Journal of Vascular Surgery
Volume 46, Issue 5 , Pages 1065-1076, November 2007

Iliofemoral venous thrombosis

Jobst Vascular Center, The Toledo Hospital, Toledo, Ohio.

Received 9 April 2007; accepted 8 June 2007.

Article Outline

Iliofemoral deep vein thrombosis (DVT) is associated with serious short- and long-term physical, social, and economic sequelae for patients. Most physicians treat patients with acute iliofemoral DVT in the same manner as they treat all acute DVT patients: with anticoagulation alone. Yet a growing body of evidence suggests that, in this subset of DVT patients, a treatment strategy that includes thrombus removal plus optimal anticoagulation significantly improves outcomes. This article reviews the evidence supporting this strategy and discusses current and promising techniques of thrombus removal, including contemporary venous thrombectomy, intrathrombus catheter-directed thrombolysis, and pharmacomechanical thrombolysis.

 

Iliofemoral deep venous thrombosis (DVT) is associated with serious short-term and long-term physical, social, and economic sequelae for patients.1, 2, 3 Yet, despite evidence demonstrating that patients with iliofemoral DVT have more severe post-thrombotic morbidity than patients with infrainguinal DVT, most physicians treat all DVT patients alike—with anticoagulation alone. A treatment approach that includes a strategy of thrombus removal plus optimal anticoagulation is not considered by most clinicians, even in patients with extensive venous thrombosis.

Certainly, advances in anticoagulation have been enormous. The low-molecular-weight heparins (LMWH) and pentasaccharides, as well as new direct thrombin inhibitors, limit the progression of thrombosis, reduce recurrence with a proper duration of therapy, and can properly manage patients with heparin-induced thrombocytopenia (with or without thrombosis). However, none of these agents remove existing thrombus from the deep venous system.

After anticoagulation alone for management of iliofemoral DVT, post-thrombotic chronic venous insufficiency, leg ulceration, and venous claudication are common.1, 2, 3 O’Donnell et al1 were among the first to describe the increased severity of post-thrombotic symptoms in these patients: 67% required recurrent (≥5) hospitalizations and 81% experienced loss of financial productivity. Akesson et al2 demonstrated that 95% of patients treated with anticoagulation alone had ambulatory venous hypertension at 5 years, 90% had signs and symptoms of chronic venous insufficiency, venous ulcers developed in 15%, and 15% showed symptoms of venous claudication. According to Delis et al,3 40% of patients with prior iliofemoral DVT treated with anticoagulation alone had venous claudication when exercised.

Recurrent DVT is known to be a high risk factor for post-thrombotic morbidity.4 Patients with iliofemoral DVT have been shown to have a 2.6-fold higher risk of recurrence when treated with conventional anticoagulation than patients with less extensive DVT.5

Considering the body of evidence to date, patients with acute iliofemoral DVT should be offered a strategy of thrombus removal6, 7 as the preferred initial management to improve long-term outcome by reducing post-thrombotic morbidity.

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Understanding post-thrombotic venous insufficiency 

Many physicians fail to recognize the difference in the pathophysiology of primary vs post-thrombotic venous insufficiency. As a consequence, they underestimate the value of thrombus removal in preventing post-thrombotic morbidity, especially in patients with iliofemoral DVT.

The pathophysiology of chronic venous insufficiency is ambulatory venous hypertension, which is defined as an elevated venous pressure during exercise.8 The anatomic components that contribute to ambulatory venous hypertension are venous valvular incompetence and luminal obstruction. Studies consistently show that patients with chronic venous obstruction have the most severe post-thrombotic morbidity.8, 9 Although this is generally true for all segments of the venous system, multisegment venous involvement10, 11 and iliofemoral obstruction result in the most profound morbidity.

Venous obstruction is not synonymous with occlusion. Obstruction can include mild, moderate, or severe luminal compromise, or even occlusion; therefore, obstruction is a relative term whereas occlusion is absolute. Unfortunately, technology has not advanced to the point that allows physicians to assess the pathophysiologic impact of partial luminal obstruction in an individual patient. Fig 1 is an illustrative example of a patient who had multichannel (partial) recanalization of his femoral vein lumen after iliofemoral DVT. Despite most of the vein lumen remaining obstructed, phlebography and physiologic testing failed to identify obstruction as part of the patient’s pathophysiology. There remains widespread under-appreciation for the importance of luminal obstruction contributing to post-thrombotic morbidity and, therefore, widespread under-appreciation of the benefit of thrombus removal when the patient presents with acute iliofemoral DVT.

  • View full-size image.
  • Fig 1. 

    A, Ascending phlebography in a patient with post-thrombotic chronic venous disease was interpreted as “no evidence of obstruction” and the result of an impedance plethysmography was normal. B, Results of a classic Linton procedure revealed considerable luminal obstruction of the femoral vein, which neither phlebography nor hemodynamic measurements diagnosed accurately. Adapted from Comerota et al.7 Permission requested.

