Percutaneous Transcatheter Treatment of Deep Venous Thrombosis
Percutaneous transcatheter treatment of patients with deep venous thrombosis (DVT) consists of thrombus removal with catheter-directed thrombolysis, mechanical thrombectomy, angioplasty, and/or stenting of venous obstructions. In some cases, patients may also be given pulmonary embolism (PE) prophylaxis by means of filter placement in the inferior vena cava.
The goals of endovascular therapy include reducing the severity and duration of lower-extremity symptoms, preventing PE, diminishing the risk of recurrent venous thrombosis, and preventing postthrombotic syndrome (PTS).
The decision whether to use percutaneous transcatheter treatment and, if so, which technique to choose, is complicated by the lack of data from multicenter prospective randomized trials regarding the safety and efficacy of these therapies. Problems in the existing literature are variability in patient selection and the lack of standard definitions of short-term or long-term efficacy and complications. Nevertheless, a consensus regarding indications exists, although it is based on midlevel evidence from nonrandomized, controlled trials.
When an invasive procedure is considered, the benefit must be weighed against the added risk compared with standard anticoagulant therapy. If it is to be performed, the intervention must improve the results of current medical therapy. With heparin therapy, the risk of PE is 2%, the risk of recurrent DVT is 4%, and the risk of major bleeding is 5%.
For more information, see Deep Venous Thrombosis.
Catheter-directed thrombolysis involves the acceleration of the body’s natural thrombolytic pathway. The basic mechanism of action is the activation of fibrin-bound plasminogen, which promotes thrombus resolution. 
Observational studies from the University of Washington demonstrated that early lysis resulted in preserved valve function, while persistent thrombus resulted in the most severe forms of postthrombotic morbidity. 
Direct intrathrombus injection of the thrombolytic agent protects the medication from deactivation by circulating inhibitors and achieves higher drug concentration at the site of thrombosis with a lower total dose than would be used for systemic intravenous thrombolytic therapy. The lower circulating drug levels are the suggested mechanism for the lower incidence of systemic and, in particular, intracranial hemorrhagic complications reported with catheter-directed thrombolysis.
Thrombolytic therapy offers significant advantages over conventional anticoagulant therapy, including the prompt resolution of symptoms, the prevention of PE, the restoration of normal venous circulation, the preservation of venous valvular function, and the prevention of PTS. However, thrombolytic therapy does not prevent clot propagation, rethrombosis, or subsequent embolization. Heparin therapy and oral anticoagulant therapy must always follow a course of thrombolysis.
Success rates with catheter-directed thrombolytics vary depending on the age of the thrombus and the proximity to the inferior vena cava. Success with thrombolytic use in acute iliofemoral venous thrombosis has been reported to be 80-85%, with 1-year patency at 60-65%. Major bleeding complication rates vary from 5-11%; most bleeding occurs at the puncture site. [6, 7]
A prospective registry of 287 patients treated with a mean 53-hour infusion of urokinase-type plasminogen activator (uPA) showed anatomic success in 83%. About 34% of patients received adjunctive stent placement for underlying lesions. Major bleeding and rethrombosis were observed in 11% and 25% of patients, respectively, at 30-day follow-up. [7, 8]
Three studies demonstrated improved long-term venous function after catheter-directed thrombolysis versus anticoagulation alone. Two showed a decrease in reflux or symptoms from 41-70% to 11-22%. In a retrospective case-control study, quality-of-life scores (including stigmata, health distress, physical function, and symptoms) were superior at 22-month follow-up after catheter-directed thrombolysis with anticoagulation than after anticoagulation alone. 
The transcatheter approach facilitates the diagnosis of predisposing anatomic lesions or anomalies. In patients with iliofemoral DVT, catheter-directed thrombolysis was successful for recanalization in 92-100% of patients, and it revealed an underlying lesion in 50-66%. Treatment of these stenoses with angioplasty and stent placement reestablished unobstructed flow and achieved a prompt clinical response. Studies with 2-year follow-up documented a 5-11% incidence of valvular incompetence.
Indications for intervention include the relatively rare phlegmasia or symptomatic inferior vena cava thrombosis that responds poorly to anticoagulation alone, or symptomatic iliofemoral or femoropopliteal DVT in patients with a low risk of bleeding. In the last groups, the goal is to reduce the high risk of PTS or to achieve symptomatic relief in conjunction with angioplasty or stent placement.
Phlegmasia cerulea dolens is an indication for emergency catheter-directed thrombolysis in patients with moderate or low bleeding risks.  This recommendation is based on reports of limb salvage, which stand in contrast to the high rates of limb amputation and death seen with standard therapies.  Surgical thrombectomy remains an effective option in patients at high risk for hemorrhagic complications, although it often results in incomplete thrombus removal, recurrent DVT, and an increased incidence of systemic complications.
