Venous disease in women: Epidemiology,

manifestations, and treatment

Joann M. Lohr, MD,a and Ruth L. Bush, MD, MPH,b Cincinnati, Ohio; and Round Rock, Tex

Until the past decade, venous disease was commonly underdiagnosed and undertreated due to lack of interest on the part
of providers and to reluctance to undergo procedures on the part of patients. Modern venous interventions, improved
diagnostic modalities, and increased awareness through education, training, and screening programs have all raised
enthusiasm for venous disease in recent years. This has been crucial to gain control over a disease that affects a signicant
proportion of the population, with women being affected more than men. This article will discuss epidemiologic studies
that highlight some of the gender-related issues and review the risk factors for venous disease. We will also discuss the
physiologic venous changes that occur with pregnancy and highlight functional venous disease in women. Finally, we will
review the indications for and treatment of supercial venous disease. (J Vasc Surg 2013;57:37S-45S.)

Venous disease of the lower extremities is very common,
affecting w25% of adults in westernized societies. The
discomfort and disability is usually progressive, with the
spectrum of disease presentation ranging from simple telan-
giectasias to venous ulcerations. Cost estimates put the
health care costs at upwards of 2% of national resources.
Of course, as the venous disease process advances from
venous incompetence and supercial varicose veins to
chronic venous insufciency with associated skin changes,
the amount of care needed and costs required increases.
Venous disease traditionally has been ignored or consid-
ered of less clinical importance because it is frequently not
life-threatening and only minimally interferes with work or
pleasure activities. Surgical interventions were invasive and
morbid, often requiring the patient to endure prolonged
recovery times. Many patients with venous disease chose
not to have treatments, such as saphenous ligation and strip-
ping, because of family or work obligations, or both.
However, the last decade has ushered in many signicant
advances in the breadth and extent of treatment modalities
for venous insufciency, primarily the minimally invasive
option of endovenous thermal ablation. Furthermore, the
understanding of patterns of reux and the pathophysiology
of venous disease has progressed, allowing for more precise
treatment planning. More providers are offering therapy,
and more patients are choosing intervention.
This review will present the epidemiology and prevalence
of venous disease. Women, due to many etiologies and risk
From Lohr Surgical Specialists, Cincinnatia; and the Texas A&M Health
Science Center College of Medicine, Round Rock.b
Author conict of interest: none.
Reprint request: Ruth L. Bush, MD, MPH, Texas A&M Health Science
Center College of Medicine, Round Rock Campus, 3950 North A.W.
Grimes Blvd, Ste N403G, Round Rock, TX 78665 (e-mail: rbush@
medicine.tamhsc.edu).
The editors and reviewers of this article have no relevant nancial relationships
to disclose per the JVS policy that requires reviewers to decline review of any
manuscript for which they may have a conict of interest.
0741-5214/$36.00
Published by Elsevier Inc. on behalf of the Society for Vascular Surgery.
http://dx.doi.org/10.1016/j.jvs.2012.10.121
factors that will be discussed, are particularly prone to venous
disease. Because pregnancy is one of the main causes of
venous disease in women, the physiologic basis for venous
changes associated with pregnancy is included. We will also
review functional venous disease of the supercial and deep
venous systems. Lastly, the indications and treatment of
supercial venous insufciency will be reviewed.
EPIDEMIOLOGY OF VENOUS DISEASE
Many epidemiologic studies looking at the incidence
and prevalence of venous disease in Western countries
have been performed. The results vary according to the
geographic location of the population being studied. The
most commonly cited studies looking at this chronic condi-
tion have been performed in Europe; however, a large
population-based study in the United States has been re-
ported from San Diego.
In a summary of the available epidemiologic literature,
Beebe-Dimmer et al1 reviewed results and study methodolo-
gies with regard to varicose veins and chronic venous insuf-
ciency. The overall estimates of the prevalence of simple
uncomplicated varicose veins ranges dramatically from 2%
to 56% in men and from <1% to 73% in women. Estimates
for the prevalence of chronic venous insufciency vary, albeit
not as widely, from <1% to 17% in men and <1% to 40% in
women. It has been acknowledged that the large variations in
prevalence are due to the population being studied. In
general, prevalence rates tend to be much higher in western-
ized, developed countries and in certain ethnic groups.
Most studies use a variation of the CEAP classication,
which groups together classes of venous disease severity,
for assessing and analyzing venous disease.2 This clinical
(C)-etiologic (E)-anatomic (A)-pathophysiologic (P) clas-
sication system aids in the organization and categorization
of venous disease severity. Spider veins, or intradermal
visible veins, would be recognized as CEAP C1. The pres-
ence of varicose veins is usually not classied as asymptom-
atic or symptomatic, thus C2 and C3 may be combined
together. Skin trophic changes usually refer to lipoderma-
tosclerosis, venous eczema, atrophie blanche, hemosiderin

