Percutaneous Mechanical Thrombectomy Combined with Thrombolysis for the Treatment of Deep Venous Thromboses
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Multiple sequellae may occur after deep venous thrombosis (DVT), including acute limb symptoms such as swelling and pain, valvular damage and reflux leading to chronic symptoms, and, the most serious, pulmonary embolism and death. Venous thromboembolic disease, including both DVT and pulmonary embolism, is an under-diagnosed medical problem that results in high rates of significant patient morbidity and mortality. Conventional therapy consists of anticoagulation with heparin and warfarin in the setting of an acute DVT, which prophylaxes against clot propagation and pulmonary embolism, but does not relieve thrombus burden. The delayed complications of DVT, known as the post-phlebitic syndrome, are due to valvular damage from chronic thrombus and scarring.
Techniques aimed at venous valve preservation and restoration of venous patency should theoretically decrease venous hypertension, reducing the incidence and degree of post-thrombotic symptoms. The ability of interventions such as anticoagulation therapy, thrombolytic therapy, and surgical/ endovascular thrombectomy to restore venous patency, remove obstruction, and ultimately decrease the incidence and severity of reflux in a diseased extremity can be used to return patients to their normal way of life. Unfortunately, no therapeutic options or interventions to date have demonstrated superiority over anticoagulation. Consequently, anticoagulation remains the “gold standard” of care while new modalities are being evaluated.
Endovascular management utilizing percutaneous mechanical thrombectomy (PMT) alone or in combination with pharmacological thrombolytic agents is safe and effective in reducing thrombus burden. Along with possible preservation of venous valve function, inciting anatomic lesions may be treated simultaneously. However, the experience is limited. We advocate adjunctive measures, such as the addition of lytic agent to the PMT therapy, to increase the speed and efficacy of thrombus removal. We will present herein a novel technique of percutaneous mechanical thrombectomy with concomitant lytic therapy for the treatment of venous thrombotic disease with an example of successful use.
A 53-year-old male presented to the emergency room with a two-day history of right lower leg swelling. He had just completed an eight-hour transatlantic flight four days prior to presentation. He described significant right calf and thigh swelling and pain. There was no significant past medical history and no recent trauma to his lower extremity. Physical examination revealed marked swelling of right lower extremity, involving the calf and the thigh, that was tender to touch. Venous duplex ultrasound revealed a large, echolucent density in the right common femoral vein, which was non-compressible, consistent with acute deep venous thrombosis (DVT). The thrombus extended proximally to the external and common iliac veins as well as distally to the superficial femoral and popliteal veins.
Percutaneous Mechanical Thrombectomy (PMT)
Relief of clot burden by directly extracting thrombus surgically or via lytic dissolution should hypothetically decrease the risk of pulmonary embolism and also that of post-thrombotic syndrome, which may lead to manifestations of chronic venous insufficiency. Primarily because of the bleeding risks of catheter-directed thrombolysis, PMT has emerged as an advantageous option for the treatment of acute DVT (
Several authors have evaluated multiple PMT catheters in the treatment of DVT. However, to date, there is no prospective, randomized trial data available. In one review, Vedantham et al. used percutaneous mechanical thrombectomy with catheter-directed thrombolysis (CDT) for the treatment of lower extremity DVT (several devices tested included the Amplatz Thrombectomy Device, Microvena, White Bear Lake, MN; AngioJet, Possis Medical Inc, Minneapolis, MN; Trerotola Percutaneous Thrombectomy Device, Arrow International, Reading, PA; Oasis, Boston Scientific/Meditech, Natick, MA).2 Procedural success was achieved in 82%, with underlying culprit stenoses uncovered and stented in 15 patients (18 limbs). These authors reported substantial thrombus removal with the two techniques combined compared to either alone. Another group (Delomez), using only the Amplatz Thrombectomy Device, reported successful recanalization of the thrombosed segment in 83% of patients with proximal DVT.3 At 29.6 months follow-up, 10 patients had minimal symptoms relating to the episode and only one patient had developed post-thrombotic sequellae.
