Treating Proximal Deep Vein Thrombosis

An aggressive approach favors early thrombus removal to preserve outflow and function of the valves.

By Bo Eklof, MD, PhD, and Karthikeshwar Kasirajan, MD
 

To view all tables and figures related to this article, please refer to the print version our April 2003 issue, page 17.

There are few areas in vascular disease in which a conservative approach is more prevalent than in the management of venous disease. Acute venous thrombosis—regardless of localization—is usually treated with anticoagulants, even more so now after the advent of low-molecular-weight heparin. Chronic venous disease, whether due to primary or secondary (postthrombotic) etiology, with complications such as pain and ulceration, is usually treated with salves, bandages, and forced changes of lifestyle.
The objectives in treatment of proximal deep vein thrombosis (DVT) are to prevent:
• extension of the thrombus with subsequent pulmonary embolism, which will occur in >60% of patients with proximal DVT
• fatal pulmonary embolism
• progressive swelling of the leg and increased compartmental pressure, which can lead to phlegmasia cerulea dolens, venous gangrene, and limb loss
• severe postthrombotic syndrome (by preserving the venous outflow and valve function)
• chronic pulmonary hypertension.

PRESERVING VALVULAR FUNCTION
Data from various studies on the inflammatory response to DVT were recently presented at the 4th Pacific Vascular Symposium on Venous Disease in Honolulu. These studies demonstrated how the leukocyte adhesion molecule P-selectin activates the leukocytes emigrating into the venous wall, creating an inflammation that destroys the venous wall and the valves. Another study demonstrated in an experimental model that if the thrombus was removed early, the inflammatory changes were reversible.1 Previous studies have demonstrated that remaining thrombotic proximal occlusions in human leg veins will lead to progressive distal valvular incompetence.2 From these data, we can propose that it is imperative to remove the thrombus as early and completely as possible.3

Modern venous reconstructive surgery using valvuloplasty, which was pioneered by Robert Kistner, MD, can show good long-term results in primary venous disease with severe deep vein reflux, whereas the results of vein segment transfer and autologous vein transplantation in secondary (postthrombotic) venous disease are much less promising. It is, therefore, important to treat thrombosis of the leg early and successfully to avoid obstruction of the venous outflow tract and preserve valvular function in order to prevent the development of a severe postthrombotic syndrome.

In our Swedish prospective randomized study4,5,6 of patients with acute iliofemoral DVT, we compared anticoagulation with thrombectomy and temporary arteriovenous fistula. At the 5-year follow-up, we found that basically all patients who were treated conservatively with anticoagulants had developed venous hypertension with a combination of venous obstruction and reflux.

OPTIONS FOR EARLY THROMBUS REMOVAL
To avoid the sequelae of DVT with obstruction and reflux leading to venous hypertension with pain, swelling, and ulceration, one of the following options for early thrombus removal should be pursued:
• catheter-directed thrombolysis
• mechanical destruction of the thrombus with and
without thrombolysis
• thrombectomy.

Catheter-Directed Thrombolysis
My experience with thrombolysis goes back to the 1960s when we used streptokinase for flow-directed thrombolysis in Boras, Sweden. We treated a group of 12 patients by directing a catheter into the distal great saphenous vein at the ankle. We were able to follow-up with 11 of those patients: 8 had complete thrombolysis with normal looking valves. In the 1970s we treated 47 patients with systemic streptokinase at the University of Lund, Sweden with poor results: after 2.5 years follow-up, only 6% had normal venous function and were free from symptoms and signs of the postthrombotic syndrome.7,8

The new era of catheter-directed thrombolysis started at Stanford University with Semba and Dake, who between 1990 and 1993 treated 27 limbs in patients with iliofemoral DVT using urokinase (Abbokinase; Abbott Laboratories, Abbott Park, IL). These clinicians observed complete lysis in 18 of 25 limbs (72%).9 In 16 of 25 limbs they performed additional angioplasty and stenting. At 3 months postprocedure, 11 of 12 patients (92%) had continued patency of treated segments. Their work initiated the 1995 establishment of the National Venous Registry, in which 67 centers recruited patients with symptomatic DVT of the legs. The results were reported in 1999 by Mewissen et al.10 Three hundred three limbs in 287 patients were treated with catheter-directed thrombolysis using urokinase. Mortality was 0.4%: one fatal PE and one intracranial bleed. Major bleeds in 11% of the patients. Complete lysis was obtained in 31% of the patients, 50% to 99% lysis in 52% of the patients, and <50% lysis in 17% of the limbs. A complete listing of the thrombolytic agents available today is set forth in Table 1.