37S

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 JOURNAL OF VASCULAR SURGERY
38S Lohr and Bush April Supplement 2013

pigmentation, or active or healed ulcerations and would Table I. Visible and functional disease by gender, San
represent CEAP C4 through C6 disease. Diego, Calif, 1994-1998a
The San Diego Population Study, published in 2003,
represents an ethnically diverse population within the All
Variable participants Women Men
United States.3 This study, along with the Edinburgh
Vein Study,4,5 classied venous disease not only by visible Total patients, No. (%) 2211 (100) 1431 (64.7) 780 (35.3)
ndings but also by functional disease. Both studies used Visible disease, %
duplex ultrasound imaging to delineate visible from func- Normal 19.0 11.0 33.6
tional venous abnormalities. There were some differences Spider veins 51.6 55.9 43.6
Varicose veins 23.3 22.7 15.0
in the way the studies were conducted; however, these
Trophic changes 6.2 5.3 7.8
technical differences would only account for small varia- Functional disease, %
tions in results. In the Edinburgh study, only reux was Normal 72.1 70.1 75.6
evaluated, not obstructive venous disease. Supercial 19.0 22.2 13.1
In the United States, very important epidemiologic Deep 9.0 7.8 11.3
data comes from the San Diego study,3 in which 36% of a
Adapted from Criqui MH, Jamosmos M, Fronek A, Denenberg JO,
the randomly selected invited people actually participated. Langer RD, Bergan J, et al. Chronic venous disease in an ethnically diverse
As may be expected, the 2211 participants (4422 legs) population: The San Diego Population Study. Am J Epidemiol
2003;158:448-56, with permission.
were more likely to be older, women, and non-Hispanic
whites; however, minorities were well represented. The
the denition of varicose veins and the limitations of self-
average age of men and women was about 60 years. The
reported data collected in the France study. This study
legs of men were three times more likely to have no visible
did explore the effect of occupational factors on venous
signs of venous disease than women, who had more gross
disease, which will be discussed in the next section.
varicosities and telangiectasias (33.6% vs 11.0%). Skin, or
trophic, changes were more common in men. Table I SCREENING PROGRAMS
summarizes the distribution of visible and functional
venous disease among men and women in this study The American Venous Forum has sponsored a national
cohort. screening program for chronic venous disease and venous
In both men and women, the number of spider veins did thromboembolism (VTE). The program began in 2005
not increase with age; however, there was a linear relation- with 17 participating sites and was expanded 1 year later
ship between age and varicose veins and trophic changes to include 2234 participants who received the free
(Table II). When functional disease was assessed, the pres- screening.7,8 With the initial goal of increasing awareness
ence of supercial reux was seen more in women (22.1%) of venous disease, the National Venous Screening Program
than in men (13.1%); conversely, deep venous reux was (NVSP) has been a tremendous success in its outreach
more common in men (11.3% vs 7.8%). Deep and supercial objective and as a source of robust epidemiologic data.
venous reux both increased with advancing age in men and As is typical of attendance at free health screening
women alike. Edema was most prevalent in men and also programs, most participants (77%) were women. They
increased dramatically with age. Supercial thrombotic were an older population (mean age, 60 years) and had
events were more common in women, whereas deep venous an average body mass index (BMI) bordering on obese
thrombotic (DVT) events were more common in men. (29 kg/m2). In the analysis for risk of VTE among the
Multivariate analyses in this population showed female participants, 40% were low risk, 22% were moderate risk,
gender and age were strongly correlated with varicose veins, 21% were high risk, and 17% were very high risk.
whereas women were at less risk for trophic changes. Spider The NVSP found venous reux in 37%, and venous
veins were more common, increasing with age, in non- obstruction was seen in 5% on duplex ultrasound imaging.
Hispanic whites. The presence of edema correlated to visible Interestingly, in contrast to other population-based studies,
and functional venous disease. BMI did not correlate with the presence of venous reux or
Similarly, a cross-sectional population-based study was obstruction. These data corroborate the ndings of other
performed in France at four locations.6 Two thousand indi- studies that conclude that venous disease occurs or
viduals underwent a telephone interview, and a sample of increases in prevalence as age increases. Also, women,
these had a physical examination. Although the locations more so than men, perhaps attend venous screenings
did not vary in results, the sexes did demonstrate differ- because of their higher incidence of varicose veins than
ences, with an overall high prevalence of venous disease men and concern for personal health. Thus, reporting
in the general population of France. Varicose veins and selection bias need to be considered in the interpreta-
(C2-C3) were seen in 50.5% of women and in 30.1% of tion of results when participation is by volunteerism.
men, and trophic skin changes (C4-C6) were found in
2.8% of women and 5.4% of men. Women were also RISK FACTORS FOR VENOUS DISEASE
more symptomatic than men. These ndings showed Many of the populationbased studies cited above also
a much higher percentages of varicose veins than the San discuss risk factors for venous disease. The risk factors may
Diego study; however, the studies may differ in terms of be modiable or nonmodiable and include environmental

