CLINICAL STUDY
Pharmacomechanical Thrombolysis of Symptomatic Acute and Subacute Deep Vein Thrombosis with a Rotational Thrombectomy Device Cüneyt Köksoy, MD, M. Fatih Yilmaz, MD, H. Serdar Bas¸buğ, MD, Eyüp Serhat Çalik, MD, Bilgehan Erkut, MD, Mehmet Ali Kaygın, MD, Ahmet Peker, MD, and Umman N. Sanlıdilek, MD
ABSTRACT Purpose: To retrospectively evaluate the efficacy and safety of pharmacomechanical thrombolysis (PMT) with the use of a rotational thrombectomy device for symptomatic deep vein thrombosis (DVT). Materials and Methods: Between July 2012 and August 2013, 41 patients with acute or subacute DVT underwent PMT. The Cleaner thrombectomy device was used in a single-session technique for patients with lower-extremity DVT. Based on contrast venography, the extent of lysis was graded from I (o 50%) to III (complete). Results: Sixteen patients (39.0%) had a femoropopliteal thrombosis and 25 (61.0%) had an iliofemoral venous thrombosis. The mean duration of symptoms was 11.0 days (range, 3–25 d). The mean quantity of tissue plasminogen activator was 20.7 mg (range, 10–50), and the mean duration of the procedure was 74.3 minutes (range, 30–240 min). At the end of the PMT procedure, 29 patients (70.7%) had complete (grade III) thrombus resolution. Grade I and II lysis were noted in one (2.4%) and 11 (26.8%) patients, respectively. Thirty-eight of the 41 patients were treated with PMT in a single session, and three (7.3%) required an additional lytic infusion as a result of residual thrombi. The overall grade III, II, and I thrombus resolution rates, including the supplemental thrombolysis, were 73.2% (n ¼ 30), 22.0% (n ¼ 9), and 4.9% (n ¼ 2), respectively. There was no mortality. Conclusions: Use of the Cleaner thrombectomy device is a promising alternative to current treatment modalities for the management of DVT in a single session of PMT.
ABBREVIATIONS CDT = catheter-directed thrombolysis, DVT = deep vein thrombosis, IVC = inferior vena cava, PMT = pharmacomechanical thrombolysis, PTS = postthrombotic syndrome, TPA = tissue plasminogen activator
Deep vein thrombosis (DVT) affects a significant proportion of the population, many of whom go on to develop postthrombotic syndrome (PTS) (1). During the past decade, PMT has emerged as an effective alternative to open surgical thrombectomies and
From the Division of Vascular Surgery (C.K.) and Department of Radiology (A.P., U.N.S.), Ankara University, Ankara; Department of Cardiovascular Surgery (M.F.Y.), Kayseri Training and Research Hospital, Kayseri; Department of Cardiovascular Surgery (H.S.B.), Kafkas University, Kars; and Department of Cardiovascular Surgery (E.S.C., B.E., M.A.K.), Erzurum Training and Research Hospital, Erzurum, Turkey. Received May 4, 2014; final revision received and accepted August 18, 2014. Address correspondence to C.K., Tunalı Hilmi Cad. 91/109, Kavaklıdere 06700, Ankara, Turkey; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2014 J Vasc Interv Radiol 2014; XX:]]]–]]] http://dx.doi.org/10.1016/j.jvir.2014.08.018
catheter-directed thrombolysis (CDT) in patients with acute DVT (2). Pharmacomechanical approaches have been suggested as viable and possibly preferable approaches to the management of acute DVT (3). Although several observational studies have demonstrated the successful implementation of PMT (4–6), no multicenter, randomized controlled trials have yet demonstrated the long-term effects of this therapy. Several PMT devices have been developed during the past two decades (5–7). The Cleaner thrombectomy device (Argon Medical Devices, Plano, Texas) is a battery-operated percutaneous mechanical thrombectomy catheter that functions by spinning a flexible “S”shaped guide wire within the vessel to be treated (Fig 1). This function allows the clot to be macerated and aspirated through an introducer sheath. Information about the efficacy of this device is limited. Therefore, the aim of the present study was to evaluate the efficacy
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PMT Technique
Figure 1. The Cleaner thrombectomy device. (Available in color online at www.jvir.org.)
and safety of pharmacomechanical thrombectomies performed with the use of this rotational thrombectomy device for the treatment of DVT.
MATERIALS AND METHODS Patients Following institutional review board approval, consecutive patients who underwent PMT with recombinant tissue plasminogen activator (TPA) for a symptomatic lower-extremity DVT over a 1-year period between July 2012 and August 2013 were identified from one clinical database combined from four nationwide centers. The records were retrospectively reviewed for demographic data, indications for treatment, periprocedural complications, clinical outcomes, and follow-up with duplex ultrasound (US) imaging, and reporting was done in accordance with the Society of Interventional Radiology (SIR) reporting standards for the endovascular treatment of lower-extremity DVT (8). Based on these criteria, symptom duration was defined as acute (r 14 d), subacute (15–28 d), or chronic (4 28 d). Records of 41 symptomatic patients with acute or subacute lower-extremity DVT were reviewed. All patients had leg swelling, pain, or symptoms related to phlegmasia cerulea dolens. The patients consisted of 29 men and 12 women, with a mean age of 54.9 years ⫾ 19.6 (range, 17–84 y). The initial diagnosis of DVT was made in all patients with venous duplex imaging. The definitive delineation of the extent of the involved venous segments was established by venography at the time of intervention. To be included in the study, patients required first-time verified acute or subacute symptomatic DVT involving the femoropopliteal, iliofemoral, or iliocaval segments. The criteria excluded patients who were not 16–85 years of age; patients with an upper-extremity thrombosis, established PTS, severe renal failure, or active gastrointestinal bleeding; patients who could not receive tPA or anticoagulation therapy; terminally ill patients; and patients with contraindications to thrombolytic treatment, such as hemorrhagic stroke or other intracranial diseases, recent (o 10 d) major trauma or surgery, pregnancy, recent obstetric delivery, bleeding disorder, and prolonged traumatic cardiopulmonary resuscitation. Patients who did not meet the inclusion did not undergo PMT.
