Eur. Radiol.
7, 996–1001 (1997)  Springer-Verlag 1997
Original article
Catheter-directed lysis of iliofemoral vein thrombosis
with use of rt-PA
R. Verhaeghe2, L. Stockx1, H. Lacroix3, J. Vermylen2, A. L. Baert1
1
Department of Radiology, Centre of Vascular Pathology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
2
Department of Vascular Diseases, Centre of Vascular Pathology, University Hospital Gasthuisberg, Herestraat 49,
B-3000 Leuven, Belgium
3
Department of Vascular Surgery, Centre of Vascular Pathology, University Hospital Gasthuisberg, Herestraat 49,
B-3000 Leuven, Belgium
Received 26 August 1996; Revision received 20 December 1996; Accepted: 30 December 1996
Abstract. The aim of our study was to evaluate the re-
sults of catheter-directed thrombolysis and comple-
mentary procedures to treat acute iliofemoral deep
vein thrombosis (DVT). A total of 24 consecutive pa-
tients with acute iliofemoral DVT underwent intra-
thrombus drip infusion of alteplase (3 mg/h; mean
dosage 86 mg, range 45–174 mg), while intravenous
heparin (1000 U/h) was continued. Complementary
procedures were hydrodynamic thrombectomy in 3
and primary insertion of a Wallstent in 9 patients. Pa-
tency of 19 thrombosed veins (79 %) was restored
with prompt symptomatic relief. An underlying ana-
tomical anomaly or lesion was present in 13 patients:
iliac vein compression syndrome (n = 8), absent
(n = 2) or obstructed (n = 1) vena cava or venous
stenosis (n = 2). Ten of the abnormalities were un-
known before lysis and eight were relieved by stent
deployment. Puncture site bleeding was the only
complication but led to transfusion in 6 patients
(25 %). Symptomatic reocclusion occurred in 4 pa-
tients. Catheter thrombolysis of iliofemoral vein
thrombosis revealed many anatomical abnormalities
which may predispose to thrombosis and are often
amenable to stenting.
Key words: Thromboembolism – Thrombolytic ther-
apy – Vascular stent – Hydrodynamic thrombectomy
Introduction
Deep venous thrombosis extending into the iliac veins is
associated with significant acute and late morbidity de-
spite adequate conventional treatment with heparin
and oral anticoagulants [1, 2]. Recently, an aggressive
Correspondence to: R. Verhaeghe
European
Radiology
multidisciplinary approach with catheter-directed
thrombolysis was advocated with the aim to eliminate il-
iofemoral venous thrombus, to provide unobstructed
venous drainage from the affected limb and to prevent
recurrent thrombosis [3, 4]. We report our own initial
experience with catheter-directed thrombolysis for il-
iofemoral venous thrombosis.
Materials and methods
Patients were selected for catheter-directed thromboly-
sis on the basis of the following four criteria: (a) leg ve-
nous thrombosis confirmed by duplex ultrasound or
venography; (b) thrombus extending into the common
iliac vein; (c) severe clinical symptoms of thrombosis
(pain and swelling which prohibit standing on the leg)
but no associated ischaemia; and (d) no standard con-
traindication to infusion of a thrombolytic agent (partic-
ularly no surgery within the past 10 days). Over an 18-
month period (September 1994 to February 1996) 26 pa-
tients fulfilled these criteria and catheter thrombolysis
was proposed. One patient refused and one withdrew
consent after a failed attempt to position the catheter
properly (they are not included). The 24 patients who
gave fully informed consent were 9 males and 15 females
with a mean age of 38 years (range 16–76 years). The left
leg was involved in 17, the right in 6 and the last patient
had a bilateral thrombosis. Sixteen patients presented
with their first episode of thrombosis and the remaining
8 had recurrent thrombosis. The thrombus extended
proximally into the common iliac vein in 20 and into the
vena cava in the other 4 patients. The approximate age
of thrombosis varied from 2 to 24 days (mean 7 days).
