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452 Chapter 48/Temporary Filters and Prophylactic Indications
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Patients with Advanced Malignancy
Patients with advanced malignancy have been shown to
be at increased risk of VTE, and AC therapy may not be
adequately protective. Prophylactic VCF use has been
debated but the trend now favors therapeutic use (i.e., only
after VTE). Risk factors have been identifi ed.19 Univariate
analysis and logistic regression models identifi ed the following as signifi cant risk factors for recurrent VTE: the appearance of new metastases, a history of DVT, and neutropenia
as a result of chemotherapy. Other studies have identifi ed
stage of disease and type of malignancy as specifi c risk
factors for VTE. The effectiveness of VCFs in preventing
PE has not in itself been challenged, but use of this indication for VCF placement clearly must be balanced by patient
prognosis as demonstrated by two sobering reports. Jarrett
et al.20 reported on 116 patients with VCFs placed for
advanced malignant disease. Its effectiveness was suggested
by the fact that two had recurrent DVT, three had PE after
VCF, but it was the issue of patient survival that was challenged. Life table analysis showed survival to be 68% at 30
days, 49.4% at three months, and 26.8% at one year. Of
those with stage IV disease, 46% died within six weeks and
only 13.7% were alive at one year. Schunn et al.
97.5% protection against PE in 40 patients with advanced
malignancy receiving VCFs, but also a high (20%) complication rate. Added to this, 30% survived less than 30 days!
It can be concluded from these experiences that prevention
of PE may be of little benefi t in patients with advanced
(e.g., stage IV) disease due to short life expectancy.
21
reported
of DVT
Certain categories of major surgery have a predicted high
VTE risk, and yet the use of AC prophylaxis may be contraindicated or presumed ineffective. In such patients, VCF
has been felt to be indicated. Some well-known examples of
such VCF use include pelvic surgery, hip surgery, major
surgery with history of DVT, major surgery with known or
suspected hypercoagulable state, major venous reconstructions with VTE risk, and gastric bypass surgery for morbid
obesity. As a general criticism, in many of these applications, the risk of VTE, the duration of risk, and the benefi ts
of VCFs are poorly documented in the literature, and few
studies involve valid comparisons with alternative methods
of prophylaxis. Nevertheless, it is clear that individual highrisk patients can be identifi ed, and when alternative methods
of prophylaxis are either contraindicated or ineffective, VCF
placement should be considered. As a general rule, in this
subcategory, a temporary/retrievable fi lter should be used if
the patient can be ambulatory or AC therapy can be instituted in about three weeks, otherwise a permanent fi lter may
be preferable. Thus, although supporting data are scant, indi-
vidual high-risk patients can be reasonably chosen on their
own merits, and it is diffi cult to take exception with this
practice.
Bariatric surgery has received much recent attention, and
though the intervention itself has been challenged by many,
some data and guidelines have emerged for prophylactic
VCF use with this operation. Open gastric bypass for morbid
obesity carries a 1 to 4% PE risk in spite of other methods
of prophylaxis including IC, LMW heparin, and a push
for early ambulation. Using retrievable VCFs, Gargiulo22
reported a reduced PE rate in open gastric bypass for patients
with a BMI >55, but there was 14% complication rate.
Factors associated with a high risk of VTE have been identifi ed23 to include BMI >60, truncal obesity, venous stasis
dermatitis, and hypoventilation/sleep apnea syndrome. Logically, one would add those with a history of VTE and a
known or probable hypercoagulable state. It has been said
that this operation has a short, defi ned period of risk for VTE
that is ideal for retrievable VCFs. On the other hand, VCF
placement can be challenging in morbidly obese patients,
especially the super-obese (BMI >60). Duplex ultrasound
guidance is impossible but intravascular ultrasound can be
used to advantage in placing a fi lter in these patients. In the
face of great enthusiasm for this indication for prophylactic VCF use, the author would insert a word of caution:
no prospective studies, comparing VCFs with alternative
methods of VTE prophylaxis, have been carried out, and
most of the published reports related to its use have dealt
with open gastric bypass. It is quite conceivable that the
laparoscopic approach, with its earlier ambulation, may signifi cantly reduce the VTE risk. Whether this is suffi cient to
allow the adjunctive use of IPC and LMW heparin to be
effective deserves investigation. In the meantime, the risk
factors listed earlier should serve as guidelines for selective
VCF use.