Before the procedure, a retrievable inferior vena cava (IVC) filter (Option retrievable vena cava filter; Argon Medical Devices) was placed via contralateral femoral or internal jugular vein access. Under local anesthesia, a percutaneous 6-F sheath was placed in an antegrade fashion into the popliteal or posterior tibial vein under US guidance. Unfractionated heparin was administered into a peripheral vein, with a target of two- to threefold activation of the partial thromboplastin to provide anticoagulation at the lytic site and in the systemic circulation. Venography was performed, and the location of the thrombus was established. Then, a 6-F Cleaner thrombectomy device was inserted through the introducer sheath. A recombinant form of TPA (alteplase; Actilyse; Boehringer Ingelheim, Ingelheim am Rhein, Germany) was delivered through the side port of the device. The device was activated to spin the S-shaped wire, which was then advanced in an antegrade fashion (Fig 2). Following a 2–5-minute thrombolysis, the device was deactivated and temporarily withdrawn. The macerated thrombus and residual lytic agent were suctioned through the sheath, and control venograms were obtained to evaluate the treated segments. The device was then reinserted and repositioned into the upper thrombosed segment. Thrombolysis was performed in a segmental antegrade fashion. The most cranial portion was lysed last to prevent the embolization of a thrombus fragment. The vein was treated in approximately 5–10-cm intervals by injecting 10 mL of saline solution containing 1 mg of the TPA solution for 2–5 minutes; the rate depended on the patient’s condition and weight and the size of the thrombus. This procedure was repeated until the end of the thrombus was reached. Finally, the device was removed, and a completion venogram was obtained. When the extent of the thrombus resolution was less than 50% of the occluded segment, the device was reinserted and activated for an additional pass. If the control venogram revealed a residual occluding or significantly obstructing thrombus after the second or third pass, the procedure was terminated or a 4-F infusion catheter (Cragg McNamara valved infusion catheter; ev3, Irvine, California) was inserted, and an infusion of 1 mg/h TPA was initiated for 24 hours. Percutaneous transluminal angioplasty and venous stent placement were performed selectively to treat underlying severe stenoses or nonresponding iliocaval obstructions. If there was a significant compression of the left common iliac vein or if there was severe stenosis as a result of a residual thrombus that could not be removed with the device or a following CDT in the iliac veins or the IVC, self-expanding stents were placed. With use of the same access, large (16–18 mm in diameter) Wallstents (Boston Scientific, Natick, Massachusetts) were placed with at least 1–2 cm at the stent joints after predilation to normal vein caliber for the location.
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Figure 2. (a) Initial venogram of the left leg demonstrates extensive femoral venous thrombosis (prone position, arrows indicate thrombus). The patient was subsequently treated with the Cleaner device (b). Final image demonstrates a patent femoral vein with no residual thrombus and good flow (c).
Following the interventional therapy, all patients continued to receive subcutaneous low molecular weight heparin, with a subsequent conversion to oral warfarin. The therapy was adjusted to attain an International Normalized Ratio in the range of 2–3. The retrievable IVC filters were removed within 1 month. Posttreatment duplex US imaging of the affected leg was performed at weekly intervals for 1 month and then monthly thereafter. Study endpoints were the extent of clot lysis, major bleeding, and pulmonary emboli during PMT and DVT evolution during follow-up. Postinterventional venography was performed, and the venograms were graded for the quantity of the thrombus extraction compared with the venograms from before and after the treatment by the same interventionalist who performed the procedure. The extent of the lysis was graded from I to III. Grade III lysis was defined as the complete resolution of the thrombus on a visual assessment of the venogram (9). Grades II and I lysis were defined as an extent of thrombus resolution of 50%–99% and less than 50%, respectively. After the completion venogram, a final IVC venogram was obtained to search for thrombi trapped in the IVC filter. Before discharge, a clinical evaluation and duplex US were performed on the treated vein segments.
Complication Definitions According to SIR reporting standards (8), major bleeding was defined as intracranial bleeding or bleeding severe enough to result in death, surgery, cessation of therapy, or blood transfusion. Minor bleeding was
defined as less severe bleeding that was manageable with local compression, sheath upsizing, or dose alterations of a pharmacologic thrombolytic agent, anticoagulant, or antiplatelet drug.
Follow-up Assessments The efficacy outcome assessments were conducted by using duplex US at follow-up. The valve function was not examined routinely. Recurrent DVT and pulmonary embolisms were recorded during follow-up. After 3 months, the PTS was assessed per the Villalta scale (10), which includes five symptoms (pain, cramps, heaviness, pruritus, and paresthesia) and six objective signs (edema, skin induration, hyperpigmentation, venous ectasia, redness, and pain during calf compression). Each symptom or sign was rated as 0 (absent), 1 (mild), 2 (moderate), or 3 (severe). The points were then added to determine the total score. Scores of less than 5 indicated the absence of PTS, scores of 5–9 indicated mild PTS, scores of 10–14 indicated moderate PTS, and scores greater than 15 or ulceration indicated severe PTS (11). Statistical analysis was performed by using (SPSS software (version 18.0; IBM, Armonk, New York). Continuous data are reported as means ⫾ standard deviation. Nominal data are reported as the number of subjects. Student t test was used to compare the mean differences between the two groups. Frequencies of complete thrombus removal and PTS were compared by χ2 test. A P value o .05 was considered statistically significant.
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RESULTS The mean symptom duration was 11.0 days ⫾ 6.0 (range, 3–25 d). Eight patients (19.5%) had subacute symptoms (ie, 4 14 d). Phlegmasia cerulea dolens was noted in three patients (7.3%). The thrombosis was on the left side in 23 patients (56.1%). Sixteen patients (39.0%) had a femoropopliteal thrombosis, and 25 (61.0%) had an iliofemoral venous thrombosis. The patients were taken to the angiography suite within 48 hours ⫾ 12 of presentation. A retrievable IVC filter was inserted in all but one patient. The access site for PMT was the posterior tibial vein in one patient and the popliteal vein in all other patients. The mean amount of TPA infused was 20.7 mg ⫾ 11.3 (range, 10– 50 mg), and the mean procedure duration was 74.3 minutes ⫾ 44.5 (range, 30–240 min). Iliocaval stent placement was required in two of the 25 patients with an iliofemoral thrombosis (8%). Thirty-eight of the 41 patients were treated in a single session, and three (7.3%) required an additional lytic infusion for 24 hours as a result of residual thrombi. There were no device failures or adverse events associated with the device.