Fifteen patients were referred from other centres be-
cause of aggravating symptoms despite adequate hepa-
rin therapy (n = 12) or systemic infusion of streptokinase
(n = 3). Of the 11 patients diagnosed in our own centre,
catheter thrombolysis was the immediate therapeutic
R. Verhaeghe et al.: Catheter-directed lysis of iliofemoral vein thrombosis with use of rt-PA 997

Table 1. Treatment and outcome in patients with restoration of antegrade flow. T transfusion required; ven venography; dup duplex sonog-
raphy
Sequence Total dose of Duration of Post-lysis Adjunctive Bleeding Follow-up; events; remarks
rt-PA (mg) infusion (h) venography procedure complication
1 66 22 Iliac vein compression Wallstent Access site (T) Reocclusion stent (8 m; ven);
factor V-Leiden
2 60 20 Iliac vein compression Wallstent None Clinically well; factor V-Leiden
3 117 39 Residual thrombi None Access site (T) Clinically well
4 45 15 Residual thrombi None Access site (T) Clinically well
5 45 15 Full patency None None Clinically well; hyperhomo-
cysteinaemia
6 72 24 Iliac vein compression Wallstent None Stent open (1 year; dup)
8 114 51 Lumbo-azygos drainage None Mild epistaxis Clinically well; hyperhomo-
(thrombosed vena cava) cysteinaemia
9a 72 24 Reopening of stented vein None None Stent open (1 year; dup)
10 54 18 Iliac vein compression Wallstent None Clinically well
11 174 53 Lumbo-azygos drainage None None Clinically well; factor V-Leiden
(absent vena cava)
13 126 42 Iliac vein compression Wallstent Access site Stent open (9 m; ven)
14 64 26 Common femoral vein Wallstent None Clinically well
stenosis
15 60 20 Residual thrombi None Access site Short thrombosis superior femoral
vein (3 days)
16 69 23 Residual thrombi Hydrodynamic Access site (T) Clinically well; factor V-Leiden
thrombectomy
17 60 20 Iliac vein compression Wallstent None Stent open (6 m; ven); protein-S
deficiency
18 93 31 Residual thrombi Hydrodynamic None Clinically well; factor V-Leiden
thrombectomy hyperhomocysteinaemia
22 144 48 Residual thrombi Hydrodynamic Access site Short thrombosis superior femoral
thrombectomy vein (4 days)
Three Wallstents Stents open (6 m; ven); protein-S
deficiency
23 105 51 Lumbo-azygos drainage None Access site Clinically well
(absent vena cava)
24 66 22 Iliac vein stenosis Two Wallstents Access site (T) Rethrombosis of stented vein
(postirradiation) (6 days)
Second successful lysis
Rethrombosis (6 weeks)
a
Patient with Wallstent for iliac vein compression, inserted after thrombectomy for first thrombosis

option in 6, whereas the remaining 5 first received con-
ventional heparin without symptomatic relief. Previous
episodes of thrombosis involved the same leg in 7 of the
8 patients with recurrent thrombosis. Predisposing fac-
tors to thrombosis were trauma leading to surgical inter-
vention (n = 2) or to immobilization (n = 2), and post-
partum (n = 1). One patient had a history of surgery for
colon cancer followed by pelvic irradiation a few years
earlier. The remaining 18 cases were considered as “idio-
pathic” thrombosis at the time of diagnosis. In 10 of
these cases 11 haematological abnormalities, often re-
ferred to as “thrombophilia” factors ,were discovered: 5
were heterozygous for the factor V-Leiden mutation,
2 had protein S- and 1 antithrombin-III deficiency and 3
an elevated plasma level of homocysteine.
A 5-F straight catheter with ten sideholes was intro-
duced via the contralateral femoral vein and advanced
over the caval bifurcation with its tip into the thrombus.