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Benefits of thrombus removal 

It has become increasingly evident that thrombus removal or early thrombus resolution after the onset of acute DVT is associated with improved outcomes. Experimental observations, natural history studies of acute DVT, venous thrombectomy data, and observations after systemic and catheter-directed thrombolysis all confirm that a strategy of thrombus removal reduces post-thrombotic morbidity.

Experimental observations of acute DVT in canine models demonstrated that thrombolysis preserves endothelial function and valve competence immediately and at 4 weeks after therapy compared with placebo. There was less residual thrombus in veins treated with a plasminogen activator, thereby preserving the vein’s structural integrity.12, 13

These experimental observations translate into improved clinical outcomes when spontaneous clot lysis was observed in a natural history study of acute DVT in patients treated with anticoagulation.14, 15, 16 These investigators found that distal valvular incompetence developed in patients with persistent proximal vein obstruction, even when distal veins had no thrombus involvement.14 They confirmed that the combination of venous obstruction and valve incompetence was associated with the most severe post-thrombotic morbidity.15 Spontaneous clot lysis naturally restored venous patency. Moreover, if spontaneous lysis occurred early (≤90 days), valve function was frequently preserved.16

Persistent thrombus at termination of anticoagulation is associated with recurrent DVT. Two prospective cohort studies of acute DVT treated with conventional anticoagulation monitored patients with venous ultrasound imaging.17, 18 Both found that residual venous thrombus significantly reduced the risk of recurrence. Therefore, normalization of vein segments involved with acute thrombosis would appear to significantly reduce the risk of recurrence and post-thrombotic syndrome. Patients with iliofemoral DVT have a larger thrombus burden at the outset of treatment and, therefore, will likely have a larger residual thrombus burden at the completion of anticoagulation. Douketis et al5 documented the anticipated observation that patients with iliofemoral DVT treated with anticoagulation alone had a significantly higher risk of recurrent DVT compared with patients with infrainguinal DVT. It is well recognized that recurrent DVT significantly increases the risk of post-thrombotic morbidity.4

The early trials of thrombolytic therapy for acute DVT involved systemic infusion of the plasminogen activator. The cumulative results of these trials revealed that although 45% of patients had substantial or complete lysis, most did not.19 However, those whose clot was successfully lysed had a significant reduction in post-thrombotic morbidity and preservation of venous valve function. Goldhaber et al20 reviewed the results from eight trials of systemic streptokinase treatment for acute DVT and found that moderate or significant lysis was achieved nearly three times more frequently in patients treated with thrombolysis than in patients treated with anticoagulation alone. However, a four-fold increased risk of major bleeding in those patients receiving thrombolysis focused physician attention on the hemorrhagic morbidity of lytics rather than on their potential for long-term benefit.

The long-term efficacy of thrombus removal in patients with acute iliofemoral DVT was further substantiated by the Scandinavian investigators who performed a randomized trial of iliofemoral venous thrombectomy with an arteriovenous fistula and anticoagulation vs anticoagulation alone.21, 22, 23 Follow-up at 6 months, 5 years, and 10 years demonstrated clear benefit in patients randomized to venous thrombectomy. Early thrombus removal resulted in improved patency of the iliofemoral venous system, lower venous pressures, less edema, and fewer post-thrombotic symptoms.21, 22 Although 10-year follow-up showed consistent benefit of thrombectomy, the number of patients surviving to 10 years was small, thereby reducing the statistical power of these observations.

The above observations, extending from the basic research laboratory through systemic thrombolysis and operative venous thrombectomy, support the concept that thrombus removal in patients with acute iliofemoral DVT results in significantly less post-thrombotic morbidity. Unfortunately, the favorable results of contemporary venous thrombectomy have not generated much enthusiasm for the operative procedure in the United States. In addition, physicians are unwilling to accept the higher risk of bleeding complications with lytic therapy; therefore, systemic thrombolysis for acute DVT is infrequently used and not recommended, which is appropriate in light of the improved results with catheter-directed lysis.

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Treatment strategies of thrombus removal 

Systemic thrombolysis 

Initial attempts to treat acute DVT with thrombolytic therapy were by peripheral intravenous administration. Although treatment has evolved to catheter-directed intrathrombus delivery, it is instructive to review the information generated by trials of systemic thrombolytic therapy vs anticoagulation for acute DVT.