Acute or subacute inferior vena cava thrombosis that causes at least moderate pelvic congestion, limb symptoms, or compromised visceral venous drainage warrants catheter-directed thrombolysis. Involvement of the suprarenal cava, renal veins, and/or hepatic veins may precipitate acute renal or hepatic failure. Thrombus that involves the upper inferior vena cava may make it impossible to place an inferior vena cava filter for PE prophylaxis.
Subacute and chronic iliofemoral DVT is accompanied by moderate to severe pelvic or limb symptoms with a low bleeding risk. Because recanalization of the iliac vein is unlikely, iliofemoral DVT often produces valvular reflux.
This combination of outflow obstruction and reflux is associated with the most symptomatic forms of PTS. In this situation, patients have venous damage, and the alternative is venous bypass. In these instances, catheter-directed thrombolysis is seldom expected to completely clear the vein, but it is often used to remove any acute component of thrombus and to uncover chronic stenoses or underlying anatomic abnormality as an adjunct to angioplasty or stent placement. Compared with systemic thrombolysis, catheter-directed thrombolysis improves the preservation of valve competence (44% vs 13%).
Whether catheter-directed thrombolysis is indicated in the relatively common event of acute iliofemoral or femoropopliteal DVT is somewhat controversial. Catheter-directed thrombolysis may be superior to anticoagulation with regard to decreasing the incidence of recurrent DVT and PTS. However, the evidence is not conclusive.
Catheter-directed thrombolysis improves thrombus clearance compared with systemic thrombolysis. Few DVT cases resolve after heparin therapy, but systemic thrombolysis improves the rate to 30%, and catheter-directed thrombolysis removes 80% of thrombi.  Reports of catheter-directed thrombolysis for the management of acute DVT between 1994 and 2004 described anatomic and clinical success rates of 76-100%. The incidence of major hemorrhagic complications was 0-24%.
Asymptomatic DVT is not considered an indication for endovascular intervention at this time. The incidence of PTS at 5 years after asymptomatic calf or proximal DVT is low, at 5%.  The absence of symptoms may reflect the lack of the obstructive effect that is proposed to initiate the syndrome. On the other hand, while the incidence of PTS may not warrant endovascular treatment, some reports suggest that treatment of asymptomatic DVT may be necessary to prevent most cases of PE that are diagnosed at autopsy. Asymptomatic proximal DVT had a mortality risk of 13.7% versus 2% in patients without DVT.
Contraindications for percutaneous transcatheter treatment are the same as those for thrombolysis in general. Absolute contraindications include active internal bleeding or disseminated intravascular coagulation, a cerebrovascular event, trauma, and neurosurgery within 3 months.
Relative contraindications include major surgery within 10 days, obstetric delivery, major trauma, organ biopsy, intracranial or spinal cord tumor, uncontrolled hypertension, major GI hemorrhage (within 3 mo), serious allergic reaction to a thrombolytic agent, known right-to-left cardiac or pulmonary shunt or left-heart thrombus, and an infected venous thrombus. Unfortunately, most patients with DVT have absolute contraindications to thrombolytic therapy.
Thrombolytic therapy is also not effective once the thrombus is adherent and begins to organize. Venous thrombi in the legs are often large and associated with complete venous occlusion. In these cases, thrombolytic agents act on the surface of the clot but may not be able to penetrate and lyse the entire thrombus.
Nevertheless, the data from many published studies indicate that thrombolytic therapy is more effective than heparin in achieving vein patency. The unproven assumption is that the degree of lysis observed on posttreatment venography is predictive of future venous valvular insufficiency and late (5-10 y) development of PTS. Preliminary evidence suggests that thrombolytic therapy reduces but unfortunately does not entirely eliminate the incidence of PTS at 3 years.
The hemorrhagic complications of thrombolytic therapy are formidable (approximately 3 times higher than that of anticoagulant therapy) and include the small, but potentially fatal, risk of intracerebral hemorrhage. The uncertainty regarding thrombolytic therapy is likely to continue. Currently, the American College of Chest Physicians (ACCP) consensus guidelines recommend catheter-directed thrombolytic therapy only for selected patients with extensive acute proximal DVT (eg, those with iliofemoral DVT, symptoms for less than 14 days, good functional status, and life expectancy of >1 year) who are at low risk of bleeding. 
Access to the iliofemoral venous circulation is usually obtained via the popliteal vein, using ultrasonographic guidance, although the common femoral, tibial, or internal jugular veins are also used. When thrombolysis is planned, use of ultrasonography and a micropuncture 21-gauge needle are recommended to minimize bleeding risk. 