If this failed, the ipsilateral popliteal vein was punctured
antegradely (n = 8). In the patient with recent bilateral
thrombosis which occluded the vena cava totally, the in-
ternal jugular vein was the access site. Alteplase (rt-PA,
Boehringer Ingelheim, Biberach, Germany) was infused
into the thrombus at a rate of 3 mg/h with the aid of an in-
fusion pump. Seven patients did not strictly follow this
protocol: they received 6 mg/h for the initial hours
(n = 2), had a prolonged infusion of 1 mg/h in an attempt
to lyse residual thrombi once antegrade flow was restored
(n = 4) or both (n = 1). Intravenous heparin was adminis-
tered simultaneously at a fixed rate of 1000 IU/h. Progres-
sion of lysis was controlled by injection of contrast fluid at
least at early morning and late afternoon, and the cathe-
ter was repositioned, if required, or withdrawn stepwise.
The infusion of lytic drug was stopped if no residual
thrombotic material was visible or if no further lysis was
observed between two consecutive control venographies.
998 R. Verhaeghe et al.: Catheter-directed lysis of iliofemoral vein thrombosis with use of rt-PA

Fig. 1. Thrombosis of the left

iliofemoral vein (left). Thromboly-
sis reveals an iliac vein compression
syndrome (middle), which is
relieved by inserting a stent (right)

No prophylactic inferior vena caval filters were placed Table 2. Treatment and outcome in patients with failure of throm-
prior to thrombolysis, except in one patient who had bolysis. T transfusion required; P popliteal; F femoral; I iliac; C ca-
val vein; bil bilaterally
symptomatic pulmonary embolism before referral.
In 3 patients hydrodynamic thrombectomy with the Se- Exten- Total dose Duration Bleeding Postthrom-
Hydrolyser (Cordis, Roden, The Netherlands) was car- quence sion of of rt-PA of infu- compli- botic
thrombus (mg) sion (h) cation symptoms
ried out to further reduce the mass of lysis resistent
thrombus [5]. Nine patients received Wallstents 7 P, F, I 100 24 Access site Disabling
(Schneider, Bülach, Switzerland) with a diameter rang- 12 a
P, F, I 78 26 None Disabling
ing from 9 to 16 mm for remaining flow obstruction af- 19 P, F, I, 144 48 Access site Mild
ter thrombolysis (see Results). (bil), C (T)
After thrombolysis, all patients received conven- 20b P, F, I 117 39 Access site Mild
tional anticoagulant treatment for at least 6 months 21 I, C 69 23 None Mild
(heparin, dosage adjusted to aPTT prolongation of 1.5– a
Patient with known iliac vein compression syndrome since first
2.5 times the control value, relayed with fenprocoumon,
thrombotic episode
dosage adjusted to obtain an INR of 2.0–3.0) to prevent b
Patient with protein-S deficiency
recurrent thromboembolism. Clinical follow-up was
scheduled trimonthly in the first year and every
6 months thereafter. Imaging, if obtained, is mentioned
for each individual patient in Table 1. The mean follow- 9 months when she underwent lysis for recurrent throm-
up was 13 months (range 6–23 months). bosis 3 months after interruption of anticoagulant treat-
ment. Cockett’s syndrome had been discovered when
she redeveloped swelling of her left leg, 8 months after a
Results venous thrombectomy for a phlegmasia coerulea dolens.
Two additional patients received a stent: one had an ir-
Immediate outcome regular narrowing secondary to pelvic irradiation a few
years earlier and the second had an unexplained stenosis
Antegrade flow in the thrombosed iliofemoral venous of the common femoral vein with flow obstruction.
tract was restored in 19 of the 24 patients (Table 1). In Three patients with reopened iliac vein had venous
6 of these patients, residual thrombi adjacent to the drainage through a lumbo-azygos collateral system. No
vein wall resisted even prolonged exposure to the inferior vena cava was seen on computed tomography
thrombolytic agent. In 3 patients the remaining clot did in two young males; the renal veins drained via the
not impede normal venous flow, but in the other three same collaterals and one had a horseshoe kidney. The
it caused flow obstruction and complementary hydrody- third one had a previous history of well-documented
namic thrombectomy was carried out. This adjunctive vena cava thrombosis.
procedure was completely successful in two, but only In 5 patients lysis was only partial and the procedure
partially successful in the third, in whom Wallstents failed to restore normal antegrade flow (Table 2). One
were inserted to further improve the calibre of the patient had a known iliac vein compression syndrome.