Thirteen studies have been reported comparing anticoagulant therapy with thrombolytic therapy for acute DVT (Table I).24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38 The diagnosis in these studies was established with ascending phlebography, which was repeated after treatment to assess outcome. Pooled analysis (Table II) indicates that only 4% of patients treated with anticoagulation alone had significant or complete lysis and an additional 14% had partial lysis. Most patients (82%) had either no objective phlebographic clearing or actually had extension of their thrombi; therefore, few patients had sufficient clearing of thrombus to expect return of normal venous valvular function. In patients treated with thrombolysis, 45% had significant or complete clot resolution, 18% had partial clearing, and 37% failed to improve or worsened. Although 10 times as many patients had significant or complete clearing with thrombolysis compared with anticoagulation, less than half of the lytic patients had a good-to-excellent phlebographic outcome.

Table 1. Review of anticoagulation versus systemic lytic therapy for deep vein thrombosis
First author, yearInvestigation type/patients (n)Treatment groupsResolution results, n (%)Complications, n (%)
Significant or completePartialNone or propagationBleedingPEDeath due to Rx
MinorMajor
Browse,24 1968PR/10SK/53(60)1(20)1(20)0(0)0(0)NoneNone
Hep/50(0)(0)5(100)0(0)0(0)NoneNone
Robertson,25 1968PRB/16SK/85(63)2(25)1(12)2(25)2(25)NANone
Hep/81(12)2(25)5(63)1(12)1(12)⁎NA1(12)⁎
Kakkar,26 1969PR/18SK/96(67)1(11)2(22)0(0)3(33)NoneNone
Hep/92(22)2(22)5(56)0(0)2(22)None1(11)
Tsapogas,27 1973PR/34SK/1910(53)0(0)9(47)0(0)4(21)NANone
Hep/150(0)1(7)14(93)NANANANone
Duckert,28 1975PNRB/134SK/9239(42)23(25)30(33)24(26)58(62)7None
Hep/420(0)4(10)38(90)4(10)2(5)5None
Porter,29 1975§PR/48SK/229(40)1(5)12(55)4(17)6(25)⁎11(4)⁎
Seaman,30 1976§ Hep/262(8)5(19)19(73)1(0.4)7(27)NoneNone
Rosch,31 1976§
Marder,32 1977PR/24SK/125(42)2(16)5(42)NANANA1(8)⁎
Hep/120(0)3(25)9(75)NANANANone
Arnesen,33 1978PR/42SK/2111(52)4(19)6(29)1(5)2(10)1†None
Hep/212(10)2(14)16(76)1(5)2(10)NoneNone
Elliot,34 1979PR/51SK/2617(65)1(4)8(31)1(4)2(8)NoneNone
Hep/250(0)0(0)25(100)0(0)0(0)2‡None
Watz,35 1979PR/35SK/188(44)4(22)6(34)3(12)0(0)1None
Hep/171(6)5(29)11(65)2(12)0(0)1None
Jeffery,36 1989PR/40SK/2011(55)0(0)9(45)NANANANone
Hep/201(5)0(0)19(95)NANANANone
Turpie,37 1990PRB/82rt-PA/4013(33)9(22)18(45)3(8)2(5)NANone
Hep/422(5)7(17)33(78)1(2)1(2)NANone
Goldhaber,38 1990PRB/67rt-PA/4515(33)14(31)16(36)11(24)1(2)⁎NANone
Hep/120(0)2(17)10(83)0(0)0(0)NANone

PR, Prospective, randomized; PRB, prospective, randomized, blinded interpretation; PNRB, prospective, nonrandomized, blinded interpretation; SK, streptokinase; Hep, heparin; rt-PA, recombinant tissue plasminogen activator; PE, pulmonary embolism; NA, not available.

⁎Intracranial hemorrhage.

†Nonfatal PE before therapy.

‡Fatal PE during therapy.

§Same study population.

Table II. Phlebographic results of anticoagulation versus lytic therapy for acute deep venous thrombosis (13 studies)24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38
Rx (n)Lysis
None/worsePartialSignificant or complete
Heparin (254)82%14%4%
Lytic Rx37%18%45%

Two randomized trials monitored patients long term and reported symptomatic results (Table III).34, 39 Although the Elliot et al follow-up period of 1.6 years was shorter than the 6.5 years for Arnesen et al, both treatment protocols were similar and used the same drug, streptokinase. The investigators found that most patients who were free of post-thrombotic symptoms were those treated with streptokinase, whereas most patients with severe post-thrombotic symptoms received anticoagulation alone.

Table III. Long-term, symptomatic results of heparin versus lytic therapy for deep venous thrombosis (two studies)34, 39
RxPost-thrombotic symptoms
Patients (n)Severe, n (%)Moderate, (%)None, (%)
Heparin398(21)23(59)8(21)
Streptokinase392(5)12(31)25(64)

A practical question is whether lysis of DVT preserves venous valvular function. In a long-term follow-up of a randomized study, Jeffery et al36 have shown significant functional benefit to patients 5 to 10 years after successful thrombolysis for acute DVT. Popliteal valve function and overall venous insufficiency were assessed using photoplethysmography, foot volumetry, and direct Doppler examination. Patients who had initially successful lysis demonstrated normal venous function tests compared with patients who did not lyse (P < .001). Only 9% of patients who successfully lysed had an incompetent popliteal valve compared with 77% of those who failed to lyse (P < .001).

