swelling. Physical examination may reveal tenderness, warmth and increased calf circumference of the affected limb when compared to the contralateral extremity. Patients may have palpable cords or evidence of superficial venous dilation, which may represent underlying obstruction in the venous system.3–7 Alternatively, patients with lower-extremity DVT may present with symptomatic PE manifested as dyspnea, cough, pleuritic chest pain, shock and even sudden death. Clinical signs include tachycardia, tachypnea, hypoxia, hypotension and cardiac arrest secondary to cardiac arrhythmia, most commonly pulseless electrical activity. Despite a common origin from DVT of the lower extremities, less than one-third of patients presenting with PE will have any clinical evidence of DVT at the time of presentation.4–8 In the chronic setting, patients with DVT may progress to develop symptoms of post-thrombotic syndrome. This syndrome may present months to years after initial diagnosis with lower-extremity venous hypertension, venous claudication, swelling, pain, discoloration and ulceration.13–16

Diagnostic imaging and hypercoagulable evaluation. While venography remains the gold standard for DVT diagnosis, this is both invasive and impractical as a standard diagnostic tool. Alternatively, lower-extremity duplex ultrasound can accurately diagnose DVT and is minimally invasive, low-risk, convenient and more cost-effective. Ultrasonographic evidence of DVT includes non-compressible or partially compressible venous segments, continuous venous flow patterns and the absence of normally phasic flow variation. The sensitivity and specificity of duplex ultrasonography in diagnosing proximal lower-extremity DVT is 95–97%, respectively.17,18 While the sensitivity and specificity drop to only 75% when used for the diagnosis of distal calf DVT, these patients may be screened with a repeat ultrasound in 5–7 days if clinical suspicion is high.12,17,18 Workup with a hypercoagulable panel has been suggested in patients < 50 years of age, an absence of additional risk factors for DVT, a family history of thromboembolic disorders, unusual thrombus location or recurrence of DVT. These patients should be screened for protein C or S deficiency, antithrombin deficiency, factor V Leiden, protein C resistance, prothrombin gene mutation 2021A and antiphospholipid antibody syndrome.12 Further, it mat be prudent to screen patients < 50 years of age presenting with left lower-extremity DVT for May-Thurner syndrome, a condition caused by compression of the left common iliac vein by the right common iliac artery against the fifth lumbar vertebra, which can predispose patients to DVT. Diagnosis of these conditions is important, as these patients may require additional treatment.19

Conventional Treatment

Anticoagulation remains the gold standard for treatment of lower-extremity DVT. This therapy is well suited for patients with isolated calf DVT who are at low risk of short- and long-term complications. Anticoagulation prevents clot propagation, PE and DVT recurrence, thereby reducing post-thrombotic morbidity and mortality. When contraindications to anticoagulation exist, patients with isolated calf DVT may also be managed with serial duplex ultrasound imaging. Patients who continue to have DVT isolated to the calf at 1 week will have less than a 1% risk of embolization, a 2% chance of recurrence and a low incidence of post-thrombotic syndrome.7–9 However, while anticoagulation also continues to be the most common treatment for patients with proximal DVT, this may be inadequate in a large number of patients. Clot resolution during anticoagulation therapy relies on the endogenous fibrinolytic pathways. This process is slow, particularly in patients with proximal DVT. When patients with proximal DVT underwent repeat venography 6 months after initiation of anticoagulation, complete clot lysis was seen in only 21%, incomplete lysis > 50% in 41%, incomplete lysis < 50% in 28% and extension of DVT in 7% of patients.13 Additionally, up to 50% of patients with proximal DVT treated with anticoagulation alone still have incompressible veins on follow-up duplex ultrasonography completed 1 year after initiation of treatment.14 Prolonged time from initial DVT development to venous recanalization may result in permanent valvular damage. As a direct consequence, patients may develop symptoms of post-thrombotic syndrome. Akesson demonstrated that during a 5-year follow-up of patients with iliofemoral DVT treated with anticoagulation alone, 95% developed venous hypertension, 90% had venous reflux, 15% had venous claudication and another 15% developed venous ulceration.15 Delis and colleagues confirmed these findings, demonstrating a 50% incidence of venous claudication and 15% with limited ambulation during a 5-year follow-up of patients with iliofemoral DVT treated with anticoagulation. This study further noted a poor quality of life reported by these patients following treatment.16