vein. Thus, patency by lysis alone was 16 of 24 (67 %) It was diagnosed in another centre 3 years earlier when
and by lysis plus adjunctive techniques 19 of 24 (79 %). a first-episode of left leg thrombosis was treated suc-
Six of the patients in whom thrombolysis completely cessfully with systemic thrombolysis, but left untouched.
lysed all thrombotic material in the left leg, had evidence Her second thrombosis was managed with conventional
of an iliac vein compression syndrome on their post-lysis anticoagulant therapy elsewhere and she was referred a
venogram. The catheter procedure was then completed few weeks later when aggravating symptoms suggested
by primary stenting of this segment to ensure adequate recurrent thrombosis. Two other patients had their two
expansion of the common iliac vein (Fig. 1). Another pa- iliac veins and the vena cava occluded: in one this was
tient already had a Wallstent in her left iliac vein for due to recent bilateral thrombosis, whereas the second
R. Verhaeghe et al.: Catheter-directed lysis of iliofemoral vein thrombosis with use of rt-PA
b opment of extensive collateral net-
had a non-recanalized iliac vein from a previous throm-
botic episode and a recent contralateral thrombosis.
Complications
Puncture site haematoma was the only complication of
thrombolysis: it caused a drop in haemoglobin larger
than 2 g/dl in 12 patients, 6 of whom needed blood trans-
fusion after completion of the procedure. One patient
had a transient mild epistaxis during rt-PA infusion.
The stenting procedure as such was uncomplicated in
all patients. There were no episodes of symptomatic pul-
monary embolism during the lysis procedure.
Follow-up
Patients with a successful interventional procedure had
a prompt relief of their symptoms of acute thrombosis.
999
Fig. 2. a Total thrombosis of left il-
iofemoral vein tract (left panel).
Thrombolysis restores patency,
but tight stenosis remains at ilio-
caval junction (right three panels).
b This obstruction is relieved with
Wallstent (left panel), but 7 months
later reocclusion occurs with devel-
work (right panel)
Clinical follow-up since thrombolysis and stent place-
ment was uneventful in 15 patients: no new episode of
acute clinical thrombosis occurred. One patient noticed
development of an enlarged collateral vein on the ab-
dominal wall after 7 months. Her stented iliac vein ap-
peared reoccluded at control venography despite con-
tinued anticoagulant treatment (Fig. 2). Three patients
had a rethrombosis within the first few days while still
hospitalized: in two the symptoms were minor and a
short segment only of the superficial femoral vein was
involved so that conventional anticoagulant treatment
was continued; the third underwent a second successful
thrombolytic procedure. Retraction and kinking of her
iliac stent (inserted for postirradiation narrowing)
caused inflow obstruction that was relieved by deploy-
ment of an additional short stent. However, recurrent
thrombosis developed 6 weeks later and no further at-
tempt at thrombolysis was made. Cumulative patency
of successfully reopened veins (life-table method) was
84.2 ± 8.4 % at 3 months and 78.2 ± 11 % at 1 year.
1000 R. Verhaeghe et al.: Catheter-directed lysis of iliofemoral vein thrombosis with use of rt-PA
The 5 patients with failure of thrombolysis received
conventional anticoagulant treatment. They had persist-
ing postthrombotic symptoms, which disabled two in
their professional activities.
Discussion
Lysis of thrombi is the primary objective of throm-
bolytic therapy in deep venous thrombosis. The infusion
of thrombolytic agent through a peripheral vein results
in a significant reduction in thrombus size in comparison
with standard heparin therapy [6, 7]. The results of
many descriptive trials are reported in categories of lysis
or in reduction of clot extension as assessed with scoring
systems, and rates of complete recanalization or com-
plete lysis – if mentioned separately- vary enormously,
e. g. from nil [8] to almost two thirds in very fresh throm-
bosis [9]. Local intraclot delivery with better diffusion of
the drug into the entire thrombus mass may be expected
to result in higher recanalization rates. This working hy-
pothesis is now widely accepted for leg arterial throm-
bosis and the present data together with published se-
ries [3, 4, 10] appear promising for venous thrombosis
as well. The use of complementary percutaneous – be
they still experimental– techniques of clot removal may
further improve the final results. Catheter-directed
thrombolysis has two drawbacks: it is labor intensive
and there is the bleeding risk. In the present series all
bleeding was confined to puncture sites, but was impor-
tant in 25 % of patients, even if it did never lead to pre-
mature interruption of therapy.
