- Email: [email protected]
Pharmacomechanical thrombectomy for iliofemoral deep vein thrombosis: An alternative in patients with contraindications to thrombolysis
From the American Venous Forum
Pharmacomechanical thrombectomy for iliofemoral deep vein thrombosis: An alternative in patients with contraindications to thrombolysis Atul S. Rao, MD, Gerhardt Konig, BS, Steven A. Leers, MD, Jae Cho, MD, Robert Y. Rhee, MD, Michel S. Makaroun, MD, and Rabih A. Chaer, MD, Pittsburgh, Pa Objective: Venous lysis is usually reserved for symptomatic patients with acute deep vein thrombosis (DVT) and low risk for bleeding. This study reports the use of pharmacomechanical thrombectomy (PMT) in patients with contraindications to thrombolysis. Methods: A retrospective review of all patients with symptomatic DVT treated between 2007 and 2008 with PMT was performed. All patients were treated by a combination of local tissue plasminogen activator (tPA) with the Angiojet (Possis Medical, Minneapolis, Minn) or Trellis device (Bacchus Vascular, Santa Clara, Calif). Catheter-directed lysis was used sparingly. Results: Forty-three patients (mean age, 48.4 ⴞ 16.6 years) presented with symptoms averaging 13.6 ⴞ 9.6 days in duration. Nineteen (44%) had symptoms for >14 days, and 15 (35%) had a high risk for bleeding. Symptomatic subclavian thrombosis occurred in eight (19%), and 35 (81%) presented with disabling lower extremity DVT (4 phlegmasia) despite anticoagulation. Fifteen patients had a thrombosed indwelling permanent filter. Sixty-three percent were treated in one session, but 16 patients required a lytic infusion after suboptimal PMT. Iliac stenting was required in 35% of limbs treated. Successful lysis (>50%) was achieved in 95% of patients and symptom resolution in 93%. All patients became ambulatory with no or minimal limitation. There were no major systemic bleeding complications, but access site hematoma occurred in two patients and worsening of pre-existing rectus sheath hematoma requiring transfusion occurred in another two. Limb salvage was maintained in 100% of patients who presented with phlegmasia. Mean follow-up was 5.0 ⴞ 4.8 months. Freedom from DVT recurrence and reintervention was 95% at 9 months by life-table analysis. Conclusions: PMT can be safely and effectively used for subacute iliocaval and iliofemoral DVT and in patients with contraindications for lytic therapy, resulting in improved functional outcomes relative to their debilitated state before the procedure. ( J Vasc Surg 2009;50:1092-8.)
Deep venous thrombosis (DVT) has been associated with the development of post-thrombotic sequelae1,2 manifested by persistent symptoms of ambulatory venous hypertension, chronic edema, and venous ulceration. Ulcers can develop in up to 80% of patients by 10 years,3 and worsening venous reflux develops in 95% over 5 years. Abnormal ambulatory venous pressures develop in up to 80%,4 which functionally results in up to 43% of patients with iliofemoral DVT suffering from disabling venous claudication.4,5 The incidence of the post-thrombotic syndrome (PTS) in patients presenting with DVT appears to increase progressively over time to approximately 30%, with reported ranges of 16% to 82%.6-8 Treatment strategies for DVT have traditionally centered on anticoagulation alone. However, the occurrence
From the Division of Vascular Surgery, University of Pittsburgh Medical Center. Competition of interest: none. Reprint requests: Rabih A. Chaer, MD, Assistant Professor of Surgery, University of Pittsburgh Medical Center, Division of Vascular Surgery, 200 Lothrop St, Ste A1011, Pittsburgh PA 15213 (e-mail: [email protected]). 0741-5214/$36.00 Copyright © 2009 by the Society for Vascular Surgery. doi:10.1016/j.jvs.2009.06.050
1092
of PTS has been consistent despite adequate treatment with anticoagulation regimens.2-4 Patients with iliofemoral DVT represent a specific subset in whom not only is PTS more prone to develop but is also more apt to recur with conventional anticoagulation therapy alone.9 This has led to alternative treatment paradigms, including the advent of early reduction of thrombus burden. Although different strategies for thrombus removal have been described, intralesional thrombolysis has gained wide acceptance and is currently advocated by the American College of Chest Physicians (ACCP) in the recently published updated “Evidence-Based Clinical Practice Guidelines” for antithrombotic and thrombolytic therapy.10 In select patients, the use of catheter-directed thrombolysis (CDT) and, preferentially, pharmacomechanical thrombectomy (PMT) were specifically recommended for the treatment of acute iliofemoral DVT to decrease post-thrombotic morbidity. Candidates include those patients with symptoms for ⬍14 days and with low risk of bleeding. The purpose of this study was to assess the feasibility and safety of PMT in patients with iliofemoral DVT with contraindications for treatment based on the most recent ACCP guidelines, namely those with symptoms ⬎14 days and those with contraindications to thrombolysis due to a high risk for hemorrhagic complications.
JOURNAL OF VASCULAR SURGERY Volume 50, Number 5
METHODS This study was approved by the Institutional Review Board at the University of Pittsburgh. Patients. Individuals who underwent PMT for symptomatic iliofemoral DVTs from May 2007 to February 2009 were identified from a prospectively collected database. The records were retrospectively reviewed for demographics, indication for treatment, chronicity of symptoms, contraindications to lysis, DVT risk factors, adjunctive interventions, periprocedural complications, clinical outcomes, and follow-up with duplex ultrasound (DU) imaging. All treated patients were severely symptomatic despite therapeutic anticoagulation and most commonly presented with a combination of pain, limb swelling, or phlegmasia. In all high-risk patients, a discussion was undertaken about the increased potential for bleeding complications. The ACCP guidelines were also discussed in detail in those patients treated after June of 2008, when the guidelines were issued. Patients treated before the publication of the guidelines were told that the standard of care was anticoagulation and that lysis was not supported by current guidelines, whether they were at high-risk or standard-risk for treatment. Only after informed consent was obtained did we proceed. All interventions were performed by vascular surgeons in endovascular suites equipped with fixed imaging capability (GE Healthcare, Giles, UK). The degree of residual thrombus was characterized as no lysis, ⬍50% lysis (partial), or ⬎50% lysis on venography. Absolute contraindication to therapy included any source of active internal bleeding. Major relative contraindications included recent gastrointestinal hemorrhage, recent (ⱕ10 to 14 days) major trauma or surgery, recent obstetric delivery, coagulation disorder, severe liver disease, pregnancy, and recent organ biopsy.11 The preoperative workup included venous DU imaging as well as computed tomography of the chest, abdomen, and pelvis with intravenous contrast and a venous phase. A hypercoagulable hematologic workup was performed on most patients in conjunction with consultation with a hematology specialist. All patients were placed in graduated compression stockings as recommended by the ACCP Guidelines. PMT technique. Caval interruption with temporary inferior vena cava (IVC) filters was performed selectively at the beginning of the procedure. If an IVC filter was to be placed, this was done preferentially through the internal jugular approach. Our technique was modified to involve filter access only through the jugular approach if a femoral hematoma developed while the patient was undergoing lysis in the prone position. After filter deployment, a 9F sheath was left in the jugular vein to minimize the risk of potential hematoma. This access was also maintained for filter retrieval at the completion of the procedure. Next, the patient was placed prone, and access was obtained under ultrasound guidance. Popliteal venous access was performed in 77% of patients, and basilic (14%), jugular (7%), and small saphenous vein access (2%) was
