Catheter-directed thrombolytic therapy in deep venous thrombosis of the lower extremity: Patient selection and administration

INTRODUCTION — Thrombolytic agents activate plasminogen to form plasmin, which accelerates the lysis of thrombi. Thrombolytic therapy may be used in a variety of thrombotic disorders including deep vein thrombosis (DVT) of the lower extremity. Catheter-directed rather than systemic thrombolytic therapy is now the most common method of administering thrombolytic agent.

The indications, contraindications, adverse effects, and outcomes of thrombolytic therapy in acute DVT of the lower extremity are discussed here. Thrombolytic therapy for the treatment of acute pulmonary embolism and upper extremity DVT are discussed separately. (See "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration" and "Primary (spontaneous) upper extremity deep vein thrombosis", section on 'Thrombolytic therapy'.)

PATIENT ASSESSMENT

Confirm the diagnosis — The diagnosis of lower extremity DVT should be unequivocal because the adverse effects of thrombolytic therapy can be severe or life-threatening (eg, hemorrhage or bleeding in a critical location such as the brain). DVT is typically diagnosed using compression ultrasound (CUS), the details of which are provided separately. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

Assess risk:benefit ratio — Most patients with DVT of the lower extremity do not need thrombolytic therapy. However, select patients with extensive DVT may benefit. In such patients, the benefits of reducing the risk of venous gangrene and improving symptoms should be weighed against the risk of bleeding, particularly intracerebral hemorrhage. While this evaluation is ongoing, patients should be immediately anticoagulated, provided that the bleeding risk is low, and confined to bed. We typically use intravenous unfractionated heparin or low molecular weight heparin; further details regarding acute anticoagulation of patients with DVT are provided separately. (See "Venous thromboembolism: Initiation of anticoagulation".)

●Assess severity of symptoms and for risk of digital ischemia – In every patient who has extensive DVT, clinicians should assess for the severity of pain and swelling and for the symptoms and signs of phlegmasia cerulea dolens (PCD). PCD is an uncommon but fulminant massive venous occlusion with high mortality and amputation rates, if left untreated. The clinical signs and symptoms of PCD comprise a spectrum that ranges from phlegmasia alba dolens to venous gangrene, resulting in limb ischemia. Patients with severe PCD need immediate thrombolysis, particularly those with signs of active ischemia. Further details regarding the clinical presentation of PCD are provided separately. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Phlegmasia cerulea dolens'.)

●Assess the risk of bleeding – The approach to assessing for the risk of bleeding from thrombolytic agent and the contraindications to thrombolysis are similar to that described for patients with pulmonary embolism (table 1). (See "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration", section on 'Bleeding'.)

PATIENTS SUITABLE FOR THROMBOLYTIC THERAPY — In patients with acute DVT of the lower extremity, we reserve thrombolytic therapy for patients with severe symptomatic swelling and/or those with limb- or life-threating extensive proximal or iliofemoral DVT. The goal in this population is to alleviate symptoms and prevent gangrene. This approach is based upon evidence from small randomized trials and observational studies in unselected patients with DVT. These data report that thrombolytic therapy (systemic and catheter-directed) results in more rapid and complete lysis of clot, compared with anticoagulant therapy alone, but has no impact on recurrent thromboembolism or mortality [1-8]. Importantly, any benefit occurs at the expense of a higher rate of major bleeding. Thrombolysis does not unequivocally reduce the incidence of post-thrombotic syndrome but may reduce its severity. While efficacy data mostly studied systemic thrombolysis, lower rates of bleeding and practice trends have resulted in the widespread use of catheter-directed thrombolysis (CDT) such that systemic agents are never or rarely used. (See 'Efficacy' below and 'Route of administration (catheter-directed)' below.)

