Catheter-Directed and Pharmacomechanical Thrombolysis for the Treatment of Acute Iliofemoral Deep Venous Thrombosis
- Volume 6 - Issue 3 - May/June 2009
- Posted on: 6/5/09
- 1 Comments
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Anthony J. Comerota, MD, FACS, FACC, Nina Grewal, MD
Quality-of-life results were directly related to the initial success of thrombolysis. Patients with successful thrombus resolution reported a significantly better health utilities index, improved physical functioning, less stigma of CVD, reduced health distress, and fewer overall postthrombotic symptoms. Patients in whom catheter-directed thrombolysis failed had similar outcomes to patients treated with anticoagulation alone. These efficacy data combined with the observed reduction in complications with intrathrombus infusion of plasminogen activators offer a sound argument for the management of patients with iliofemoral DVT with catheter-directed thrombolysis. Subsequently, a randomized trial was performed by Elshawary et al,27 comparing catheter-directed thrombolysis to anticoagulation alone. These authors demonstrated that catheter-directed thrombolysis resulted in significantly better outcomes at 6 months. This was measured by restoration of patency of 72% in lytic group versus 12% in the anticoagulation-only group and by evidence of venous reflux in 11% of patients lysed versus 41% of patients receiving anticoagulation alone.
Assuming patients are properly managed with anticoagulation, thereby avoiding recurrent DVT, this 6-month observation should reflect their long-term outcome.
Now that it has been established that catheter-directed thrombolysis can be performed safely with minimal systemic complications, the next question becomes whether the risk of bleeding complications may be further decreased. An interesting therapeutic approach was reported by Chang et al28 when they used repeated intrathrombus bolus dosing of rt-PA in 12 lower extremities of 10 patients with acute DVT. They infused rt-PA intrathrombus using the pulse-spray technique and no more than 50 mg per treatment. Following the pulse-spray bolus, patients were returned to their rooms and brought back the following day for repeat phlebographic evaluation and repeat infusion, if necessary. Treatment was repeated up to four times. Eleven of the 12 extremities had significant or complete lysis and one had 50–75% lysis. Although the average total dose of rt-PA was 106 mg, bleeding complications were minor, and no patient dropped their hematocrit more than 2%. This intriguing technique deserves further study to evaluate its applicability to the general population of DVT patients.
Preserving venous valve function and luminal patency is the goal of all strategies of thrombus removal for acute DVT. Generally, the preferred method has been catheter-directed thrombolysis, but adding mechanical methods as an adjunct to catheter-directed lytic therapy is quickly setting a new standard for catheter-based treatment of acute DVT.29–31 However, using percutaneous mechanical thrombectomy alone is less successful than catheter-directed thrombolysis, and there appears to be a higher incidence of embolic complications with mechanical thrombectomy. In a prospective evaluation of pulse-spray pharmacomechanical thrombolysis of clotted hemodialysis grafts,32 it was found that PE (documented by ventilation perfusion scan) occurred in 18% of patients treated with a plasminogen activator pulse-spray solution versus 64% of patients treated with a heparinized saline pulse-spray solution (P = .04). Since clotted hemodialysis grafts are in direct communication with the venous circulation, they can be considered similar to proximal veins with acute DVT treated with mechanical thrombus disruption alone (in terms of embolic potential). Observations would likely be magnified when treating larger venous thromboses. This is an important concept, suggesting that mechanical intervention without protection and without adding plasminogen activators will increase the risk of embolization.
This concept was reinforced by Greenberg et al,33 who, in an experimental model, evaluated mechanical, pharmacomechanical, and pharmacologic thrombolysis. Their findings, consistent with anecdotal clinical observations, as well as the results reported by Kinney et al,32 demonstrated that pulse-spray mechanical thrombectomy alone was associated with the largest number and greatest size of distal emboli. When urokinase was added to the pulse-spray solution, the embolic particles diminished in number and size and the speed of lysis increased while time-to-reperfusion shortened. Catheter-directed thrombolysis alone was associated with the slowest time-to-reperfusion but the fewest distal emboli. In general, mechanical thrombectomy alone is generally inadequate. Hemolytic complications of rheolytic mechanical thrombectomy are common and occasionally can result in anemia and renal dysfunction.