Rao et al 1093
Table I. Risk factors for deep vein thrombosis Risk factor Malignancy Hypercoagulable state Recent surgery Previous deep vein thrombosis Immobility Thoracic outlet syndrome Indwelling catheter Oral contraceptives
No. (N ⫽ 43) 8 15 5 3 3 5 4 2
obtained for all others. Heparin anticoagulation was routine and was dosed at 100 U/kg. A 6F or 8F sheath was placed, an ascending venogram was performed, and the PMT device was placed into the region of interest. When the AngioJet (Possis Medical, Minneapolis, Minn) was used, the DVX catheter was used in power pulse mode initially12 with 6 to 8 mg of tissue plasminogen activator (tPA; Alteplase, Genentech, San Francisco, Calif) per segment treated. It was then reactivated in regular thrombectomy mode after a 15-minute dwell time. Similarly, when the Trellis device (Bacchus Vascular, Santa Clara, Calif) was used, 6 to 8 mg of tPA were used per treatment segment. In patients with a thrombosed indwelling IVC filter, the distal balloon was inflated above the filter. CDT was initiated as needed for residual thrombus using a multisidehole catheter or DU-assisted CDT with the EKOS catheter (EKOS Corp, Bothell, Wash). In patients with contraindications to thrombolysis due to high risk for hemorrhagic complications, suction thrombectomy was performed using an aspiration catheter and no CDT was performed, even in the setting of residual thrombus. Residual iliac vein lesions on venography were treated with stenting at the discretion of the operating surgeon using self-expanding stents. Temporary IVC filters were universally removed. All patients were maintained on Coumadin (Bristol-Myers Squibb, Princeton, NJ) and were prescribed antiplatelet therapy if a stent was placed. Statistical analysis. An independent statistician performed all advanced statistical analyses. The data have been summarized as mean ⫾ standard deviation for continuous variables and as percentages for categoric data. The incidence for the need to perform a reintervention was calculated by the Kaplan-Meier method. The time component started on the date of the initial procedure. RESULTS During the 1.5-year period, 43 patients (24 men, 19 women), with a mean age of 48.4 ⫾ 16.6 years were treated with PMT, of whom 35 were treated for lower limb, and eight for upper extremity/central venous thrombosis. Of those patients treated for lower extremity disease, 16 underwent bilateral PMT, for a total of 51 lower limbs treated. Risk factors for DVT are listed in Table I. All patients had been prescribed anticoagulation before treatment but con-
JOURNAL OF VASCULAR SURGERY November 2009
1094 Rao et al
Table II. Hemorrhagic contraindications to lysis Contraindications
Single session or CDT
Lysis, degree
Bleeding complications
Single session Single session Single session Single session Single session Single session
⬍50% ⬍50% ⬍50% ⬍50% ⬍50% ⬍50%
Worsened rectus hematoma None None Worsened rectus hematoma None None
Single session
⬍50%
None
Single session
⬍50%
None
CDT Single session Single session Single session CDT Single session Single session
⬍50% ⬍50% ⬍50% ⬍50% ⬍50% ⬍50% ⬍50%
None None None None None None None
Rectus sheath hematoma Ongoing gross hematuria Ongoing excessive menses Rectus sheath/retroperitoneal hematoma Liver biopsy with intraperitoneal bleed Recent gastrointestinal bleed Recent surgery—abdominal wall and intra-abdominal debridement, removal of infected mesh Recent procedure—ileoscopy via stoma with biopsies; inflamed, bleeding stoma Recent surgery—lower extremity fasciotomy for trauma, muscle debridement Intra-abdominal organ biopsy Recent gastrointestinal bleeding Recent surgery—rib resection for thoracic outlet syndrome Recent surgery—pulmonary resection Postpartum, epidural anesthesia Recent intraperitoneal bleeding—adrenal hemorrhage CDT, Catheter-directed thrombolysis.
tinued to have debilitating symptoms, compromising ambulation in those with lower limb DVT. High-risk patients with persistence of debilitating symptoms were treated for at least 1 week before a consult for possible lysis was placed. All patients presented with severe swelling or pain, or both, and four patients had evidence of phlegmasia. Mean duration of symptoms before treatment was 13.6 ⫾ 9.6 days (range, 1-31 days), and 19 of 43 patients (44%) had symptoms for ⬎14 days before treatment, with a mean duration of 22.9 days (range, 15-31 days). Thrombolysis was contraindicated in 15 patients because they were at a high-risk for hemorrhagic complications (Table II). Caval involvement was present in 22 of the patients with lower extremity DVT, and 16 had a pre-existing IVC filter, 15 of which had thrombus extension with involvement of the filter up to the renal veins. Treatment was with the AngioJet device in 12 patients, the Trellis device in 13, and a combination of both in 17. The two-device combination was most commonly used for patients with persistent thrombus after initial PMT, specifically for residual thrombus in indwelling IVC filters in patients at high risk for bleeding with CDT where a one-session intervention was planned. Sixteen patients (37%) underwent catheterdirected thrombolysis secondary to ⬍50% lysis after PMT. Two of these had a contraindication to thrombolysis and were treated with a short 4- to 6-hour infusion with the EKOS catheter, and six had subacute or chronic DVT (Table III). Technical success was defined by ⬎50% angiographic lysis because this value has been shown to correlate with significantly improved 1-year venous patency rates.13 This was achieved in 41 of 43 patients (95%), including 14 of 15 patients with contraindications to thrombolysis, of whom 12 were treated with a limited one-session PMT. Both patients in whom complete or significant lysis could not be achieved had symptoms for ⬎14 days (Table IV). Iliac vein stents were placed in 18 of the 51 limbs (35%) treated.
Table III. Pharmacomechanical thrombectomy procedural data Variable
No.
IVC involvement Pre-existing IVC filter Thrombosed OptEase/TrapEasea Simon Nitinolb Greenfieldc Gunther Tulipd Patent (Greenfield)c Mechanical thrombectomy device AngioJet (Possis Medical) Trellis (Bacchus Vascular) AngioJet and Trellis Catheter-directed thrombolysis High risk Subacute/chronic DVT Multihole infusion catheter EKOS ultrasound-assisted catheter Stent placed Unilateral Bilateral
22 16 15 12 1 1 1 1 12 13 17 16 2 6 8 8 18 15 3
DVT, Deep vein thrombosis; IVC, inferior vena cava. a Cordis, Bridgewater, NJ. b Bard Peripheral Vascular, Tempe, Ariz. c Boston Scientific, Natick, Mass. d Cook Medical, Bloomington, Ind.
There were no periprocedural deaths and six periprocedural morbidities. Arrhythmias developed in two patients, which subsequently resolved. There were no systemic bleeding complications. Four bleeding complications were documented: two with worsening of pre-existing rectus sheath hematomas that occurred several days after intervention, at which time both patients were supratherapeutic on their anticoagulant regimen, and two access site hematomas occurred at the filter insertion site. Two pa-
JOURNAL OF VASCULAR SURGERY Volume 50, Number 5
Rao et al 1095
Table IV. Lysis success in subacute/chronic deep vein thrombosis Duration of symptoms, d 21 20 16 16 21 28 26 18 30 30 20 16 30 25 22 15 31 30 21
Bleeding risk
Single session vs CDT
Technical success
No Yes Yes No No No Yes No No Yes No No No No No No Yes No No
Single session Single session Single session CDT Single session Single session Single session Single session Single session Single session CDT Single session CDT Single session Single session Single session CDT CDT CDT
No Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes
CDT, Catheter-directed thrombolysis.