SUMMARY AND CONCLUSIONS
The current use of prophylactic indications for caval fi lter
placement and the temporary retrievable fi lters that have
been developed for this purpose has been reviewed. Based
on this some recommendations can be confi dently made, but
there is a clear need better information, clarifying higher
level studies on which to base prophylactic indications.
Also, there appears to room for further improvements in
retrievable vena cava fi lter design, or possibly the modifi cation of an existing permanent fi lter with good long-term
outcomes so that it can be retrieved if necessary. It may or
may not be possible to design a truly optional fi lter, one that
can be retrieved as needed or left in permanently without
penalty. If not, the use of two types of fi lters will persist as
the best strategy—the best temporary/retrievable and best
permanent fi lter being chosen matching duration of patient
References 453
https://t.me/med1917
risk with safe indwelling time in the former. Better supporting data are required to support either use. It is also apparent
that, in respect to categories of prophylactic indications,
current practice is not based on a high level of medical evidence and, in fact, the use of VCFs in some of these settings
appears to be excessive and subjectively determined. It is
hoped that prophylactic indications within each subcategory
will be refi ned in the future by indication-specifi c prospective analyses of critical outcome data compared with alternative methods of prophylaxis, and that these studies also will
identify the factors signifi cantly affecting outcome as a basis
for more objective guidelines for application. The need for
evidence-based medicine here is obvious. Industry-driven
trials of single devices are not, in themselves, acceptable for
this purpose and tend to promote excessive prophylactic use
rather than control it. On the other hand, if one believes, as
does the author, in the potential of new technology in bringing about continuing improvements, industry can be expected
to develop even better retrievable caval fi lters, those which
ultimately could be proven safe and effective for prophylactic use in patients temporarily at high risk for VTE, specifi cally fi lters that can be retrieved or repositioned safely,
without being compromised by entrapped clot or contact
point endothelialization for longer periods of time relative
to the risk of VTE. Until then, it is hoped that this critical
appraisal of the prophylactic use of VCFs, and the current
temporary fi lters that increasingly are linked to it, will help
guide physicians engaged in this practice.
References
1. Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P
et al. for the Prevention du Risque d’Embolie Pulmonaire par Interruption Cave (PREPIC) study group. A clinical trial of vena cava fi lters
in the prevention of pulmonary embolism in patients with proximal
deep-vein thrombosis, N Engl J Med. 1998. 338: 409–415.
2. Laporte S, Decousus H. A randomized clinical trial of vena cava fi lters
in the prevention of pulmonary embolism in patients with proximal
deep-vein thrombosis: Preliminary results of a long-term follow-up, J
Thromb Haemost. Suppl 1, 2001.
3. Decousus H. Eight years follow-up of a randomized trial investigating
vena caval fi lters in the prevention of PE in patients presenting with
proximal DVT: The PREPIC trial, J Thromb Haemost. Suppl 1, 2003
pp. 416–422.
4. Asch MR. Initial experience in humans with a new retrievable inferior
vena cava fi lter, Radiology. 2002. 225: 835–844.
5. Rosenthal D, Wellons ED, Levitt AB, Shuler FW, Conner RE,
Henderson VJ. Role of prophylactic temporary inferior vena cava
fi lter placed at the ICU bedside under ultrasound guidance in patients
with multiple trauma, J Vasc Surg. 2004. 40: 958–964.
6. Offner PJ, Hawkes A, Madayag R, Seale F, Mains C. The role of
temporary IVC fi lters in critically ill surgical patients, Arch Surg. 2003.
138: 591–592.
7. de Gregorio MA, Gamboa P, Gimeno MJ et al. The Gunther Tulip
retrievable fi lter: Prolonged temporary fi ltration by repositioning
within the inferior vena cava, J Vasc Inter Radiol. 2003. 14:
1259–1265.
8. Peterson L. Inferior vena cava fi lters, Trends-in-Medicine. October
2003 pp.
