Endovascular Thrombolysis and Mechanical Clot Removal for Acute Symptomatic Lower Extremity Deep Vein Thrombosis



Endovascular Thrombolysis and Mechanical Clot Removal for Acute Symptomatic Lower Extremity Deep Vein Thrombosis



Mazen Bazzi and Anthony J. Comerota


The postthrombotic syndrome (PTS) is a debilitating complication of iliofemoral deep vein thrombosis (IFDVT) that markedly compromises patients’ quality of life. Postthrombotic morbidity is also associated with serious socioeconomic implications. Kahn and colleagues estimated the incidence of PTS to be 25% to 46% in all patients with DVT treated with anticoagulation alone. Patients with IFDVT have a greater incidence of and more severe PTS than those with infrainguinal DVT. In addition, these patients have a 2.6-fold higher risk of recurrence when treated with conventional anticoagulation than patients with less extensive DVT. A large thrombus burden results in more severe injury to the vein wall and more extensive persistent obstruction. Prandoni and coworkers concluded that residual thrombus in the proximal veins following treatment with anticoagulation alone was a significant risk factor for recurrence. Although systemic anticoagulation alone remains the mainstay of therapy, adopting a strategy of thrombus removal using catheter-directed therapy is often indicated for the treatment of iliofemoral symptomatic DVT.


Initial attempts to treat acute IFDVT with thrombolytics were by peripheral intravenous administration. Systemic thrombolysis has major limitations when the thrombosis is occlusive and the surface area exposed to the lytic agent is minimal because there is reduced plasminogen activator penetration of the thrombus and less clot resolution. The cumulative results of early trials involving systemically delivered thrombolysis revealed that although 45% of patients had substantial or complete lysis, most did not. However, those whose clot was successfully lysed had a significant reduction in postthrombotic morbidity and preservation of vein valve function.


In 1999, Mewissen and colleagues reported the results of the National Venous Registry, where the majority of patients were treated with catheter-directed thrombolysis (CDT) and 83% of patients achieved complete or partial lysis. Major bleeding complications occurred in 11%; however, these patients received very large doses of urokinase during their course of therapy. The majority of the bleeding complications occurred at the venous puncture site. At 1 year, the primary patency rate was 60%. The initial degree of lysis predicted 1-year primary patency. In patients who came to the hospital with a first-time IFDVT who had successful lysis, 96% of the veins remained patent at 1 year.



Mechanism of Thrombolysis


During thrombosis, circulating Glu-plasminogen binds to fibrin and is converted to Lys-plasminogen, which has more binding sites for plasminogen activators and is more efficiently activated to plasmin then Glu-plasminogen. Alkjaersig and colleagues investigated the basic mechanism of clot lysis and found that the plasminogen activator penetration of clot, with subsequent activation of fibrin-bound plasminogen to form plasmin, is the active enzyme that dissolves the clot. If plasmin then escapes into the systemic circulation, it is rapidly neutralized by α2-antiplasmin or, secondarily, α2-macroglobulin. Catheter-directed delivery of plasminogen activators into the thrombus accelerates thrombolysis, thereby increasing the likelihood of a successful outcome. Because of the local and regional delivery of the plasminogen activator, lower doses of the lytic agent are required and improved outcomes can be expected with fewer bleeding complications.



Evaluation


Patients with IFDVT have a large thrombus burden. Asymptomatic pulmonary embolism (PE) is present in at least 50% of these patients, and 25% become symptomatic once the inflammatory pulmonary process extends to the pleura. If a PE is not recognized early, a clinician might mistakenly assume that the subsequent pleuritic pain is caused by a new PE resulting from treatment failure. It is appropriate to evaluate these patients early with computed tomography of the chest, abdomen, and pelvis to evaluate for thrombus in the vena cava and to examine for any other undiagnosed pathology. Inferior vena cava filters are indicated if there is a free-floating thrombus in the inferior vena cava.


When the initial venogram is performed in preparation for treatment, patients are positioned prone. Under ultrasound guidance, the popliteal vein is accessed and an infusion catheter is advanced in an antegrade fashion. Adjunctive mechanical techniques are used initially to shorten the duration of lysis and to decrease the amount and duration of lytic agent infused. The typical dosage of recombinant tissue plasminogen activator (rt-PA) is generally 1 mg/hour infused in a volume of 50 to 100 mL. We have observed that lower doses of plasminogen activator can be effective when delivered in a larger volume. This is a departure from the early treatment protocols; these used a high dose of plasminogen activators delivered in small volumes of saline, which results in improved lytic success and reduced bleeding complications.


After treatment, a completion phlebogram is performed; any lesion in the iliac venous segments is corrected to provide unobstructed venous drainage to the vena cava, thereby reducing the risk for recurrent thrombosis. Most commonly, a stenosis is found in the left common iliac vein secondary to right common iliac artery obstruction. The common iliac vein is usually stented using a 14- to 16-mm Wallstent (Boston Scientific, Natick, MA). Subsequently, the patient is continued on anticoagulation and switched to vitamin K antagonists.



Endovascular Strategies of Thrombus Removal


Catheter-Directed Thrombolysis


Based on the mechanism of action of plasminogen activators, it seems logical that an intrathrombus infusion would be superior to systemic thrombolysis for all acute thrombotic events. Reports of intrathrombus CDT have shown good outcomes. Bleeding complications occurred in approximately 5% to 10% of cases, with most at the venous access site. Intracranial bleeding was rare, occurring in only three patients in the National Venous Registry. Symptomatic PE occurred in less than 1%. Most reports demonstrated a good or excellent lytic response, resulting in less residual thrombus, less vein valve reflux, and a greater number of asymptomatic patients at 1-year follow-up.


To date, results from two randomized trials of CDT for IFDVT have been reported. The Egypt trial randomized IFDVT patients to either CDT or anticoagulation. Streptokinase was infused into the clot, and at 6 months iliofemoral patency was observed in 72% of the lysed patients versus 12% of those anticoagulated. Enden’s group reported preliminary results of 103 patients from the CaVent trial who were randomized to either CDT or anticoagulation. The primary outcome of this study is the incidence of PTS at 2 years and the patency of the iliofemoral venous segment at 6 months. After analysis of 50% of target enrollment, 6-month patency of the iliofemoral veins was 64%, versus 36% in the anticoagulated group. Valve function did not differ between the groups.



Pharmacomechanical Thrombolysis


Complementing CDT with adjunctive mechanical methods is rapidly becoming the preferred method of catheter-based management of extensive DVT (Figure 1). Percutaneous mechanical thrombectomy alone is less successful than CDT and is associated with prolonged thrombolytic infusion times, prolonged intensive care unit stay, higher drug costs, and greater risks of hemorrhagic complications. Preliminary observations suggest that combining mechanical techniques with lytic infusion (pharmacomechanical thrombolysis, or PMT) results in a more effective lytic response in a shorter time.


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FIGURE 1 A 36-year-old woman came to the hospital with acute left limb swelling from iliofemoral deep vein thrombosis. A, Venogram of the left iliofemoral segment before the initiation of pharmacomechanical thrombolysis demonstrates extensive venous obstructive disease. B, The Trellis catheter is deployed with the patient in the prone position. C, A phlebogram after 24 hours of recombinant tissue plasminogen activator (rt-PA) infusion shows increased blood flow through the treated segment. D, Completion phlebogram following placement of a 16-mm Wallstent for May–Thurner syndrome.

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Aug 25, 2016 | Posted by in CARDIOLOGY | Comments Off on Endovascular Thrombolysis and Mechanical Clot Removal for Acute Symptomatic Lower Extremity Deep Vein Thrombosis

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