Comparing Short-Term Outcomes of

Femoral-Popliteal and Iliofemoral Deep

Venous Thrombosis: Early Lysis and
Development of Reflux

Harvir Singh, BS,1 and Elna M. Masuda, MD,2 Stanford, California and Honolulu, Hawaii

This study compares the development of reflux, recanalization, and clinical outcomes of patients
with femoral-popliteal and iliofemoral deep venous thrombosis (DVT). Emphasis is placed on the
relationship between early lysis of clot through thrombolysis and the development of reflux and
post-thrombotic syndrome (PTS) for iliofemoral patients. A retrospective chart review was
conducted of 27 femoral-popliteal DVT limbs and 11 iliofemoral DVT limbs with average follow-
up of 2.3 and 2.1 years, respectively. Rates of recanalization, development of reflux, and post-
thrombotic syndrome were recorded through review of duplex scans and physical examinations.
All femoral-popliteal patients received anticoagulant therapy. Nine of 11 iliofemoral patients
(82%) received thrombolytic therapy in addition to anticoagulants. Statistical analysis included
Kaplan-Meier estimation to take into account dropout in follow-up times, and chi-squared
analysis to compare final outcomes. A significantly greater proportion of iliofemoral patients
(73%) than femoral patients (31%) remained asymptomatic at the end of their follow-up (p <
0.025). Because of thrombolytic therapy, 82% of iliofemoral limbs showed partial or complete
lysis 4 weeks after diagnosis of clot. As expected, only 22% of femoral-popliteal limbs developed
some recanalization 4 weeks after diagnosis (p < 0.005). Interestingly, no significant difference
in reflux development was observed between the two groups. After an average of 2.1 years,
60% of femoral-popliteal limbs developed reflux in the deep veins vs. 64% for iliofemoral limbs.
The iliofemoral DVT patients showed improved clinical outcomes in the short term compared to
that of femoral-popliteal patients in this pilot study. The improved clinical outcomes could be
attributed to the early lysis of clot via thrombolytic therapy for the iliofemoral group. Although the
extent of reflux development was similar in both groups, iliofemoral patients still showed fewer
clinical symptoms after follow-up. This may suggest that the presence of both residual
obstruction and reflux, rather than either one alone, significantly increases the chances for
development of PTS. Since thrombolytics eliminates at least one of these factors, residual
obstruction, it may aid in decreasing development of PTS in the short term. The data in this
retrospective study warrant further long-term prospective analysis of thrombolysis and its rela-
tionship with PTS.

INTRODUCTION patients, potentially because of the effects of early

The advent of thrombolysis in the treatment of
deep venous thrombosis (DVT) has been thought to
contribute to the improved quality of life for DVT
1
Stanford University, Stanford, CA.
2
Vascular Division, Straub Clinic and Hospital, Honolulu, HI.
Correspondence to: H. Singh, BS, Straub Foundation, P.O. Box
12512, Stanford, CA 94309, USA, E-mail: harvir@stanford.edu
Ann Vasc Surg 2005; 19: 74-79
DOI: 10.1007/s10016-004-0133-3
Ó Annals of Vascular Surgery Inc.
Published online: January 11, 2005
lysis of clot.1 There have been few studies, how-
ever, examining the physiological effects of
thrombolytic therapy. The use of thrombolysis has
been largely limited to iliofemoral DVT patients.
The potential benefits, however, may warrant dis-
cussion of extending thrombolytic therapy to pa-
tients with femoral-popliteal DVT.
Studies have shown that DVT of the distal calf veins
has a relatively low occurrence of post-thrombotic
syndrome (PTS).2,3 DVT of the more proximal
veins, however, including the popliteal (knee),
femoral (thigh), and iliac (pelvic) veins, has been

74
Vol. 19, No. 1, 2005
shown to have higher rates of PTS and pulmonary
embolism.4 Unfortunately, few studies have fo-
cused on comparisons between specific venous re-
gions such as the femoral-popliteal segments and
iliofemoral segments. Although it is generally ac-
cepted that patients with iliofemoral DVT have
greater risks for PTS than those with femoral-pop-
liteal DVT, the advent of thrombolytic therapy for
iliofemoral patients potentially challenges this
generally accepted belief.