Intrathrombus catheter-directed thrombolysis 

It is reasonable to expect that catheter-directed intrathrombus delivery of thrombolytic agents will have improved lytic outcomes compared with systemic delivery. The basic mechanism of thrombolysis is the activation of fibrin-bound plasminogen to form the active enzyme plasmin, which dissolves clot.40 During thrombosis, circulating Glu-plasminogen binds to fibrin and is converted to Lys-plasminogen, which has more binding sites for plasminogen activators and is more efficiently activated to plasmin than Glu-plasminogen. Intrathrombus delivery naturally protects plasminogen activators from neutralization by circulating plasminogen activator inhibitor (PAI-1) and also protects the resultant active enzyme plasmin from instantaneous neutralization by circulating antiplasmins. Catheter-directed delivery of plasminogen activators into the thrombus accelerates thrombolysis, increasing the likelihood of a successful outcome. Because accelerated lysis reduces the overall dose and duration of plasminogen activator infusion, it is reasonable to expect that complications also will be reduced.

Numerous reports have demonstrated good outcomes of catheter-directed thrombolysis for acute DVT (Table IV).41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 Three large reports document a success rate of about 80%44, 45, 46 (Table V). Initial success rates likely would have been higher in these series if treatment had been restricted only to patients with acute iliofemoral DVT. However, as clinicians gained technical expertise, patients with more chronic and extensive thrombus were treated, resulting in somewhat lower overall success rates. In these three studies, 422 patients were treated with consistent rates of both success and complications. Notably, underlying iliac vein stenoses were treated with balloon angioplasty, stenting, or both, to achieve unobstructed venous drainage into the vena cava, thereby reducing the risk of recurrent thrombosis.

Table IV. Review of studies of catheter-directed thrombolysis for acute deep venous thrombosis
First author, yearNo of patients (limbs)Intervention/nResolution results, n (%)Complications, n (%)
Significant or completePartialNoneBleedingPEDeath due to Rx
MinorMajor
Semba,41 199421(27)CDT with UK, angioplasty + stenting for residual stenosis18(72)5(25)2(8)1(4)0(0)NoneNone
Semba,42 199632(41)CDT with UK, angioplasty + stenting for residual stenosis21(32)9(28)2(6)0(0)0(0)NoneNone
Verhaeghe,43 199724CDT with rt-PA, stenting for residual stenosis19(79)5(21)0(0))0(0)6(25)NoneNone
Bjarnason,44 199777(87)CDT with UK, angioplasty, stenting, thrombectomy, bypass for residual stenosis69(793)0(0)18(21)11(14)5(6)1None
Mewissen,45 1999287(312)CDT with UK, stenting for residual stenosis; systemic lysis/696(31)162(52)54(17)15(28)54(11)62(<1)
Comerota,46 200054CDT with UK or rt-PA, thrombectomy for residual stenosis14(26)28(52)6(11)8(15)4(7)1None
Horne,47 200010CDT with rt-PA9(90)1(10)0(0)3(30)None2(20)None
Kasirajan,48 20019CDT with UK, rt-PA, or rPA7(78)1(11)1(11)NANANANA
AbuRahma,49 200151CDT w/ UK or rt-PA, stents/1815(83)NRNR3(17)2(11)NoneNone
Hep/331(3)NRNR3(9)2(6)2(6)None
Vedantham,50 200220(28)CDT with UK, rt-PA, or rPA, thrombectomy, stenting23(82)NRNRNone3(14)NoneNone
Elsharawy,51 200235CDT w/ SK, angio, stent/1813(72)5(28)0(0)NoneNoneNoneNone
Hep/172(12)8(47)7(41)NoneNoneNoneNone
Castaneda,52 200215CDT with rPA15(100)NRNRNoneNoneNoneNone
Grunwald,53 200474(82)CDT with UK, tPA, or rPA, angioplasty, stenting54(73)26(32)NR6(8)4(5)NoneNone
Laiho,54 200432CDT with rt-PA/168(50)5(31)NR4(25)2(13)2(13)None
Systemic lysis with rt-PA/165(31)8(50)NR6(38)1(6)5(31)None
Sillesen,55 200545CDT with rt-PA, angioplasty, stenting42(93)NRNR4(8)None1(2)None
Jackson ,20055628CDT with UK or rPA, stenting5(18)20(72)NR2(7)NoneNoneNone
Ogawa,57 200524CDT with UK/100(0)10(100)NoneNoneNoneNoneNone
CDT with UK + IPC/145(36)9(64)NoneNoneNoneNoneNone
Kim,58 200637(45)CDT with UK/2321(81)3(11)2(8)1(4)2(7)1(4)None
CDT + PMT/1416(84)3(16)NoneNone1(5)1(5)None
Lin,59 200693(98)CDT with rPA, rt-PA, or UK, angioplasty, stenting/4632(70)14(30)5(11)2(4)1(2)NoneNone
PMT with rPA, rt-PA, or UK, angioplasty, stenting/5239(75)13(25)4(8)2(4)NoneNoneNone