Extensive proximal or iliofemoral DVT — Widely accepted indications for thrombolytic therapy for lower extremity DVT include extensive or large proximal lower extremity DVT (ie, popliteal or femoral DVT) or iliofemoral thrombosis associated with either or both of the following:

●Severe symptomatic swelling (ie, considered "at risk" of ischemia)

●Limb-threatening ischemia (ie, phlegmasia cerulea dolens [PCD])

Clinical assessment should ensure that the clot burden truly explains the swelling and symptomatic findings and evaluation of proximal thrombus extension proximally into the inferior vena cava.

In some cases, we also use thrombolysis for patients with persistent, severe symptoms or swelling despite therapeutic anticoagulation, although there are no data to support that practice.

The administration of thrombolysis in this population is predicated on symptoms being present for less than 14 days, life expectancy >1 year, good functional status, and low bleeding risk. In most centers, multidisciplinary teams contribute to the decision and the procedure is generally performed by interventional radiologists or vascular surgeons. (See "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration", section on 'Pulmonary embolism response team'.)

Rationale — The rationale for treating this population of patients with thrombolytic agents is that rapid or immediate clot lysis provides symptom relief and restores limb perfusion, thereby avoiding digital or limb gangrene. In most cases, catheter-directed approaches have the additional advantage of combining thrombolysis with thrombus removal, if the latter is considered beneficial (eg, signs of gangrene). (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Phlegmasia cerulea dolens'.)

Efficacy — Most studies examining the effect of thrombolysis in patients with extensive DVT include a mix of patients with a broad range of both DVT severity (ie, patients with unselected DVT) and interventions and devices. There are no data specifically examining the effect in patients with extensive DVT or PCD only. Data in unselected patients are discussed below. (See 'Efficacy and safety (unselected patients)' below.)

Administration

Route of administration (catheter-directed) — Once the decision to administer thrombolytic therapy has been made, we prefer CDT, provided that resources and expertise are available [9]. The rationale for CDT preference is based upon limited data that suggest similar or improved rates of clot lysis compared with systemic agents and the lower likelihood of bleeding due to the administration of lower total doses of thrombolytic agent [5,10]. In addition, CDT can be combined with (or replaced by) mechanical methods of thrombolysis (eg, angioplasty, aspiration, rotational, rheolytic, or ultrasound). As such, systemic therapy has largely become obsolete and is only used when CDT is unavailable or when patients have an indication for systemic thrombolysis such as hemodynamically unstable acute pulmonary embolism. (See 'Efficacy' above and "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration".)

CDT refers to the infusion of a thrombolytic drug directly into the deep venous thrombus via a multi-sidehole catheter. A number of different catheter devices have been utilized for this purpose, and their placement is usually performed by an interventional radiologist or vascular surgeon. Access sites for CDT include the popliteal, common femoral, internal jugular, or posterior tibial vein. Venography is usually performed to locate the clot and evaluate its extension. Then, a guidewire is passed through the thrombus to a thrombus-free component of the vein (ie, inferior to the thrombus); using a Seldinger technique, the catheter is placed deep into the thrombus, the guidewire is removed, and the agent is infused via the catheter. During CDT, some clinicians place a temporary, retrievable filter in the inferior vena cava to trap thrombus fragments [11]. (See "Placement of vena cava filters and their complications".)

Agents and dosing — Tissue plasminogen activator (tPA) is the most commonly employed agent for CDT. The usual dose of tPA is approximately 0.5 to 1 mg/hour.

Systemic agent is almost never administered. However, if CDT is unavailable, then intravenous (IV) tPA at a dose similar to that administered in patients with pulmonary embolism (PE) is appropriate; streptokinase and urokinase are no longer available in the United States. (See "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration", section on 'Dosing (continuous infusion)'.)

Anticoagulant therapy — Anticoagulant therapy (typically unfractionated heparin [UFH]) is generally continued before, during, and after the thrombolytic infusion when CDT is used but held for those undergoing thrombolysis with systemic agents. When IV UFH is given during CTD, we generally aim for a lower activated partial thromboplastin time (aPTT) or anti-factor Xa. However, considerable variation exists in how this is achieved (eg, reduced UFH infusion rates of 300 to 500 international units per hour during CDT, omission of the initial bolus of UFH). Therapeutic aPTT or anti-factor Xa should be targeted after CDT.