We selected an infusion rate of 3 mg/h of rt-PA for
this initial experience of venous thrombolysis because
we had a 10-year-long experience with this dosage
scheme in arterial thrombolysis. Choice and dosage
scheme of lytic agent for catheter-directed thrombolysis
in leg arterial occlusion are dictated by local preference,
rather than by solid scientific data. A pilot trial with rt-
PA suggested that an infusion rate of 3 or 5 mg/h pro-
duced similar results as 10 mg/h [11]. Similar infusion
rates (0.1 and 0.05 mg/kg per hour) were tested in the
trial evaluating surgery vs thrombolysis for ischaemia
of the lower extremity (STILE), but in other countries
lower infusion rates (e. g. 0.5 or 1.0 mg/h) are being ad-
vocated [12–14]. An interrelationship between infusion
rate, duration of lysis and risk of bleeding is not firmly
established in peripheral arterial thrombolysis. In the
present series of venous thrombolysis, patients with a
bleeding complication received on average rt-PA for
9 more hours (34 vs 25 h) than those who did not bleed,
but the difference is not significant. Puncture site bleed-
ing starts during lysis and obviously the haematoma
keeps growing as long as the infusion lasts; its full extent
is only appreciated the day after termination of the pro-
cedure. Whether a lower infusion rate would reduce the
bleeding risk from the access site is an unanswered ques-
tion that would require a comparative trial.
The present series contained 13 patients in whom an-
atomical anomalies and lesions prevented normal ve-
nous flow and may have contributed to thrombosis; 10
of them were newly discovered as a result of the current
thrombolytic procedure. If this anatomical element is ta-
ken into consideration as a prothrombotic factor in addi-
tion to the discovered haematological anomalies, only
two cases of thrombosis remain “idiopathic”. Semba
and Dake found underlying haemodynamically signifi-
cant venous stenosis in two thirds of the affected limbs
after lysis, but their report does not provide full details
on the nature of these lesions [3]. Their population also
differed with, for instance, almost half of the thromboses
secondary to surgery or to radiation injury, whereas only
one of our patients had a postirradiation venous lesion
and two had been operated on 3 weeks prior for trauma.
Two young patients had an aplasia or hypoplasia of
the inferior vena cava. This congenital anomaly is rarely
reported and causes in most patients few symptoms and
clinical signs, although associated venous thrombosis
has been mentioned [15]. Eight patients had an iliac
vein compression syndrome [16], two already known
and six newly discovered after thrombolysis. It is hardly
possible to diagnose iliac vein compression underlying
an acute iliac vein thrombosis by either venography or
ultrasound before removal of the obstructing thrombus.
Catheter-directed thrombolysis appears a particularly
elegant approach in these patients since it dissolves the
thrombus and at the same time discloses the underlying
anatomical problem if present. Although the current se-
ries suggests that an iliac vein compression syndrome is
a fairly common anatomical contribution to acute left il-
iofemoral vein thrombosis, the particular selection of
patients fit for thrombolysis, thus largely eliminating
postoperative thrombosis, may overestimate the real in-
cidence of anatomical anomalies.
Venous stents are being used to relieve malignant ob-
struction and benign strictures; thus, their use in the iliac
vein compression syndrome appears suitable [17]. Fail-
ure to eliminate the underlying anatomical obstacle to
normal flow may lead to recurrence upon interruption
of anticoagulants, as occurred in a patient with an iliac
compression syndrome of the present series. The stent-
ing procedure linked to catheter thrombolysis is rela-
tively simple and appears safe in experienced hands,
but questions remain on the rethrombosis risk and a po-
tential risk of late arterial erosion. An extensive fibrotic
reaction develops at the point of intimate contact be-
tween vein and artery in the iliac compression syn-
drome, resulting from chronic irritation induced by the
arterial pulsations. Conceivably, the presence of a stent
in such an area may potentially lead to late wall erosion
and false aneurysm formation.