9. Greenfi eld LJ, Michna BA. Twelve year clinical experience with the
Greenfi eld vena cava fi lter, Surgery. 1988. 104: 706–712.
10. Greenfi eld LJ, Proctor MC. Twenty-year clinical experience with the
Greenfi eld fi lter, Cardiovasc Surg. 1995. 3: 199–205.
11. Greenfi eld LJ, Cho KJ, Proctor MC et al. Results of a multi-center
study of the modifi ed hook-titanium Greenfi eld fi lter, J Vasc Surg.
1991. 14: 253–257.
12. Cho KJ, Greenfi eld LJ, Proctor MC et al. Evaluation of a new percutaneous stainless steel Greenfi eld fi lter, J Vasc Interv Radiol. 1997. 8:
181–187.
13. Girard P, Stern JB, Parent F. Medical literature and vena cava fi lters:
So far so weak, Chest. 2002. 122: 963–967.
14. Langhan EM, Miller RS, Casey, WJ et al. Prophylactic inferior vena
cava fi lters in trauma patients at high risk: Follow-up examination and
risk benefi t assessment, J Vasc Surg. 1999. 30: 484–490.
15. Duperier T, Mosenthal A, Swan KG, Kaul S. Acute complications
associated with Greenfi eld fi lter insertions in high risk patients, J Vasc
Surg. 2003. 37: 976–983.
16. Knudsen MM, Ikossi DG, Khaw L et al. Thromboembolism after
trauma: An analysis of 1602 episodes from the American College
of Surgeons National Trauma Data Bank, Ann Surg. 2004. 240:
96–104.
17. Maxwell RA, Chavarria-Aguilar M et al. Routine prophylactic vena
caval fi ltration is not indicated after spinal cord injury, J Trauma. 2002.
53: 1032–1034.
18. No authors listed. Deep venous thrombosis and thromboembolism in
patients with cervical cord injuries, Neurosurgery. 2002. 50(3 Suppl):
S73–S80.
19. Lin J, Proctor MC, Varma M. Factors associated with recurrent VTE
in patients with malignant disease, J Vasc Surg. 2003. 37: 976–983.
20. Jarrett BP, Dougherty MJ, Calligaro KD. Inferior vena cava fi lters in
malignant disease, J Vasc Surg. 2002. 36: 704–707.
21. Shunn CD, Shunn GB, Vona-Davis L, Waheed U. Inferior vena cava
fi lter placement in late stage cancer. Presented at the 17th Annual
Meeting of the American Venous Forum, San Diego, California,
February 10, 2005.
22. Gariulo NJ. Patient selection for retrievable inferior vena cava fi lters,
Endovasc Today. 2004. 3: 42–44.
23. Sappala Ja, Wood MH, Schuhknecht MP et al. Fatal pulmonary emboli
after bariatric operations for morbid obesity: A 24 year retrospective
analysis, Obs Surg. 2003. 13: 819–825.
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CHAPTER
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49
Thrombolytic Therapy for
Acute Venous Thrombosis
ANTHONY J. COMEROTA and SANTIAGO CHAHWAN
INTRODUCTION
Despite evidence demonstrating that patients with iliofemoral venous thrombosis suffer more severe postthrombotic sequelae than patients with infrainguinal deep venous
thrombosis (DVT), the majority of physicians treat all
patients with acute DVT with anticoagulation alone. A treatment approach that includes a strategy of thrombus removal
and optimal anticoagulation is not adopted by most clinicians, even in patients with extensive venous thrombosis.
Unquestionably, there have been enormous advances
in anticoagulation. Anticoagulants, such as low-molecularweight heparins (LMWH) and pentasaccharides, and other
families of agents, such as the direct thrombin inhibitors,
serve to limit progression of thrombosis and, with proper
duration of therapy, prevent recurrences; however, they are
not designed to clear thrombus from the deep venous system.