Monitoring, bleeding, and adverse effects — Patients with extensive DVT who undergo thrombolysis should be evaluated for symptom improvement. The lower extremities should also be examined for a reduction in swelling and pulses should be assessed by manual palpation or by Doppler to ensure that arterial flow is intact. We also assess clinically for pulmonary embolism and for any changes in neurologic or mental status. Every six hours, we also check fibrinogen levels and factor Xa levels. We sometimes stop the infusion if fibrinogen is <100 mg/dL. Complete blood count is also typically checked daily. Other aspects of monitoring for a clinical response and for bleeding during the thrombolytic infusion is similar to that described for patients undergoing thrombolysis for acute PE. (See "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration", section on 'Monitoring and management of bleeding'.)

Venography is generally performed 12 to 24 hours after initiating the infusion, at which time, a decision is made to continue or discontinue the infusion and/or perform manual extraction. Venography (with or without intravascular ultrasound) may also uncover an underlying stenotic lesion responsible for the DVT, such as that seen in May-Thurner syndrome (extrinsic venous compression by the arterial system against bony structures in the iliocaval territory). After 24 to 48 hours of the infusion, most if not all of the thrombus should be dissolved. Infusions rarely extend beyond 48 hours. At that point, the infusion is discontinued and the catheter is removed. (See "Overview of iliocaval venous obstruction" and "May-Thurner syndrome".)

Bleeding is the most common adverse effect (<2 percent for major bleeding, <1 percent for intracranial hemorrhage (see 'Efficacy and safety (unselected patients)' below)). Occasionally, reperfusion of the limb may be complicated by further swelling and ischemia when arterial flow improves, such that a fasciotomy may be required. Other adverse effects include local complications from the catheter such as misplacement, perforation, infection, and hematoma. (See "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration", section on 'Monitoring and management of bleeding' and "Acute compartment syndrome of the extremities".)

Follow-up — Once the thrombolytic infusion is complete, patients should be transitioned to therapeutic anticoagulation similar to those who have not undergone CDT for lower extremity DVT [12]. While the ideal transition time is uncertain, we typically start anticoagulation within 12 to 24 hours after infusion completion. Unless heparin is indicated, we usually start with a direct oral anticoagulant such as apixaban or rivaroxaban. If there is a contraindication of anticoagulation, an inferior vena cava filter should be placed. (See "Venous thromboembolism: Anticoagulation after initial management" and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)

Options for patients who fail thrombolysis are discussed below. (See 'Patients who fail thrombolysis' below.)

PATIENTS WHO FAIL THROMBOLYSIS — Options for patients who fail thrombolysis include repeat catheter-directed thrombolysis (CDT), catheter-directed mechanical thrombectomy, or surgical thrombectomy. Choosing among these options is dependent upon local expertise and surgical candidacy of the patient. Several catheter-directed techniques are available (eg, angioplasty, aspiration, rotational, rheolytic, and ultrasound-accelerated devices), similar to those available for patients with pulmonary embolism [13-16]. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Catheter-directed modalities'.)

Data to support the use of catheter-directed thrombectomy in those at high risk of bleeding or in those who have failed thrombolysis are extrapolated from observational studies in patients with DVT who have not yet undergone therapy and are at low bleeding risk:

●In one systematic review of 16 observational studies, percutaneous mechanical thrombectomy (PMT) resulted in a venous patency rate of 75 to 100 percent at 12 months [17]. Rates of post-thrombotic syndrome (PTS) and bleeding complications were lower in patients treated with PMT compared with CDT.

●Another meta-analysis of six trials reported that PMT significantly reduced the thrombus score and thrombolysis time compared with CDT alone; bleeding events were similar [18].