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JOURNAL OF VASCULAR SURGERY
Volume 57, Number 4S
factors as well. Most risk factors are applicable to women
and men alike. The most commonly discussed risk factors
are age and family history, neither of which is a modiable
factor. It stands to reason that as one gets older, with
ongoing environmental and occupational exposures, the
severity of venous disease will progress if no intervention
is undertaken. Other risk factors have been studied but
have not been conclusively linked to venous disease
development or progression. These include diet, smoking,
and socioeconomic status. Furthermore, in women, the
number of pregnancies has been shown to be positively
associated with venous dysfunction.4,6 The impact of preg-
nancy will be discussed later in the article.
Many population studies have shown that venous
reux is associated with lifestyle factors, such as increased
BMI, lack of physical activity, standing or sitting vocations,
and constipation, all of which can be modied, with the
potential exception of ones occupation. Symptoms of vari-
cose veins are often vague but may include dull pain, heavi-
ness, tiredness, restlessness, itching, burning, tension of the
skin, cramping, and mild edema. More severe symptoms
may include soft tissue edema, dermatitis, hyperpigmenta-
tion, lipodermatosclerosis, ulceration, skin erosion, or
potentially, hemorrhage. Because venous disease may be
asymptomatic, the risk factors specically correlated with
venous symptoms are female gender, varicose veins them-
selves, and prolonged standing or sitting.
Trophic changes of the skin related to venous disease are
mainly seen in the gaiter distribution of the lower leg,
a circumferential region between the medial malleolus and
upper part of the calf. Thickened skin, hemosiderin deposi-
tion, dermatitis, atrophie blanche, and ulceration or ulcer
scars are all manifestation of severe chronic venous insuf-
ciency. These skin changes are mainly seen in patients with
venous disease or varicose veins, or both. One epidemiologic
study from France found age and the presence of pitting
edema were the most signicant risk factors.6 The data anal-
ysis showed, to a lesser degree, that VTE (P .052) and
family history of varicose veins (P .044) were also risk
factors.
Overall, these epidemiologic studies, including the
NVSP, demonstrate that chronic venous disease is wide-
spread, progressive as one ages, and multifactorial in etiol-
ogies. Venous disorders are more commonly encountered
in women, although anecdotally, the number of men pre-
senting with venous dysfunction and symptomatic varicose
veins appears to be increasing.
FUNCTIONAL VENOUS DISEASE IN WOMEN
Symptoms associated with venous disease of the lower
extremities are related to chronic venous dysfunction and
venous hypertension. Leg heaviness, fatigue, swelling that
worsens throughout the day, aching, and pain are often
described, along with the visible protrusion of the varicos-
ities. Deciphering the patterns of chronic venous disorders
is paramount to any treatment algorithm. Depending on
the history given by the patient, the supercial and deep
venous systems will need interrogation. The most common
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Lohr and Bush 39S
modality is duplex ultrasound imaging evaluating for
reux, dilatation, and possibly, obstruction using a stan-
dardized protocol. This modality and the ultrasound
nding have been well described in many publications.
The clinical pattern of venous disease and associated
varicosities is variable, and prior vein surgery always has
to be ascertained. Important to note is that the term
vein stripping may have differing denitions to a patient
or lay person than to a surgeon. Thus, all incisions on the
lower extremities need to be examined because the patient
may have had stab avulsion phlebectomies, not true saphe-
nous vein stripping, but may refer to the procedure as vein
stripping. The prevalence of varicosities tends to generally
be in an axial distribution along the great saphenous vein
(GSV) or one of its major tributaries and less commonly
along the course of the small saphenous vein.
In the French population study, the distribution of
varicose veins was compared between men and women.
This is one of the few studies to do this type of assessment
and subset analysis. The prevalence of varicose veins was
similar between the sexes for saphenous varicose veins and
GSV and main branches. However, there was a trend toward
more varicosities associated with the small saphenous vein in
women. Furthermore, women had statistically signicantly
more nonsaphenous varicose veins. Whether these nonaxial
varicosities were in patients with prior saphenous vein
surgery is unclear from the study. This study did nd
a stronger association of skin trophic changes with saphe-
nous vein varicosities than with nonsaphenous varicosities.
The NVSP found higher CEAP scores in patients with
venous reux or venous hypertension.8 Furthermore, wors-
ening quality of life scores were also seen with increasing
CEAP classication, demonstrating the disability associated
with severity of venous disease, particularly ulcerations. In
the participants with a history of VTE, the CEAP scores
were also higher, as were the ndings of reux or obstruction.
The anatomic distribution for symptomatic reux may
include the deep and supercial systems. In the supercial
system, the great and small saphenous veins will need to
be interrogated on ultrasound imaging. Perforator vein
insufciency becomes implicated in patients with C5 or
C6 (healed or active ulcers) disease. Most noninvasive labo-
ratories have adopted a standardized imaging protocol to
improve diagnostic accuracy and the sensitivity and positive
predictive value of the examination.9 Extending the
imaging to the area directly beneath the ulcer beds can
reveal supercial varicose veins and incompetent perforator
veins. Treatment of these localized veins may improve ulcer
healing and recurrence rates.10
The treatment of perforator veins remains controver-
sial.11,12 Perforator veins have been treated in addition to
the saphenous vein to improve venous hemodynamics in
patients with advanced venous disease and, more often,
venous ulceration. The diagnosis and surgical management
of incompetent perforator veins (IPV) has improved signif-
icantly since Linton rst described his approach in 1938 for
the treatment of chronic venous insufciency and ulcera-
tions. However, little evidence exists today that clearly