Effect of PMT on Venous Patency At the end of the single-session PMT procedure, lysis of more than 50% was obtained in 40 patients (97.6%). Twenty-nine patients (70.7%) had a complete (ie, grade III) thrombus resolution. Grades II and I lysis were noted in 11 (26.8%) and one (2.4%) patient, respectively. There was an inverse relationship between the duration of symptoms and the degree of lysis (Table). Following supplemental CDT, the overall grade III, II, and I thrombus resolution rates were 73.2% (n ¼ 30), 22.0% (n ¼ 9), and 4.9% (n ¼ 2), respectively. Immediate clinical improvement was observed in 39 patients (95.1%). Limb salvage was achieved in all three patients who presented with phlegmasia cerulea dolens. The duplex US imaging performed before discharge demonstrated patent veins in 38 patients (92.7%). There was an association between the success of PMT and inhospital recurrent thrombosis. Only one of the 29
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patients with complete thrombus resolution after PMT (3.4%) experienced recurrent thrombosis. However, the recurrent thrombosis rates for patients with grade I or II resolution were 100% (n ¼ 1) and 9.1% (one of 11), respectively (P o .05). Four patients with patent iliocaval venous systems (9.8%) showed recurrent femoral vein thrombosis while in the hospital. No further intervention was performed for these patients. The mean follow-up was 3.8 months ⫾ 3.1 (range, 2–12 mo). The final clinical and imaging studies at the last follow-up visit revealed patent veins in 39 patients (95.1%). Duplex US imaging also showed that the iliac stents in two patients were patent. Two patients had occlusions of the femoral vein without recurrent symptoms.
Complications No periprocedural deaths or symptomatic pulmonary embolisms occurred. After completion venography, the final IVC venogram revealed no trapped thrombi in the IVC filter. There were no systemic bleeding complications. Minor bleeding at the access site occurred in six patients (14.6%). Major bleeding caused by an access hematoma developed in one patient (2.4%), who required a blood transfusion. This patient underwent concomitant iliac vein stent placement with the use of a 10-F sheath at the popliteal vein after several failed puncture attempts, and a popliteal hematoma and bleeding developed as a result of the very short period of compression at the popliteal access site.
Effect of PMT on Postthrombotic Symptoms Twenty-nine patients had at least 3 months of follow-up. At 3 months, the average Villalta score as a measure of PTS was 2.68 ⫾ 1.4 (range, 1–5). Based on the Villalta score, no PTS was observed in 21 patients (72.4%), and mild PTS was observed in eight patients (27.6%). None of the patients had moderate PTS. There was no difference in Villalta score between patients with acute and subacute DVT (2.47 ⫾ 1.4 vs 3.2 ⫾ 1.2, respectively; P ¼ .17). There was also no relationship between the PTS category based on the Villalta scores and the duration of symptoms at admission (Table).
Table . Effects of Symptom Duration at Admission on Degree of Clot Lysis and PTS Category Parameter
Acute DVT
Subacute DVT
Grade III Grade II
26 (78.8) 6 (18.2)
3 (37.5) 5 (62.5)
Grade I
1 (2.4)
0
16 (76.2)
5 (62.5)
5 (23.8)
3 (37.5)
Extent of lysis
PTS category None Mild
P Value .03
.46
Values in parentheses are percentages. DVT ¼ deep vein thrombosis, PTS ¼ postthrombotic syndrome.
DISCUSSION Without effective therapy, many patients with DVT experience persistent venous obstruction and deep venous reflux, both of which are known to contribute to the development of PTS. In view of the suboptimal long-term results of anticoagulation therapy alone, catheter-based techniques have been employed to decrease the thrombus burden and to correct the underlying obstructions when present (4). The present study demonstrates the safety and efficacy of pharmacomechanical thrombectomy in the treatment of
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symptomatic DVT with the use of a new rotational PMT device. With the use of this device, a greater than 50% thrombus resolution was achieved in 97.6% of patients, without significant morbidity, in a single-session procedure. This rate is comparable with the success rates reported by others (4,12,13). In a retrospective study of patients receiving CDT (14), patients who had greater than 50% clot removal with CDT experienced a reduced PTS and better quality of life than patients whose CDT did not achieve substantial clot removal (14). The successful use of PMT has been described in a number of published observational DVT studies but not in any multicenter randomized trials to our knowledge. In the present series, the treatment of lower-extremity DVT with single-session rotational PMT resulted in promising primary success with minimal rates of complications. Achievement of grade III lysis is considered the optimal result, and was achieved in 70.7% of patients. Additional CDT in two patients who had grade II lysis with single-session PMT resulted in a complete lysis in one patient and less than 50% thrombus resolution in the other patient. Worsening of thrombus resolution with additional CDT in this patient may be related to a short (24 h) CDT treatment time. In the present series, 19.5% of patients had subacute (4 2 wk) DVT, with the oldest DVT treated being 25 days. The time frame from DVT onset to the initiation of PMT may play a role in successful thrombolysis. The successful thrombolysis of an acute DVT is most likely to be achieved in patients with recently formed thrombi, as evidenced by a DVT symptom duration of fewer than 10–14 days (9). Grade III lysis was achieved in 78.8% of our patients with acute DVT (o 2 wk). It is generally accepted that treatment of subacute DVT has a lower technical success rate, as demonstrated in the present results. In the setting of subacute DVT, grade III lysis was obtained in 37.5% of our patients. A symptom duration of greater than 10 days has been reported to result in a low rate of complete thrombolysis and in infrequent treatment failures with less than 50% thrombus removal (15). One of the most important permanent sequelae of DVT is PTS (1). The predictors of the development of PTS are only partially understood. However, the final physiologic pathway leading to PTS appears to involve the development of ambulatory venous hypertension, which is caused by venous obstruction and valvular reflux following DVT (16). Therefore, the elimination of venous obstruction is an important step in the prevention of PTS. In addition to several case series, a randomized trial by Enden et al (17) demonstrated that the use of CDT was associated with a 28% relative reduction in the risk of PTS over a 2-year follow-up period. As we did not have a control group and had a very short follow-up period, we did not observe the beneficial effects of PMT on postthrombotic symptoms. Bleeding is a feared complication of thrombolysis. PMT offers a reasonable solution in patients with venous