tients with contraindications to lysis had bleeding complications from their high-risk bleeding site. Four patients required blood transfusions after the procedure. No clinically significant pulmonary embolization developed. Two patients required reinterventions secondary to rethrombosis after initial technical success with PMT. One patient, who had a congenital narrowing of the IVC, recurred 3 weeks after the procedure and was not receiving therapeutic anticoagulation. He underwent subsequent successful relysis using a combination of PMT and CDT. Rethrombosis in the second patient occurred 5 days after the procedure. She had significant residual thrombus after the first intervention at the site of an existing filter but was at high risk for bleeding complications due to recent epidural placement during childbirth. She underwent successful CDT using the EKOS catheter. Both patients remain asymptomatic and free from recurrence. Mean follow-up was 5.0 ⫾ 4.8 months. One patient had an asymptomatic recurrence noted on office DU imaging for an overall 95% freedom from DVT recurrence or reintervention by life-table analysis. Of those patients not requiring reinterventions, 98% achieved complete or significant resolution of symptoms on clinical follow-up, and one patient in whom technical success had never been achieved had only minimal symptom relief. Follow-up DU imaging showed iliac stents were patent in 17 of 18 limbs (94%). The patient who had an occluded stent and had an indwelling filter that was partially deployed in the iliac vein was asymptomatic on follow-up and had a patent contralateral stent. DISCUSSION Although the use of thrombolysis for the treatment of acute iliofemoral DVTs is still debated, ample evidence
supports its use to reduce the occurrence of the PTS. The pathophysiology of the PTS appears to involve a combination of venous reflux secondary to valvular incompetence and luminal obstruction,2,7,14 with patients with PTS being three times more likely to have combined reflux and obstruction.15 This has engendered the notion of thrombus debulking to mitigate post-thrombotic sequelae.16 Clinically, thrombolysis revealed itself early on as an effective means of achieving clot lysis compared with anticoagulation therapy alone in 13 randomized studies, as reviewed by Comerota et al.2,17 In this pooled analysis, 45% of patients who underwent thrombolysis achieved “complete or significant” lysis with decreased long-term PTS versus only 4% of patients treated with anticoagulation alone. A high failure rate of systemic thrombolysis in patients with iliofemoral DVTs was noted, however, implying a role for intrathrombus lysis. CDT has indeed proven to be more effective than conventional treatment in several series,13,18-20 including one small randomized study.19 These reports cite improved short-term and longterm venous patency, with patency rates ranging from 54% to 89% at 1 year, as well as sustained symptom resolution or improvement. These factors have therefore led to the emergence of PMT as a potentially faster, less invasive, safe alternative to venous thrombectomy or CDT,21,22 promising to limit the dose and duration of treatment. It has been well-studied recently,23-25 with comparable or better success rates compared with CDT but with the added benefit of a shorter hospital and intensive care stay and decreased costs.25 Given this large body of evidence in favor of thrombolysis based on several retrospective series and registries, a large multicenter randomized trial evaluating CDT for iliofemoral DVTs was planned and is currently underway.26 Although early studies primarily focused on patients with acute DVT (symptoms duration ⬍10 to 15 days), Vedantham et al23 did treat six limbs in four patients with chronic (⬎10-day-old) DVT. Results were mediocre for all six limbs, noted by grade I or grade II lysis and no grade III or complete lysis. Similarly, Bush et al22 speculate that some of the failures of treatment may have been a result of the age of the thrombus. In addition, these groups either excluded or did not intentionally treat those patients at increased risk of hemorrhagic complications with thrombolysis. According to the most recent ACCP guidelines for antithrombotic and thrombolytic therapy,10 PMT is similarly advocated in patients with acute (⬍14-day-old) iliofemoral DVT who have low risk of bleeding in preference to anticoagulation alone to mitigate post-thrombotic symptoms. In the current study, we examined our cohort of patients treated with PMT for DVT of the upper or lower extremity to specifically evaluate patients not specifically covered by the current ACCP guidelines. As such, we included those treated with subacute/chronic DVT (duration of symptoms ⬎14 days) and those with contraindications to lysis secondary to bleeding risks. These patients represented a group who continued to have severe symptoms despite treatment with anticoagulation and in whom
1096 Rao et al
JOURNAL OF VASCULAR SURGERY November 2009
Fig. Ascending venogram and cavogram of patient before the procedure shows extensive (A) femoropopliteal and (B) iliocaval thrombosis with thrombus extending up to inferior vena cava filter, and (C) after a single-session pharmacomechanical thrombectomy.
PMT was deemed appropriate to shorten treatment times, with the purported benefit of reducing the bleeding risk. Although we did note four bleeding complications, two of these were expansions of rectus sheath hematomas that existed before treatment. The growth of hematoma occurred not immediately after the procedure, but several days after, at which time both patients had supratherapeutic international normalized ratio values. In another patient, a hematoma developed at the filter placement access site. This patient underwent femoral vein puncture for filter placement before prone positioning for PMT through the popliteal approach. We have since changed our protocol to routinely place filters using the internal jugular approach, maintaining a 9F sheath in situ until completion of the procedure. Our definition of technical success was achieving ⬎50% lysis as visualized on venography (Fig). A national multicenter registry report of CDT for DVT13 had used similar measurements and defined success by grade, with grade I representing ⬍50% lysis, grade II ⬎50%, and grade III complete lysis. Vedantham et al23 reported that 31% of patients with iliofemoral DVT treated with PMT achieved grade III lysis, whereas two other groups similarly looking at PMT for lower extremity DVTs reported rates of complete thrombus removal of 100% and 70%.24,25 Two of these three studies, however, used PMT after overnight lytic infusion. The third study did not clarify whether patients treated by PMT underwent any adjunctive CDT. More importantly, none of these series report cases in which they specifically aimed to minimize treatment duration in high-risk patients. The main treatment goal in the current high-risk series was not necessarily complete lysis, but significant lysis (⬎50%). Achieving complete lysis in many of these patients might have been possible by alternative means (prolonged CDT), albeit at the cost of increased hemorrhagic compli-
cations. As a result, we accepted significant but incomplete lysis in several of these patients and managed to safely treat 13 of 15 (87%) patients who had contraindications to lysis in a single session with PMT. Freedom from DVT recurrence or reintervention at the midterm follow-up was 95%, and 98% of those patients remained symptom-free, indicating that partial ⬎50% lysis appears to be as effective clinically as complete lysis and, more importantly, is associated with fewer major bleeding complications. Of note, however, we used a combination of both the Trellis and Angiojet devices in well over one-third of our patients, highlighting the need for diligent and persistent therapy to achieve single-session success. Other recent studies have implicated the duration of symptoms and DVT as a factor in achieving successful lysis,22,23 with chronic DVT potentially posing a greater challenge to effective therapy. Our results do indeed support this notion, given that both patients in whom we were unable to achieve successful lysis were patients with chronic DVT (Table IV). However, 17 patients (89%) presenting with symptoms ⬎14 days achieved successful lysis and clinical outcomes. One patient with DVT duration of ⬎14 days in whom success was not achieved had recently undergone surgery, and the other showed minimal response with PMT and was deemed unlikely to benefit from further lysis. They were therefore both treated in a single session and not offered CDT. In the absence of bleeding risks, however, some subacute patients would likely benefit from adjunctive CDT to achieve better reduction of thrombus burden. We used venography alone to determine the degree of underlying venous obstruction after PMT to determine the need for stenting. As such, we may have underestimated the true degree of residual disease, given the 2-dimensional nature of venography. We placed stents in slightly more than one-third of our patients treated. This is markedly less than rates reported in the literature, where up to 75% of