This retrospective pilot study compares the
development of reflux, recanalization, and PTS of
femoral-popliteal and iliofemoral DVT patients.
This study examines the relationship between early
lysis of clot and development of reflux and PTS in
iliofemoral patients who have undergone throm-
bolytic therapy. A comparison is made with femo-
ral-popliteal patients to highlight the differences of
treatment on physiological and clinical outcomes
and to initiate discussion of extending thrombolysis
to femoral-popliteal patients.
METHODS
A retrospective chart review was conducted of 34
patients with 40 limbs diagnosed with femoral-
popliteal or iliofemoral DVT between 1988 and
2003. Patient records were obtained through the
vascular lab at Straub Hospital in Honolulu, Hawaii,
with approval of the Institutional Review Board.
Diagnosis of DVT was confirmed through review of
color-flow duplex scans performed in the vascular
laboratory by experienced registered vascular
technologists. Diagnosis of DVT was made on the
basis of the finding of all four criteria: (1) non-
compressibility of the vein, (2) dilation of the vein,
(3) lack of a Doppler signal, and (4) lack of visible
flow.
Charts were selected randomly from all patients
who reported to the vascular lab at Straub Clinic
and Hospital between 2000 and 2003 for follow-up
of their DVT. Most patients were initially diagnosed
with DVT within this time period, although eight
patients were diagnosed in the mid to late 1990Õs
and one patient was diagnosed in 1988. Only those
patients who were found to have femoral-popliteal
or iliofemoral DVT, as confirmed through review of
duplex scans, were chosen for this study. Femoral-
popliteal DVT was defined as any deep vein clot
involving at least the femoral vein, but not the iliac
veins. Femoral-popliteal DVT was found in 27
limbs with an average follow-up of 2.3 years. Ili-
ofemoral DVT, defined as any deep vein clot
involving the iliac veins or lower, was identified in
Outcome of femoral-popliteal and iliofemoral DVT 75
11 limbs with an average follow up of 2.1 years.
Venous segments analyzed included the common
iliac (CIV), external iliac (EIV), common femoral
(CFV), profunda femoris (PFV), femoral (FV),
popliteal (pop), posterior tibial (PTV), peroneal
(Per), and greater saphenous (GSV).
Incidence of recanalization, development of re-
flux, and post-thrombotic symptoms were re-
corded. Development of recanalization was defined
as any resolution or lysis of the clot involving the
deep veins through comparison of subsequent du-
plex scans.
Valvular reflux of patients was studied by review
of color duplex scans. Patients were examined by
ValsalvaÕs maneuver in the 15° reversed Trendel-
enburgÕs position, and with pneumatic cuff defla-
tion in the standing position. We chose to be widely
inclusive in our definition of reflux. Therefore, we
defined significant reflux as retrograde flow that
lasts more than 0.5 seconds in the deep veins by
any test with any methods to elicit reflux in any
position.5
Although the American Venous Forum has
established guidelines for venous clinical severity
scoring, these specific guidelines could not be used
to portray the clinical results of our study because
of the retrospective nature of the data. The Venous
Clinical Severity Score (VCSS) uses a point system
whereby 10 factors (pain, edema, etc.) are rated
from 0 = absent to 3 = severe. This level of detail
was simply not available through review of physical
examinations. The physical examinations, how-
ever, did contain enough description of the patient
condition to allow us to classify the limb into one of
three levels to reflect the clinical outcomes of pa-
tients at the end of their follow-up. As shown in
Table I, patients were classified as asymptomatic,
mild PTS, or moderate to severe PTS.
Analysis of data included Kaplan-Meier estima-
tion and life-table analysis6 of cumulative rates of
reflux and recanalization to take into account
varied follow-up times for patients. Chi-squared
analysis was conducted on final results to test for
significance. Analysis of clinical outcomes for both
cases was conducted using the severity levels in
Table I.