Early Thrombus Removal — Initial Strategies

Early clot removal strategies have been proposed for patients with proximal DVT to prevent valvular damage and symptoms of post-thrombotic syndrome. The first attempts at thrombus removal were reported by Fogarty and colleagues in 1966 by means of surgical embolectomy.20 This technique involved operative exposure of the femoral vein and balloon embolectomy of the proximal and distal veins. Improved venographic and clinical outcomes after surgical thrombectomy for proximal DVT have been reported compared to patients receiving anticoagulation alone. Plate and colleagues demonstrated normal venograms in 76%, 78% and 84% of patients post thrombectomy at 6 months, 5 years and 10 years, compared to only 35%, 50% and 41% of patients who received anticoagulation alone at the same time intervals.21–23 Furthermore, a reduced incidence of post-thrombotic symptoms was observed in the surgical thrombectomy cohort. The administration of systemic intravenous thrombolytic drugs demonstrated similar promising results without the need for operative exposure. When thrombus removal with lytic therapy was successful, valvular function was preserved and a reduced incidence of post-thrombotic syndrome was observed.24 While the results of surgical thrombectomy and systemic thrombolytic therapy illustrated the benefits of early thrombus removal in patients with proximal DVT, these therapies have not been widely utilized. Surgical thrombectomy is invasive, requiring operative exposure and risks damage to the venous endothelium and valves during embolectomy. The administration of systemic thrombolytics is associated with an unacceptably high rate of bleeding complications including retroperitoneal hemorrhage and intracranial hemorrhage. Further, complete clot resolution is not always achievable with either intervention. In fact, complete clot resolution after systemic thrombolytic administration was only achievable in 50% of patients with non-occlusive thrombus and 10% of patients with occlusive thrombus.24Nonetheless, these initial strategies have paved the route for the development of safer, more effective endovascular treatment strategies for thrombus removal in patients with proximal DVT.

Endovascular Management of DVT

Endovascular intervention for DVT should be considered in all patients with proximal lower-extremity DVT and a reasonable life expectancy. While multiple techniques and devices are available for endovascular DVT intervention, the majority of available treatment options may be separated by mechanism of action and include catheter-directed thrombolysis, ultrasound accelerated thrombolysis and percutaneous mechanical thrombectomy. Figure 1 demonstrates the pre- and post-operative images of a patient treated with the Trellis device. Percutaneous access for endovascular interventions is most often achieved in the vein distal to the occluded segment. For isolated iliac DVT, an ipsilateral common femoral puncture is most appropriate. Alternatively, a retrograde approach from the contralateral femoral vein may be used for isolated iliac and femoral vein DVT. More commonly, however, patients present with more extensive iliofemoral or iliofemoral popliteal thrombosis, in which case access is best obtained from the ipsilateral popliteal vein while the patient is positioned prone. Ultrasound guidance should be considered for access of the popliteal or tibial veins and for any access obtained while the patient is fully anticoagulated. Further, a micropucture technique with a 22-gauge needle and 0.014-inch guidewire may minimize bleeding complications and vessel wall trauma. Following initial access, the thrombus is crossed with a guidewire to facilitate catheter or device positioning. The use of retrievable inferior vena caval (IVC) filters during catheter-directed thrombolysis (CDT) or percutaneous mechanical thrombectomy (PMT) may be prudent for prevention of periprocedural pulmonary embolization as clot is disrupted.25–43 In an animal model, IVC filters were shown to decrease the incidence of angiographically diagnosed PE after mechanical thrombolysis of DVT.26 Further, Thery et al have demonstrated that 31% of patients (41/132) undergoing thrombolysis for lower-extremity DVT after placement of retrievable IVC filters had significant thrombus in the filter at the end of the procedure. More importantly, no patients in this study suffered a PE.27 A subsequent study confirmed these results, demonstrating a 40% incidence of thrombus debris in implanted filters following mechanical thrombectomy.28 It is our standard practice, and recommendation, to use retrievable IVC filters prior to thrombolysis or mechanical thrombectomy.29 In over 100 patients treated at our institution with IVC filters, mechanical thrombectomy and catheter-directed thrombolysis, there have been no occurrences of symptomatic PE, no filter-related complications and all IVC filters have been successfully removed when they have been placed. Other authors have reported similar success with IVC filters in this setting.29,30 Filters placed prior to CDT or PMT should be placed in standard fashion below the renal veins. In addition, access for filter deployment should be planned such that the endovenous delivery route is free of thrombus. Often, filters may be placed from the contralateral femoral vein in a percutaneous fashion. Extension of DVT into the IVC, however, may require filter placement from the internal jugular vein to avoid thrombus disruption during placement. Timing of filter retrieval is largely a matter of surgeon preference. It is generally accepted that filters may be removed at the end of the procedure if the completion venogram reveals no substantial clot burden. However, filter thrombus or persistent post-procedural contraindications to anticoagulation mandate longer filter indwell times.19,29,30In our experience, these filters may be removed without complications at a later date.