One of the more promising pharmacomechanical treatment options for patients with acute iliofemoral DVT is isolated segmental pharmacomechanical thrombolysis (ISPMT), which uses the Trellis Peripheral Infusion System (Bacchus Vascular, Santa Clara, California). The Trellis is a hybrid catheter that isolates the segment of thrombosed vein between two occluding balloons and infuses a small dose of a lytic agent into the target segment. The intervening catheter assumes a spiral configuration which, when activated, spins at approximately 1500 revolutions per minute for 15 to 20 minutes. Following aspiration of the liquefied and fragmented thrombus, the treated vein segment is re-evaluated and re-treated, if necessary. Once the vein is cleared of thrombus, the catheter is repositioned to treat the next thrombosed segments. Phlebographic evaluation of the result is performed before treating additional segments of the thrombosed vein.
1. O'Donnell TF, Browse NL, Burnand KG, Thomas ML. The socioeconomic effects of an iliofemoral venous thrombosis. J Vasc Surg 2008;48:1532–1537.
2. Akesson H, Brudin L, Dahlstrom JA, et al. Venous function assessed during a 5-year period after acute ilio-femoral venous thrombosis treated with anticoagulation. Eur J Vasc Surg 1990;4:43–48.
3. 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;239:118–126.
4. Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: ACCP evidence-based clinical practice guidelines (8th ed). Chest 2008;133:454S–545S.
5. Shull KC, Nicolaides AN, Fernandes E, et al. Significance of popliteal reflux in relation to ambulatory venous pressure and ulceration. Arch Surg 1979;114:1304–1306.
6. Johnson BF, Manzo RA, Bergelin RO, Strandness DE, Jr. 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;21:307–312.
7. Strandness DE, Jr., Langlois Y, Cramer M, et al. Long-term sequelae of acute venous thrombosis. JAMA 1983;250:1289–1292.
8. Beyth RJ, Cohen AM, Landefeld CS. Long-term outcomes of deep-vein thrombosis. Arch Intern Med 1995;155:1031–1037.
9. Cho JS, Martelli E, Mozes G, et al. Effects of thrombolysis and venous thrombectomy on valvular competence, thrombogenicity, venous wall morphology, and function. J Vasc Surg 1998;28:787–799.
10. Rhodes JM, Cho JS, Gloviczki P, et al. Thrombolysis for experimental deep venous thrombosis maintains valvular competence and vasoreactivity. J Vasc Surg 2000;31:1193–1205.
11. Killewich LA, Bedford GR, Beach KW, Strandness DE, Jr. Spontaneous lysis of deep venous thrombi: Rate and outcome. J Vasc Surg 1989;9:89–97.
12. Markel A, Manzo RA, Bergelin RO, Strandness DE, Jr. Valvular reflux after deep vein thrombosis: Incidence and time of occurrence. J Vasc Surg 1992;15:377–382.
13. Meissner MH, Manzo RA, Bergelin RO, et al. Deep venous insufficiency: The relationship between lysis and subsequent reflux. J Vasc Surg 1993;18:596–605.
14. Comerota AJ, Aldridge SE. Thrombolytic therapy for acute deep vein thrombosis. Semin Vasc Surg 1992;5:76–84.
15. Goldhaber SZ, Buring JE, Lipnick RJ, Hennekens CH. Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis. Am J Med 1984;76:393–397.
16. Plate G, Einarsson E, Ohlin P, et al. Thrombectomy with temporary arteriovenous fistula: The treatment of choice in acute iliofemoral venous thrombosis. J Vasc Surg 1984;1:867–876.
17. Plate G, Akesson H, Einarsson E, et al. Long-term results of venous thrombectomy combined with a temporary arterio-venous fistula. Eur J Vasc Surg 1990;4:483–489.
18. Plate G, Eklof B, Norgren L, et al. Venous thrombectomy for iliofemoral vein thrombosis —10-year results of a prospective randomised study. Eur J Vasc Endovasc Surg 1997;14:367–374.
19. Comerota AJ, Gale SS. Operative venous thrombectomy. In: Bergan JJ (Ed). The Vein Book. San Diego: Elsevier. 2006, pp. 405–416.
20. Alkjaersig N, Fletcher AP, Sherry S. The mechanism of clot dissolution by plasmin. J Clin Invest 1959;38:1086–1095.
21. Comerota AJ, Gravett MH. Iliofemoral venous thrombosis. J Vasc Surg 2007;46:1065–1076.
22. Bjarnason H, Kruse JR, Asinger DA, et al. Iliofemoral deep venous thrombosis: Safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy. J Vasc Interv Radiol 1997;8:405–418.
23. Mewissen MW, Seabrook GR, Meissner MH, et al. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: Report of a national multicenter registry. Radiology 1999;211:39–49.
24. Comerota AJ, Kagan SA. Catheter-directed thrombolysis for the treatment of acute iliofemoral deep venous thrombosis. Phlebology 2000;15:149–155.