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thromboembolisms and is associated with a lower risk of bleeding. Major bleeding is estimated to occur in 2%–4% of patients receiving CDT (2). We did not encounter any systemic bleeding complications. Minor bleeding at the access site occurred in 14.6% of patients, but only one additional patient with an access-site hematoma required a transfusion. Therefore, the rate of major bleeding episodes for this treatment modality was 2.4%. A retrospective study by Rao et al (12) demonstrated that thrombolytic agent doses and infusion durations were reduced with PMT compared with conventional CDT. No major bleeding complications were reported in a systematic literature review of 2,528 patients with DVT treated with PMT (18). PMT may also decrease the risk of hemorrhagic complications because of its shorter infusion intervals and lower doses of thrombolytic agents, making it a more attractive modality in highrisk cases in postoperative patients. However, PMT is not free from bleeding complications. The total lytic agent amount is greater with CDT that lasts 2 days or longer. However, during the 1–2-hour PMT procedure, the dose of thrombolytic agent is higher. In other words, in the present study, 20.7 mg (range, 10–50 mg) TPA was used during 74.3 minutes (range, 30–240 min) of the procedure, and, because PMT involves a higher dose in a short period of time, there is a potential bleeding risk. The placement of a prophylactic IVC filter before thrombolytic procedures is still under debate. In the present series, we attempted to use IVC filters in almost all patients and did not diagnose any symptomatic pulmonary embolisms. In a large prospective registry of 473 patients with proximal DVT undergoing infusion CDT (without percutaneous mechanical thrombectomy) (9), symptomatic pulmonary embolisms occurred in only six patients (1.3%), one of whom died (0.2%). The relative rarity of a major pulmonary embolism in CDT recipients may partially arise from the ability of the thrombolytic drug to quickly dissolve any circulating thrombus fragments. However, for patients being treated with PMT methods, which can involve more clot manipulation, a major pulmonary embolism can occur iatrogenically (4). The recently published Filter Implantation To Lower Thromboembolic Risk in Percutaneous Endovascular Intervention trial (19) demonstrated that IVC filter implantation during endovenous procedures reduces the risk of iatrogenic pulmonary embolism eightfold, without a mortality benefit. We used iliac stents for only two of the 25 patients with an iliofemoral venous thrombosis (8%). Both of these patients had iliac vein compression that was resistant to lytic therapy. Although most interventionalists use venous stent deployment liberally during thrombolysis, we are aware of no prospective randomized trial supporting the use of iliac venous stent placement in the endovascular management of venous thrombosis. There are also conflicting data regarding the efficacy of the concomitant use of stents during
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thrombolysis (9,17). No specific recommendations for stent placement are given in the SIR reporting standards for endovascular treatment of lower-extremity DVT (8). As there are no existing criteria that indicate additive stent implantation during CDT for iliofemoral DVT, we limited ourselves to concomitant stent deployment during PMT. The present study has several limitations, including the nature of a retrospective analysis of one combined database, the small number of patients, and a heterogeneous study population in terms of the duration of symptoms and the locations of the thrombi, as well as the limited use of adjunctive balloon dilation and stent placement. After 3 months, PTS was assessed based on the Villalta scale, an easily applied measure that includes patient-reported symptoms and physician-assessed signs of venous disease. Although a 3-month period may be too soon for the evaluation of PTS, 3-month Villalta scales have been used by others (20). Conversely, the mean follow-up of the study is too short to evaluate a problem such as PTS, which develops over a number of years. During the follow-up duplex examinations, we did not attempt to record venous valve function, focusing instead on the veins’ patency. In summary, based on the present data, use of the Cleaner thrombectomy device may prove to be a safe and feasible single-session PMT method for the treatment of acute DVT in broader patient populations, and warrants further investigation in large-scale studies.
REFERENCES 1. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125:1–7. 2. Vedantham S. Interventional approaches to deep vein thrombosis. Am J Hematol 2012; 87(suppl 1):S113–S118. 3. Vedantham S, Thorpe PE, Cardella JF, et al. Quality improvement guidelines for the treatment of lower extremity deep vein thrombosis with use of endovascular thrombus removal. J Vasc Interv Radiol 2006; 17:435–447. 4. Lin PH, Zhou W, Dardik A, et al. Catheter-directed thrombolysis versus pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis. Am J Surg 2006; 192:782–788.
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5. O’Sullivan GJ, Lohan DG, Gough N, Cronin CG, Kee ST. Pharmacomechanical thrombectomy of acute deep vein thrombosis with the Trellis-8 isolated thrombolysis catheter. J Vasc Interv Radiol 2007; 18:715–724. 6. Cynamon J, Stein EG, Dym J, et al. A new method for aggressive management of deep vein thrombosis: Retrospective study of the power pulse technique. J Vasc Interv Radiol 2006; 17:1043–1049. 7. Baker R, Samuels S, Benenati JF, Powell A, Uthoff H. Ultrasoundaccelerated vs standard catheter-directed thrombolysis—a comparative study in patients with iliofemoral deep vein thrombosis. J Vasc Interv Radiol 2012; 23:1460–1466. 8. Vedantham S, Grassi CJ, Ferral H, et al. Reporting standards for endovascular treatment of lower extremity deep vein thrombosis. J Vasc Interv Radiol 2009; 20(suppl):S391–S408. 9. 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. 10. Kahn SR, Partsch H, Vedantham S, et al. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009; 7:879–883. 11. Strijkers RH, Wittens CH, Kahn SR. Villalta scale: goals and limitations. Phlebology 2012; 27(suppl 1):130–135. 12. Rao AS, Konig G, Leers SA, et al. Pharmacomechanical thrombectomy for iliofemoral deep vein thrombosis: an alternative in patients with contraindications to thrombolysis. J Vasc Surg 2009; 50:1092–1098. 13. Chaudhry MA, Pappy R, Hennebry TA. Use of the trellis device in the management of deep vein thrombosis: a retrospective single-center experience. J Invasive Cardiol 2013; 25:296–299. 14. Grewal NK, Martinez JT, Andrews L, Comerota AJ. Quantity of clot lysed after catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with postthrombotic morbidity. J Vasc Surg 2010; 51:1209–1214. 15. Park SI, Lee M, Lee MS, Kim MD, Won JY. Lee do Y. Single-session aspiration thrombectomy of lower extremity deep vein thrombosis using large-size catheter without pharmacologic thrombolysis. Cardiovasc Intervent Radiol 2014; 37:412–419. 16. Nicolaides AN, Hussein MK, Szendro G, et al. The relation of venous ulceration with ambulatory venous pressure measurements. J Vasc Surg 1993; 17:414–419. 17. Enden T, Haig Y, Klow N, et al. Long-term outcomes after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet 2012; 379:31–38. 18. Dasari TW, Pappy R, Hennebry TA. Pharmacomechanical thrombolysis of acute and chronic symptomatic deep vein thrombosis: a systematic review of literature. Angiology 2012; 63:138–145. 19. Sharifi M, Bay C, Skrocki L, Lawson D, Mazdeh S. Role of IVC filters in endovenous therapy for deep venous thrombosis: the FILTER-PEVI (Filter Implantation to Lower Thromboembolic Risk in Percutaneous Endovenous Intervention) trial. Cardiovasc Intervent Radiol 2012; 35:1408–1413. 20. Engelberger RP, Fahrni J, Willenberg T, et al. Fixed low-dose ultrasound-assisted catheter-directed thrombolysis followed by routine stenting of residual stenosis for acute ilio-femoral deep-vein thrombosis. Thromb Haemost 2014; 111:1153–1160.