Endovascular Treatment Options

Catheter-directed thrombolysis (CDT). Catheter-directed thrombolysis allows infusion of thrombolytics directly into the venous thrombosis, limiting systemic drug exposure. Thrombolytic agents used with CDT include: urokinase (ImaRx Therapeutics, Tucson, Arizona), tissue plasminogen activator (tPA) (Activase, Genentech, South San Francisco, California), recombinant tissue plasminogen activator (r-tPA) (Retavase, PDL BioPharma, Fremont, California) or tenecteplase (Genentech). Most commonly, patients treated with CDT undergo percutaneous access in the operating room and initial venography to determine the extent of thrombus. A small infusion catheter is placed just proximal to the location of thrombus and is secured in place externally. Patients are monitored in the intensive care unit (ICU) and thrombolytics are slowly administered through the catheter. The patient undergoes repeat venography in the operating room to assess clot lysis once every 24 hours until complete lysis is achieved. This option has proven effective in proximal DVT resulting in early clot resolution, prevention of PE, prevention of recurrent DVT, preservation of valve function and improved quality of life compared to treatment with isolated anticoagulation. Results have demonstrated 60–90% clot resolution in proximal DVT,31–34 with the degree of clot removal correlating directly with improvements in long-term patency and a reduced incidence of post-thrombotic syndrome.34 Unfortunately, this therapy is still associated with significant bleeding complications in 11–43% of patients.31–37 Ouriel et al demonstrated insertion-site bleeding in 22–44%, transfusion requirements in 12–22% and intracranial hemorrhage in 0.6–3% of patients undergoing CDT with urokinase and r-tPA, respectively.37 Further limitations to the widespread use of this technique include prolonged lytic infusion times of 36–72 hours, prolonged ICU stay and expensive drug costs.31–37