RESULTS
Patient Distribution
Femoral-popliteal. Femoral-popliteal DVT was
identified in 27 limbs of 23 patients. Of these pa-
tients, 9 (39%) were female and 14 (61%) were
male. The average age of patients was 60 years
76 Singh and Masuda Annals of Vascular Surgery

Table 1. Clinical severity levels Table II. Location and extent of femoral-popliteal
thrombus
Clinical severity level Symptom classification
Vein involvement n Distribution of limbs (%)
L0 Asymptomatic
L1 Mild pain, occasional swelling FV 2 7.4
L2 Moderate pain, chronic FV-pop 4 14.8
swelling, or multiple symptoms FV-pop-calf 11 40.7
(slight varicose veins, CFV-FV 1 3.7
slight discoloration) CFV-FV-pop 2 7.4
CFV-FV-pop-calf 3 11.1
CFV-PFV-FV-pop 2 7.4
(range, 16-82 years.) DVT was involved in the left
CFV-PFV-GSV-FV-pop 1 3.7
leg in 14 (52%) cases and in the right leg in 13
CFV-PFV-FV-pop-calf 1 3.7
(48%) cases. Four patients had bilateral DVT. Total 27 100
Iliofemoral. Iliofemoral DVT was identified in 11
limbs of 11 patients. Of these patients, 8 (73%) were
female, 3 (27%) were male. The average age of
Table III. Location and extent of iliofemoral
patients was 52 years (range, 16-83). Nine (82%)
thrombus
had DVT in the left leg, two (18%) in the right leg.
Vein involvement n Limbs (%)
Treatments
CIV-EIV 1 9.09
Femoral-popliteal. All femoral-popliteal patients CIV-EIV-CFV 1 9.09
received some kind of anticoagulant therapy, either CIV-EIV-CFV-PFV-FV-pop 1 9.09
low-molecular-weight heparin or intravenous CIV-EIV-CFV-FV-pop-calf 1 9.09
heparin followed by oral warfarin (Coumadin). CIV-EIV-CFV-PFV-FV-GSV-pop 1 9.09
Seventeen (63%) wore compression stockings. EIV-CFV-FV 2 18.18
Iliofemoral. All iliofemoral patients received some EIV-CFV-FV-pop-calf 1 9.09
sort of anticoagulant therapy, with 100% receiving EIV-CFV-PFV-FV-GSV-pop-calf 1 18.18
IVC-CIV-EIV-CFV-PFV-FV-pop 1 9.09
oral warfarin. Nine patients (82%) received cath-
Total 11 100
eter-directed thrombolytic therapy of Urokinase
(Abbott) along with anticoagulants. Of these nine
cases, seven had complete lysis of clot, and two had
partial lysis. Seven patients (64%) were recorded to (27%) the clot spanned the iliac-femoral-popliteal
have received compression stockings. system, and the same amount spanned the iliac-
femoral system. Only one limb (9%) spanned the
Location of Clot iliac veins alone.
Femoral-popliteal. The locations of thrombi are
Development of Reflux
shown in Table II. The most common venous seg-
ment involved in femoral-popliteal DVT was the Femoral-popliteal. Seventeen limbs (63%) devel-
FV; all 27 limbs (100%) had some FV involvement. oped reflux in at least one deep venous segment
Twenty-four limbs (89%) had some popliteal over an average follow-up of 2.3 years. Kaplan-
involvement. The majority of limbs, 15 (56%), had Meier estimation projected 86.8% of limbs to de-
calf involvement and in these cases the clot span- velop reflux in the deep veins after a period of 50
ned nearly the entire femoral-popliteal-calf deep- months (4.2 years). Figure 1 shows the develop-
vein system. Nine limbs (33%) spanned the ment of deep vein reflux of femoral-popliteal and
femoral-popliteal segments, and three limbs (11%) iliofemoral patients over 24 months. Figure 2 shows
spanned only the FV or CFV-FV segments. the distribution of reflux by vein segment of limbs
Iliofemoral. The locations of thrombi are shown in that developed reflux.
Table III. The most common venous segment in- Iliofemoral. Seven limbs (64%) developed reflux
volved in iliofemoral DVT was the EIV; all 11 limbs in the deep veins over an average follow-up of 2.1
(100%) had some EIV involvement. The CFV had years. Kaplan-Meier estimation projected a 56.4%
the next greatest involvement with 10 limbs (91%). development of reflux over a period of 27 months.