Pharmacomechanical Thrombolysis of Symptomatic Acute and Subacute Deep Vein Thrombosis with a Rotational Thrombectomy Device Cüneyt Köksoy, MD, M. Fatih Yilmaz, MD, H. Serdar Bas¸buğ, MD, Eyüp Serhat Çalik, MD, Bilgehan Erkut, MD, Mehmet Ali Kaygın, MD, Ahmet Peker, MD, and Umman N. Sanlıdilek, MD
ABSTRACT Purpose: To retrospectively evaluate the efficacy and safety of pharmacomechanical thrombolysis (PMT) with the use of a rotational thrombectomy device for symptomatic deep vein thrombosis (DVT). Materials and Methods: Between July 2012 and August 2013, 41 patients with acute or subacute DVT underwent PMT. The Cleaner thrombectomy device was used in a single-session technique for patients with lower-extremity DVT. Based on contrast venography, the extent of lysis was graded from I (o 50%) to III (complete). Results: Sixteen patients (39.0%) had a femoropopliteal thrombosis and 25 (61.0%) had an iliofemoral venous thrombosis. The mean duration of symptoms was 11.0 days (range, 3–25 d). The mean quantity of tissue plasminogen activator was 20.7 mg (range, 10–50), and the mean duration of the procedure was 74.3 minutes (range, 30–240 min). At the end of the PMT procedure, 29 patients (70.7%) had complete (grade III) thrombus resolution. Grade I and II lysis were noted in one (2.4%) and 11 (26.8%) patients, respectively. Thirty-eight of the 41 patients were treated with PMT in a single session, and three (7.3%) required an additional lytic infusion as a result of residual thrombi. The overall grade III, II, and I thrombus resolution rates, including the supplemental thrombolysis, were 73.2% (n ¼ 30), 22.0% (n ¼ 9), and 4.9% (n ¼ 2), respectively. There was no mortality. Conclusions: Use of the Cleaner thrombectomy device is a promising alternative to current treatment modalities for the management of DVT in a single session of PMT.
ABBREVIATIONS CDT = catheter-directed thrombolysis, DVT = deep vein thrombosis, IVC = inferior vena cava, PMT = pharmacomechanical thrombolysis, PTS = postthrombotic syndrome, TPA = tissue plasminogen activator
Deep vein thrombosis (DVT) affects a significant proportion of the population, many of whom go on to develop postthrombotic syndrome (PTS) (1). During the past decade, PMT has emerged as an effective alternative to open surgical thrombectomies and
From the Division of Vascular Surgery (C.K.) and Department of Radiology (A.P., U.N.S.), Ankara University, Ankara; Department of Cardiovascular Surgery (M.F.Y.), Kayseri Training and Research Hospital, Kayseri; Department of Cardiovascular Surgery (H.S.B.), Kafkas University, Kars; and Department of Cardiovascular Surgery (E.S.C., B.E., M.A.K.), Erzurum Training and Research Hospital, Erzurum, Turkey. Received May 4, 2014; final revision received and accepted August 18, 2014. Address correspondence to C.K., Tunalı Hilmi Cad. 91/109, Kavaklıdere 06700, Ankara, Turkey; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2014 J Vasc Interv Radiol 2014; XX:]]]–]]] http://dx.doi.org/10.1016/j.jvir.2014.08.018
catheter-directed thrombolysis (CDT) in patients with acute DVT (2). Pharmacomechanical approaches have been suggested as viable and possibly preferable approaches to the management of acute DVT (3). Although several observational studies have demonstrated the successful implementation of PMT (4–6), no multicenter, randomized controlled trials have yet demonstrated the long-term effects of this therapy. Several PMT devices have been developed during the past two decades (5–7). The Cleaner thrombectomy device (Argon Medical Devices, Plano, Texas) is a battery-operated percutaneous mechanical thrombectomy catheter that functions by spinning a flexible “S”shaped guide wire within the vessel to be treated (Fig 1). This function allows the clot to be macerated and aspirated through an introducer sheath. Information about the efficacy of this device is limited. Therefore, the aim of the present study was to evaluate the efficacy
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Figure 1. The Cleaner thrombectomy device. (Available in color online at www.jvir.org.)
and safety of pharmacomechanical thrombectomies performed with the use of this rotational thrombectomy device for the treatment of DVT.
MATERIALS AND METHODS Patients Following institutional review board approval, consecutive patients who underwent PMT with recombinant tissue plasminogen activator (TPA) for a symptomatic lower-extremity DVT over a 1-year period between July 2012 and August 2013 were identified from one clinical database combined from four nationwide centers. The records were retrospectively reviewed for demographic data, indications for treatment, periprocedural complications, clinical outcomes, and follow-up with duplex ultrasound (US) imaging, and reporting was done in accordance with the Society of Interventional Radiology (SIR) reporting standards for the endovascular treatment of lower-extremity DVT (8). Based on these criteria, symptom duration was defined as acute (r 14 d), subacute (15–28 d), or chronic (4 28 d). Records of 41 symptomatic patients with acute or subacute lower-extremity DVT were reviewed. All patients had leg swelling, pain, or symptoms related to phlegmasia cerulea dolens. The patients consisted of 29 men and 12 women, with a mean age of 54.9 years ⫾ 19.6 (range, 17–84 y). The initial diagnosis of DVT was made in all patients with venous duplex imaging. The definitive delineation of the extent of the involved venous segments was established by venography at the time of intervention. To be included in the study, patients required first-time verified acute or subacute symptomatic DVT involving the femoropopliteal, iliofemoral, or iliocaval segments. The criteria excluded patients who were not 16–85 years of age; patients with an upper-extremity thrombosis, established PTS, severe renal failure, or active gastrointestinal bleeding; patients who could not receive tPA or anticoagulation therapy; terminally ill patients; and patients with contraindications to thrombolytic treatment, such as hemorrhagic stroke or other intracranial diseases, recent (o 10 d) major trauma or surgery, pregnancy, recent obstetric delivery, bleeding disorder, and prolonged traumatic cardiopulmonary resuscitation. Patients who did not meet the inclusion did not undergo PMT.