Open surgical thrombectomy is poorly studied. One meta-analysis of 15 mostly observational studies reported that compared with systemic anticoagulation, surgical thrombectomy reduced the incidence of PTS (relative risk [RR] 0.67, 95% CI 0.52-0.87) and venous reflux (RR 0.68, 95% CI 0.46-0.99) [19]. However, the quality of evidence was very low.

PATIENTS NOT SUITABLE FOR THROMBOLYTIC THERAPY

Uncomplicated DVT — For most patients with uncomplicated DVT, we suggest against the use of thrombolytic therapy (systemic or catheter-directed). This approach is based upon data in unselected patients which report that thrombolytic therapy only achieves faster clot lysis at the expense of increased bleeding and does so without having an impact on clinically meaningful outcomes such as mortality or recurrent DVT, when compared with anticoagulation alone [9,20]. These patients should be therapeutically anticoagulated, the details of which are provided separately. (See 'Efficacy' above and "Venous thromboembolism: Initiation of anticoagulation" and "Venous thromboembolism: Anticoagulation after initial management".)

However, catheter-directed thrombolysis (CDT) is rarely considered in a small subset of patients with uncomplicated DVT who have severe or worsening symptoms but lack features of pending or overt ischemia. In those patients, the focus of thrombolytic therapy is to improve symptoms and the urgency of thrombolysis is not as apparent; clinicians have time (hours to days) to determine if there is satisfactory improvement with anticoagulation alone. The potential risks and benefit can be discussed with the patient and other experts before proceeding with thrombolysis. (See 'Extensive proximal or iliofemoral DVT' above and 'Administration' above.)

Efficacy and safety (unselected patients) — Several studies in unselected patients with DVT have demonstrated thrombolysis is of no or limited benefit.

●CDT – Several observational studies and randomized trials in patients with unselected DVT have consistently reported that, despite improved venous patency, the addition of CDT to anticoagulation has no effect on mortality, DVT recurrence, or rates of post-thrombotic syndrome (PTS) [5,7-10,21,22]. As examples:

•CDT versus anticoagulation alone – One randomized trial of 692 patients (ATTRACT) reported that the addition of pharmacomechanical catheter-directed thrombolysis (ie, tissue plasminogen activator [tPA] plus clot extraction or maceration with or without stenting) to anticoagulation did not alter the rates of recurrent venous thromboembolism compared with patients treated with anticoagulation alone (12 versus 8 percent) [8]. Rates of PTS were also similar (47 versus 48 percent). However, pharmacomechanical thrombolysis did lead to more bleeding events (1.7 versus 0.3 percent). A prespecified subgroup analysis and a subsequent subgroup analysis suggested a reduction in the proportion of patients with moderate to severe PTS and severity of PTS symptoms in those with severe iliofemoral DVT [8,22].

An older and smaller randomized trial of 209 patients with iliofemoral DVT also found that CDT resulted in that higher rates of venous patency (66 versus 47 percent) but found lower rates of PTS at two years (41 versus 56 percent) compared with those who were treated with anticoagulant alone [5].

An observational database study of 3649 patients with acute DVT reported no difference in mortality between patients treated with CDT plus anticoagulation compared with patients treated with anticoagulation alone (1.2 versus 0.9 percent) [7]. However, patients treated with CDT had an increased rate of blood transfusion (11 versus 7 percent), pulmonary embolism (18 versus 11 percent), intracranial hemorrhage (0.9 versus 0.3 percent), and inferior vena cava filter placement (36 versus 16 percent).

•CDT versus systemic thrombolysis – One trial randomly assigned 32 patients with iliofemoral DVT to undergo either systemic thrombolysis or CDT, followed by anticoagulation [10]. Venous valvular competence was preserved in more patients treated with CDT when compared with patients treated with systemic thrombolytic therapy (44 versus 13 percent). CDT also resulted in less reflux in both the deep veins (44 versus 81 percent) and superficial veins (25 versus 63 percent).

