Treatment of Axillosubclavian Vein Thrombosis: A Novel Technique for Rapid Removal of Clot Using Low-Dose Thrombolysis

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1 J ENDOVASC THER 733 RAPID COMMUNICATION Treatment of Axillosubclavian Vein Thrombosis: A Novel Technique for Rapid Removal of Clot Using Low-Dose Thrombolysis Frank R. Arko, MD; Paul Cipriano, MD; Eugene Lee, MD, PhD; Konstantinos A. Filis, MD, PhD; Christopher K. Zarins, MD; and Thomas J. Fogarty, MD Division of Vascular Surgery, Stanford University Medical Center, Stanford University, Stanford, California, USA Purpose: To report successful combined percutaneous mechanical thrombectomy and pharmacological lysis for axillosubclavian vein thrombosis, with rapid clot removal at a single setting using low-dose thrombolysis. Case Reports: Two consecutive patients presented with arm swelling; the diagnosis of axillosubclavian vein thrombosis was confirmed with duplex ultrasound. Both patients were treated percutaneously with the Solera mechanical thrombectomy device, after which 5 mg of tissue plasminogen activator were delivered within 10 minutes via the Trellis infusion catheter to remove any residual thrombus. Completion venography and serial duplex ultrasound scans in follow-up demonstrated widely patent axillosubclavian veins with no residual thrombus in both cases. Conclusions: Standard treatment of axillosubclavian vein thrombosis may require 12 to 36 hours, with multiple trips to the angiography suite. The novel technique combining mechanical thrombectomy and pharmacological lysis can be performed safely and successfully at a single setting with a small dose of the lytic drug. J Endovasc Ther Key words: axillosubclavian vein, upper extremity vein thrombosis, mechanical thrombectomy, thrombolysis, tissue plasminogen activator, Solera Bacchus Thrombectomy Catheter, Trellis Infusion System Upper extremity deep vein thrombosis (DVT) can occur for a variety of reasons. Primary subclavian vein thrombosis, or Paget- Schroetter syndrome, usually affects young, active people and can lead to serious morbidity if not recognized and appropriately treated. Primary objectives of treatment for Paget- Schroetter syndrome include relief of venous obstruction and prevention of recurrent thrombosis with correction of any underlying anatomical abnormality associated with thoracic outlet syndrome, which typically involves thrombolytic therapy to restore patency followed by first rib resection. 1,2 Secondary development of axillosubclavian thrombosis typically is associated with long-standing placement of central venous catheters. Regardless of etiology, thrombolysis is often successful in removing acute thrombus, restoring patency, and relieving venous hypertension in patients with axillosubclavian vein thrombosis. Usually, the arm swelling associated with this condition is improved as well. However, significant bleeding complica- Address for correspondence and reprints: Frank R. Arko, MD, Director, Endovascular Surgery, Division of Vascular Surgery, 300 Pasteur Drive, H3600, Stanford, CA USA. Fax: ; farko@stanford.edu 2003 by the INTERNATIONAL SOCIETY OF ENDOVASCULAR SPECIALISTS Available at