JOURNAL OF VASCULAR SURGERY Volume 50, Number 5
patients treated for venous occlusive disease undergo iliac stenting.27 To optimize imaging sensitivity, we have now incorporated the use of intravascular ultrasound into our protocol for treatment. However, despite the reliance on venography in the current series, we were still able to achieve good success with selective stent placement, with no treatment failures occurring as a result of undiagnosed residual iliac disease. Another subject of current controversy concerns IVC placement before venous lysis. To our knowledge, there are no data to suggest that an IVC should be placed routinely during lytic procedures. However, Protack et al28 report no increase in pulmonary emboli in patients undergoing CDT without filter placement. These data, however, may not necessarily be translatable to lysis procedures involving PMT. Our practice has therefore evolved to include the placement of temporary filters whenever there is caval or iliac vein involvement, especially when PMT is anticipated. These are routinely removed at the completion of the procedure, unless there is a significant amount of embolic clot lining the filter, in which case the filter itself is treated with PMT, followed by filter retrieval. Although the disposable costs associated with PMT can be significant, the ability to minimize treatment duration, intensive care, and hospital length of stay makes this approach cost-effective compared with CDT.25 In addition, mitigating the socioeconomic cost of post-thrombotic complications after DVT is significant. Venous stasis ulceration develops in up to 86% of patients with acute DVT over 10 years, requiring multiple hospitalizations and various medical and surgical modalities for management.3 Moreover, patients with chronic venous disease incur an opportunity cost secondary to loss of work days.3 Although we did not perform a cost analysis, the immediate and long-term cost savings of PMT compared with other DVT treatment modalities are worth investigating. CONCLUSIONS This series demonstrates the safety and efficacy of pharmacomechanical thrombectomy in the treatment of symptomatic DVT in patients with contraindications to lysis, namely those with high risk for bleeding and those with chronic DVT. Although it appears that the most effective lysis results from a combination of pharmacomechanical thrombectomy and catheter-directed thrombolysis, we suggest the use of one-session pharmacomechanical thrombectomy alone to achieve success in those patients with a high risk of bleeding. Careful patient selection, however, is mandatory, with clear delineation of risks and expectations. AUTHOR CONTRIBUTIONS Conception and design: AR, JC, RR, MM, RC Analysis and interpretation: AR, GK, JC, RR, MM, RC Data collection: AR, GK, RC Writing the article: AR, GK, RC Critical revision of the article: AR, JC, RR, MM, RC Final approval of the article: AR, GK, JC, RR, MM, RC Statistical analysis: AR, RC
Rao et al 1097
Obtained funding: RC Overall responsibility: RC REFERENCES 1. Bauer G. Roentgenological and clinical study of the sequels of thrombosis. Acta Chir Scand 1942:42 (suppl 74). 2. Comerota AJ, Gravett MH. Iliofemoral venous thrombosis. J Vasc Surg 2007;46:1065-76. 3. O’Donnell TF, Browse NL, Burnand KG, Thomas ML. The socioeconomic effects of an iliofemoral venous thrombosis. J Surg Res 1977;22: 483-8. 4. Akesson H, Brudin L, Dahlstrom JA, Eklof B, Ohlin P, Plate G. Venous function assessed during a 5-year period after acute ilio-femoral venous thrombosis treated with anticoagulation. Eur J Vasc Surg 1990;4:43-8. 5. Delis KT, Bountouroglou D, Mansfield AO. Venous claudication in iliofemoral thrombosis: long-term effects on venous hemodynamics, clinical status, and quality of life. Ann Surg 2004;239:118-26. 6. Kearon C. Natural history of venous thromboembolism. Circulation 2003;107(23 suppl 1):I22-30. 7. Peden E, Zhou W, Bush RL, Lumsden AB, Lin PH. The case for thrombolysis for iliofemoral venous thrombosis. Semin Vasc Surg 2005; 18:139-47. 8. Mohr DN, Silverstein MD, Heit JA, Petterson TM, O’Fallon WM, Melton LJ. The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study. Mayo Clin Proc 2000; 75:1249-56. 9. Douketis JD, Crowther MA, Foster GA, Ginsberg JS. Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis? Am J Med 2001;110:515-9. 10. Hirsh J, Guyatt G, Albers GW, Harrington R, Schunemann HJ. American College of Chest Physicians. (2008). Executive summary: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133(6 suppl):71-109S. 11. Angle N, Quinones-Baldrich WJ. Thrombolytic therapy for vascular disease. In: Moore WS, editor. Vascular and endovascular surgery: a comprehensive review. 7th ed. Philadelphia: Saunders-Elsevier; 2006. p. 414-42. 12. Allie DE, Hebert CJ, Lirtzman MD, Wyatt CH, Keller VA, Khan MH, et al. Novel simultaneous combination chemical thrombolysis/ rheolytic thrombectomy therapy for acute limb ischemia: the power pulse spray technique. Catheter Cardiovasc Interv 2004;63:512-22. 13. Mewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, Haughton SH. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology 1999;211:39-49. 14. O’Shaughnessy AM, Fitzgerald DE. Natural history of proximal deep vein thrombosis assessed by duplex ultrasound. Intl Angiol 1997;16: 45-9. 15. Johnson BF, Manzo RA, Bergelin RO, Strandness DE. Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: a one- to six-year follow-up. J Vasc Surg 1995;21:30712; discussion 313. 16. Comerota AJ, Paolini D. Treatment of acute iliofemoral deep venous thrombosis: a strategy of thrombus removal. Eur J Vasc Endovasc Surg 2007;33:351-60; discussion 361-2. 17. Comerota AJ, Aldridge SC. Thrombolytic therapy for deep venous thrombosis: a clinical review. Can J Surg 1993;36:359-64. 18. AbuRahma AF, Perkins SE, Wulu JT, Ng HK. Iliofemoral deep vein thrombosis: conventional therapy versus lysis and percutaneous transluminal angioplasty and stenting. Ann Surg 2001;233:752-60. 19. Elsharawy M, Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial. Eur J Vasc Endovasc Surg 2002;24:209-214. 20. Bjarnason H, Kruse JR, Asinger DA, Nazarian GK, Dietz CA, Caldwell MD, et al. Iliofemoral deep venous thrombosis: safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy. J Vasc Interv Radiol 1997;8:405-18.
1098 Rao et al
21. Lin PH, Mussa FF, Hedayati N, Naoum JJ, Zhou W, Yao Q, et al. Comparison of AngioJet rheolytic pharmacomechanical thrombectomy versus AngioJet rheolytic thrombectomy in a porcine peripheral arterial model. World J Surg 2007;31:715-722. 22. Bush RL, Lin PH, Bates JT, Mureebe L, Zhou W, Lumsden AB. Pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis: safety and feasibility study. J Vasc Surg 2004;40:965-70. 23. Vedantham S, Vesely TM, Sicard GA, Brown D, Rubin B, Sanchez LA, et al. Pharmacomechanical thrombolysis and early stent placement for iliofemoral deep vein thrombosis. J Vasc Intervent Radiol 2004;15: 565-74. 24. Lee KH, Han H, Lee KJ, Yoon CS, Kim SH, Won JY, et al. Mechanical thrombectomy of acute iliofemoral deep vein thrombosis with use of an arrow-trerotola percutaneous thrombectomy device. J Vasc Intervent Radiol 2006;17:487-95. 25. Lin PH, Zhou W, Dardik A, Mussa F, Kougias P, Hedayati N, et al. Catheter-direct thrombolysis versus pharmacomechanical thrombec-
JOURNAL OF VASCULAR SURGERY November 2009
tomy for treatment of symptomatic lower extremity deep venous thrombosis. Am J Surg 2006;192:782-8. 26. Enden T, Sandvik L, Klow NE, Hafsahl G, Holme PA, Holmen LO, et al. Catheter-directed venous thrombolysis in acute iliofemoral vein thrombosis—the CaVenT study: rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771). Am Heart J 2007;154:808-14. 27. Neglen P, Raju S. Balloon dilation and stenting of chronic iliac vein obstruction: technical aspects and early clinical outcomes. J Endovasc Ther 2000;7:79-91. 28. Protack CD, Bakken AM, Patel N, Saad WE, Waldman DL, Davies MG. Long-term outcomes of catheter directed thrombolysis for lower extremity deep venous thrombosis without prophylactic inferior vena cava filter placement. J Vasc Surg 2007;45:992-7; discussion 997.