Mechanical Thrombectomy Devices for DVT
Numerous percutaneous devices are currently available for clearing thrombus from clotted dialysis grafts. This accessibility has allowed the ?off-label? use of these devices for minimally invasive thrombus extraction in patients with extensive DVT. However, the use of the majority of these devices results in embolization of the macerated clot, and there is significant potential for endothelial and venous valve damage due to direct wall contact by the macerating component. Hence, effective thrombus aspiration (not embolization) with minimal endothelial damage must be the key features of any mechanical thrombectomy device that can be successfully used to treat patients with extensive, symptomatic DVT. Two such devices have had the most widespread use for treating DVT.
The Angiojet catheter (Possis Medical, Minneapolis, MN) consists of a pump-drive, a pump-set, a choice of catheters (Xpeedior [6F/0.035-inch], XVG [5F/0.014-inch]), and a collection bag. The catheter works by redirecting saline that is pumped from the drive-unit at 10,000 psi back toward the evacuation lumen (Figure 1). Unlike various other thrombectomy devices, the Angiojet catheter is not a wall-contact device, and it results in effective thrombus removal. Results from a multicenter registry are given in Table 2. Other devices that similarly use the Venturi effect of fluid jets have not gained widespread clinical use because the lower pressure (800 psi from standard power injectors) they use to drive the saline results in a much weaker suction vortex.

The Trellis device (Bacchus Vascular, Santa Clara, CA) consists of a lytic infusion catheter with a proximal and distal occlusion balloon. The balloons protect against release of thrombotic debris and help isolate the thrombolytic agent within the selected treatment zone. A hand-held motor drive unit oscillates the sine-shaped dispersion wire (the dispersion wire replaces the 0.035-inch guidewire) and helps accelerate the speed of thrombus dissolution (Figure 2). The dissolved thrombus is then aspirated via an integrated aspiration port. Results of a retrospective registry are given in Table 1. Although this device requires the use of thrombolytic agents, in the multicenter registry, 6 of 20 patients with significant bleeding risks did not have any exacerbation of their bleeding potential, because the lytic agent is localized by the integrated occlusion balloons. The occlusion balloons also help prevent the risk of pulmonary embolism (PE) during device use. Fortunately, the risk of PE related to use of mechanical thrombectomy devices seems to be insignificant. In the Angiojet registry, only 23% of patients had an inferior vena cava filter, but no PE was clinically observed. All complications were minor in both device registries and did not require any additional therapy.

The Fino device (Bacchus Vascular, Santa Clara, CA) is the only product currently being evaluated in a prospective clinical trial for patients with extensive lower-extremity DVT. The device consists of an outer protective nitinol basket to prevent wall contact of the inner macerating nitinol wire. Thrombus aspiration is performed concomitant with the maceration via a sheath that has an inner Archimedes screw that helps direct the liquefied clot to the collection syringe (Figure 3). Results of the trial are not yet available.

Mechanical devices may have a significant role to play in the minimally invasive treatment of DVT aimed at active thrombus removal. Numerous trials have established that patients report a better quality of life after aggressive therapy aimed at removing thrombus. However, the ideal means to achieving this awaits the results of numerous trials evaluating lytic therapy and mechanical devices.

Thrombectomy With a Temporary Arteriovenous Fistula
When there are contraindications or failure of catheter-directed thrombolysis, thrombectomy with a temporary arteriovenous fistula is a valid alternative.11 Both interventions should be followed by anticoagulation. The objectives of both interventions are to (1) restore patency of the femoroiliocaval segment; and (2) preserve the valves in the popliteo-femoral segment.