●Systemic thrombolysis – In a Cochrane meta-analysis of 19 small randomized trials and observational studies (15 of which studied systemic agents and four of which studied CDT), thrombolysis increased the rates of clot lysis when compared with patients treated with anticoagulation alone (risk ratio [RR] 4.75, 95% CI 1.83-12.33 at early follow-up; RR 2.42, 95% CI 1.42-4.12 at later follow-up) [23]. Thrombolysis also resulted in a slight reduction in the rates of PTS (50 versus 53 percent; RR 0.78, 95% CI 0.66-0.93). This benefit occurred at the expense of increased bleeding (6.7 versus 2.2 percent; RR 2.45, 95% CI 1.58-3.78). There was insufficient evidence to report on the rate of venous thromboembolism recurrence. Limitations of the analysis include variable administration methods and doses of agent, different exclusion criteria among studies, inconsistent reporting of bleeding events as major or minor, inclusion of retrospective data, and small sample sizes. The discrepancy between reduced rates of PTS found in this analysis and the lack of effect found in ATTRACT [8] may be explained by the high rates of systemic thrombolysis in this meta-analysis. Noteworthy is that systemic thrombolysis is no longer used for the treatment of lower extremity DVT, except perhaps in the rare setting of lack of access to CDT and inability to transfer the patient to a facility with CDT expertise.

●Any clot removal strategy (thrombolysis or mechanical or combined) – In a 2021 meta-analysis of 45 studies of patients with DVT, compared with heparin alone, any strategy that involved thrombolysis and/or mechanical clot removal resulted in improved incidence of PTS at five years (RR 0.56, 95% CI 0.43-0.73) but at the expense of increased major bleeding (RR 2.45, 96% CI 1.58-3.78; 6.7 versus 2.3 percent) and without an effect on pulmonary embolism or mortality [20].

Patients at high risk of bleeding or contraindications to thrombolysis — For patients in whom CDT is indicated but have contraindications to thrombolysis or are at high risk of bleeding, options include catheter-directed clot extraction or surgical thrombectomy. Data to support these options are discussed below. (See 'Patients who fail thrombolysis' above.)

In this population, an inferior vena cava filter should also be placed to prevent embolization to the lung. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Patients at high risk of bleeding' and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Inferior vena cava filter'.)

Poor functional status, limited life expectancy, DVT >14 days — Options in patients with poor functional status, limited life expectancy, and DVT older than 14 days are limited to anticoagulation alone, provided that the bleeding risk is low, or to catheter-directed clot extraction if the bleeding risk is high. (See 'Patients who fail thrombolysis' above.)

LONG TERM FOLLOW-UP — We follow patients in outpatient clinics in a similar fashion to those with DVT who did not undergo thrombolysis. Duration of anticoagulation, screening for underlying disorders, and recurrence are discussed separately. (See "Venous thromboembolism: Anticoagulation after initial management", section on 'Duration' and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation" and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Monitoring and follow-up' and "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors" and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Suspected recurrent DVT'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)" and "Patient education: Pulmonary embolism (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Patient assessment – Thrombolytic therapy can be used to treat a select group of patients with deep vein thrombosis (DVT) of the lower extremity. To assess candidacy for thrombolysis, patients with DVT should be assessed for the severity of their symptoms, risk or presence of digital gangrene, and risk of bleeding. (See 'Patient assessment' above.)

●Uncomplicated DVT – For most patients with uncomplicated lower extremity DVT, we recommend that thrombolytic therapy not be administered (Grade 1B). This approach is based upon evidence from small randomized trials and observational studies in unselected patients with acute DVT, which report that thrombolytic therapy (systemic and catheter-directed) results in more rapid and complete lysis of clot, compared with anticoagulant therapy alone, but has no impact on recurrent thromboembolism or mortality; moreover, this lack of benefit comes at the expense of a higher rate of major bleeding. (See 'Patients not suitable for thrombolytic therapy' above and 'Uncomplicated DVT' above.)