CDT, Catheter-directed thrombolysis; Hep, heparin; IPC, intermittent pneumatic compression; rPA, recombinant plasminogen activator; PMT, pharmacomechanical thrombolysis; rt-PA, recombinant tissue plasminogen activator; tPA, tissue plasminogen activator; UK, urokinase.

Table V. Efficacy and complications of catheter-directed thrombolysis in three series
ResultsFirst author of study
Bjarnason44 (n = 77)Mewissen45 (n = 287)Comerota,46 (n = 58)
Efficacy
Initial success79%83%84%
Iliac63%64%78%
Femoral40%47%—
Primary patency at 1 yr
Iliac63%64%78%
Femoral40%47%—
Iliac stent: patency at 1 yr
+ stent54%74%89%
− stent75%53%71%
Complications
Major bleed5%11%9%
Intracranial bleeding0%<1%0%
Pulmonary embolism1%1%0%
Fatal pulmonary embolism0%0.20%0%
Death secondary to lysis0%0.40%0%(?2%)⁎

⁎Death due to multiorgan system failure 30 days post lysis, thought not related to lytic therapy.

Major bleeding complications occurred in 5% to 10% of cases, with most located at the venous access site. Intracranial bleeding was rare, occurring in only three patients in the National Venous Registry.45 Symptomatic pulmonary embolism occurred in 1% of patients in the series reported by Bjarnason et al44 and the National Venous Registry,45 and fatal pulmonary embolism occurred in only one of the 422 patients; therefore, death as a result of catheter-directed thrombolysis was rare.

Chang et al60 reported an interesting therapeutic approach using intrathrombus bolus dosing of recombinant tissue plasminogen activator (rt-PA) in 12 lower extremities of 10 patients with acute DVT. Using the pulse-spray technique, they limited a single treatment session to 50 mg. Patients were returned to their rooms and brought back the next day for repeat phlebographic evaluation and repeat infusion, if necessary, for a maximum of four sessions of pulse-spray thrombolysis. Significant or complete lysis was achieved in 11 of the 12 extremities, and one had 50% to 75% lysis. Although the average total dose of rt-PA was 106 mg, bleeding complications were minor and no patient had a decrease in hematocrit of >2%. This interesting technique of intermittent pressure infusion of lytic agents deserves further study to evaluate its applicability to the general population of DVT patients.

The National Venous Registry44 reported 287 patients treated in both academic and community medical centers. Of these, 66% had acute DVT, 16% had chronic DVT, 19% had an acute episode superimposed upon a chronic condition, 71% presented with iliofemoral DVT, and 25% had femoropopliteal DVT. Catheter-directed thrombolysis with intrathrombus infusion of urokinase was the preferred approach. In the subgroup of patients with acute, first-time iliofemoral DVT, 65% of the patients enjoyed complete clot resolution.

During follow-up, 65% of patients were thrombus-free at 6 months and 60% at 12 months. There was a significant correlation (P < .001) of thrombus-free survival with the results of initial therapy. At 1 year, 78% of patients with complete clot resolution initially had patent veins compared with only 37% of those who had <50% lysis. An important observation was made in the subgroup of patients with acute, first-time iliofemoral DVT who had initially successful thrombolysis: 96% of the veins in these patients remained patent at 1 year. Initial lytic success also directly correlated with valve function at 6 months: 62% of patients with <50% thrombolysis had venous valvular incompetence, whereas 72% of patients who had complete lysis had normal valve function (P < .02).

National Venous Registry patients with iliofemoral DVT who were treated with catheter-directed thrombolysis were compared with a contemporary cohort of patients with iliofemoral DVT from the same institutions who were treated with anticoagulation alone.61 All patients treated only with anticoagulation were candidates for lytic therapy; however, the choice of treatment was determined by physician preference. A validated quality-of-life (QOL) questionnaire62 was used to query patients at 16 and 22 months after treatment. Of the 98 patients evaluated, 68 were treated with catheter-directed thrombolysis and 30 with anticoagulation alone. Those treated with catheter-directed thrombolysis reported significantly better QOL than those treated with anticoagulation alone.61 The QOL results were directly related to the initial success of thrombolysis. Patients who had a successful lytic outcome reported a significantly better health utilities index, increased physical functioning, less stigma of chronic venous disease, less health distress, and fewer overall post-thrombotic symptoms. Patients in whom catheter-directed thrombolysis failed had outcomes similar to those treated with anticoagulation alone. These efficacy data combined with the reduced complications of intrathrombus infusion offer a convincing argument for managing patients with iliofemoral DVT with catheter-directed thrombolysis.