Ultrasound-accelerated thrombolysis — EKOS EndoWave. The EKOS EndoWave (EKOS Corporation, Bothell, Washington) uses low-power, high-frequency ultrasound (2 MHz) in combination with catheter-directed thrombolysis to achieve clot disruption (Figure 2). Ultrasound waves generated by the unit do not directly macerate the clot, but rather create microstreams that increase thrombus permeability via alteration of fibrin composition. Increased permeability results in augmented lytic dispersion within the thrombus.38–40 In fact, a 65% increase in the number of fibrin strands exposed to thrombolytic drugs has been demonstrated to occur with a 44% ultrasound-mediated reduction in the diameter of fibrin strands.39 This translates to increased thrombus uptake of r-tPA by 48%, 84% and 89% at 1, 2, and 4 hours, respectively.40 Further, the ultrasound waves penetrate past valves, allowing for thrombus removal behind the valves that may be inaccessible with other PMT devices. The device consists of an infusion/aspiration catheter, an ultrasound core wire and a drive unit. The catheter, available in treatment lengths of 6–50 cm, contains a central lumen that accommodates the 0.035-inch ultrasound core wire and normal saline infusate used for central cooling. In a triangular distribution around the central lumen are three separate infusion channels containing microinfusion pores for drug delivery and thermocouples to monitor changes in temperature and flow patterns. The ultrasound core wire has transducers (2.2 MHz) located at 1-centimeter intervals. When the drive unit is activated, ultrasound waves are delivered to the core wire and transmitted through the catheter, penetrating thrombus and allowing lytic dispersion. Access is obtained with a 6 Fr introducer sheath and the lesion is crossed with a 0.35-inch guidewire. The catheter is positioned such that the treatment zone extends through the length of the thrombosed venous segment. After positioning, the guidewire is exchanged for the ultrasound core wire. The three separate drug infusion lumens are primed with unfractionated heparin. The control unit is activated and delivers ultrasound energy via the core wire while the thrombolytic agent of choice is administered through micropores located throughout the length of the treatment zone on each of the three catheters. Normal saline is infused through the central lumen continuously during the procedure to dissipate heat production. The drive unit automatically adjusts power according to changing vessel conditions, reducing power as flow is restored. The procedure is continued until complete lysis is achieved. Early evaluation of the EKOS EndoWave system in 53 patients, including 32 patients with lower-extremity DVT, demonstrated > 90% clot lysis in 70% of patients and at least partial thrombus resolution in 91%. Importantly, at least partial lysis was achieved in 96% of acute DVT cases (< 14 days), 100% of subacute DVT (15–28 days) and 77.8% of chronic (> 28 days) and acute or chronic DVT cases. Median lytic infusion time was 22 hours and bleeding complications were low (3.8%). Furthermore, median infusion times and median total drug dosages administered were lower with ultrasound-mediated thrombolysis compared to standard CDT when using urokinase, tPA, or r-tPA. The median dosages and infusion times were similar for CDT and ultrasound-mediated thrombolysis when tenecteplase was used.41The EKOS EndoWave system is used and functions in the same manner as the EndoWave system, however, the company is promoting faster clot lysis with this newer device.

Percutaneous Mechanical Thrombectomy

Percutaneous mechanical thrombectomy offers the benefit of early thrombus removal, while limiting thrombolytic dosages and bleeding complications. PMT additionally offers a treatment option for patients with absolute contraindications for lytic therapy as the AngioJet (Medrad, Inc., Warrendale, Pennsylvania), a PMT device discussed below, is the only device that can be used without the addition of lytics. PMT has further been shown to be more cost-effective than alternative treatment regimens when considering the lower thrombolytic dosages administered, the decreased length of ICU stay compared to CDT42 and the decreased long-term morbidity from post-thrombotic syndrome compared to traditional anticoagulation.

AngioJet Rheolytic Thrombectomy System — Pulse Power Spray Technique. The AngioJet catheter system is comprised of a single-use catheter, a single-use pump set and a drive unit. The catheter, which is available in working lengths of 60, 100 and 120 cm, contains a central lumen for infusate and a larger lumen encompassing the central channel, the guidewire and aspirate from the thrombus. The drive unit generates 10,000 psi of pulsatile infusion flow, which is released from the catheter in retrograde-directed high-velocity saline jets. These jets create a localized low-pressure zone (Bernoulli’s principle) at the catheter tip, macerating thrombus and redirecting flow and debris into outflow channels directed behind the catheter tip for aspiration and removal. Access for the AngioJet system requires a 6 Fr introducer sheath. The AngioJet catheter is then advanced over a 0.035 inch guidewire through the thrombus load (Figure 3). While this system was originally intended for use without adjunctive thrombolytics, it has been demonstrated that the addition of lytics to the infusion solution results in decreased treatment time and improved results. We recommend that thrombolytics be routinely used except when contraindicated, as is our practice. While thrombolytic choice and dose will vary dependent upon surgeon preference, we have experienced good results using 10 mg of tenecteplase in 50 ml of sodium chloride infusing solution.29 With the aspiration port clamped, infusate is released into the thrombosed venous segment during a slow pullback of the catheter, effectively lacing the clot with thrombolytic drug. After 10 minutes the aspiration function of the catheter is turned on. The catheter is then advanced through the thrombosed segment a second time, removing macerated thrombus through the aspiration ports as the catheter is advanced. This process may be repeated if there is remaining thrombus burden at the end of the first pass. Alternatively, as is often our preference, the patient may then undergo catheter-directed thrombolysis in the ICU overnight and return to the operating room the following day for re-evaluation with venography and possible repeat thrombectomy or venous stenting if indicated. Success in thrombus removal, restoration of venous patency and preservation of valvular function have been demonstrated with the use of the AngioJet pulse-power spray technique. While Kasirajan reported only 24% of patients had > 90% clot resolution, 35% had 50–90% resolution and 41% had < 50% resolution,43 improved results have been demonstrated with the addition of lytics to the infusate as discussed above. Bush et al reported complete thrombus resolution in 65% of patients, with at least partial resolution seen in all of the remaining patients.30 Lin et al demonstrated that PMT with the AngioJet system was at least as effective as CDT in treating lower-extremity DVT. They showed complete clot lysis in 75% of patients treated with AngioJet versus 70% in patients treated with CDT (p = NS), with similar patency rates at 1-year follow-up of 64% and 68%, respectively. Additionally, they demonstrated a reduced ICU stay, hospital length of stay and reduced costs in the PMT cohort.42 In our series we demonstrated a 90% venous patency restoration and maintenance of venous valvular function in 88% of patients at a mean follow-up of 6 months.29 This therapy is associated with a low incidence of hemorrhagic complications. Isolated case reports of pancreatitis resulting from massive hemolysis with use of the AngioJet system have been reported but appear to be rare occurrences.44