Submitted Apr 7, 2009; accepted Jun 21, 2009.
Pharmacomechanical thrombectomy for iliofemoral deep vein thrombosis: An alternative in patients with contraindications to thrombolysis Atul S. Rao, MD, Gerhardt Konig, BS, Steven A. Leers, MD, Jae Cho, MD, Robert Y. Rhee, MD, Michel S. Makaroun, MD, and Rabih A. Chaer, MD, Pittsburgh, Pa Objective: Venous lysis is usually reserved for symptomatic patients with acute deep vein thrombosis (DVT) and low risk for bleeding. This study reports the use of pharmacomechanical thrombectomy (PMT) in patients with contraindications to thrombolysis. Methods: A retrospective review of all patients with symptomatic DVT treated between 2007 and 2008 with PMT was performed. All patients were treated by a combination of local tissue plasminogen activator (tPA) with the Angiojet (Possis Medical, Minneapolis, Minn) or Trellis device (Bacchus Vascular, Santa Clara, Calif). Catheter-directed lysis was used sparingly. Results: Forty-three patients (mean age, 48.4 ⴞ 16.6 years) presented with symptoms averaging 13.6 ⴞ 9.6 days in duration. Nineteen (44%) had symptoms for >14 days, and 15 (35%) had a high risk for bleeding. Symptomatic subclavian thrombosis occurred in eight (19%), and 35 (81%) presented with disabling lower extremity DVT (4 phlegmasia) despite anticoagulation. Fifteen patients had a thrombosed indwelling permanent filter. Sixty-three percent were treated in one session, but 16 patients required a lytic infusion after suboptimal PMT. Iliac stenting was required in 35% of limbs treated. Successful lysis (>50%) was achieved in 95% of patients and symptom resolution in 93%. All patients became ambulatory with no or minimal limitation. There were no major systemic bleeding complications, but access site hematoma occurred in two patients and worsening of pre-existing rectus sheath hematoma requiring transfusion occurred in another two. Limb salvage was maintained in 100% of patients who presented with phlegmasia. Mean follow-up was 5.0 ⴞ 4.8 months. Freedom from DVT recurrence and reintervention was 95% at 9 months by life-table analysis. Conclusions: PMT can be safely and effectively used for subacute iliocaval and iliofemoral DVT and in patients with contraindications for lytic therapy, resulting in improved functional outcomes relative to their debilitated state before the procedure. ( J Vasc Surg 2009;50:1092-8.)
Deep venous thrombosis (DVT) has been associated with the development of post-thrombotic sequelae1,2 manifested by persistent symptoms of ambulatory venous hypertension, chronic edema, and venous ulceration. Ulcers can develop in up to 80% of patients by 10 years,3 and worsening venous reflux develops in 95% over 5 years. Abnormal ambulatory venous pressures develop in up to 80%,4 which functionally results in up to 43% of patients with iliofemoral DVT suffering from disabling venous claudication.4,5 The incidence of the post-thrombotic syndrome (PTS) in patients presenting with DVT appears to increase progressively over time to approximately 30%, with reported ranges of 16% to 82%.6-8 Treatment strategies for DVT have traditionally centered on anticoagulation alone. However, the occurrence
From the Division of Vascular Surgery, University of Pittsburgh Medical Center. Competition of interest: none. Reprint requests: Rabih A. Chaer, MD, Assistant Professor of Surgery, University of Pittsburgh Medical Center, Division of Vascular Surgery, 200 Lothrop St, Ste A1011, Pittsburgh PA 15213 (e-mail: [email protected]). 0741-5214/$36.00 Copyright © 2009 by the Society for Vascular Surgery. doi:10.1016/j.jvs.2009.06.050
1092
of PTS has been consistent despite adequate treatment with anticoagulation regimens.2-4 Patients with iliofemoral DVT represent a specific subset in whom not only is PTS more prone to develop but is also more apt to recur with conventional anticoagulation therapy alone.9 This has led to alternative treatment paradigms, including the advent of early reduction of thrombus burden. Although different strategies for thrombus removal have been described, intralesional thrombolysis has gained wide acceptance and is currently advocated by the American College of Chest Physicians (ACCP) in the recently published updated “Evidence-Based Clinical Practice Guidelines” for antithrombotic and thrombolytic therapy.10 In select patients, the use of catheter-directed thrombolysis (CDT) and, preferentially, pharmacomechanical thrombectomy (PMT) were specifically recommended for the treatment of acute iliofemoral DVT to decrease post-thrombotic morbidity. Candidates include those patients with symptoms for ⬍14 days and with low risk of bleeding. The purpose of this study was to assess the feasibility and safety of PMT in patients with iliofemoral DVT with contraindications for treatment based on the most recent ACCP guidelines, namely those with symptoms ⬎14 days and those with contraindications to thrombolysis due to a high risk for hemorrhagic complications.
JOURNAL OF VASCULAR SURGERY Volume 50, Number 5
METHODS This study was approved by the Institutional Review Board at the University of Pittsburgh. Patients. Individuals who underwent PMT for symptomatic iliofemoral DVTs from May 2007 to February 2009 were identified from a prospectively collected database. The records were retrospectively reviewed for demographics, indication for treatment, chronicity of symptoms, contraindications to lysis, DVT risk factors, adjunctive interventions, periprocedural complications, clinical outcomes, and follow-up with duplex ultrasound (DU) imaging. All treated patients were severely symptomatic despite therapeutic anticoagulation and most commonly presented with a combination of pain, limb swelling, or phlegmasia. In all high-risk patients, a discussion was undertaken about the increased potential for bleeding complications. The ACCP guidelines were also discussed in detail in those patients treated after June of 2008, when the guidelines were issued. Patients treated before the publication of the guidelines were told that the standard of care was anticoagulation and that lysis was not supported by current guidelines, whether they were at high-risk or standard-risk for treatment. Only after informed consent was obtained did we proceed. All interventions were performed by vascular surgeons in endovascular suites equipped with fixed imaging capability (GE Healthcare, Giles, UK). The degree of residual thrombus was characterized as no lysis, ⬍50% lysis (partial), or ⬎50% lysis on venography. Absolute contraindication to therapy included any source of active internal bleeding. Major relative contraindications included recent gastrointestinal hemorrhage, recent (ⱕ10 to 14 days) major trauma or surgery, recent obstetric delivery, coagulation disorder, severe liver disease, pregnancy, and recent organ biopsy.11 The preoperative workup included venous DU imaging as well as computed tomography of the chest, abdomen, and pelvis with intravenous contrast and a venous phase. A hypercoagulable hematologic workup was performed on most patients in conjunction with consultation with a hematology specialist. All patients were placed in graduated compression stockings as recommended by the ACCP Guidelines. PMT technique. Caval interruption with temporary inferior vena cava (IVC) filters was performed selectively at the beginning of the procedure. If an IVC filter was to be placed, this was done preferentially through the internal jugular approach. Our technique was modified to involve filter access only through the jugular approach if a femoral hematoma developed while the patient was undergoing lysis in the prone position. After filter deployment, a 9F sheath was left in the jugular vein to minimize the risk of potential hematoma. This access was also maintained for filter retrieval at the completion of the procedure. Next, the patient was placed prone, and access was obtained under ultrasound guidance. Popliteal venous access was performed in 77% of patients, and basilic (14%), jugular (7%), and small saphenous vein access (2%) was