It appears that patients with iliofemoral DVT are a clinically relevant subset of patients with acute DVT who suffer
severe postthrombotic morbidity.
leagues1 were among the fi rst to bring to our attention the
high incidence of postthrombotic venous ulceration, the
large number of recurrent hospitalizations, and the loss in
fi nancial productivity in these patients. Akesson et al.2
showed that 95% of patients with iliofemoral DVT treated
with anticoagulation alone had ambulatory venous hypertension at fi ve years, and 90% suffered symptoms of chronic
venous insuffi ciency. During this relatively short follow-up,
15% of patients already developed venous ulceration and
another 15% had debilitating symptoms of venous claudication. Delis et al.3 demonstrated that venous claudication
occurred in 40% of patients with iliofemoral DVT treated
with anticoagulation when they were studied with exercise
testing.
1–3
O’Donnell and col-
UNDERSTANDING POSTTHROMBOTIC
VENOUS INSUFFICIENCY
Many physicians fail to recognize the difference in the
pathophysiology of primary versus postthrombotic venous
insuffi ciency. As a result, the value of thrombus removal in
preventing postthrombotic morbidity in patients with acute
DVT is underestimated. The pathophysiology of chronic
venous insuffi ciency is ambulatory venous hypertension,
which is defi ned as an elevated venous pressure during exercise. In individuals with a normal deep venous system,
ambulatory venous pressures in the lower leg and foot
should drop to less than 50% of the standing venous pressure. In patients with postthrombotic syndrome, the ambulatory venous pressure drops very little, and in those with
persistent proximal venous occlusion, the ambulatory pressures may actually rise above standing pressure. This degree
of ambulatory venous hypertension often leads to the debilitating symptoms of venous claudication.
The anatomic components contributing to ambulatory
venous hypertension are venous valvular incompetence and
luminal obstruction. It has been consistently shown that
the most severe postthrombotic sequelae and the highest
ambulatory venous pressures occur in patients with valvular incompetence accompanied by luminal venous
obstruction.
Venous obstruction is not synonymous with occlusion.
Occlusion is complete obliteration whereas obstruction (for
the most part) is relative narrowing of the lumen. Although
relative degrees of obstruction are reliably quantitated on the
arterial side of the circulation, technology has not advanced
to the point that allows this degree of accuracy on the venous
side. Furthermore, physicians often cannot put venous
obstruction into proper perspective pathophysiologically in
4,5
The Vein Book
455
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Copyright © 2006, Elsevier Inc.
456 Chapter 49/Thrombolytic Therapy for Acute Venous Thrombosis
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FIGURE 49.1 Chronic venous disease in a patient who had iliofemoral DVT 10 years earlier. The patient suffered
with the postthrombotic syndrome leading to multiple hospitalizations due to venous ulcers. Ascending phlebography
showed chronic venous disease with “no evidence of obstruction.” An IPG was normal. A classic Linton procedure,
which includes ligation of the femoral vein distal to its junction with the profunda, was performed, showing recanalization of the femoral vein with signifi cant luminal obstruction.
terms of its contribution to postthrombotic discomfort or
distal leg soft tissue damage. Our ability to identify and
quantitate venous obstruction is so poor that there is widespread underappreciation regarding the importance of the
contribution of obstruction to postthrombotic morbidity.
Unfortunately, physiologic testing on the venous side of
the circulation has not kept pace with similar advances on
the arterial side of the vascular tree. Vascular laboratories
have traditionally (and paradoxically) tested the hemodynamics of venous obstruction with patients in the resting,
supine position with their legs elevated, which is the standard position for measuring maximum venous outfl ow, the
commonly accepted test for venous obstruction. However,
the pathophysiology of chronic venous disease is defi ned in
the upright, exercising patient, with increased arterial infl ow
stressing venous return. Phlebograms of postthrombotic
recanalized veins frequently document patency, and noninvasive studies may indeed show normal maximal venous
outfl ow values, giving the mistaken impression that venous
obstruction contributes little to postthrombotic morbidity.
This is clearly illustrated by the patient represented in
Figure 49.1, who had iliofemoral DVT 10 years earlier and
was suffering with severe postthrombotic syndrome and a
venous ulcer. Noninvasive testing demonstrated that the
patient had valvular incompetence but a normal three-second
maximal venous outfl ow. An ascending phlebogram was
interpreted as “the classic tree-barking appearance of chronic
venous disease. There is no evidence of venous obstruction.”