40S Lohr and Bush
Table II. Edema and location of venous disease by
gender and age, San Diego, Calif, 1994-1998a
Deep throm-
Supercial
Variable Edema, % events, %
All 5.8 2.4
Men 7.4 1.5
Women 4.9 2.8
Age, years
<50 2.6 2.1
50-59 4.1 2.5
60-69 6.1 2.2
>70 10.7 2.7
a
Adapted from Criqui MH, Jamosmos M, Fronek A, Denenberg JO,
Langer RD, Bergan J, et al. Chronic venous disease in an ethnically diverse
population: The San Diego Population Study. Am J Epidemiol
2003;158:448-56 with permission.
denes the role of IPV interruption as a modern treatment
for complicated venous insufciency of the lower
extremity.12,13 The results of most studies are confounded
by the inconsistent concomitant treatment of the GSV in
addition to the IPVs.11 Many surgeons prefer to treat
patients in a staged manner by rst treating the reuxing
GSV. Intervention for the IPV is reserved for patients
who do not have complete ulcer healing or have recurrent
ulcerations.13
PHYSIOLOGIC VENOUS CHANGES
ASSOCIATED WITH PREGNANCY
Multiple physiologic hemodynamic changes occur
during pregnancy that lead to a prominence of venous
disease in women especially associated with pregnancy.
Pregnancy changes that result in increased venous promi-
nence include smooth muscle relaxation, vasodilatation,
valvular incompetence, expanded blood volume, decreased
blood velocity, and stasis, with varicose veins developing in
8% to 20% of women.14 Varicose veins are seen in 13% of
primiparous women, in 30% of secundiparous women,
and in up to 57% of multiparous women.14
Compression of the iliac veins is attributable to the
enlarging uterus, which results in increased venous pres-
sure. Venous ow patterns are less responsive to respira-
tion, and patients may have hypotension and reduced
cardiac output. However, turning the patient on her side
can reverse these changes. Skudder et al15 found that
venous dysfunction persists after delivery. Their plethys-
mography studies measured venous capacitance and
outow at term and 1, 6, and 12 weeks after delivery.15
Decreased capacitance and venous outow at term were
identied. There was no improvement at 1 week after
delivery and only modest improvement after 6 weeks.
However, a statistically signicant improvement occurred
in both parameters at 3 months, suggesting that factors
other than pelvic venous compression may be responsible
for this change.
Dixon and Mitchell16 reported that vulvar varicosities
will also develop in 33% of women who develop varicose
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JOURNAL OF VASCULAR SURGERY
April Supplement 2013
veins during pregnancy. Twelve percent of these veins
will persist after childbirth and many will connect to the
internal iliac vein. Pelvic venous congestion syndrome
may also be seen, which presents as dyspareunia, dysmenor-
botic
rhea, and menorrhagia. Treatment for vulvar varicosities
events, %
can include ligation of the internal pudendal vein, ligation