25. Comerota AJ, Throm RC, Mathias SD, et al. Catheter-directed thrombolysis for iliofemoral deep venous thrombosis improves health-related quality of life. J Vasc Surg 2000;32:130–137.
26. Mathias SD, Prebil LA, Putterman CG, et al. A health-related quality of life measure in patients with deep vein thrombosis: A validation study. Drug Inf J 1999;33:1173–1187.
27. 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.
28. Chang R, Cannon RO III, Chen CC, et al. Daily catheter-directed single dosing of t-PA in treatment of acute deep venous thrombosis of the lower extremity. J Vasc Interv Radiol 2001;12:247–252.
29 Lee KH, Han H, Lee KJ, et al. Mechanical thrombectomy of acute iliofemoral deep vein thrombosis with use of an Arrow-Trerotola percutaneous thrombectomy device. J Vasc Interv Radiol 2006;17:487–495.
30. Cynamon J, Stein EG, Dym RJ, 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.
31. Vedantham S, Vesely TM, Sicard GA, et al. Pharmacomechanical thrombolysis and early stent placement for iliofemoral deep vein thrombosis. J Vasc Interv Radiol 2004;15:565–574.
32. Kinney TB, Valji K, Rose SC, et al. Pulmonary embolism from pulse-spray pharmacomechanical thrombolysis of clotted hemodialysis grafts: Urokinase versus heparinized saline. J Vasc Interv Radiol 2000;11:1143–1152.
33. Greenberg RK, Ouriel K, Srivastava S, et al. Mechanical versus chemical thrombolysis: An in vitro differentiation of thrombolytic mechanisms. J Vasc Interv Radiol 2000;11:199–205.
34. Martinez J, Comerota AJ, Kazanjian S, et al. The quantitative benefit of isolated, segmental, pharmacomechanical thrombolysis for iliofemoral DVT. J Vasc Surg 2008: In press.
35. Steffen W, Fishbein MC, Luo H, et al. High intensity, low frequency catheter-delivered ultrasound dissolution of occlusive coronary artery thrombi: An in vitro and in vivo study. J Am Coll Cardiol 1994;24:1571–1579.
36. Rosenschein U, Gaul G, Erbel R, et al. Percutaneous transluminal therapy of occluded saphenous vein grafts: Can the challenge be met with ultrasound thrombolysis? Circulation 1999;99:26–29.
37. Tachibana K, Tachibana S. Ultrasound energy for enhancement of fibrinolysis and drug delievery: Special emphasis on the use of a transducer-tipped ultrasound system. In: Siegel RJ (Ed). Ultrasound Angioplasty. Boston: Kluwer. 1996. pp. 121–133.
38.Tachibana K, Tachibana S. Prototype therapeutic ultrasound emitting catheter for accelerating thrombolysis. J Ultrasound Med 1997;16:529–535.
39. Trubestein G, Engel C, Etzel F, et al. Thrombolysis by ultrasound. Clin Sci Mol Med Suppl 1976;3:697s–698s.
40. Ariani M, Fishbein MC, Chae JS, et al. Dissolution of peripheral arterial thrombi by ultrasound. Circulation 1991;84:1680–1688.
41. Rosenschein U, Bernstein JJ, DiSegni E, et al. Experimental ultrasonic angioplasty: Disruption of atherosclerotic plaques and thrombi in vitro and arterial recanalization in vivo. J Am Coll Cardiol 1990;15:711–717.
42. Lauer CG, Burge R, Tang DB, et al. Effect of ultrasound on tissue-type plasminogen activator-induced thrombolysis. Circulation 1992;86:1257–1264.
43. Hong AS, Chae JS, Dubin SB, et al. Ultrasonic clot disruption: An in vitro study. Am Heart J 1990;120:418–422.
44. Drobinski G, Brisset D, Philippe F, et al. Effects of ultrasound energy on total peripheral artery occlusions: Initial angiographic and angioscopic results. J Interv Cardiol 1993;6:157–163.
45. Atar S, Luo H, Nagai T, Siegel RJ. Ultrasonic thrombolysis: Catheter-delivered and transcutaneous applications. Eur J Ultrasound 1999;9:39–54.
46. EKOS Corporation, Bothell, WA. Retrospective evaluation of thrombolysis with EKOS Lysus System. 2005.
47. Martinez J, Paolini D, Comerota AJ. Chest and abdominopelvic CT scans are important tools for evaluating patients with iliofemoral venous thrombosis. Presented at Peripheral Vascular Surgery Society, San Diego 2008.
48. Comerota AJ, Paolini D. Treatment of acute iliofemoral deep venous thrombosis: A strategy of thrombus removal. Eur J Vasc Endovasc Surg 2007;33:351–360.