The following day the patient underwent a classic Linton
procedure, which included femoral vein ligation with division just below its junction with the profunda femoris vein.
A cross-section of the divided femoral vein is shown in
Figure 49.1, along with its corresponding level on the
ascending phlebogram. The vein shows multiple recanalization channels and substantial luminal obstruction. This
severity of luminal obstruction becomes hemodynamically
important in the exercising limb, in which substantial
increases in arterial fl ow occur as a result of exercise. With
exercise, venous outfl ow becomes restricted by the luminal
obstruction, signifi cantly contributing to ambulatory venous
hypertension. Of course, the valves within these diseased
veins are destroyed, and patients also have valvular
incompetence.
It makes intuitive sense that eliminating the acute thrombus leading to the persistent venous obstruction would
benefi t patients over the long term, and indeed it does. Furthermore, thrombus extraction not only eliminates venous
obstruction but also preserves valvular function.
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BENEFITS OF THROMBUS REMOVAL
There is increasing evidence that thrombus removal or
early thrombus resolution after acute DVT is associated with
improved outcomes. Benefi ts of thrombus removal derive
from data generated from experimental animal studies,
fi ndings from natural history studies of acute DVT treated
with anticoagulation, venous thrombectomy data, and
observations following systemic and catheter-directed
thrombolysis.
Cho and colleagues6 and Rhodes and associates7 have
used a canine experimental model of acute DVT to compare
the results of thrombolysis versus placebo and mechanical
thrombectomy. They demonstrated that thrombolysis with
urokinase preserves endothelial function and valve competence, both immediately and at four weeks after therapy.
There was less residual thrombus in veins treated with urokinase, thereby preserving the vein’s structural integrity.
The aforementioned experimental observations translated
into clinical outcome when the University of Washington
investigators performed a natural history study of acute
DVT treated with anticoagulation.
effort resulted in observations indicating that persistent
obstruction of proximal veins was associated with distal
valve incompetence. The combination of venous obstruction
and valve incompetence was associated with the most severe
postthrombotic morbidity. Spontaneous clot lysis naturally
restored venous patency. If spontaneous lysis occurred early
(within 90 days), valve function was frequently preserved.
The initial trials of thrombolytic therapy for acute DVT
involved systemic administration of the plasminogen activators. The cumulative results of these trials demonstrated that
although 45% of patients had substantial or complete lysis,
the majority did not.12 Those whose clot was successfully
lysed had a signifi cant reduction in postthrombotic morbidity and preservation of venous valve function. Goldhaber et
al.13 reviewed the results from eight trials of systemic streptokinase treatment for acute DVT and found that moderate
or signifi cant thrombolysis was achieved almost three times
more frequently among patients treated with thrombolytic
therapy than among patients treated with anticoagulation
alone. However, there was nearly a fourfold increased risk
of major bleeding in those receiving thrombolytic therapy,
thereby focusing the attention of clinicians on the hemorrhagic morbidity of lytics rather than their potential for longterm benefi t.
The long-term effi cacy 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 fi stula (AVF) and anticoagulation versus anticoagulation alone.
14–16
Follow-up at six months, fi ve years, and 10
years demonstrated clear benefi t in patients randomized to
8–11
This NIH-supported
venous thrombectomy. Early thrombus removal resulted in
improved patency of the iliofemoral venous system, lower
venous pressures, less edema, and fewer postthrombotic
symptoms.
These 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
signifi cantly less postthrombotic morbidity. Unfortunately,
the favorable results of contemporary venous thrombectomy
have not led to much enthusiasm for the operative procedure
in the United States. Additionally, 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.
INTRATHROMBUS CATHETER-DIRECTED
THROMBOLYSIS
Rationale
The mechanism by which thrombolysis results in clot
dissolution is the activation of fi brin-bound plasminogen.17
When circulating GLU-plasminogen binds to fi brin, it is
modifi ed to LYS-plasminogen, which has greater affi nity for
plasminogen activators. When delivered into the thrombus,
a plasminogen activator effi ciently activates LYS-plasminogen. The intrathrombus delivery protects the plasminogen
activator from neutralization by circulating plasminogen
activator inhibitors and also protects the resultant plasmin
from neutralization by circulating alpha 2-antiplasmins.