3.2 of the obturator vein, ligation of veins of the round liga-
4.0 ment, or ligation of the upper tributaries of the GSV;
2.7 hysterectomy may also be indicated.16
Increased venous distensibility, increased capacity,
2.4
2.5 reduction in velocity of lower limb blood ow, and hyper-
3.8 coagulability all may also result in stasis changes.15 The
4.1 Virchows triad is signicantly affected during pregnancy.
All three components of Virchows triad are affected: vessel
wall injury, hypercoagulation, and venous stasis. Fibrin-
ogen levels double in pregnancy; factors VII, VIII, IX, X,
and XII all increase. In addition, brinolytic activity is
decreased; there is a 40% decrease in free protein S, an
inborn anticoagulant, and there is increased venous stasis.
Also, vascular injury may be associated with delivery, and
activation of platelets is increased.17 Phillips18 reported
that during pregnancy, women may have increased von
Willebrand factor, increased generation of brinogen and
brin split products, and an increase in plasminogen activa-
tors (plasminogen activator inhibitor 1 and 3). In addition,
there is inhibition of the brinolytic system (ie, decrease in
activation of factors XI, XII and antithrombin III), a reduc-
tion in free protein S, and progressive resistance to acti-
vated protein C.
There are also patient risk factors associated with VTE
that occur with pregnancy in women aged >35 years.18
These include obesity (BMI >29 kg/m2 in early preg-
nancy), thrombophilia, history of VTE (especially if idio-
pathic or thrombophilia-associated), the presence of gross
varicose veins, and signicant current medical problems,
including nephrotic syndrome, anemia, diabetes, cardiac
disease, and hypertension. Other patient factors include
current infection or inammatory process (ie, active inam-
matory bowel disease or urinary tract infection), immobility
(ie, bed rest or limb fracture), paraplegia, recent long-
distance travel, dehydration or intravenous drug abuse.
Specic pregnancy and obstetrical factors include ovarian
hyperstimulation and infertility issues, cesarian-section,
particularly in emergencies associated with labor, compli-
cated vaginal delivery, major obstetrical hemorrhage,
multiparity ($4 deliveries), hyperemesis gravidarum, pre-
eclampsia, and the use of estrogen to suppress lactation.
Pulmonary embolism is the leading cause of maternal
death in the United States. Pregnancy is associated with
a vefold to tenfold increase in the incidence of VTE.
The absolute risk factor is between 0.5 and 3 per 1000
women, whereas the overall risk outside of pregnancy
is <1 per 1000.18 The diagnosis of VTE during pregnancy
is not clinically reliable for DVT or pulmonary embo-
lism.19,20 There is a 20% to 30% incidence in nonpregnant
patients with suggestive symptoms and an 8% prevalence of
DVT and <5% prevalence of pulmonary embolism in
a pregnant patients. Objectively proven DVT has a similar
JOURNAL OF VASCULAR SURGERY
Volume 57, Number 4S Lohr and Bush 41S