2 734 AXILLOSUBCLAVIAN DVT J ENDOVASC THER tions, including intracranial hemorrhage, can complicate lytic therapy when prolonged infusion of the drug is necessary. Thrombolysis in the management of axillosubclavian vein thrombosis with tissue plasminogen activator (tpa) requires between 12 and 24 hours at a rate of 0.5 mg/h. 1 4 We describe a novel technique for rapid thrombolysis in axillosubclavian vein thrombosis using minimal thrombolytic agent. Furthermore, patency is restored at a single setting, avoiding multiple trips to the angiography suite. The technique utilizes a percutaneous mechanical thrombectomy device for rapid clot removal followed by low-dose localized thrombolysis to remove any residual clot. CASE REPORTS A 63-year-old woman with chronic sinusitis and a history of ruptured cerebral aneurysm was admitted to the hospital with a 3-day history of progressive left arm swelling. A peripherally inserted central catheter (PICC) had been introduced in her left arm 4 weeks earlier for intravenous antibiotic therapy to treat the sinusitis. A duplex ultrasound demonstrated thrombus in the subclavian, axillary, brachial, and basilic veins. The PICC line was removed, and intravenous heparin was administered in an attempt to avoid conventional thrombolysis owing to the intracranial bleeding event in the past. However, the patient did not improve on heparin therapy. Repeat duplex imaging again found thrombus in the basilic, brachial, axillary, and subclavian veins, with extension of free floating thrombus into the innominate vein. The patient gave informed consent to a percutaneous mechanical thrombectomy procedure from the left brachial vein. Owing to the mobile clot in the innominate vein, the left internal jugular vein was punctured first, and a 9-F Pinnacle sheath (Boston Scientific, Natick, MA, USA) was inserted. To prevent distal embolization of this thrombus, an 8-F Fogarty venous embolectomy catheter (Baxter, Irvine, CA, USA) was placed into the innominate vein and inflated with contrast (Fig. 1A). The left brachial vein was then accessed with a 7-F Avanti sheath (Cordis, Miami, FL, USA), and a inch Glidewire (Boston Scientific) was advanced through the clot and into the right atrium. Heparin was given to maintain the activated coagulation time 250 seconds. The inch wire was then exchanged for a inch steel core wire (Guidant, Temecula, CA, USA). A venogram was performed confirming the duplex findings (Fig. 1B). The Solera Bacchus Thrombectomy Catheter (Bacchus Vascular, Inc., Santa Clara, CA, USA) was advanced over the inch wire for maceration and aspiration of the clot in the brachial vein. The device was advanced proximally into the axillary and subclavian veins. Following mechanical thrombectomy, a repeat venogram (Fig. 1C) demonstrated patent axillary and subclavian veins with residual thrombus. Therefore, a 100-cm Trellis Infusion System (Bacchus Vascular, Inc.) (Fig. 1D) was advanced into the axillosubclavian region. The proximal and distal balloons were inflated with a 3:1 concentration of angiographic dye, effectively isolating the thrombotic segment. With the balloons inflated, 2.5 ml of alteplase (Genentech, South San Francisco, CA, USA) was infused; the dispersion wire within the central lumen of the catheter was activated for 5 minutes to disperse the thrombolytic agent. The procedure was repeated with another 2.5 ml of alteplase. The proximal occlusion balloon was then deflated, and the segment of thrombus that was seen between the occlusion balloons was aspirated through the sheath, yielding both acute and chronic clot. The Fogarty balloon was advanced further into the innominate vein to treat the adjacent thrombus. Following lysis, a repeat venogram (Fig. 1E) showed 95% clot removal. The Solera was advanced one more time to address the proximal thrombus, followed by dilation of the proximal subclavian vein with a 12-mm Blue Max balloon (Boston Scientific). The Fogarty venous embolectomy balloon was deflated and removed. A completion venogram (Fig. 1F) demonstrated 100% removal of clot and patency of the brachial, axillary, and subclavian veins. The patient was placed in a stepdown unit and anticoagulated. Duplex imaging at 1 month demonstrated patency of all veins of the left upper extremity, without stenosis or residual thrombosis. Anticoagulation

3 J ENDOVASC THER AXILLOSUBCLAVIAN DVT 735 Figure 1(A, B) In the initial pretreatment venograms, the brachial, axillary and subclavian veins were occluded, with minimal collateral veins. A Fogarty embolectomy balloon was placed in the innominate vein to prevent embolization. (C) Mechanical thrombectomy of the brachial, axillary, and subclavian veins was performed with the Solera Plus catheter, after which the brachial, axillary, and subclavian veins were widely patent (D), with residual thrombus noted proximally and distally. (E) The Trellis infusion catheter was used for localized thrombolysis between the inflated proximal and distal balloons. (F) Completion venogram demonstrated a widely patent axillary and subclavian vein without any residual thrombus. was continued to 6 months posttreatment. The patient was symptom free and had patent veins at the latest follow-up 10 months after treatment. The second patient was a 30-year-old male cyclist who presented to an outside institution with a 1-day history of right upper extremity swelling after cycling. Axillosubclavian deep vein thrombosis was detected by duplex imaging. He was begun on heparin and transferred to our institution. Repeat duplex scans (Fig. 2A) confirmed the diagnosis, with complete echogenic filling of the axillary and subclavian veins, non-compressible veins, and