Trellis-8 Infusion System — Pharmacomechanical Thrombectomy. The Trellis-8 infusion system (Bacchus Vascular, Inc., Santa Clara, California) incorporates the use of both chemical thrombolysis and mechanical thrombectomy (Figure 4). The Trellis device consists of a single-use catheter, a dispersion wire and an integral drive unit. The catheter contains proximal and distal occlusion balloons that allow infusion of thrombolytics to an isolated segment of thrombosed vein. Catheters are available in lengths of 80 or 120 cm, with varied distances between occlusion balloons allowing treatment of 10, 15, or 30 cm venous segments. Catheter selection will depend on the location and length of the thrombosed segment determined on initial venography, with the goal of minimizing treatment length of the non-thrombosed vein. The drive unit is attached to the sinusoidal dispersion wire, which creates catheter oscillatation at 500–3,500 rpm, causing dispersion of lytics within the thrombus load and mechanical clot disruption. Aspiration of thrombus debris and lytic remaining in the isolated segment completes treatment of the isolated venous segment. Access for the Trellis-8 infusion system requires an 8 Fr introducer sheath. A 0.35 inch glidewire is used to cross the thrombosed venous segment and the Trellis-8 catheter is advanced over the glidewire. With proximal and distal balloons inflated, 5–10 mg of lytics are infused within the thrombus. After 10 minutes, the dispersion wire is inserted into the catheter. Catheter vibration between the occlusion balloons aids in clot maceratation and increases the thrombus surface area exposed to the lytics. The dispersion wire may further be advanced and retracted once per minute during the treatment interval to further assure mixing of the lytics with the thrombus. After 5–15 minutes, the distal balloon is deflated and the catheter aspirated via a side port to remove macerated thrombus and a substantial portion of the remaining lytics. The proximal balloon is left inflated during aspiration to prevent embolization of clot. After aspiration, with both balloons deflated, the system may be removed or advanced into adjacent thrombosed segments, repeating the procedure until the thrombus load is resolved. Hilleman et al reported success with the Trellis-8 infusion system for the treatment of proximal lower-extremity DVT in 135 patients. They demonstrated superior clot lysis with the Trellis-8 compared to conventional catheter-directed thrombolysis, with 93% achieving grade II (50–99% clot resolution) or III lysis (100% clot resolution) versus 79%, respectively. They additionally demonstrated that pharmacomechanical lysis required a lower lytic dose, was more cost-effective and was associated with significantly lower rates of hemorrhage (0% vs. 8.5%; p < 0.001).45 Arko et al further demonstrated that 80% of patients experienced complete clot resolution with this technique in a single setting, with venous patency maintained in 88% of patients treated with this device at a mean follow-up period of 6 months.29 O’Sullivan demonstrated grade II or III lysis in 96% of patients in a single setting, with 100% assisted primary patency at 30 days.46