Table III. Outcomes after endovenous laser ablationa

First author Veins, No. Follow-up period, months Successful ablation, % Signicant complications

Navarro33 40 4.2 100 None

Proebstle34 41 6 100 6% thrombophlebitis
Chang35 252 19 96.8 36.5% paresthesia
4.8% skin burn
1.6% thrombophlebitis
Oh36 15 3 100 None
Timperman37 111 7 77.5 1% deep vein thrombosis
1% skin burn
Goldman19 24 6-12 100 None
Huang20 230 6 100 1% skin burn
7% paresthesia
Vuylsteke21 118 9 94 4% skin burn
14% paresthesia
38
Almeida 819 5.3 98.3 0.2% deep vein thrombosis
0.2% paresthesia
Disselhof39 93 29 84 2% thrombophlebitis
Min40 121 24 93.4 None
Meyers41 404 36 80 0.2% severe pain
2.2% thromboembolism
0.3% nerve palsy
a
American Venous Forum Handbook, 3rd Edition.

frequency in each of the three trimesters.19 Postpartum, it
is more common after caesarean section than after
a vaginal delivery.21 The development of post-thrombotic
syndrome will depend on the location and extent of the
initial thrombosis, the persistence of risk factors for DVT,
the presence of primary venous reux before the develop-
ment of DVT, and if iliofemoral thrombosis occurs. Tread-
mill testing for venous claudication will be positive in up to
43% of patients, and 15% of these patients will experience
lifestyle-limiting venous claudication.
TREATMENT OF SUPERFICIAL VENOUS
INSUFFICIENCY
The decision to treat supercial venous insufciency
can be motivated by several factors. The appropriate treat-
ment is determined according to the CEAP system
described earlier. Selection of the proper treatment option
is determined by the patients symptoms and the patients
ultimate goals of treatment. Pain may worsen with the
menstrual cycle or with pregnancy secondary to increased
total body uid and volume of higher circulating levels of
estrogen. The treatment for all is to provide good skin,
foot, and nail care and to control soft tissue edema.
Adequate external compression will decrease dermatologic
changes. Depending on the presentation, history, and
physical examination, multiple diagnostic options and
modalities exist. It is important to stratify patients into
categories to select the appropriate treatment to achieve
the desired end point.
Duplex scanning to evaluate for valvular incompetence
allows patients to be selected for appropriate therapies.22
Evaluation of the deep, supercial, and perforating systems
should be performed. A conservative approach to supercial
varicosities should always be considered, especially in elderly
patients or in those with signicant comorbidities.
Compression hosiery is the mainstay of conservative treat-
ment, along with skin emollients and leg elevation. Gradu-
ated elastic compression with at least 20 mm Hg at the
ankle helps to relieve symptoms, conceal varicosities, and
reduce the progression of skin changes. Compliance remains
the main problem of wearing stockings, particularly in
young patients, who often refuse, and for older patients
who have difculty with hosiery application and removal.22
Surgery remains the gold standard; however, this has
recently come into question. Long-term data on less invasive
laser ablation, duplex-guided foam sclerotherapy, and
radiofrequency techniques will provide a better guide in
the future for selection of specic treatment modalities. As
a general rule, we treat the larger veins rst and the smaller
veins secondarily. Frequently symptoms may be improved
with ablation or removal of the saphenous vein reux.
A less invasive alternative to vein stripping for elimina-
tion of saphenous reux is the percutaneous, catheter-
based radiofrequency Closure system (VNUS Medical
Technologies, San Jose, Calif), which was introduced in
Europe in 1998 and in the United States in 1990. Reux
of the saphenofemoral junction can be eliminated by obliter-
ation of the GSV in the thigh without dissection and ligation
of all of the contributing branches near the saphenofemoral
junction, therefore eliminating the need for a groin incision
and the potential for minor or even major complications that
can occur after traditional ligation and stripping and leaving
intact venous return and lymphatic drainage from the
abdominal wall and lower extremity.23
Pichot et al22 coordinated an extensive 2-year follow-
up ultrasound evaluation from ve of the venous registry
centers that showed 92.1% treated GSV segments remained
free of reux. Junction tributary reux was seen in
11.1% of limbs, four of which were associated with the
saphenofemoral junction as the sole source of reux.