Before the procedure, a retrievable inferior vena cava (IVC) filter (Option retrievable vena cava filter; Argon Medical Devices) was placed via contralateral femoral or internal jugular vein access. Under local anesthesia, a percutaneous 6-F sheath was placed in an antegrade fashion into the popliteal or posterior tibial vein under US guidance. Unfractionated heparin was administered into a peripheral vein, with a target of two- to threefold activation of the partial thromboplastin to provide anticoagulation at the lytic site and in the systemic circulation. Venography was performed, and the location of the thrombus was established. Then, a 6-F Cleaner thrombectomy device was inserted through the introducer sheath. A recombinant form of TPA (alteplase; Actilyse; Boehringer Ingelheim, Ingelheim am Rhein, Germany) was delivered through the side port of the device. The device was activated to spin the S-shaped wire, which was then advanced in an antegrade fashion (Fig 2). Following a 2–5-minute thrombolysis, the device was deactivated and temporarily withdrawn. The macerated thrombus and residual lytic agent were suctioned through the sheath, and control venograms were obtained to evaluate the treated segments. The device was then reinserted and repositioned into the upper thrombosed segment. Thrombolysis was performed in a segmental antegrade fashion. The most cranial portion was lysed last to prevent the embolization of a thrombus fragment. The vein was treated in approximately 5–10-cm intervals by injecting 10 mL of saline solution containing 1 mg of the TPA solution for 2–5 minutes; the rate depended on the patient’s condition and weight and the size of the thrombus. This procedure was repeated until the end of the thrombus was reached. Finally, the device was removed, and a completion venogram was obtained. When the extent of the thrombus resolution was less than 50% of the occluded segment, the device was reinserted and activated for an additional pass. If the control venogram revealed a residual occluding or significantly obstructing thrombus after the second or third pass, the procedure was terminated or a 4-F infusion catheter (Cragg McNamara valved infusion catheter; ev3, Irvine, California) was inserted, and an infusion of 1 mg/h TPA was initiated for 24 hours. Percutaneous transluminal angioplasty and venous stent placement were performed selectively to treat underlying severe stenoses or nonresponding iliocaval obstructions. If there was a significant compression of the left common iliac vein or if there was severe stenosis as a result of a residual thrombus that could not be removed with the device or a following CDT in the iliac veins or the IVC, self-expanding stents were placed. With use of the same access, large (16–18 mm in diameter) Wallstents (Boston Scientific, Natick, Massachusetts) were placed with at least 1–2 cm at the stent joints after predilation to normal vein caliber for the location.
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Figure 2. (a) Initial venogram of the left leg demonstrates extensive femoral venous thrombosis (prone position, arrows indicate thrombus). The patient was subsequently treated with the Cleaner device (b). Final image demonstrates a patent femoral vein with no residual thrombus and good flow (c).
Following the interventional therapy, all patients continued to receive subcutaneous low molecular weight heparin, with a subsequent conversion to oral warfarin. The therapy was adjusted to attain an International Normalized Ratio in the range of 2–3. The retrievable IVC filters were removed within 1 month. Posttreatment duplex US imaging of the affected leg was performed at weekly intervals for 1 month and then monthly thereafter. Study endpoints were the extent of clot lysis, major bleeding, and pulmonary emboli during PMT and DVT evolution during follow-up. Postinterventional venography was performed, and the venograms were graded for the quantity of the thrombus extraction compared with the venograms from before and after the treatment by the same interventionalist who performed the procedure. The extent of the lysis was graded from I to III. Grade III lysis was defined as the complete resolution of the thrombus on a visual assessment of the venogram (9). Grades II and I lysis were defined as an extent of thrombus resolution of 50%–99% and less than 50%, respectively. After the completion venogram, a final IVC venogram was obtained to search for thrombi trapped in the IVC filter. Before discharge, a clinical evaluation and duplex US were performed on the treated vein segments.
Complication Definitions According to SIR reporting standards (8), major bleeding was defined as intracranial bleeding or bleeding severe enough to result in death, surgery, cessation of therapy, or blood transfusion. Minor bleeding was
defined as less severe bleeding that was manageable with local compression, sheath upsizing, or dose alterations of a pharmacologic thrombolytic agent, anticoagulant, or antiplatelet drug.
Follow-up Assessments The efficacy outcome assessments were conducted by using duplex US at follow-up. The valve function was not examined routinely. Recurrent DVT and pulmonary embolisms were recorded during follow-up. After 3 months, the PTS was assessed per the Villalta scale (10), which includes five symptoms (pain, cramps, heaviness, pruritus, and paresthesia) and six objective signs (edema, skin induration, hyperpigmentation, venous ectasia, redness, and pain during calf compression). Each symptom or sign was rated as 0 (absent), 1 (mild), 2 (moderate), or 3 (severe). The points were then added to determine the total score. Scores of less than 5 indicated the absence of PTS, scores of 5–9 indicated mild PTS, scores of 10–14 indicated moderate PTS, and scores greater than 15 or ulceration indicated severe PTS (11). Statistical analysis was performed by using (SPSS software (version 18.0; IBM, Armonk, New York). Continuous data are reported as means ⫾ standard deviation. Nominal data are reported as the number of subjects. Student t test was used to compare the mean differences between the two groups. Frequencies of complete thrombus removal and PTS were compared by χ2 test. A P value o .05 was considered statistically significant.
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RESULTS The mean symptom duration was 11.0 days ⫾ 6.0 (range, 3–25 d). Eight patients (19.5%) had subacute symptoms (ie, 4 14 d). Phlegmasia cerulea dolens was noted in three patients (7.3%). The thrombosis was on the left side in 23 patients (56.1%). Sixteen patients (39.0%) had a femoropopliteal thrombosis, and 25 (61.0%) had an iliofemoral venous thrombosis. The patients were taken to the angiography suite within 48 hours ⫾ 12 of presentation. A retrievable IVC filter was inserted in all but one patient. The access site for PMT was the posterior tibial vein in one patient and the popliteal vein in all other patients. The mean amount of TPA infused was 20.7 mg ⫾ 11.3 (range, 10– 50 mg), and the mean procedure duration was 74.3 minutes ⫾ 44.5 (range, 30–240 min). Iliocaval stent placement was required in two of the 25 patients with an iliofemoral thrombosis (8%). Thirty-eight of the 41 patients were treated in a single session, and three (7.3%) required an additional lytic infusion for 24 hours as a result of residual thrombi. There were no device failures or adverse events associated with the device.