Adjunctive Endovascular Procedures

Use of multiple PMT devices or adjunctive CDT. Recalcitrant thrombus after initial treatment with PMT may require further therapy. While small residual thrombus may respond to venous angioplasty and stenting, as discussed in the text to follow, larger amounts of residual thrombus may require the use of a second PMT device or overnight catheter-directed thrombolysis.19,29,30,38 Use of an adjunctive device or CDT should not be regarded as a failure of the first device, but rather as complementary procedures.38 The initial device achieves significant clot burden reduction, paving an easier path for the second intervention. Use of a second PMT device can be performed in the same setting, often with lower doses of thrombolytics.19,29 Alternatively, overnight CDT therapy may be sufficient to eliminate residual thrombus after clot debulking with PMT.19,29,30 This significantly reduces the time required for effective CDT and thereby reduces the associated bleeding risks with this treatment modality.19,29,30Patients should then undergo a second evaluation with intravascular ultrasound and/or completion venography to evaluate vessel conditions.

Adjunctive Venoplasty and Stenting

Post-treatment evaluation of the venous segment may reveal areas of venous compression, stenosis or recalcitrant thrombus in > 90% of patients.19,29,30 May-Thurner anatomy is the most common anatomic variant found on completion imaging during the treatment of proximal DVT (Figure 5). This syndrome is characterized by compression of the left common iliac vein by the right common iliac artery against the fifth lumbar vertebra, resulting in venous compression, development of venous scar tissue and eventually venous stenosis. This condition then predisposes the patient to left iliofemoral DVT.47,48 With anticoagulation alone, untreated iliac vein obstruction prevents vessel recanalization in 70–80% of patients and clot propagation may continue in up to 40% of cases.49,50 Further, patients with iliofemoral DVT and untreated May-Thurner anatomy experience an increased risk of recurrent DVT and universally experience symptoms of post-thrombotic syndrome during follow-up.5,51 Adequate treatment of anatomic compression, stenosis or persistent small thrombus after CDT or PMT requires angioplasty and stenting.52–60 Patel et al demonstrated 100% symptom resolution in May-Thurner syndrome and acute DVT treated with early thrombus removal and venous stenting. They further demonstrated preservation of valvular function in all patients on follow-up ultrasonography.56 Additionally, we have reported on the use of PMT and iliac vein stenting in 12 women with May-Thurner syndrome, demonstrating 100% intraoperative clot resolution and 100% primary stent patency with follow-up out to 45 months. All patients have had complete symptom resolution and there were no occurrences of post-thrombotic syndrome.19

Follow-up After Endovascular DVT Management

Patients should be anticoagulated post procedure with unfractionated heparin or low-molecular-weight heparin and transitioned to oral warfarin for 6 months (goal international normalized ratio 2.0–3.0). Patients with recurrent DVT or hypercoagulable disorders may require a longer duration of anticoagulation and consultation with primary care physicians is recommended. Patients with venous stents require lifelong aspirin therapy. Follow-up with duplex ultrasonography is also recommended at 1- and 6-month intervals and yearly thereafter (Figure 6).

Conclusions

Endovascular options are more effective in reducing long-term morbidity after proximal DVT when compared to anticoagulation alone. These options should be considered for all patients with proximal lower-extremity DVT and a reasonable life expectancy. Percutaneous mechanical thrombectomy is at least as effective as catheter-directed thrombolysis, with reduced ICU and hospital stays and decreased overall costs. Further, use of a second PMT device or adjunctive CDT may provide optimal results. Venous angioplasty and stenting may be required to treat recalcitrant thrombus or anatomic causes of DVT. With widespread implementation of these advanced treatment options for DVT, we can achieve a significant reduction in long-term morbidity after proximal DVT.

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From the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas. The authors report no conflicts of interest regarding the content herein. Address for correspondence: Frank R. Arko, MD, Associate Professor, Division of Vascular and Endovascular Surgery, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas. E-mail: Frank.Arko@utsouthwestern.edu

Clinical Review

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