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 JOURNAL OF VASCULAR SURGERY
42S Lohr and Bush April Supplement 2013

Table IV. Randomized controlled trials: foam sclerotherapy

Randomized/
First author label Trial arms Participants Targets Follow-up Outcomes Complications

Bountourogloul42 Yes/open 1. SFJ ligation 53% female Primary 3 months 87% group 1 and Group 1, 17%
foama 30 (mean age symptomatic with DUS 93% group resolving skin
43) varices occlusion of pigmentation;
targets on DUS 10%
(no statistical thrombophlebitis.
difference). Group 2, 9%
Shorter procedure, saphenous nerve
less expensive, injury
faster return to
work, better
quality of life
scores for
group 1
2. Surgery (SFJ
ligation, GSV
saphenectomy)
28

Alos et al43 Yes/open 1. Liquid 75 92% female Reticular varices, 1 year, 85% 94% foam and None except 4%
2. Foama 75 (mean age postoperative Follow-up with 54% liquid Severe pain
59) varices SFJ DUS by blinded foam and 0%
observed liquid
Patient as own Occlusion of
control target at 3
months
(P < .001)

Kern et al44 Yes/single 1. Liquid 48 100% female Primary 5 weeks, 97% Comparable 33% and 17% show
blind (mean age telangiectasias Photographs by efcacy in matting,
47) and thigh two blinded terms microthrombi, and
reticular veins. observers of vessel pigmentation in
clearance liquid and foam
score groups, respectively
2. Foamb 51

Hammel-Desmos Yes/open 1. Liquid 43 Not stated GSV 1 year, percentage 84% foam and One case of
et al45 incompetence follow-up not 40% liquid slight vagal
with varices stated elimination of discomfort
reux at
3 weeks.
At 1 year, two
foam and six
liquid
recurrences
2. Foamc 45

Belcaro et al,46 Yes/open 1. Liquid123 70% female Uncomplicated 10 year, 84% 10-year None stated; 12
VEDICO trial (mean age primary reintervention/ negative lung
43) varicose veins failure rates: scintigraphy
examinations
reported
2. Highdose 1. 10%/46%
liquid 112
3. Multiple 2. 8%/44%
ligations 132
4. Stab avulsions 3. 11%/32%
122
5. Foamd 129 4. 30%/34%
6. SFJ ligation 5. 8%/40%
liquid131
6. 6%/29%

DUS, Duplex ultrasound scanning; GSV, great saphenous vein; SFJ, saphenofemoral junction; VEDICO, foam-sclerotherapy, surgery, sclerotherapy, and
combined treatment for varicose veins.
a
Tessari technique (sodium tetradecyl sulfate or polidocanol) with duplex ultrasound guidance.
b
Monfreux technique (polidocanol) without duplex ultrasound guidance.
c
Double-syringe system (polidocanol) with duplex ultrasound guidance.
d
Irvine technique (Tessari-like technique predecessor; polidocanol) with duplex ultrasound guidance.