Diagnostic venography is used to identify the extent of DVT. Fluoroscopic guidance is the most accurate and straightforward means of placing infusion catheters or devices. A sheath is placed, and a multiple–side-hole catheter or wire is used to maximize delivery of the thrombolytic agent to the surface area of the thrombus.
During thrombolysis, patients remain on bed rest, with frequent monitoring of vital signs and puncture sites performed. Pericatheter oozing, enlarging hematoma, or evidence of gastrointestinal or genitourinary bleeding warrant immediate attention. Additional punctures, particularly arterial or intramuscular ones, should be avoided.
A separate IV access facilitates blood sampling, which is performed at 6-hour intervals to monitor the patient’s hematocrit; platelet count; activated partial thromboplastin time (aPTT), if concomitant heparinization is used; and possibly fibrinogen values. Monitoring of fibrinogen levels is controversial, although levels < 4.4 µmol/L (150 mg/dL) might indicate a clinically significant systemic effect.
Plasminogen activators include streptokinase, uPA, tissue-type plasminogen activator (tPA; alteplase), tenecteplase (TNK), and recombinant tPA (r-tPA; reteplase). The FDA has approved only streptokinase for systemic thrombolytic therapy of DVT. However, this agent is not currently recommended because of high rates of allergic reaction and bleeding complications and because of the availability of lower-risk agents. In the 1980s and 1990s, uPA was used extensively, but when it was temporarily taken off the market, tPA and r-tPA subsequently became the agents of choice.
In a retrospective analysis of catheter-directed thrombolysis for DVT, no significant differences were observed between uPA, tPA, and r-tPA with regard to success rate (>97%) or major complications (3-8%), although tPA and r-tPA were significantly less expensive than uPA. 
Recommended continuous dosages for catheter-directed thrombolysis of unilateral leg DVT are as follows:
tPA – 0.5-1.0 mg/h
r-tPA – 0.25-0.75 U/h
TNK – 0.25-0.5 mg/h
Other dosing options include an initial lacing dose, which entails an initial bolus given throughout the target thrombus, and a front-loaded dose, which is a high concentration given for the first few hours. No advantage to either approach has been demonstrated.
Most practitioners use concomitant heparinization. Full heparinization was commonly used in conjunction with uPA, whereas the current trend is to administer subtherapeutic heparin with tPA. Low-molecular-weight heparin (LMWH) has not been studied in this setting.
In the coronary literature, enoxaparin improved outcomes (death and myocardial infarction reduced from 12% to 9.9%), but it significantly increased bleeding complications (from 1.4% to 2.1%).
The Society of Interventional Radiology (SIR) published a position paper supporting the adjunctive use of catheter-directed thrombolysis in addition to anticoagulant therapy for carefully selected patients with acute iliofemoral DVT. The authors evaluated this therapeutic option in the context of the major therapeutic goals for the treatment of DVT: (1) provision of early symptom relief, (2) prevention of PTS, and (3) prevention of PE. 
The position statement cites a number of comparative studies that support the use of catheter-directed thrombolysis to prevent PTS and provide rapid symptom relief. The authors explain that the natural history of iliofemoral DVT is different than that of isolated femoropopliteal DVT. In the latter group, recanalization and collateral venous blood flow limit the degree of PTS. However, in the iliac veins, adequate recanalization is unlikely and collateral venous blood flow is minimal. This leads to persistent venous outflow obstruction and an increased risk of PTS.
Long-term studies of patients with iliofemoral DVT reported a 44% incidence of venous claudication at 5-year follow-up with standard anticoagulant therapy alone. Furthermore, the rate of recurrence of DVT is twice as high in patients with an iliofemoral DVT than in those with more distal, femoropopliteal DVT. The authors referenced a meta-analysis that demonstrated a 90% success rate with catheter-directed thrombolysis for thrombus removal, as well as a case-control study that reported a decreased incidence of PTS compared with anticoagulant therapy alone.
The SIR recognized that the main risk of adjunctive catheter-directed thrombolysis is bleeding. Their pooled review of 19 published studies reported an 8% incidence of major bleeding (mostly at the catheter insertion site) and an intracranial bleeding rate of only 0.2%, which is less than that reported for systemic thrombolytic therapy. However, the range of major bleeding risk in the studies reviewed was actually 0-24%. The incidence of PE was 1%, which is also less than the incidence of PE complicating standard anticoagulant therapy.
However, the authors conceded that no prospective, randomized study has yet been conducted to compare catheter-directed thrombolysis with standard anticoagulant therapy for iliofemoral DVT. In conclusion, the SIR affirmed that the available evidence defended a clinical benefit of catheter-directed thrombolysis in the specific subgroup of patients with iliofemoral DVT, limb-threatening disease, and low bleeding risk. 