4 736 AXILLOSUBCLAVIAN DVT J ENDOVASC THER Figure 2(A) The preoperative duplex image demonstrates no flow in the right subclavian and axillary veins in the second patient. The Solera Plus and Trellis infusion catheters were used in a single procedure. (B) Following treatment, repeat duplex imaging demonstrates a widely patent right subclavian vein without any residual thrombus. loss of normal phasicity. The patient was treated percutaneously in the same manner as the first patient. Following heparin administration, the clot was first removed with the Solera device, followed by local thrombolytic infusion through the Trellis catheter. A total of 5 mg of tpa was infused over 10 minutes with 100% clot removal. Residual stenosis of the subclavian vein between the clavicle and first rib was treated with balloon angioplasty. Completion venography with the arm neutral and then abducted confirmed a thoracic outlet syndrome with near occlusion of the subclavian vein. The patient was anticoagulated in anticipation of a first rib resection in the future. Repeat duplex ultrasound (Fig. 2B) revealed a widely patent axillosubclavian vein without thrombosis; the patient was asymptomatic at his latest follow-up 7 months after treatment. DISCUSSION Deep vein thrombosis of the upper extremities, which is not as innocuous as it was thought to be in the past, is diagnosed with increasing frequency today. Acute symptoms can include venous gangrene and pulmonary embolism in between 7% and 20% of cases. 3 6 Long-term sequelae include postphlebitic symptoms in the upper extremity with functional disability in 25% to 40% of patients who are untreated. 6,7 The long-term outcome depends on the extent of recanalization, underlying abnormality, collateral formation, activity level, and occupation. This report highlights two distinct causes of axillosubclavian vein thrombosis: long-standing central venous catheterization and thoracic outlet syndrome. Most of these patients experience severe symptoms with a poor response to anticoagulation, 8 as we saw in our cases. Such patients should be considered for interventional treatment because early removal of clot is important to minimize subsequent intimal scarring and fibrosis. Systemic thrombolysis has been largely abandoned due to the high incidence of bleeding complications. 9 However, the results of catheter-directed thrombolysis for upper extremity DVT are encouraging, regardless of etiology, with near complete thrombus clearance in 72% to 88%; the response is dependent mostly on the chronicity of the thrombus Current experiences support the safety profiles and efficacy of most of these regimens