Rao et al 1093
Table I. Risk factors for deep vein thrombosis Risk factor Malignancy Hypercoagulable state Recent surgery Previous deep vein thrombosis Immobility Thoracic outlet syndrome Indwelling catheter Oral contraceptives
No. (N ⫽ 43) 8 15 5 3 3 5 4 2
obtained for all others. Heparin anticoagulation was routine and was dosed at 100 U/kg. A 6F or 8F sheath was placed, an ascending venogram was performed, and the PMT device was placed into the region of interest. When the AngioJet (Possis Medical, Minneapolis, Minn) was used, the DVX catheter was used in power pulse mode initially12 with 6 to 8 mg of tissue plasminogen activator (tPA; Alteplase, Genentech, San Francisco, Calif) per segment treated. It was then reactivated in regular thrombectomy mode after a 15-minute dwell time. Similarly, when the Trellis device (Bacchus Vascular, Santa Clara, Calif) was used, 6 to 8 mg of tPA were used per treatment segment. In patients with a thrombosed indwelling IVC filter, the distal balloon was inflated above the filter. CDT was initiated as needed for residual thrombus using a multisidehole catheter or DU-assisted CDT with the EKOS catheter (EKOS Corp, Bothell, Wash). In patients with contraindications to thrombolysis due to high risk for hemorrhagic complications, suction thrombectomy was performed using an aspiration catheter and no CDT was performed, even in the setting of residual thrombus. Residual iliac vein lesions on venography were treated with stenting at the discretion of the operating surgeon using self-expanding stents. Temporary IVC filters were universally removed. All patients were maintained on Coumadin (Bristol-Myers Squibb, Princeton, NJ) and were prescribed antiplatelet therapy if a stent was placed. Statistical analysis. An independent statistician performed all advanced statistical analyses. The data have been summarized as mean ⫾ standard deviation for continuous variables and as percentages for categoric data. The incidence for the need to perform a reintervention was calculated by the Kaplan-Meier method. The time component started on the date of the initial procedure. RESULTS During the 1.5-year period, 43 patients (24 men, 19 women), with a mean age of 48.4 ⫾ 16.6 years were treated with PMT, of whom 35 were treated for lower limb, and eight for upper extremity/central venous thrombosis. Of those patients treated for lower extremity disease, 16 underwent bilateral PMT, for a total of 51 lower limbs treated. Risk factors for DVT are listed in Table I. All patients had been prescribed anticoagulation before treatment but con-
JOURNAL OF VASCULAR SURGERY November 2009
1094 Rao et al
Table II. Hemorrhagic contraindications to lysis Contraindications
Single session or CDT
Lysis, degree
Bleeding complications
Single session Single session Single session Single session Single session Single session
⬍50% ⬍50% ⬍50% ⬍50% ⬍50% ⬍50%
Worsened rectus hematoma None None Worsened rectus hematoma None None
Single session
⬍50%
None
Single session
⬍50%
None
CDT Single session Single session Single session CDT Single session Single session
⬍50% ⬍50% ⬍50% ⬍50% ⬍50% ⬍50% ⬍50%
None None None None None None None
Rectus sheath hematoma Ongoing gross hematuria Ongoing excessive menses Rectus sheath/retroperitoneal hematoma Liver biopsy with intraperitoneal bleed Recent gastrointestinal bleed Recent surgery—abdominal wall and intra-abdominal debridement, removal of infected mesh Recent procedure—ileoscopy via stoma with biopsies; inflamed, bleeding stoma Recent surgery—lower extremity fasciotomy for trauma, muscle debridement Intra-abdominal organ biopsy Recent gastrointestinal bleeding Recent surgery—rib resection for thoracic outlet syndrome Recent surgery—pulmonary resection Postpartum, epidural anesthesia Recent intraperitoneal bleeding—adrenal hemorrhage CDT, Catheter-directed thrombolysis.
tinued to have debilitating symptoms, compromising ambulation in those with lower limb DVT. High-risk patients with persistence of debilitating symptoms were treated for at least 1 week before a consult for possible lysis was placed. All patients presented with severe swelling or pain, or both, and four patients had evidence of phlegmasia. Mean duration of symptoms before treatment was 13.6 ⫾ 9.6 days (range, 1-31 days), and 19 of 43 patients (44%) had symptoms for ⬎14 days before treatment, with a mean duration of 22.9 days (range, 15-31 days). Thrombolysis was contraindicated in 15 patients because they were at a high-risk for hemorrhagic complications (Table II). Caval involvement was present in 22 of the patients with lower extremity DVT, and 16 had a pre-existing IVC filter, 15 of which had thrombus extension with involvement of the filter up to the renal veins. Treatment was with the AngioJet device in 12 patients, the Trellis device in 13, and a combination of both in 17. The two-device combination was most commonly used for patients with persistent thrombus after initial PMT, specifically for residual thrombus in indwelling IVC filters in patients at high risk for bleeding with CDT where a one-session intervention was planned. Sixteen patients (37%) underwent catheterdirected thrombolysis secondary to ⬍50% lysis after PMT. Two of these had a contraindication to thrombolysis and were treated with a short 4- to 6-hour infusion with the EKOS catheter, and six had subacute or chronic DVT (Table III). Technical success was defined by ⬎50% angiographic lysis because this value has been shown to correlate with significantly improved 1-year venous patency rates.13 This was achieved in 41 of 43 patients (95%), including 14 of 15 patients with contraindications to thrombolysis, of whom 12 were treated with a limited one-session PMT. Both patients in whom complete or significant lysis could not be achieved had symptoms for ⬎14 days (Table IV). Iliac vein stents were placed in 18 of the 51 limbs (35%) treated.
Table III. Pharmacomechanical thrombectomy procedural data Variable
No.
IVC involvement Pre-existing IVC filter Thrombosed OptEase/TrapEasea Simon Nitinolb Greenfieldc Gunther Tulipd Patent (Greenfield)c Mechanical thrombectomy device AngioJet (Possis Medical) Trellis (Bacchus Vascular) AngioJet and Trellis Catheter-directed thrombolysis High risk Subacute/chronic DVT Multihole infusion catheter EKOS ultrasound-assisted catheter Stent placed Unilateral Bilateral
22 16 15 12 1 1 1 1 12 13 17 16 2 6 8 8 18 15 3
DVT, Deep vein thrombosis; IVC, inferior vena cava. a Cordis, Bridgewater, NJ. b Bard Peripheral Vascular, Tempe, Ariz. c Boston Scientific, Natick, Mass. d Cook Medical, Bloomington, Ind.
There were no periprocedural deaths and six periprocedural morbidities. Arrhythmias developed in two patients, which subsequently resolved. There were no systemic bleeding complications. Four bleeding complications were documented: two with worsening of pre-existing rectus sheath hematomas that occurred several days after intervention, at which time both patients were supratherapeutic on their anticoagulant regimen, and two access site hematomas occurred at the filter insertion site. Two pa-
JOURNAL OF VASCULAR SURGERY Volume 50, Number 5
Rao et al 1095
Table IV. Lysis success in subacute/chronic deep vein thrombosis Duration of symptoms, d 21 20 16 16 21 28 26 18 30 30 20 16 30 25 22 15 31 30 21
Bleeding risk
Single session vs CDT
Technical success
No Yes Yes No No No Yes No No Yes No No No No No No Yes No No
Single session Single session Single session CDT Single session Single session Single session Single session Single session Single session CDT Single session CDT Single session Single session Single session CDT CDT CDT
No Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes
CDT, Catheter-directed thrombolysis.