Rationale for Use of Pharmaco-mechanical Thrombectomy
Rapid relief of thrombus burden by directly extracting thrombus surgically or via lytic dissolution, or a combination of the two modalities, should hypothetically decrease the risk of pulmonary embolism and also that of post-thrombotic syndrome resulting in manifestations of chronic venous insufficiency. Due to the hemorrhagic complications associated with catheter-directed thrombolysis, PMT has emerged as an advantageous option for the treatment of acute DVT. Various thrombectomy catheters with different mechanisms of clot removal are commercially available. A full discussion of each of the catheters is beyond the scope of this article. The catheters fall into one of two categories for clot extraction mechanism: microfragmentation or thrombo-aspiration (Venturi effect). Several PMT catheters have the ability for combination with adjunctive thrombolytic agents for more complete and rapid thrombus removal. The combination of therapies allows for lower mean lytic infusion doses and durations. Reducing the dosage and/or time for complete thrombolysis should translate into reduced morbidity (fewer hemorrhagic complications) and cost savings. Furthermore, underlying anatomic lesions that precipitated the thrombotic event may be unmasked with PMT (with or without adjunctive lysis). Venous stenoses can be treated following thrombectomy at the same setting, resulting in more efficient patient care.
The AngioJet® rheolytic thrombectomy catheter (Possis Medical, Minneapolis, MN) may be used in combination with adjunctive thrombolytic agents for more complete and rapid thrombus removal with lower mean lytic infusion doses and durations. The AngioJet thrombectomy device has no direct contact with the vessel wall, causing only minimal endothelial denudation.4 Because thrombus removal is not produced by the actual mechanical force of the infusion solution, but rather, by an indirectly created negative pressure zone, risk of luminal endothelial damage is minimal. By maintaining the structural integrity of the native venous endothelium, viability and the anti-thrombotic activities of the intact endothelium are preserved. Nonetheless, prolonged contact time between thrombus and endothelium increases endothelial damage. Furthermore, reducing the dosage and/or time for complete thrombolysis should translate into cost savings and decreased bleeding complications. Moreover, adjunctive endovascular techniques, such as balloon angioplasty with or without stent placement, can be successfully performed in the same setting of pharmaco-mechanical thrombectomy.
Power Pulse Spray
The Power Pulse™ Delivery Kit recently received U.S. Food and Drug Administration (FDA) clearance for use with the AngioJet 6 Fr. Expeedior catheter. The catheter has 2 lumens — one for saline infusion and one for aspiration of fluid and clot. By attaching a 3-way stopcock to the aspiration channel, the flow may be completely regulated by the surgeon. The approval from the FDA is for a Power Pulse Kit, which includes a y-set, stopcock and instructions for use. Two solution bags should be set up, including one with saline alone and one with a lytic agent added. With the stopcock in the “off” position and the outflow port in occluded, the AngioJet catheter effectively becomes a one-way infusion system, similar to a traditional infusion catheter for thrombolytic agents. The y-connector allows the physician to alternate between regular saline solution and a second solution for infusion into the target thrombotic lesion.
The AngioJet catheter is FDA-approved for the control and selected infusion of physician-specified fluids, including thrombolytic agents into the peripheral vascular system. The goals of therapy for DVT are to diminish the severity and duration of acute lower-extremity pain and edema, in addition to preventing pulmonary embolism, decreasing the rate of recurrence and the development of post-thrombotic syndrome. The appeal of catheter-directed thrombolysis is that it is effective in achieving patency of the venous lumen. PMT and now, PMT with the additional of a lytic agent to the infusion solution, should offer the advantage over pharmacologic thrombolysis in that the thrombus is very rapidly cleared from the occluded venous segments. Three agents are available that have been anecdotally described as adjunctive lytics for PMT. These are urokinase (UK; Abbokinase, Abbott Laboratories, Chicago, IL), the recombinant plasminogen activator alteplase (tissue plasminogen activator-TPA; Activase, Genentech, San Francisco, CA), and reteplase (recombinant plasminogen activator-RPA, Centocor, Malvern, PA).
The Power Pulse Kit enables the AngioJet catheter to deliver a pulsed infusion of a physician-specified fluid to the local treatment area, which in this case is a lower extremity DVT. The treatment approach in this patient included mechanical thrombectomy, using the AngioJet system via a right popliteal vein approach. As this catheter does not remove thrombus by contact and mechanical force with the endothelium, but rather by indirectly created negative pressure zone, luminal endothelial damage is kept to a minimum.
The following are recommended* doses for the various concomitant thrombolytic agents.
a. 100,000 Units per 100 cc saline
b. 250,000 Units per 50 cc saline
a. 25 mg per 50 cc saline
a. 2-4 Units per 50 cc saline
*The recommended lytic dosing is based on the authors’ personal experience and any dosing should be at the physician’s discretion.