Acknowledgement. J. Vermylen is holder of the Dr J. Choay Chair
in Haemostasis Research.
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Book reviews
Skorton, D. J., Schelbert, H., Wolf, G., Brundage, B.: Marcus Car-
diac Imaging: A Companion to Braunwald’s heart disease, 2nd
edn. Philadelphia: W. B. Saunders 1996. 1218 pp., (ISBN 0-7216-
4687-5), $ 205.00.
Five years after the first edition of this memorable handbook of
cardiac imaging was published, a new two-volume edition was ed-
ited and named Marcus Cardiac Imaging in acknowledgment and
honor of the late Dr. Melvin Marcus, founding editor of the book.
Edited by four internationally recognized experts in the field, this
new edition represents much more than a simple revision. Approx-
imately half the chapters are new or were written by new authors,
and both volumes are replete with spectacular new illustrations.
To guide the clinician to the specific technique required for
addressing specific clinical issues a entire new section entitled
‘Integrated clinical approach to diagnosis using imaging methods’
has been added to this edition.
Since the first edition virtually all modalities of cardiac imaging
have experienced exponential growth and development. All chap-
ters in the echocardiography section have been updated and re-
vised. The chapter on transesophageal echocardiography has been
extensively revised since this technique allows assessment of car-
diac morphology and function not only in the clinic but also in the
emergency room and operating suite. A new chapter on intravas-
cular ultrasound has been added. The chapters on fast computed
tomography have also been updated, as well as those on radionu-
clide methods focusing on the assessment of myocardial viability
with thallium-201 and technetium-99m labeled radionuclides and
on the assessment of the absolute myocardial blood flow quantifi-
cation with positron emission tomography (PET). The section on
magnetic resonance imaging (MRI) has been extensively rewritten
and includes a new chapter by E. A. Zerhouni summarizing the
amount of information that can be obtained in a 1-h integrated car-
diac MRI examination.
In conclusion, this book can be strongly recommended as the
reference work for anyone dealing with cardiac imaging, in partic-
ular the cardiovascular radiologist, cardiologist and cardiovascular
1001
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HM (1994) Catheter-directed thrombolysis following vena
cava filtration for severe deep venous thrombosis. Ann Vasc
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artery thrombolysis with intra-arterial infusion of recombinant
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Vasc Surg 2: 155
12. The STILE investigators (1994) Results of a prospective ran-
domized trial evaluating surgery versus thrombolysis for is-
chemia of the lower extremity. Ann Surg 220: 251
13. Berridge DC, Gregson RHS, Hopkinson BR, Makin GS (1991)
Randomized trial of intra-arterial recombinant tissue plasmi-
nogen activator, intravenous recombinant tissue plasminogen
activator and intra-arterial streptokinase in peripheral arterial
thrombolysis. Br J Surg 78: 988
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nant tissue-type plasminogen activator is superior to streptoki-
nase for local intra-arterial thrombolysis. Br J Surg 79: 272
15. Halbmayer WM, Radek J, Duschet P et al. (1993) Rezidivie-
rende Venenthrombosen bei Vena-Cava-Inferior-Hypoplasie
und Faktor-XII-Mangel. Dtsch Med Wochenschr 118: 1561
16. Cockett FB, Lea Thomas M (1965) The iliac compression syn-
drome. Br J Surg 52: 816
17. Berger A, Jaffe JW, York TN (1995) Iliac compression syn-
drome treated with stent placement. J Vasc Surg 21: 510
European
Radiology
surgeon, with the ultimate goal of improvement in patient care. It
represents the perfect ‘Companion’ to Braunwald’s new (fifth) edi-
tion of Heart Disease: A Textbook of Cardiovascular Medicine.
J. Bogaert, Leuven
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