In a combined series of studies from Hawaii, Kuwait, and Sweden, the mortality of more than 300 patients was <1%, and no patient died from PE. 11 There are few studies on “long-term” results after thrombectomy with AVF. There are eight studies of clinical results in 521 patients with more than 2 years follow-up in which “clinical success” is claimed in 62% of the patients.11 There are five studies on iliac vein patency in 247 patients with more than 2 years follow-up, showing 82% patency.11 There are five studies on femoropopliteal valvular competence in 259 patients with more than 2 years follow-up showing 60% competency.11 In the prospective randomized study from Sweden, we found a highly significant patency of those veins in thrombectomized patients after 6 months, 5 years, and 10 years as set forth in Table 3.4,5,6

In addition, femoropopliteal valvular competence at 6 months was 52% in the surgical group compared with 26% in the conservatively treated group, using descending venography with Valsalva. After 5 years, the patients who underwent surgery had significantly lower ambulatory venous pressures, improved venous emptying (as shown by plethysmography), and a better calf pump function with less reflux (as measured by foot-volumetry). At 10 years using duplex scanning popliteal reflux was found in 32% in the surgical group compared with 67% in the conservative group. Six patients who had successful thrombectomy 10 years before without obstruction of the iliac vein at the time of surgery were all asymptomatic with patent iliac veins, and 50% had competent popliteal veins. Successful thrombectomy seems to be beneficial in the long term.4,5,6

CURRENT TREATMENT OF ACUTE ILIOFEMORAL DVT
In our opinion, early and quick removal of the thrombus is indicated to avoid the late postthrombotic syndrome in active patients with acute iliofemoral DVT. The first line of treatment should be catheter-directed thrombolysis with or without adjunct procedures, such as angioplasty and stenting. When there are contraindications or failure of thrombolysis, thrombectomy with a temporary AVF is a valid alternative. Both interventions will be followed by anticoagulation. These aggressive interventions are not justified in chronically ill, bedridden, high-risk, or aged patients, or those with serious intercurrent disease and/or limited life expectancy. In this group of patients these interventions can only be justified for limb salvage in phlegmasia cerulea dolens when conservative treatment does not prevent the development of an acute compartment syndrome with venous gangrene. 

Bo Eklof, MD, PhD, is a vascular surgeon at Straub Clinic and Hospital in Honolulu, Hawaii. Dr. Eklof holds no financial interest in any of the companies mentioned herein. He may be reached at (808) 522-3293; beklof@straub.net.

Karthikeshwar Kasirajan, MD, is an assistant professor, Vascular Surgery Division, University of New Mexico Health Science Center, Albuquerque, New Mexico. He is a consultant for Bacchus and Possis. Dr. Kasirajan may be reached at (505) 272-5850; kkasirajan@saludo.unm.edu.

1. Downing LJ, Wakefield TW, Strieter RM, et al. Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis. J Vasc Surg. 1997;25:815-828.
2. See-Tho K, Harris EJJ. Thrombosis with outflow obstruction delays thrombolysis and results in chronic wall thickening of rat veins. J Vasc Surg. 1998;28:115-122.
3. Caps MT, Manzo RA, Bergelin RO, et al. Venous valvular reflux in veins not involved at the time of acute deep vein thrombosis. J Vasc Surg. 1995;22:524-531.
4. Plate G, Einarrson 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.
5. Plate G, Akesson H, Einarrson E, et al. Long-term results of venous thrombectomy combined with a temporary arterio-venous fistula. Eur J Vasc Surg. 1990;4:483-489.
6. Plate G, Eklof B, Norgren L, et al. Venous thrombectomy for iliofemoral vein thrombosis: 10-year results of a prospective randomized trial. Eur J Vasc Endovasc Surg. 1997;14:367-473.
7. Olow B, Andersson J, Eklof B, et al. Deep venous thrombosis treated with a standard dosage of streprokinas. Acta Chir Scand. 1970;136:181-189.
8. Albrechtsson U, Andersson J, Einarsson E, et al. Streptokinase treatment of deep vein thrombosis and the postthrombotic syndrome: follow-up evaluation of venous function in the postthrombotic leg. Arch Surg. 1981;116:33-37.
9. Semba CP, Dake MD. Iliofemoral deep venous thrombosis: aggressive therapy with catheter-directed thrombolysis. Radiology. 1994;191:487-494.
10. Mewissen MW, Seabrook GR, Meissner MN, et al. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multi-center registry. Radiology. 1999;211:39-49.
11. Eklof B, Kamida C. Kistner RL, et al. Contemporary treatment of iliofemoral deep vein thrombosis. Persp Vasc Surg. 1999;11.

 

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