tients with contraindications to lysis had bleeding complications from their high-risk bleeding site. Four patients required blood transfusions after the procedure. No clinically significant pulmonary embolization developed. Two patients required reinterventions secondary to rethrombosis after initial technical success with PMT. One patient, who had a congenital narrowing of the IVC, recurred 3 weeks after the procedure and was not receiving therapeutic anticoagulation. He underwent subsequent successful relysis using a combination of PMT and CDT. Rethrombosis in the second patient occurred 5 days after the procedure. She had significant residual thrombus after the first intervention at the site of an existing filter but was at high risk for bleeding complications due to recent epidural placement during childbirth. She underwent successful CDT using the EKOS catheter. Both patients remain asymptomatic and free from recurrence. Mean follow-up was 5.0 ⫾ 4.8 months. One patient had an asymptomatic recurrence noted on office DU imaging for an overall 95% freedom from DVT recurrence or reintervention by life-table analysis. Of those patients not requiring reinterventions, 98% achieved complete or significant resolution of symptoms on clinical follow-up, and one patient in whom technical success had never been achieved had only minimal symptom relief. Follow-up DU imaging showed iliac stents were patent in 17 of 18 limbs (94%). The patient who had an occluded stent and had an indwelling filter that was partially deployed in the iliac vein was asymptomatic on follow-up and had a patent contralateral stent. DISCUSSION Although the use of thrombolysis for the treatment of acute iliofemoral DVTs is still debated, ample evidence
supports its use to reduce the occurrence of the PTS. The pathophysiology of the PTS appears to involve a combination of venous reflux secondary to valvular incompetence and luminal obstruction,2,7,14 with patients with PTS being three times more likely to have combined reflux and obstruction.15 This has engendered the notion of thrombus debulking to mitigate post-thrombotic sequelae.16 Clinically, thrombolysis revealed itself early on as an effective means of achieving clot lysis compared with anticoagulation therapy alone in 13 randomized studies, as reviewed by Comerota et al.2,17 In this pooled analysis, 45% of patients who underwent thrombolysis achieved “complete or significant” lysis with decreased long-term PTS versus only 4% of patients treated with anticoagulation alone. A high failure rate of systemic thrombolysis in patients with iliofemoral DVTs was noted, however, implying a role for intrathrombus lysis. CDT has indeed proven to be more effective than conventional treatment in several series,13,18-20 including one small randomized study.19 These reports cite improved short-term and longterm venous patency, with patency rates ranging from 54% to 89% at 1 year, as well as sustained symptom resolution or improvement. These factors have therefore led to the emergence of PMT as a potentially faster, less invasive, safe alternative to venous thrombectomy or CDT,21,22 promising to limit the dose and duration of treatment. It has been well-studied recently,23-25 with comparable or better success rates compared with CDT but with the added benefit of a shorter hospital and intensive care stay and decreased costs.25 Given this large body of evidence in favor of thrombolysis based on several retrospective series and registries, a large multicenter randomized trial evaluating CDT for iliofemoral DVTs was planned and is currently underway.26 Although early studies primarily focused on patients with acute DVT (symptoms duration ⬍10 to 15 days), Vedantham et al23 did treat six limbs in four patients with chronic (⬎10-day-old) DVT. Results were mediocre for all six limbs, noted by grade I or grade II lysis and no grade III or complete lysis. Similarly, Bush et al22 speculate that some of the failures of treatment may have been a result of the age of the thrombus. In addition, these groups either excluded or did not intentionally treat those patients at increased risk of hemorrhagic complications with thrombolysis. According to the most recent ACCP guidelines for antithrombotic and thrombolytic therapy,10 PMT is similarly advocated in patients with acute (⬍14-day-old) iliofemoral DVT who have low risk of bleeding in preference to anticoagulation alone to mitigate post-thrombotic symptoms. In the current study, we examined our cohort of patients treated with PMT for DVT of the upper or lower extremity to specifically evaluate patients not specifically covered by the current ACCP guidelines. As such, we included those treated with subacute/chronic DVT (duration of symptoms ⬎14 days) and those with contraindications to lysis secondary to bleeding risks. These patients represented a group who continued to have severe symptoms despite treatment with anticoagulation and in whom
1096 Rao et al
JOURNAL OF VASCULAR SURGERY November 2009
Fig. Ascending venogram and cavogram of patient before the procedure shows extensive (A) femoropopliteal and (B) iliocaval thrombosis with thrombus extending up to inferior vena cava filter, and (C) after a single-session pharmacomechanical thrombectomy.
PMT was deemed appropriate to shorten treatment times, with the purported benefit of reducing the bleeding risk. Although we did note four bleeding complications, two of these were expansions of rectus sheath hematomas that existed before treatment. The growth of hematoma occurred not immediately after the procedure, but several days after, at which time both patients had supratherapeutic international normalized ratio values. In another patient, a hematoma developed at the filter placement access site. This patient underwent femoral vein puncture for filter placement before prone positioning for PMT through the popliteal approach. We have since changed our protocol to routinely place filters using the internal jugular approach, maintaining a 9F sheath in situ until completion of the procedure. Our definition of technical success was achieving ⬎50% lysis as visualized on venography (Fig). A national multicenter registry report of CDT for DVT13 had used similar measurements and defined success by grade, with grade I representing ⬍50% lysis, grade II ⬎50%, and grade III complete lysis. Vedantham et al23 reported that 31% of patients with iliofemoral DVT treated with PMT achieved grade III lysis, whereas two other groups similarly looking at PMT for lower extremity DVTs reported rates of complete thrombus removal of 100% and 70%.24,25 Two of these three studies, however, used PMT after overnight lytic infusion. The third study did not clarify whether patients treated by PMT underwent any adjunctive CDT. More importantly, none of these series report cases in which they specifically aimed to minimize treatment duration in high-risk patients. The main treatment goal in the current high-risk series was not necessarily complete lysis, but significant lysis (⬎50%). Achieving complete lysis in many of these patients might have been possible by alternative means (prolonged CDT), albeit at the cost of increased hemorrhagic compli-
cations. As a result, we accepted significant but incomplete lysis in several of these patients and managed to safely treat 13 of 15 (87%) patients who had contraindications to lysis in a single session with PMT. Freedom from DVT recurrence or reintervention at the midterm follow-up was 95%, and 98% of those patients remained symptom-free, indicating that partial ⬎50% lysis appears to be as effective clinically as complete lysis and, more importantly, is associated with fewer major bleeding complications. Of note, however, we used a combination of both the Trellis and Angiojet devices in well over one-third of our patients, highlighting the need for diligent and persistent therapy to achieve single-session success. Other recent studies have implicated the duration of symptoms and DVT as a factor in achieving successful lysis,22,23 with chronic DVT potentially posing a greater challenge to effective therapy. Our results do indeed support this notion, given that both patients in whom we were unable to achieve successful lysis were patients with chronic DVT (Table IV). However, 17 patients (89%) presenting with symptoms ⬎14 days achieved successful lysis and clinical outcomes. One patient with DVT duration of ⬎14 days in whom success was not achieved had recently undergone surgery, and the other showed minimal response with PMT and was deemed unlikely to benefit from further lysis. They were therefore both treated in a single session and not offered CDT. In the absence of bleeding risks, however, some subacute patients would likely benefit from adjunctive CDT to achieve better reduction of thrombus burden. We used venography alone to determine the degree of underlying venous obstruction after PMT to determine the need for stenting. As such, we may have underestimated the true degree of residual disease, given the 2-dimensional nature of venography. We placed stents in slightly more than one-third of our patients treated. This is markedly less than rates reported in the literature, where up to 75% of