Meissner and Mewissen63 recently reported follow-up results in 102 limbs of 98 patients with acute first-time DVT treated in the National Venous Registry. The median follow-up time was 316 days. The authors correlated the lytic response with residual thrombus, vein valve function, and post-thrombotic symptoms (Table VI). A good or excellent lytic response was associated with significantly less thrombus, less vein valve reflux, and a greater number of asymptomatic patients.

Table VI. Results of catheter-directed thrombolysis for acute deep venous thrombosis: follow-up to the National Venous Registry63
Lytic response to catheter-directed thrombolysis
Outcome at follow-up (316 days median)<50% (n = 11)50%-99% (n = 53)100% (n = 38)P
Residual thrombus73%45%16%.001
Reflux89%48%39%.03
Asymptomatic36%68%84%.002

A small randomized trial performed by Elshawary et al51 compared catheter-directed thrombolysis with anticoagulation alone. These authors demonstrated that catheter-directed thrombolysis offered considerably better outcomes at 6 months. Assuming that the post-thrombolysis management of patients with anticoagulation is effective and of proper duration, this 6-month observation should reflect long-term outcome.

Contemporary venous thrombectomy 

Advances in all methods to eliminate thrombus from the deep venous system have occurred during the past 10 to 15 years. Contemporary venous thrombectomy has substantially improved the early and long-term results of patients with extensive iliofemoral DVT compared with the initial reports.21, 22, 23, 64, 65, 66, 67, 68, 69, 70 Major technical advances occurring between the initial and contemporary procedures are listed in Table VII. The technical details of contemporary venous thrombectomy have been previously reported.71, 72

Table VII. Venous thrombectomy: comparison of old and contemporary techniques
TechniqueOldContemporary
Pretreatment phlebography/CT scanOccasionallyAlways
Venous thrombectomy catheterNoYes
Operative fluoroscopy/phlebographyNoYes
Correct iliac vein stenosisNoYes
Arteriovenous fistulaNoYes
Infrainguinal thrombectomyNoYes
Intraoperative thrombolysisNoYes
Full post op anticoagulationOccasionallyYes
Catheter-directed anticoagulationNoYes
IPC post-opNoYes

CT, Computed tomography; IPC, intermittent pneumatic compression.

In an important randomized trial, Plate et al22 compared operative venous thrombectomy with arteriovenous fistula (AVF) plus anticoagulation vs anticoagulation alone in patients with iliofemoral DVT. Peer-reviewed reports occurred at 6 months,22 5 years,21 and 10 years23 of follow-up. Patients randomized to venous thrombectomy had improved patency (P < .05), reduced venous pressures (P < .05), less edema (P < .05), and fewer post-thrombotic symptoms (P < .05) than those receiving only anticoagulation. Of interest was that more patients undergoing venous thrombectomy had preserved normal venous valve function in their femoropopliteal segment than patients who were treated with anticoagulation alone.21, 22 Recall that previously discussed studies of the natural history of acute DVT treated with anticoagulation reported valve incompetence in veins distal to proximal obstruction, even when the distal veins were not involved with clot. Hence, elimination of iliofemoral thrombus (and proximal venous obstruction) potentially protected the distal valves from the hemodynamic consequences of obstructed proximal veins and resultant valvular incompetence of the distal veins.14

Blattler et al73 combined venous thrombectomy of the iliofemoral venous system with urokinase infusion into the leg with a thigh tourniquet to aid removal of the infrainguinal venous thrombi. This resulted in patent veins in all 33 patients treated in this manner, with no recurrence or post-thrombotic symptoms at 1 year. By 10 years of follow-up, three patients had recurrent DVT (not in the treated leg) and two had venous claudication.

Unfortunately, the American College of Chest Physicians (ACCP) Consensus Guidelines74 failed to recognize recently published data when they recommended against operative venous thrombectomy, focusing attention instead on reports of patients treated >40 years ago. Although randomized trial data demonstrated significant benefit of venous thrombectomy, influential guidelines such as the ACCP’s reduced or eliminated enthusiasm for operative thrombectomy.