Percutaneous mechanical thrombectomy has been developed as an attempt to shorten treatment time and avoid costly intensive care unit (ICU) stays during thrombolytic infusion. Mechanical disruption of venous thrombosis has the potential disadvantage of damaging venous endothelium and valves, in addition to thrombus fragmentation and possible pulmonary embolism. Many devices now exist and are approved for venous use.
Percutaneous mechanical thrombectomy devices are a popular adjunct to catheter-directed thrombolysis. Although these devices may not completely remove a thrombus, they are effective for debulking and for minimizing the dose and time required for infusing a thrombolytic. In patients at high risk for hemorrhagic complications, mechanical thrombectomy may obviate thrombolytic infusion. Such devices are most commonly used to initially restore antegrade flow (in cases of limb threat) or to manage a thrombus that has proved resistant to thrombolysis.
A wide variety of devices are under development or already on the market. These devices macerate thrombus by use of physical cutting blades, vortex, high-pressure or low-pressure saline jets, suction alone, or ultrasonic liquefaction.
An example is the Trellis catheter by Bacchus Vascular, which isolates the thrombosed segment with 2 occluding balloons and a rotating filament between that mechanically disrupts the thrombus while injecting a thrombolytic agent. After treatment, the thrombus and thrombolytic agent are aspirated and a venogram is performed. Published data include results with a 97% patency with a single treatment and no bleeding complications in a study group of over 700 patients. 
The most basic method for mechanical thrombectomy is thromboaspiration, or the aspiration of a thrombus through a sheath. Balloon maceration of the thrombus may be done to facilitate the procedure. The most technically advanced devices, approved primarily for interventions requiring hemodialysis access, may be divided by mechanism into categories of recirculation and fragmentation. Recirculation devices engage thrombus and destroy it by continuously mixing it by creating a hydrodynamic vortex.
Fragmentation devices leave macroscopic particulate effluent and include devices that chop, brush, or cut the clot. With these devices, concomitant lytic infusion and possible inferior vena cava filter placement are necessary to ensure PE prophylaxis.
Of recirculation devices, only the Trellis-8 Peripheral Infusion System (Bacchus Vascular, Inc., Santa Clara, CA) is FDA approved for the treatment of DVT. The AngioJet system (Possis Medical Inc., Minneapolis, MN) has the broadest FDA-approved uses, including uses in the coronary and peripheral arteries and in obtaining arteriovenous access; this is one of the most effective devices.
Reports have described use of the Arrow-Trerotola, AngioJet (Possis Medical), and Helix percutaneous thrombectomy devices for iliofemoral DVT, combined therapy (often with adjunctive thrombolysis, angioplasty and stenting, and placement of an inferior vena cava filter with the Arrow-Trerotola). These devices had 74-100% initial technical and 24-hour clinical success rates. Complete thrombus removal was variable (23-100%). The remainder improved with lytic infusion, with a mean infusion time of 6 hours.
Only 1 study had a 6% incidence of major bleeding complications. The primary patency rate at 1 year was 85%, and clinical success was obtained in 92%. At 9- to 12-month follow-up, 2 studies demonstrated an 8% rate of venous insufficiency, whereas 2 others showed repeat DVT in 15-23%.
Although the literature lacks conclusive evidence, some data support the argument that DVT treated with anticoagulation results in a high risk of PTS 5-10 years later. Active removal of the thrombus with surgery or catheter-directed lysis clears the thrombus relatively quickly and improves preservation of valvular function while reducing the incidence and severity of PTS. However, systemic or catheter-directed pharmacologic thrombolysis entails a high risk of bleeding complications. Initial data suggest that combination therapy that includes percutaneous mechanical thrombectomy, which allows a reduction in the dose and duration of thrombolytic treatment, may achieve thrombus clearance and reduce the incidence of PTS without elevating the bleeding risk.
For more information, see Deep Venous Thrombosis.
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Donald Schreiber, MD, CM Associate Professor of Surgery (Emergency Medicine), Stanford University School of Medicine
Donald Schreiber, MD, CM is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.
Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director for Emergency Medicine, Sanz Laniado Medical Center, Netanya, Israel
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, New York Academy of Medicine, New York Academy of Sciences, Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Francis Counselman, MD Program Director, Chair, Professor, Department of Emergency Medicine, Eastern Virginia Medical School
Francis Counselman, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, Association of Academic Chairs of Emergency Medicine (AACEM), Norfolk Academy of Medicine, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School
Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management position; ProceduresConsult.com Royalty Other
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
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