JOURNAL OF VASCULAR SURGERY Volume 50, Number 5
patients treated for venous occlusive disease undergo iliac stenting.27 To optimize imaging sensitivity, we have now incorporated the use of intravascular ultrasound into our protocol for treatment. However, despite the reliance on venography in the current series, we were still able to achieve good success with selective stent placement, with no treatment failures occurring as a result of undiagnosed residual iliac disease. Another subject of current controversy concerns IVC placement before venous lysis. To our knowledge, there are no data to suggest that an IVC should be placed routinely during lytic procedures. However, Protack et al28 report no increase in pulmonary emboli in patients undergoing CDT without filter placement. These data, however, may not necessarily be translatable to lysis procedures involving PMT. Our practice has therefore evolved to include the placement of temporary filters whenever there is caval or iliac vein involvement, especially when PMT is anticipated. These are routinely removed at the completion of the procedure, unless there is a significant amount of embolic clot lining the filter, in which case the filter itself is treated with PMT, followed by filter retrieval. Although the disposable costs associated with PMT can be significant, the ability to minimize treatment duration, intensive care, and hospital length of stay makes this approach cost-effective compared with CDT.25 In addition, mitigating the socioeconomic cost of post-thrombotic complications after DVT is significant. Venous stasis ulceration develops in up to 86% of patients with acute DVT over 10 years, requiring multiple hospitalizations and various medical and surgical modalities for management.3 Moreover, patients with chronic venous disease incur an opportunity cost secondary to loss of work days.3 Although we did not perform a cost analysis, the immediate and long-term cost savings of PMT compared with other DVT treatment modalities are worth investigating. CONCLUSIONS This series demonstrates the safety and efficacy of pharmacomechanical thrombectomy in the treatment of symptomatic DVT in patients with contraindications to lysis, namely those with high risk for bleeding and those with chronic DVT. Although it appears that the most effective lysis results from a combination of pharmacomechanical thrombectomy and catheter-directed thrombolysis, we suggest the use of one-session pharmacomechanical thrombectomy alone to achieve success in those patients with a high risk of bleeding. Careful patient selection, however, is mandatory, with clear delineation of risks and expectations. AUTHOR CONTRIBUTIONS Conception and design: AR, JC, RR, MM, RC Analysis and interpretation: AR, GK, JC, RR, MM, RC Data collection: AR, GK, RC Writing the article: AR, GK, RC Critical revision of the article: AR, JC, RR, MM, RC Final approval of the article: AR, GK, JC, RR, MM, RC Statistical analysis: AR, RC
Rao et al 1097
Obtained funding: RC Overall responsibility: RC REFERENCES 1. Bauer G. Roentgenological and clinical study of the sequels of thrombosis. Acta Chir Scand 1942:42 (suppl 74). 2. Comerota AJ, Gravett MH. Iliofemoral venous thrombosis. J Vasc Surg 2007;46:1065-76. 3. O’Donnell TF, Browse NL, Burnand KG, Thomas ML. The socioeconomic effects of an iliofemoral venous thrombosis. J Surg Res 1977;22: 483-8. 4. Akesson H, Brudin L, Dahlstrom JA, Eklof B, Ohlin P, Plate G. Venous function assessed during a 5-year period after acute ilio-femoral venous thrombosis treated with anticoagulation. Eur J Vasc Surg 1990;4:43-8. 5. Delis KT, Bountouroglou D, Mansfield AO. Venous claudication in iliofemoral thrombosis: long-term effects on venous hemodynamics, clinical status, and quality of life. Ann Surg 2004;239:118-26. 6. Kearon C. Natural history of venous thromboembolism. Circulation 2003;107(23 suppl 1):I22-30. 7. Peden E, Zhou W, Bush RL, Lumsden AB, Lin PH. The case for thrombolysis for iliofemoral venous thrombosis. Semin Vasc Surg 2005; 18:139-47. 8. Mohr DN, Silverstein MD, Heit JA, Petterson TM, O’Fallon WM, Melton LJ. The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study. Mayo Clin Proc 2000; 75:1249-56. 9. Douketis JD, Crowther MA, Foster GA, Ginsberg JS. Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis? Am J Med 2001;110:515-9. 10. Hirsh J, Guyatt G, Albers GW, Harrington R, Schunemann HJ. American College of Chest Physicians. (2008). Executive summary: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133(6 suppl):71-109S. 11. Angle N, Quinones-Baldrich WJ. Thrombolytic therapy for vascular disease. In: Moore WS, editor. Vascular and endovascular surgery: a comprehensive review. 7th ed. Philadelphia: Saunders-Elsevier; 2006. p. 414-42. 12. Allie DE, Hebert CJ, Lirtzman MD, Wyatt CH, Keller VA, Khan MH, et al. Novel simultaneous combination chemical thrombolysis/ rheolytic thrombectomy therapy for acute limb ischemia: the power pulse spray technique. Catheter Cardiovasc Interv 2004;63:512-22. 13. Mewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, Haughton SH. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology 1999;211:39-49. 14. O’Shaughnessy AM, Fitzgerald DE. Natural history of proximal deep vein thrombosis assessed by duplex ultrasound. Intl Angiol 1997;16: 45-9. 15. Johnson BF, Manzo RA, Bergelin RO, Strandness DE. Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: a one- to six-year follow-up. J Vasc Surg 1995;21:30712; discussion 313. 16. Comerota AJ, Paolini D. Treatment of acute iliofemoral deep venous thrombosis: a strategy of thrombus removal. Eur J Vasc Endovasc Surg 2007;33:351-60; discussion 361-2. 17. Comerota AJ, Aldridge SC. Thrombolytic therapy for deep venous thrombosis: a clinical review. Can J Surg 1993;36:359-64. 18. AbuRahma AF, Perkins SE, Wulu JT, Ng HK. Iliofemoral deep vein thrombosis: conventional therapy versus lysis and percutaneous transluminal angioplasty and stenting. Ann Surg 2001;233:752-60. 19. Elsharawy M, Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial. Eur J Vasc Endovasc Surg 2002;24:209-214. 20. Bjarnason H, Kruse JR, Asinger DA, Nazarian GK, Dietz CA, Caldwell MD, et al. Iliofemoral deep venous thrombosis: safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy. J Vasc Interv Radiol 1997;8:405-18.
1098 Rao et al
21. Lin PH, Mussa FF, Hedayati N, Naoum JJ, Zhou W, Yao Q, et al. Comparison of AngioJet rheolytic pharmacomechanical thrombectomy versus AngioJet rheolytic thrombectomy in a porcine peripheral arterial model. World J Surg 2007;31:715-722. 22. Bush RL, Lin PH, Bates JT, Mureebe L, Zhou W, Lumsden AB. Pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis: safety and feasibility study. J Vasc Surg 2004;40:965-70. 23. Vedantham S, Vesely TM, Sicard GA, Brown D, Rubin B, Sanchez LA, et al. Pharmacomechanical thrombolysis and early stent placement for iliofemoral deep vein thrombosis. J Vasc Intervent Radiol 2004;15: 565-74. 24. Lee KH, Han H, Lee KJ, Yoon CS, Kim SH, Won JY, et al. Mechanical thrombectomy of acute iliofemoral deep vein thrombosis with use of an arrow-trerotola percutaneous thrombectomy device. J Vasc Intervent Radiol 2006;17:487-95. 25. Lin PH, Zhou W, Dardik A, Mussa F, Kougias P, Hedayati N, et al. Catheter-direct thrombolysis versus pharmacomechanical thrombec-
JOURNAL OF VASCULAR SURGERY November 2009
tomy for treatment of symptomatic lower extremity deep venous thrombosis. Am J Surg 2006;192:782-8. 26. Enden T, Sandvik L, Klow NE, Hafsahl G, Holme PA, Holmen LO, et al. Catheter-directed venous thrombolysis in acute iliofemoral vein thrombosis—the CaVenT study: rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771). Am Heart J 2007;154:808-14. 27. Neglen P, Raju S. Balloon dilation and stenting of chronic iliac vein obstruction: technical aspects and early clinical outcomes. J Endovasc Ther 2000;7:79-91. 28. Protack CD, Bakken AM, Patel N, Saad WE, Waldman DL, Davies MG. Long-term outcomes of catheter directed thrombolysis for lower extremity deep venous thrombosis without prophylactic inferior vena cava filter placement. J Vasc Surg 2007;45:992-7; discussion 997.
Submitted Apr 7, 2009; accepted Jun 21, 2009.