Catheter-directed techniques that deliver the plasminogen activator into the thrombus theoretically can accelerate
thrombolysis, which increases the likelihood of a successful
outcome. By reducing the overall dose and duration of infusion of the plasminogen activator, it is reasonable that complications will be minimized.
Results
Numerous reports have emerged supporting favorable
outcomes of catheter-directed thrombolysis for acute
18–25
DVT.
mately an 80% success rate (see Table 49.1). Initial success
rates might have been higher had treatment been restricted
to only patients with acute iliofemoral DVT. However,
patients who had more distal and chronic venous thrombosis
were included, resulting in a lower overall success rate. In
these three studies, 422 patients were treated with remarkably consistent rates of success and complications.
Three of the larger reports demonstrate approxi-
18–20
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TABLE 49.1 Results of Catheter-Directed Thrombolysis
with Urokinase in Three Contemporary Series: Effi cacy and Complications
Effi cacy
Bjarnason Mewissen Comerota
et al.
(n = 77) (n = 287) (n = 58)
Initial Success 79% 83% 84%
Iliac 63% 64% 78%
Femoral 40% 47% —
Primary Patency at 1 yr
Iliac 63% 64% 78%
Femoral 40% 47% —
Iliac Stent: Patency at 1 yr
+Stent 54% 74% 89%
−Stent 75% 53% 71%
Complications
Major Bleed 5% 11% 9%
Intracranial Bleeding 0% <1% 0%
Pulmonary Embolism 1% 1% 0%
Fatal Pulmonary Embolism 0% 0.2% 0%
Death Secondary to Lysis 0% 0.4% 0% (? 2%)*
*Death due to multiorgan system failure 30 days post lysis, though not
related to lytic therapy.
18
et al.
19
et al.
20
Catheter-directed urokinase was used in each of these
studies. Underlying iliac vein stenoses were treated with
balloon angioplasty, stenting, or both to achieve unobstructed venous drainage into the vena cava and reduce
the risk of recurrent thrombosis (see Figure 49.2).
Major bleeding occurred in 5 to 10% of cases, with the
majority resulting from puncture site bleeding. Intracranial
bleeding was rare, occurring in only three patients in the
National Venous Registry.19 This resulted in the death of one
patient. Pulmonary embolism (PE) occurred in 1% of patients
in the series reported by Bjarnason et al.18 and the National
Venous Registry, and fatal PE occurred in only one out of
the 422 patients. Therefore, death as a result of catheterdirected thrombolysis was rare.
Until approximately six years ago, most patients treated
with catheter-directed thrombolysis were managed with
urokinase. Since urokinase was removed from the market,
catheter-directed alteplase and reteplase have demonstrated
similarly good results.
22–25
An interesting new therapeutic approach was reported by
Chang et al.23 when they used intrathrombus bolus dosing
of rt-PA in 12 lower extremities of 10 patients with acute
DVT. They infused rt-PA intrathrombus using the pulsespray technique and no more than 50 mg per treatment. After
the pulse-spray bolus, patients were returned to their rooms
and brought back the following day for repeat venographic
examination. Continuous infusion was not used. Patients
had treatment repeated for up to four daily sessions. Results
were excellent; 11 lower extremities had signifi cant or com-
plete lysis, and the remaining leg 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 more than 2%. This technique is deserving of
further study to evaluate whether others can obtain similarly
good results.
A further analysis of the patients treated in the National
19
Venous Registry
offers important clinical insight into
catheter-directed thrombolysis for patients with acute DVT.
Of the 287 patients treated in both academic and community
centers, 66% had acute DVT, 16% had chronic DVT, and
19% had an acute episode superimposed upon a chronic
condition. Seventy-one percent of the patients presented
with iliofemoral DVT and 25% with femoropopliteal DVT.
Catheter-directed thrombolysis with intrathrombus infusion
of urokinase was the preferred approach. However, some
patients were treated with urokinase infused into a foot vein,
which was essentially systemic thrombolysis. Phlebographic
evaluation showed that 31% of patients had complete lytic
success and 52% had 50 to 99% lytic success. In 17% of
patients, less than 50% of the thrombus was dissolved. When
urokinase was not infused intrathrombus, success rates fell
dramatically. In the subgroup of patients with acute, fi rsttime iliofemoral DVT, 65% of the patients enjoyed complete
clot lysis.