The CIV had six limbs involved (55%). In four limbs As shown in Figure 3, the incidence of reflux did
(36%) the clot spanned the entire iliac-femoral- not significantly differ from that of the femoral-
popliteal-calf deep-venous system. In three limbs popliteal cases, with approximately 60% of both
Vol. 19, No. 1, 2005
Fig. 1. Comparison of percentage of limbs developing
reflux in the deep veins over time (Kaplan-Meier esti-
mation, femoral-popliteal versus iliofemoral).
Fig. 2. Distribution of reflux by vein segment in femo-
ral-popliteal patients (n = 20).
cases developing reflux after 27 months. Figure 3
displays the distribution reflux by vein segment in
limbs that developed reflux.
Recanalization
Femoral-popliteal. Twenty-seven limbs (100%)
developed some recanalization over an average
follow-up of 2.3 years. Figure 4 compares the rates
of recanalization for femoral-popliteal versus ili-
ofemoral patients. After 1 week, 14.8% of limbs
developed some recanalization. After 4 weeks, that
number increased to 22.2% and after 10 weeks, to
44.4%. Over a period of 40 weeks, 91.9% of limbs
had developed some recanalization.
Iliofemoral. Nine of 11 (82%) patients had
thrombolysis and hence complete or partial lysis of
clot within 1 week.
Clinical Outcomes
Femoral-popliteal. To analyze the clinical out-
comes of patients on the basis of retrospective data,
we defined a general clinical severity level scheme
that could accurately represent the findings of this
study. Three levels were defined as shown in Ta-
Outcome of femoral-popliteal and iliofemoral DVT 77
Fig. 3. Distribution of reflux by vein segment in iliofe-
moral patients (n = 7).
Fig. 4. Comparison of percentage of limbs displaying
some recanalization over weeks (Kaplan-Meier estima-
tion, femoral-popliteal versus iliofemoral).
ble I. Figure 5 compares the distribution of clinical
severity for femoral-popliteal and iliofemoral limbs:
31% of limbs (n = 26) displayed L0, or no symp-
toms at the end of their follow-up times; 34% of
limbs displayed L1 symptoms; and 35% displayed
the more severe L2 post-thrombotic symptoms.
Iliofemoral. The iliofemoral cases showed a stark
contrast with the femoral-popliteal cases. Eight
patients, or 73% (n = 11), remained asymptomatic
(L0) at the end of their follow-up times, with an
average follow-up of 2.1 years. Eighteen percent
displayed L1 symptoms, and only one case (9%)
showed the more severe L2 symptoms. Chi-squared
analysis showed a significant difference
(p < 0.025) in the clinical outcomes of iliofemoral
and femoral-popliteal patients.
DISCUSSION
Among the various findings of this pilot study, one
highlight is the improved short-term clinical out-
comes for iliofemoral patients compared with that
of femoral-popliteal patients. Results of reflux,
recanalization, and clinical severity are summa-
rized in Table IV. Seventy-three percent of iliofe-
moral patients remained asymptomatic after an
78 Singh and Masuda
Fig. 5. Clinical severity distribution for femoral-popliteal
and iliofemoral patients.
average follow-up of 2.1 years compared with 31%
of femoral-popliteal patients after an average fol-
low-up of 2.3 years (p < 0.025).
These results could be attributed to the early lysis
of clots for the iliofemoral patients via thrombolysis.
Thrombolysis and thrombectomy have been shown
by Comerota1 to improve the quality of life of ili-
ofemoral patients who underwent thrombolytic
therapy. Mewissen7 has proposed in his review that
because thrombolysis eliminates obstruction early,
it could also aid in preserving valvular competence.
Hence, thrombolysis could help prevent both fac-
tors associated with the cause of PTS, residual
obstruction and valvular incompetence.
Interestingly, in this study, early lysis of clot with
thrombolysis did not correlate with prevention of
reflux. Valvular competence was not preserved in
the short term for iliofemoral patients, as after 2.1
years both femoral-popliteal and iliofemoral patients
showed a reflux incidence of approximately 60%
(Table IV). However, to accurately assess the relative
preservation of valvular competence in iliofemoral
cases, patients treated with thrombolysis should be
compared with those treated with anticoagulants
alone.