●DVT with extensive or large thrombus – Select patients with extensive DVT may benefit from thrombolytic therapy, typically catheter-directed thrombolysis (CDT). For patients who have severe symptomatic swelling and/or limb- or life-threating extensive proximal or iliofemoral DVT, we suggest CDT and anticoagulation, rather than anticoagulation alone (Grade 2C). The administration of CDT in this population is predicated on symptoms being present for less than 14 days, life expectancy >1 year, good functional status, and low bleeding risk. The rationale for CDT in this population is that rapid or immediate clot lysis provides symptom relief and restores limb perfusion, thereby avoiding digital or limb gangrene. (See 'Patients suitable for thrombolytic therapy' above and 'Extensive proximal or iliofemoral DVT' above.)

•Catheter-directed versus systemic – CDT has largely replaced systemic thrombolysis, based upon limited data suggesting similar or improved rates of clot lysis compared with systemic agents and the lower likelihood of bleeding due to the administration of lower total doses of thrombolytic agent. In addition, CDT can be combined with (or replaced by) mechanical methods of clot removal (eg, angioplasty, aspiration, rotational, rheolytic, or ultrasound). As such, systemic therapy has largely become obsolete.

•Administration – Catheters are generally placed by an interventional radiologist. Tissue plasminogen activator (tPA), the most common agent chosen for CDT, is infused directly into the deep venous thrombus via a multi-sidehole catheter. Some experts also temporarily place a retrievable filter in the inferior vena cava to trap thrombus fragments. Anticoagulation, usually unfractionated heparin, is generally continued during, before, and after CDT. (See 'Route of administration (catheter-directed)' above and 'Agents and dosing' above and 'Anticoagulant therapy' above.)

•Monitoring – During the thrombolytic infusion, patients should be monitored for a clinical response and for bleeding. We examine the lower extremities for a reduction in swelling and assess pulses by manual palpation or by Doppler to ensure that arterial flow is intact. We also monitor for pulmonary embolism and any change in neurologic or mental status. (See 'Monitoring, bleeding, and adverse effects' above and "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration", section on 'Monitoring and management of bleeding'.)

Venography is generally performed 12 to 24 hours after initiating the infusion, at which time, a decision is made to continue or discontinue the infusion and/or perform manual extraction. Venography (with or without intravascular ultrasound) may also uncover an underlying stenotic lesion responsible for the DVT, such as that seen in May-Thurner syndrome. After 24 to 48 hours of the infusion, most if not all of the thrombus should be dissolved, the infusion is discontinued, and the catheter removed.

Bleeding is the most common adverse effect (<2 percent for major bleeding, <1 percent for intracranial hemorrhage). Reperfusion of the limb may be complicated by further swelling and ischemia when arterial flow improves, such that a fasciotomy may be required. Other adverse effects include local complications from the catheter such as misplacement, perforation, infection, and hematoma. Following thrombolysis, full anticoagulation with unfractionated heparin followed by an oral agent is typical.

•Alternatives to CDT – Systemic tPA is an alternative to CDT when CDT is unavailable or when patients have an indication for systemic thrombolysis such as hemodynamically unstable acute pulmonary embolism.

●Patients who fail or have contraindications to thrombolysis – Options for patients who fail thrombolysis include repeat CDT, catheter-directed mechanical thrombectomy (eg, with angioplasty, aspiration, rotational, rheolytic, or ultrasound devices), or surgical thrombectomy. Choosing among these options depends on local expertise and surgical candidacy of the patient. (See 'Patients who fail thrombolysis' above and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Catheter-directed modalities'.)

For patients who are at moderate to high risk of bleeding or have contraindications to thrombolysis (table 1), options include catheter-directed or surgical thrombectomy. For patients with poor functional status, limited life expectancy, and DVT older than 14 days, anticoagulation alone or thrombectomy are appropriate. Choosing among these options in these special populations is individualized and institution-dependent. (See 'Patients not suitable for thrombolytic therapy' above and 'Patients who fail thrombolysis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Victor F Tapson, MD, who contributed to earlier versions of this topic review.