During follow-up, thrombosis-free survival was observed
in 65% at six months and in 60% at 12 months. There was
a signifi cant correlation (P < .001) of thrombosis-free survival with the results of initial therapy. Seventy-eight percent
of patients with complete clot resolution had patent veins at
one year, compared with only 37% of those in whom less
than 50% of the clot was dissolved. Interestingly, in the
subgroup of patients with acute, fi rst-time iliofemoral DVT
who had successful thrombolysis, 96% of the veins remained
patent at one year. In addition to sustained patency, early
success directly correlated with valve function at six months.
Sixty-two percent of patients with less than 50% thrombolysis had venous valvular incompetence, whereas 72% of
patients who had complete lysis had normal valve function
(P < .02).
The large database of the National Venous Registry
offered an opportunity to objectively evaluate the long-term
impact of catheter-directed thrombolysis on patients with
iliofemoral DVT. Since the National Venous Registry
collected data only on patients treated with thrombolytic
therapy, a contemporary cohort of patients with iliofemoral
DVT treated with anticoagulation in the same institutions
was identifi ed. All anticoagulated patients were candidates
for lytic therapy but were treated with anticoagulation alone
due to physician preference. A validated quality-of-life
(QOL) questionnaire was used to query patients at 16 and
22 months posttreatment. Of the 98 patients studied, 68
were treated with catheter-directed lysis and 30 treated with
anticoagulation alone. Those treated with catheter-directed
Intrathrombus Catheter-Directed Thrombolysis 459
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thrombolysis reported a signifi cantly better QOL than those
treated with anticoagulation alone. The QOL results were
directly related to the initial success of thrombolysis. Patients
who had a successful lytic outcome reported a signifi cantly
better Health Utilities Index, better physical functioning,
FIGURE 49.2 A. Initial phlebogram (prone iliocavagram) of a patient with extensive iliofemoral DVT who presented
with a swollen, painful left leg. Using ultrasound guidance, the catheter was positioned into the thrombus of the iliofemoral segment. A plasminogen activator (t-PA) was infused at 1 mg/hr. B. After 22 hours of catheter-directed t-PA
infusion, the patient had a good phlebographic and clinical response. A stenosis of the left iliac vein was identifi ed. C.
The stenosis was treated with balloon angioplasty and a 16-mm Wallstent was deployed and dilated. D. Final phlebogram
showing unobstructed venous drainage into the vena cava.
less stigma of chronic venous disease, less health distress,
and fewer overall postthrombotic symptoms. Patients in
whom catheter-directed thrombolysis failed had similar outcomes to patients treated with anticoagulation alone. These
effi cacy data combined with the observed reduction in
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complications offer a sound argument for the management
of patients with iliofemoral DVT with catheter-directed
thrombolysis.
A small, randomized trial performed by Elsharawy et al.26
demonstrated that catheter-directed thrombolysis versus
anticoagulation alone offered signifi cantly better outcomes
at six months. Assuming patients are properly managed with
anticoagulation, the six-month observations should refl ect
their long-term outcome.
We believe that the results available to date support a
strategy of catheter-directed thrombolysis for acute iliofemoral DVT in patients who have no contraindication to thrombolytic therapy. If a contraindication to lytic therapy exists,
a contemporary venous thrombectomy (Chapter 45) followed by long-term anticoagulation should be considered.
PATIENT EVALUATION AND TECHNIQUE
OF CATHETER-DIRECTED THROMBOLYSIS
Patient Evaluation
It is intuitive and clinically apparent that patients with
iliofemoral DVT have a greater stimulus to thrombosis than
the majority of patients with DVT and therefore warrant a
search for an underlying etiology. Asymptomatic pulmonary
emboli are present in at least 50%. It is important that the
PE be recognized early, since up to 25% will subsequently
become symptomatic, manifesting as pleuritic chest discomfort once the infl ammatory pulmonary process reaches the
pleural surface. If the PE is not recognized, the clinician
often mistakenly assumes that the pleuritic symptoms are
due to a new PE and failure of treatment. A spiral CT scan
of the chest with contrast evaluates the pulmonary vasculature for PE and other thoracic pathology (see Figure 49.3a).