Pharmacomechanical thrombolysis 

Complementing catheter-directed thrombolysis with adjunctive mechanical methods is rapidly becoming the standard for catheter-based management of extensive venous thrombosis.75, 76, 77 Percutaneous mechanical thrombectomy alone is less successful than catheter-directed thrombolysis and is associated with unacceptably high complications of pulmonary emboli (PE). Pulse-spray pharmacomechanical thrombolysis of clotted hemodialysis grafts demonstrated an 18% incidence of PE in patients treated with a plasminogen activator solution compared with a 64% incidence of PE in patients treated with a heparinized saline solution (P = .04).78 Because the hemodialysis graft is in direct communication with the venous circulation, it appears that results in these patients should be similar to patients with proximal acute DVT. The caliber of the proximal deep veins is substantially larger than a 6-mm dialysis access graft; thus, one would expect that these observations would be magnified when treating proximal DVT.

In an experimental model comparing mechanical, pharmacomechanical, and pharmacologic thrombolysis, Greenberg et al79 reported findings consistent with Kinney et al78 by demonstrating that pulse-spray mechanical thrombectomy was associated with the largest number and greatest size of distal emboli. Embolic particles diminished in number and size and the speed of lysis increased when urokinase was added to the pulse-spray solution. Catheter-directed thrombolysis alone was associated with the slowest rate of reperfusion but also the fewest number of distal emboli.

Hemolytic complications of rheolytic mechanical thrombectomy are common and occasionally result in anemia and renal dysfunction. Recent favorable observations using a modified percutaneous thrombectomy device in a table-top model80 require confirmation in a biologic model and ultimately in patients.

A new device recently released for isolated segmental and controlled pharmacomechanical thrombolysis is the re-engineered Trellis catheter (Bachus Vascular, Santa Clara, Calif). This hybrid catheter isolates the thrombosed vein segment between two occluding balloons and a lytic agent is infused into the thrombus. The intervening catheter shaft assumes a spiral configuration, which is then motor activated and spins at 1500 rpm. After 15 to 20 minutes, the liquefied thrombus and remaining fragments are aspirated. Phlebographic evaluation of the result is performed before moving on to treat additional thrombosed vein segments. The advantages of such a device include its ability to incorporate mechanical and pharmacologic therapies and to treat patients who have traditional contraindications to thrombolytic therapy. Because the infusate is aspirated and the clot more rapidly lysed, treatment times are significantly shortened.

Another interesting new adjunct to catheter-directed thrombolysis is the incorporation of ultrasound transducers into the infusion catheter. Ultrasound waves generated during t-PA infusion increases the surface area of fibrin and speeds lysis. Several reports have emerged indicating that an infusion catheter with ultrasound transducers built into the infusion end of the catheter can be used to accelerate thrombolysis.81, 82, 83, 84 In vitro studies have demonstrated that ultrasound enhances the fibrinolytic activity of t-PA.85, 86, 87 The potential mechanism for augmented clot lysis has been extrapolated from in vitro studies showing that ultrasound produces clot fragmentation in the presence of t-PA, and consequently, more fibrin-binding sites are available to t-PA owing to the larger surface area.88, 89 The concept of a transducer-tip catheter that delivers a fibrinolytic drug in combination with high-frequency, low-intensity ultrasound has been well described. In vivo models90 and clinical trials91 are now underway to assess the potential value of ultrasound enhancement of thrombolytics for the management of acute DVT.

A patient with extensive iliofemoral, popliteal, and tibial DVT was treated with pharmacomechanical thrombolysis using isolated segmental pharmacomechanical lysis with the Trellis catheter and ultrasound-accelerated thrombolysis with the Lysus catheter (EKOS Corporation, Bothell, Wash; Fig 2, Fig 3, Fig 4). Properly applied, these techniques can significantly speed thrombus resolution, restore patency, and preserve valve function.

  • View full-size image.
  • Fig 2. 

    Extensive deep vein thrombosis is demonstrated phlebographically in a patient 2 days after exploratory laparotomy. Clot was found extending from his calf veins to the proximal common iliac vein. Adapted from Comerota et al.7 Permission requested.

  • View full-size image.
  • Fig 3. 

    A, Trellis catheter (Bachus Vascular, Santa Clara, Calif) (arrows) in the iliofemoral venous segment, accessed through the popliteal vein. B, Lysus catheter (EKOS Corporation, Bothell, Wash; arrow) in the tibial-popliteal venous segment, accessed through the posterior tibial vein at the ankle. Adapted from Comerota et al.72 With permission.

  • View full-size image.
  • Fig 4. 

    Completion phlebogram after pharmacomechanical thrombolysis demonstrates a patent venous system from the calf veins to the vena cava. At 16 months’ follow-up, the patient had no post-thrombotic symptoms, a patent venous system, and normally functional venous valves. Adapted from Comerota et al.72 With permission.

Current catheter-based thrombolytic techniques are more effective and are safer. As technology continues to improve, lytic infusion times will shorten, more patients will be offered a treatment strategy that includes thrombus removal, and many more patients will be spared their otherwise certain post-thrombotic morbidity.