5 J ENDOVASC THER AXILLOSUBCLAVIAN DVT 737 in patients with no contraindications to thrombolytic therapy. Unfortunately, the average duration of therapy is typically 24 to 30 hours in the presence of extensive disease or large thrombus burden. Both of our patients had extensive clots, and one had a history of intracranial hemorrhage in the past. The combined use of the Solera and Trellis devices allowed rapid clot removal with lowdose thrombolysis in a single setting. The Solera was used first in an attempt to completely avoid lytic drugs, which was particularly important in the first patient. However, the basket diameter of the Solera is 10 mm, which is inadequate to remove all the thrombus from the outer walls of these larger veins. Fortunately, the amount of thrombus present after mechanical thrombectomy was minimal, and the Trellis device was able to completely clear the veins in the same procedure, which avoided multiple trips to the angiography suite. Furthermore, by markedly reducing the thrombolytic dose (5 mg) and duration (10 to 15 minutes), the risk of bleeding complications was potentially further reduced. Heparin is usually recommended during catheter-directed thrombolytic therapy of DVT to mitigate against pericatheter thrombosis. With urokinase, heparin is typically administrated to maintain the partial thromboplastin time at 2 to 2.5 times normal; however, when using alteplase, only a subtherapeutic dose of heparin has been recommended to avoid bleeding complications Furthermore, the fibrinogen level must be monitored every 6 hours to detect depletion, which may indicate a higher risk of bleeding. With the technique used in our cases, heparin was administered to maintain the ACT 250 seconds because the amount, duration, and infusion of thrombolytic agents was markedly diminished by initial reduction of clot burden with the Solera. The residual clot was then addressed with localized thrombolysis. Thus, continuous infusions of heparin and thrombolytic agents were completely avoided, and there was no need to monitor fibrinogen levels. In both patients, we placed a venous balloon catheter through the internal jugular vein into the superior vena cava to prevent pulmonary embolism; however, the balloon was not meant to be completely hemostatic. As seen in Figure 1D, some contrast still flowed past the balloon, but the residual thrombus was still present. There was no clinical evidence of distal embolization using the Solera and Trellis, so whether this maneuver is routinely needed is unknown. In conclusion, the use of percutaneous mechanical thrombectomy followed by localized low-dose thrombolysis via the Trellis infusion catheter quickly and safely removed large clot burdens in upper extremity veins in a single procedure. This technique limited the amount and duration of thrombolytic agents required and accomplished complete clot removal without complication. REFERENCES 1. Azakie A, McElhinney DB, Thompson RW, et al. Surgical management of subclavian vein effort thrombosis as a result of thoracic outlet compression. J Vasc Surg. 1998;28: Beygui RE, Olcott C 4th, Dalman RL. Subclavian vein thrombosis: outcome analysis based on the etiology and modality of treatment. Ann Vasc Surg. 1997;11: Bolitho DG, Elwood ET, Roberts F. Phlegmasia cerulea dolens of the upper extremity. Ann Plast Surg. 2000;45: Hingorani A, Ascher E, Lorenson E, et al. Upper extremity deep venous thrombosis and its impact on morbidity and mortality rates in a hospital-based population. J Vasc Surg. 1997;26: Monreal M, Raventos A, Lerma R, et al. Pulmonary embolism in patients with upper extremity DVT associated to venous central linesa prospective study. Thromb Haemost. 1994; 72: Gloviczki P, Kazmier FJ, Hollier LH. Axillarysubclavian venous occlusion: the morbidity of a nonlethal disease. J Vasc Surg. 1986;4: Ellis MH, Manor Y, Witz M. Risk factors and management of patients with upper limb deep vein thrombosis. Chest. 2000;117: Rutherford RB. Primary subclavian-axillary vein thrombosis: the relative roles of thrombolysis, percutaneous angioplasty, stent, and surgery. Semin Vasc Surg. 1998;11: Schweizer J, Kirch W, Koch R, et al. Short- and long-term results after thrombolytic treatment of deep venous thrombosis. J Am Coll Cardiol. 2000;36: Angle N, Gelabert HA, Farooq MM, et al. Safety

6 738 AXILLOSUBCLAVIAN DVT J ENDOVASC THER and efficacy of early surgical decompression of the thoracic outlet for Paget-Schroetter syndrome. Ann Vasc Surg. 2001;15: Chang R, Horne MK, Mayo DJ, et al. Pulsespray treatment of subclavian and jugular venous thrombi with recombinant tissue plasminogen activator. J Vasc Interv Radiol. 1996; 7: Adelman MA, Stone DH, Riles TS, et al. A multidisciplinary approach to the treatment of Paget-Schroetter syndrome. Ann Vasc Surg. 1997; 11: Semba CP. Venous thrombolysis in the posturokinase era. Tech Vasc Interv Radiol. 2000;3: Valji K. Evolving strategies for thrombolytic therapy of peripheral vascular occlusion. J Vasc Interv Radiol. 2000;11: Benenati J, Shlansky-Goldberg R, Meglin A, et al. Thrombolytic and antiplatelet therapy in peripheral vascular disease with use of reteplase and/or abciximab: the SCVIR consultants conference. May 22, 2000; Orlando, FL. Society for Cardiovascular and Interventional Radiology. J Vasc Interv Radiol. 2001;12:

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