Effect of PMT on Venous Patency At the end of the single-session PMT procedure, lysis of more than 50% was obtained in 40 patients (97.6%). Twenty-nine patients (70.7%) had a complete (ie, grade III) thrombus resolution. Grades II and I lysis were noted in 11 (26.8%) and one (2.4%) patient, respectively. There was an inverse relationship between the duration of symptoms and the degree of lysis (Table). Following supplemental CDT, the overall grade III, II, and I thrombus resolution rates were 73.2% (n ¼ 30), 22.0% (n ¼ 9), and 4.9% (n ¼ 2), respectively. Immediate clinical improvement was observed in 39 patients (95.1%). Limb salvage was achieved in all three patients who presented with phlegmasia cerulea dolens. The duplex US imaging performed before discharge demonstrated patent veins in 38 patients (92.7%). There was an association between the success of PMT and inhospital recurrent thrombosis. Only one of the 29
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patients with complete thrombus resolution after PMT (3.4%) experienced recurrent thrombosis. However, the recurrent thrombosis rates for patients with grade I or II resolution were 100% (n ¼ 1) and 9.1% (one of 11), respectively (P o .05). Four patients with patent iliocaval venous systems (9.8%) showed recurrent femoral vein thrombosis while in the hospital. No further intervention was performed for these patients. The mean follow-up was 3.8 months ⫾ 3.1 (range, 2–12 mo). The final clinical and imaging studies at the last follow-up visit revealed patent veins in 39 patients (95.1%). Duplex US imaging also showed that the iliac stents in two patients were patent. Two patients had occlusions of the femoral vein without recurrent symptoms.
Complications No periprocedural deaths or symptomatic pulmonary embolisms occurred. After completion venography, the final IVC venogram revealed no trapped thrombi in the IVC filter. There were no systemic bleeding complications. Minor bleeding at the access site occurred in six patients (14.6%). Major bleeding caused by an access hematoma developed in one patient (2.4%), who required a blood transfusion. This patient underwent concomitant iliac vein stent placement with the use of a 10-F sheath at the popliteal vein after several failed puncture attempts, and a popliteal hematoma and bleeding developed as a result of the very short period of compression at the popliteal access site.
Effect of PMT on Postthrombotic Symptoms Twenty-nine patients had at least 3 months of follow-up. At 3 months, the average Villalta score as a measure of PTS was 2.68 ⫾ 1.4 (range, 1–5). Based on the Villalta score, no PTS was observed in 21 patients (72.4%), and mild PTS was observed in eight patients (27.6%). None of the patients had moderate PTS. There was no difference in Villalta score between patients with acute and subacute DVT (2.47 ⫾ 1.4 vs 3.2 ⫾ 1.2, respectively; P ¼ .17). There was also no relationship between the PTS category based on the Villalta scores and the duration of symptoms at admission (Table).
Table . Effects of Symptom Duration at Admission on Degree of Clot Lysis and PTS Category Parameter
Acute DVT
Subacute DVT
Grade III Grade II
26 (78.8) 6 (18.2)
3 (37.5) 5 (62.5)
Grade I
1 (2.4)
0
16 (76.2)
5 (62.5)
5 (23.8)
3 (37.5)
Extent of lysis
PTS category None Mild
P Value .03
.46
Values in parentheses are percentages. DVT ¼ deep vein thrombosis, PTS ¼ postthrombotic syndrome.
DISCUSSION Without effective therapy, many patients with DVT experience persistent venous obstruction and deep venous reflux, both of which are known to contribute to the development of PTS. In view of the suboptimal long-term results of anticoagulation therapy alone, catheter-based techniques have been employed to decrease the thrombus burden and to correct the underlying obstructions when present (4). The present study demonstrates the safety and efficacy of pharmacomechanical thrombectomy in the treatment of
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symptomatic DVT with the use of a new rotational PMT device. With the use of this device, a greater than 50% thrombus resolution was achieved in 97.6% of patients, without significant morbidity, in a single-session procedure. This rate is comparable with the success rates reported by others (4,12,13). In a retrospective study of patients receiving CDT (14), patients who had greater than 50% clot removal with CDT experienced a reduced PTS and better quality of life than patients whose CDT did not achieve substantial clot removal (14). The successful use of PMT has been described in a number of published observational DVT studies but not in any multicenter randomized trials to our knowledge. In the present series, the treatment of lower-extremity DVT with single-session rotational PMT resulted in promising primary success with minimal rates of complications. Achievement of grade III lysis is considered the optimal result, and was achieved in 70.7% of patients. Additional CDT in two patients who had grade II lysis with single-session PMT resulted in a complete lysis in one patient and less than 50% thrombus resolution in the other patient. Worsening of thrombus resolution with additional CDT in this patient may be related to a short (24 h) CDT treatment time. In the present series, 19.5% of patients had subacute (4 2 wk) DVT, with the oldest DVT treated being 25 days. The time frame from DVT onset to the initiation of PMT may play a role in successful thrombolysis. The successful thrombolysis of an acute DVT is most likely to be achieved in patients with recently formed thrombi, as evidenced by a DVT symptom duration of fewer than 10–14 days (9). Grade III lysis was achieved in 78.8% of our patients with acute DVT (o 2 wk). It is generally accepted that treatment of subacute DVT has a lower technical success rate, as demonstrated in the present results. In the setting of subacute DVT, grade III lysis was obtained in 37.5% of our patients. A symptom duration of greater than 10 days has been reported to result in a low rate of complete thrombolysis and in infrequent treatment failures with less than 50% thrombus removal (15). One of the most important permanent sequelae of DVT is PTS (1). The predictors of the development of PTS are only partially understood. However, the final physiologic pathway leading to PTS appears to involve the development of ambulatory venous hypertension, which is caused by venous obstruction and valvular reflux following DVT (16). Therefore, the elimination of venous obstruction is an important step in the prevention of PTS. In addition to several case series, a randomized trial by Enden et al (17) demonstrated that the use of CDT was associated with a 28% relative reduction in the risk of PTS over a 2-year follow-up period. As we did not have a control group and had a very short follow-up period, we did not observe the beneficial effects of PMT on postthrombotic symptoms. Bleeding is a feared complication of thrombolysis. PMT offers a reasonable solution in patients with venous