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Recommendations for management of patients with iliofemoral deep venous thrombosis 

The general treatment strategy for patients with acute iliofemoral DVT is summarized in the algorithm illustrated in Fig 5. All patients undergo immediate anticoagulation, are placed in snug, long-leg, multilayered compression bandages extending from the base of the toes to the upper thigh, and treated with leg elevation.92 Patients are permitted to ambulate. When not ambulating, patients are in bed with their legs elevated.

  • View full-size image.
  • Fig 5. 

    Algorithm illustrates our current treatment protocol for patients with iliofemoral deep venous thrombosis (DVT). CT, Computed tomography; CD, catheter directed; PM, pharmacomechanical. Trellis catheter, Bachus Vascular, Santa Clara, Calif. Reprinted from Comerota et al.7 Permission requested.

A rapid computed tomography (CT) scan with contrast is performed of the chest, abdomen, and pelvis to evaluate for PE and other pathology that may be associated with their aggressive degree of thrombosis. Patients who are physically active are considered for a strategy of thrombus removal. Anticoagulation with compression is generally recommended for patients who are minimally active or have a lifespan of <2 years. A vena cava filter should be inserted in patients who have a free-floating thrombus in their vena cava.

Patients considered for a strategy of thrombus removal who have a contraindication to thrombolysis are treated either with a contemporary venous thrombectomy71 or segmental pharmacomechanical thrombolysis using the Trellis catheter. Patients with no contraindication to thrombolysis are offered catheter-directed thrombolysis with additional pharmacomechanical techniques.

Once the thrombus is removed, a completion phlebogram is performed to assess for an underlying venous lesion, which should be corrected to provide unobstructed venous drainage into the vena cava, thereby reducing the risk of recurrent thrombosis. Subsequently, therapeutic anticoagulation is important to avoid recurrent thrombosis. Intermittent pneumatic compression units are applied while patients remain hospitalized and not ambulating. If an underlying etiology for the patient’s extensive venous thrombosis cannot be identified, a thrombophilia evaluation is performed.

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Conclusion 

Post-thrombotic morbidity after iliofemoral DVT is certain.1, 2, 3 The more extensive the thrombosis and the more active the patient, the more severe the post-thrombotic sequelae. Active patients with an anticipated survival of ≥2 years should be offered a strategy of thrombus removal to avoid chronic venous obstruction and multisegment valvular incompetence.

Long-term benefits of a strategy of restoring venous patency have been documented in a randomized trial of venous thrombectomy vs anticoagulation,20, 21, 22 and short-term benefits have been shown in a trial of catheter-directed thrombolysis vs anticoagulation.55 Patients receiving venous thrombectomy had significantly better venous patency rates, lower venous pressures, better valve function, and less post-thrombotic morbidity. Patients randomized to catheter-directed thrombolysis had significantly better patency and valve function compared with patients randomized to anticoagulation. Likewise, randomized trials of systemic thrombolytic therapy show that when it is successful, patients have fewer post-thrombotic sequelae and improved venous function compared with patients treated with anticoagulation alone or when lytic therapy is unsuccessful.18

Improvements in operative technique as well as catheter-based technology now document higher rates of success and lower complication rates. As clinicians become more experienced with these techniques, technology continues to improve, and new pharmacologic agents are developed that lyse thrombus more rapidly with fewer bleeding complications, the application of these principles should expand.

The medical community awaits a large-scale randomized trial comparing an endovascular strategy of thrombus removal with anticoagulation for patients with acute DVT. Trial design is critical, however. If only patients with extensive DVT are studied, there is little question in our opinion that a strategy of thrombus removal will prove superior. However, inclusion of lesser degrees of thrombosis will reduce the relative benefit of treatment strategies designed to eliminate thrombus, because endogenous fibrinolysis will accomplish this in some treated with anticoagulation alone. Single venous segment involvement, such as the femoral vein in the thigh, often does not cause significant post-thrombotic morbidity. The femoral vein can be sacrificed (ligated) with minimal morbidity in most patients because collateral drainage exists through the profunda femoris venous system. Therefore, selecting patients most likely to benefit from a strategy of thrombus removal, such as those with multilevel venous thrombosis, is crucial to clarifying efficacy.

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Author contributions 


Conception and design: AC

Analysis and interpretation: AC

Data collection: AC, MG

Writing the article: AC, MG

Critical revision of the article: AC, MG

Final approval of the article: AC

Statistical analysis: Not applicable

Obtained funding: Not applicable

Overall responsibility: AC

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 Competition of interest: none.

PII: S0741-5214(07)00985-8

doi:10.1016/j.jvs.2007.06.021

Journal of Vascular Surgery
Volume 46, Issue 5 , Pages 1065-1076, November 2007

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