The CT is extended to the abdomen and pelvis to identify
the proximal extent of thrombus and to evaluate for abdominal or pelvic pathology (see Figure 49.3b). This has been an
important addition to the evaluation of these patients, as we
have found serious unsuspected pathology with surprising
frequency. Renal cell carcinoma, adrenal tumors, retroperitoneal lymphoma, hepatic metastases, iliac vein aneurysms,
and vena caval atresia all have been identifi ed. A full hematologic evaluation for an underlying thrombophilia is also
performed.
Technique
There has been an evolution of catheter-directed thrombolytic techniques over the past several years. The preferred
approach is through an ultrasound-guided popliteal vein
puncture with antegrade passage of the infusion catheter.
Through this approach physicians can incorporate adjunctive mechanical thrombectomy techniques.
FIGURE 49.3 Initial CT scan of the chest, abdomen, and pelvis of a 65-
year-old male with chronic low back pain who presented with left lower
extremity phlegmasia cerulea dolens. The chest CT (A) shows an asymptomatic pulmonary embolus (arrow). The abdominal CT (B) shows extensive retroperitoneal and pelvic lymphadenopathy (arrows) compressing the
distal vena cava and the left iliac system. All patients presenting with iliofemoral DVT by duplex ultrasound receive chest, abdominal, and pelvic
CT scans as part of the initial workup.
If the popliteal vein is thrombosed, an additional catheter
is placed through an ultrasound-guided tibial vein puncture.
Using catheters that achieve long segments of thrombus
infusion is advised.
There also has been an evolution in the dose and volume
of plasminogen activator. Since the activation of fi brinbound plasminogen is not dose dependent, exposure to the
plasminogen activator is all that is required. The volume of
the lytic solution has increased with a decrease in the concentration (dose) of plasminogen activator. It is now our
preference to increase the volume of lytic infusion to 80 to
100 ml per hour. The larger volume is intended to saturate
Patient Evaluation and Technique of Catheter-Directed Thrombolysis 461
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the thrombus, exposing more fi brin-bound plasminogen to
the plasminogen activator. Phlebograms are obtained at 12hour intervals and are used to monitor the success of lysis
and reposition catheters if necessary. Vena caval fi lters are
not routinely used but are recommended for patients with
free-fl oating thrombus in the vena cava. A retrievable fi lter
can be used in the patient in whom only temporary protection is needed.
Following successful thrombolysis, the venous system is
examined with completion phlebography. If a stenosis exists,
which is frequently observed in the left common iliac vein
where it is compressed by the right common iliac artery, the
vein is dilated and stented if necessary. The addition of
intravascular ultrasonography has improved the evaluation
of iliac compression and the precision of stent deployment
when these lesions are corrected. Residual areas of stenosis
must be corrected for long-term success; otherwise, the
patient faces a high risk of rethrombosis. If a stent is used,
it should be sized appropriate to the normal diameter of the
common iliac vein.
FIGURE 49.4 A, B, C. Phlebogram of a patient two days after exploratory laparotomy shows left iliofemoral, femo-
ropopliteal, and posterior tibial DVT. The treatment goal was to lyse the extensive thrombus rapidly with minimal systemic exposure to the plasminogen activator. D. This was accomplished using segmental pharmacomechanical
thrombolysis with the hybrid Trellis peripheral infusion system (Bacchus Vascular, Santa Clara, CA) and ultrasound
accelerated thrombolysis of popliteal and tibial thrombus with the EKOS LysUS® System (EKOS Corp, Bothell, WA).
The Trellis system achieves isolated thrombolysis between two occluding balloons by lytic infusion and mechanical
drug dispersion with the intervening catheter rotating at 15,000 rpm. This mechanism of thrombolysis enables focused
treatment of thrombus within the target vessel. E, F. Phlebogram 30 minutes after using the Trellis system shows resolution of the thrombus in the iliac and femoral veins.
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