Elsharawy and Elzayat8 conducted such a study,
in which they randomized and compared two
groups of iliofemoral DVT patients receiving
thrombolysis and anticoagulants versus anticoagu-
lants alone. In that study, thrombolysis was shown
to correlate with preserved valvular competence
over a period of 6 months. The fact that the
majority of iliofemoral patients in our study
developed reflux despite thrombolytic therapy,
however, suggests that early lysis does not guar-
antee valvular competence. The duration of DVT
and the time the clot is in contact with the valves
may cause irreversible damage even before
thrombolytic therapy. Further studies need to be
conducted in this area.
Annals of Vascular Surgery
Table IV. Comparison of physiologic and clinical
outcomes of femoral-popliteal vs. iliofemoral DVT
limbs
Femoral-Popliteal Iliofemoral Chi-squared
Outcome (%) (%) test
Reflux 60 64 p<1
(2.1 years)
Clot lysis 22 82 p < 0.005
(4 weeks)
Clinical L0 31 73 p < 0.025
One of the interesting features of this study is the
poor correlation between the development of reflux
and post-thrombotic symptoms. Even though over
60% of iliofemoral patients developed reflux, only
27% developed PTS symptoms. Perhaps an expla-
nation of this outcome lies in the study conducted
by Johnson et al.,9 which showed that in most pa-
tients experiencing PTS, both venous obstruction
and valvular incompetence was present. This im-
plies that a combination of reflux plus obstruction
causes significant symptoms, whereas reflux alone
will usually not cause PTS symptoms. For the ili-
ofemoral patients in this study, thrombolysis elim-
inated at least one of the PTS factors—venous
obstruction. Hence, even though the majority of
iliofemoral patients developed reflux, they did not
develop PTS symptoms because venous obstruction
was eliminated early. This could explain the im-
proved clinical outcomes of iliofemoral patients in
this study. Although valvular competence was not
preserved in most limbs, the early lysis still could
have contributed to the positive clinical outcome of
iliofemoral patients.
For femoral-popliteal limbs in this study, the
results of recanalization of venous segments are
similar to those of other studies. After 12 weeks,
55.6% of limbs showed some recanalization. These
results are similar to those of a study conducted by
Killewich et al.10 in which 53% of patients (n = 21)
experienced total recanalization within 90 days.
Despite the fairly early recanalization for both
femoral-popliteal and, especially, iliofemoral limbs
in this study, the incidence of reflux was quite high,
63% for femoral-popliteal limbs after 2.3 years, and
64% for iliofemoral limbs after 2.1 years. Markel
et al.11 also found a high incidence of reflux in their
study, with 69% of limbs developing reflux in 1
year. Although early lysis of clot has been linked to
preservation of valvular competence, the data in this
study suggest that early lysis is not the only factor in
preservation of valves. Meissner et al.12 showed that
the median lysis time for venous segments devel-
oping reflux was 2.3-7.3 times longer than that for
Vol. 19, No. 1, 2005
corresponding segments not developing reflux.
However, the fact that so many limbs in our study
developed reflux suggests that early recanalization
does not guarantee valvular competence.
The distribution of reflux by vein segment, as
shown in Figures 2 and 3, indicates a strong corre-
lation between clot location and the location of most
reflux. The data show that venous segments with a
high incidence of clotting also developed a high
incidence of reflux. Markel et al.11 also showed this
correlation. However, studies have shown the
development of reflux in segments not involved in
the clot.3,10,13
Limitations of this study include the retrospec-
tive design and the short-term follow-up, which
may limit the interpretation of these findings. The
development of long-term symptoms was not ad-
dressed, and reclotting as well as PTS may still be
observed over time in iliofemoral patients treated
with thrombolysis. Furthermore, strict symptom
classification schemes such as the VCSS could not
be used because this level of detail was simply not
available upon review of patient charts. The charts
did provide enough information to create three
levels of classification as defined in Table I. More-
over, the results of this study prompt speculation
on the relationship between reflux and PTS as well
as on the efficacy of thrombolysis as a therapeutic
measure and encourage further study along these
lines.