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thromboembolisms and is associated with a lower risk of bleeding. Major bleeding is estimated to occur in 2%–4% of patients receiving CDT (2). We did not encounter any systemic bleeding complications. Minor bleeding at the access site occurred in 14.6% of patients, but only one additional patient with an access-site hematoma required a transfusion. Therefore, the rate of major bleeding episodes for this treatment modality was 2.4%. A retrospective study by Rao et al (12) demonstrated that thrombolytic agent doses and infusion durations were reduced with PMT compared with conventional CDT. No major bleeding complications were reported in a systematic literature review of 2,528 patients with DVT treated with PMT (18). PMT may also decrease the risk of hemorrhagic complications because of its shorter infusion intervals and lower doses of thrombolytic agents, making it a more attractive modality in highrisk cases in postoperative patients. However, PMT is not free from bleeding complications. The total lytic agent amount is greater with CDT that lasts 2 days or longer. However, during the 1–2-hour PMT procedure, the dose of thrombolytic agent is higher. In other words, in the present study, 20.7 mg (range, 10–50 mg) TPA was used during 74.3 minutes (range, 30–240 min) of the procedure, and, because PMT involves a higher dose in a short period of time, there is a potential bleeding risk. The placement of a prophylactic IVC filter before thrombolytic procedures is still under debate. In the present series, we attempted to use IVC filters in almost all patients and did not diagnose any symptomatic pulmonary embolisms. In a large prospective registry of 473 patients with proximal DVT undergoing infusion CDT (without percutaneous mechanical thrombectomy) (9), symptomatic pulmonary embolisms occurred in only six patients (1.3%), one of whom died (0.2%). The relative rarity of a major pulmonary embolism in CDT recipients may partially arise from the ability of the thrombolytic drug to quickly dissolve any circulating thrombus fragments. However, for patients being treated with PMT methods, which can involve more clot manipulation, a major pulmonary embolism can occur iatrogenically (4). The recently published Filter Implantation To Lower Thromboembolic Risk in Percutaneous Endovascular Intervention trial (19) demonstrated that IVC filter implantation during endovenous procedures reduces the risk of iatrogenic pulmonary embolism eightfold, without a mortality benefit. We used iliac stents for only two of the 25 patients with an iliofemoral venous thrombosis (8%). Both of these patients had iliac vein compression that was resistant to lytic therapy. Although most interventionalists use venous stent deployment liberally during thrombolysis, we are aware of no prospective randomized trial supporting the use of iliac venous stent placement in the endovascular management of venous thrombosis. There are also conflicting data regarding the efficacy of the concomitant use of stents during
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thrombolysis (9,17). No specific recommendations for stent placement are given in the SIR reporting standards for endovascular treatment of lower-extremity DVT (8). As there are no existing criteria that indicate additive stent implantation during CDT for iliofemoral DVT, we limited ourselves to concomitant stent deployment during PMT. The present study has several limitations, including the nature of a retrospective analysis of one combined database, the small number of patients, and a heterogeneous study population in terms of the duration of symptoms and the locations of the thrombi, as well as the limited use of adjunctive balloon dilation and stent placement. After 3 months, PTS was assessed based on the Villalta scale, an easily applied measure that includes patient-reported symptoms and physician-assessed signs of venous disease. Although a 3-month period may be too soon for the evaluation of PTS, 3-month Villalta scales have been used by others (20). Conversely, the mean follow-up of the study is too short to evaluate a problem such as PTS, which develops over a number of years. During the follow-up duplex examinations, we did not attempt to record venous valve function, focusing instead on the veins’ patency. In summary, based on the present data, use of the Cleaner thrombectomy device may prove to be a safe and feasible single-session PMT method for the treatment of acute DVT in broader patient populations, and warrants further investigation in large-scale studies.
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5. O’Sullivan GJ, Lohan DG, Gough N, Cronin CG, Kee ST. Pharmacomechanical thrombectomy of acute deep vein thrombosis with the Trellis-8 isolated thrombolysis catheter. J Vasc Interv Radiol 2007; 18:715–724. 6. Cynamon J, Stein EG, Dym J, et al. A new method for aggressive management of deep vein thrombosis: Retrospective study of the power pulse technique. J Vasc Interv Radiol 2006; 17:1043–1049. 7. Baker R, Samuels S, Benenati JF, Powell A, Uthoff H. Ultrasoundaccelerated vs standard catheter-directed thrombolysis—a comparative study in patients with iliofemoral deep vein thrombosis. J Vasc Interv Radiol 2012; 23:1460–1466. 8. Vedantham S, Grassi CJ, Ferral H, et al. Reporting standards for endovascular treatment of lower extremity deep vein thrombosis. J Vasc Interv Radiol 2009; 20(suppl):S391–S408. 9. 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. 10. Kahn SR, Partsch H, Vedantham S, et al. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009; 7:879–883. 11. Strijkers RH, Wittens CH, Kahn SR. Villalta scale: goals and limitations. Phlebology 2012; 27(suppl 1):130–135. 12. Rao AS, Konig G, Leers SA, et al. Pharmacomechanical thrombectomy for iliofemoral deep vein thrombosis: an alternative in patients with contraindications to thrombolysis. J Vasc Surg 2009; 50:1092–1098. 13. Chaudhry MA, Pappy R, Hennebry TA. Use of the trellis device in the management of deep vein thrombosis: a retrospective single-center experience. J Invasive Cardiol 2013; 25:296–299. 14. Grewal NK, Martinez JT, Andrews L, Comerota AJ. Quantity of clot lysed after catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with postthrombotic morbidity. J Vasc Surg 2010; 51:1209–1214. 15. Park SI, Lee M, Lee MS, Kim MD, Won JY. Lee do Y. Single-session aspiration thrombectomy of lower extremity deep vein thrombosis using large-size catheter without pharmacologic thrombolysis. Cardiovasc Intervent Radiol 2014; 37:412–419. 16. Nicolaides AN, Hussein MK, Szendro G, et al. The relation of venous ulceration with ambulatory venous pressure measurements. J Vasc Surg 1993; 17:414–419. 17. Enden T, Haig Y, Klow N, et al. Long-term outcomes after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet 2012; 379:31–38. 18. Dasari TW, Pappy R, Hennebry TA. Pharmacomechanical thrombolysis of acute and chronic symptomatic deep vein thrombosis: a systematic review of literature. Angiology 2012; 63:138–145. 19. Sharifi M, Bay C, Skrocki L, Lawson D, Mazdeh S. Role of IVC filters in endovenous therapy for deep venous thrombosis: the FILTER-PEVI (Filter Implantation to Lower Thromboembolic Risk in Percutaneous Endovenous Intervention) trial. Cardiovasc Intervent Radiol 2012; 35:1408–1413. 20. Engelberger RP, Fahrni J, Willenberg T, et al. Fixed low-dose ultrasound-assisted catheter-directed thrombolysis followed by routine stenting of residual stenosis for acute ilio-femoral deep-vein thrombosis. Thromb Haemost 2014; 111:1153–1160.