Conclusion of Case Presentation
In the patient described herein, PMT on the power pulse mode was performed by making a single antegrade pass with the AngioJet. This patient was treated with urokinase (250,000 in 50 cc NS). A total of 25 cc (125,000 units UK) was used for lysis. After waiting approximately 20 minutes to allow for thrombolytic dissolution to occur, the AngioJet was reintroduced with the stopcock in the “on” position and the residual lytic and clot material evacuated. Completion venography demonstrated complete resolution of the DVT in the entire superficial femoral vein and the ileofemoral venous system.
The patient was given systemic heparin (100u/kg) and converted to oral warfarin anticoagulation three days later. Repeat venous duplex ultrasound was performed on the following day, which demonstrated a complete resolution of the femoral and iliac vein without evidence of DVT. He remained free of symptoms and had no recurrence of DVT at one year follow-up.
The data presented below is based on the authors’ unpublished experience and is non-randomized observational data. Over a 26-month period, 25 patients (22 men, 3 women; mean age 49 ± 7 years; range 14-79 years) with extensive upper (n=5) or lower extremity (n=23) DVT were treated with a combination of PMT using the AngioJet thrombectomy device with lytic agent (urokinase, tissue plasminogen activator, or reteplase) added to the infusion. The lytic was administered using the Power Pulse Spray modification, and the authors typically wait 10-20 minutes after lytic agent delivery before performing percutaneous mechanical thrombectomy. Three patients were treated twice after presentation with recurrent DVT. The primary endpoint was angiographic evidence restoration of venous patency at completion of the procedure. The 3 patients with recurrent ipsilateral DVTs following combination lysis and thrombectomy were included for review, as they were also treated with repeat pharmaco-mechanical thrombectomy PMT with lysis. All 3 recurrent DVTs occurred in patients who were found to have previously undiagnosed hypercoagulable states. These coagulopathies were not diagnosed until the patients presented with recurrent thrombosis, as it is not current practice or standard of care in the authors’ institution to order a panel of laboratory tests studies for the various hypercoagulable disease states when a patient presents with a de novo DVT.
Complete thrombus removal was obtained in 17 (61%) cases. The remainder (n=11; 39%) had partial resolution. Inciting occlusive lesions responsible for the acute DVT were revealed in 16 (57%) patients; angioplasty with or without stenting was performed when necessary. The 11 cases with partial resolution had additional catheter-directed thrombolysis for an average of 6.1 hours with further thrombus reduction. Immediate (
The authors can be reached at: RBush@bcm.tmc.edu
At the conclusion of this activity, the participant should be able to:
1. Discuss how DVT may result in chronic venous insufficiency and why early aggressive thrombus removal with percutaneous mechanical thrombectomy may have advantages over standard anticoagulation alone.
2. Discuss the benefits of power pulse spray or combined mechanical thrombectomy with thrombolytic therapy.
Activity instructions. Successful completion of this activity entails reading the article, answering the test questions and obtaining a score of over 70%, and submitting the test and completed evaluation form to the address listed on the form. Tests will be accepted until the expiration date listed below. A certificate of completion will be mailed to you within 60 days.
Estimated time to complete this activity: 1 hour
Initial release date: October 30, 2004 Expiration date: October 30, 2005
Target audience. This educational activity is designed for physicians specializing in the treatment of peripheral vascular disease.
Accreditation statements. Physicians: This activity is sponsored by the North American Center for Continuing Medical Education (NACCME). NACCME is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NACCME designates this continuing medical education activity for a maximum of 1 category 1 credits toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the educational activity.This activity has been planned and produced in accordance with the ACCME Essential Areas and Policies.
The American Medical Association has determined that non-US licensed physicians who participate in this CME activity are eligible for AMA PRA category 1 credit.
Commercial support disclosure. This educational activity has been supported by an educational grant from Possis Medical, Inc.
Faculty disclosure information. All faculty participating in Continuing Medical Education programs sponsored by The North American Center for Continuing Medical Education are expected to disclose to the meeting audience any real or apparent conflict(s) of interest related to the content of their presentation.
This article contains discussion of published and/or investigational uses of agents that are not indicated by the FDA. Neither North American Center for Continuing Medical Education nor Possis Medical, Inc. recommends the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings.
• Dr. Bush has disclosed that she has received a research grant from Possis. Dr. Lin has no significant financial relationship with any organization that could be perceived as a real or apparent conflict of interest in teh contexts of the subject of his presentations.