CONCLUSIONS
The highlight of this study was the improved clin-
ical outcome of iliofemoral patients compared with
that of femoral-popliteal patients. We can probably
attribute this observation to the use of thrombolysis
for the iliofemoral patients. Extremely early lysis of
clot via thrombolysis may account for the much
lower incidence of PTS for iliofemoral than for
femoral-popliteal patients in this study.
Although the extent of reflux development was
similar in both groups, iliofemoral patients still
showed fewer clinical symptoms after follow-up.
This finding may suggest that the presence of both
venous obstruction and reflux, rather than either
one alone, significantly increases the chances for
development of PTS. Since thrombolytics eliminates
at least one of these factors, venous obstruction, it
may aid in decreasing development of PTS in the
short term. Thrombolytic therapy can potentially
alter the physiologic and clinical history of femoral-
popliteal DVT, as it has for iliofemoral DVT, thus
improving quality of life for patients. The favorable
outcomes seen in these iliofemoral DVT patients
Outcome of femoral-popliteal and iliofemoral DVT 79
treated with thrombolysis would suggest that fur-
ther study should be conducted on extending the
use of thrombolysis to femoral-popliteal patients.
The data revealed in this pilot study also warrant
further prospective long-term analysis of the clini-
cal and physiological effects of thrombolysis and its
correlation with the development of reflux and
PTS.
We thank Fedor Lurie, MD, PhD, for his guidance and support
with this vascular study. We also thank the Straub Foundation
and Straub Hospital staff for their support.
REFERENCES
1. Comerota AJ. Quality-of-life improvement using thrombo-
lytic therapy for iliofemoral deep venous thrombosis. Rev
Cardiovasc Med 2002;3(Suppl 2):S61-67.
2. Franzeck UK, Schalch I, Jager KA, et al. Prospective l2-year
follow-up study of clinical and hemodynamic sequelae after
deep vein thrombosis in low-risk patients (Zurich Study).
Circulation 1996;93:74-79.
3. Masuda EM, Kessler DM, Kistner RL, Eklof B, Sato DT. The
natural history of calf vein thrombosis: lysis of thrombi and
development of reflux. J Vasc Surg 1998;28:67-73; discus-
sion 73–74.
4. Kearon C. Natural history of Venous thromboembolism.
Circulation 2003;107:I-22–I30.
5. Masuda EM, Kistner RL, Eklof B. Prospective study of du-
plex scanning for venous reflux: comparison of Valsalva and
pneumatic cuff techniques in the reverse Trendelenburg and
standing positions. J Vasc Surg 1994;20:711-720.
6. Kaplan-Meier Estimator. In: Encyclopedia of Statistical Sci-
ences, Vol 4. New York: Wiley-Interscience, 1982, pp 346-
351.
7. Mewissen MW. Catheter-directed thrombolysis for lower
extremity deep venous thrombosis. Tech Vasc Interv Radiol
2001;4:111-114.
8. Elsharawy M, Elzayat E. Early results of thrombolysis vs
anticoagulation in iliofemoral venous thrombosis. A rando-
mised clinical trial. Eur J Vasc Endovasc Surg 2002;24:209-
214.
9. Johnson BF, Manzo RA, Bergelin MS, Strandness DE.
Relationship between changes in the deep venous system
and the development of the post-thrombotic syndrome after
an acute episode of lower limb deep vein thrombosis: a one-
to-six-year follow-up. J Vasc Surg 1995;21:307-312.
10. Killewich LA, Bedford GR, Beach KW, Strandness DE.
Spontaneous lysis of deep venous thrombi: rate and out-
come. J Vasc Surg 1989;9:89-97.
11. Markel A, Manzo R, Bergelin R, Strandness E. Valvular re-
flux after deep vein thrombosis: incidence and time of
occurrence. J Vasc Surg 1989;:377-384.
12. Meissner MH, Manzo RA, Bergelin RO, Markel A, Strand-
ness DE. Deep venous insufficiency: the relationship be-
tween lysis and subsequent reflux. J Vasc Surg 1993;18:596-
608.
13. Saarinen JP, Domonyi K, Zeitlin R, Salenius J. Postthrom-
botic syndrome after isolated calf deep venous thrombosis:
the role of popliteal reflux. J Vasc Surg 2002;36:959-964.