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JOURNAL OF VASCULAR SURGERY
Volume 57, Number 4S
Neovascularization was not observed in any of the treated
limbs. The Venous Closure Treatment Study Group con-
sisted of 35 centers from Europe, the United States, and
Australia.24 They reported data from >1000 limbs without
high ligation. Merchant et al24 showed successful ablation
ranging from 93% at 1 week to 85% at 2 years with absence
of reux, dened as absence of reversal at or near the
saphenofemoral junction or any segment of the treated
vein of 90% at 2 years with patient satisfaction of 95% at
the 2-year follow-up visit.
Results of ultrasound examinations at 2 years were avail-
able on 142 limbs, and 111 were also scanned at 1 year. Of
these, only 2.8% changed from reux at 1 year to evidence of
reux with duplex ultrasound imaging at 2 years.25
The most serious complication of radiofrequency abla-
tion, although rare, is clot extension into the common
femoral vein, which may lead to DVT if not recognized
and treated early with low-molecular-weight heparin or
operative thrombectomy. Duplex ultrasound surveillance
is a crucial component of the Closure protocol and should
be performed #72 hours of the procedure.26 Nerve injury
was initially reported with much higher frequency; however,
the use of tumescent anesthesia has signicantly decreased
the occurrence of nerve injury, although areas of hypoesthe-
sia may still be noted. It is recommended that the Closure
procedure be limited to above the knee GSV to decrease
the occurrence of signicant nerve injury.26 The use of
tumescent anesthesia has signicantly decreased the rate of
skin burns.25,27 Pigmentation may occur and is usually the
result of residual blood trapping within vein segments. It
usually resolves over several weeks without any specic
treatment. There is level 1 evidence in four studies appear-
ing in peer-reviewed journals that at follow-up at 5-year
intervals, the outcomes with radiofrequency ablation of
GSV reux are similar to traditional stripping and liga-
tion.22,24,28,29 This procedure is very popular with patients.
An alternative to radiofrequency closure is laser treat-
ment of the incompetent saphenous vein with use of an
endovenous laser ber and generator to deliver electromag-
netic energy. Proebstle et al30 reported that heat injury of
the GSV removed after pulse-mode laser ablation showed
damage along the entire vein, noting more severe damage
with perforations at the site of the laser pulses. Further
evidence for steam bubble-induced laser thermal damage
has been reported.31 The risk of thermal damage to
surrounding tissue during laser ablation may be decreased
with the injection of perivenous anesthesia and measured
maximum temperature of approximately 45 C in tissue 3
to 5 mm from the GSV during ablation.32
Exclusion criteria include the presence of arterial venous
malformations, restricted ambulation, and the presence of
DVT. Multiple laser generators are available. They all use
a 60-mm laser ber. Postoperative adverse events may include
ecchymosis, pain, paresthesias, infection, cutaneous dermal
injury, supercial thrombophlebitis, and DVT (Table III).
Endovenous ablation of the supercial venous reux will
achieve satisfactory results in many patients. Adjunctive
therapy, however, may be indicated in some patients.
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Lohr and Bush 43S
Complex vein disease, perforating veins, or outow obstruc-
tion are scenarios in which adjunctive procedures may be
needed to provide denitive therapy. The use of concomi-
tant or delayed adjunctive procedures is controversial. In
short, there is no standard solution to this complex issue.
Endovenous chemical ablation with ultrasound-guided
foam sclerotherapy using catheter-directed or injection scle-
rotherapy is the nal system that may be applied to obliterate
the saphenous vein. It is the third available method to
achieve ablation of the diseased vein segment. Sclerosis
causes irreversible damage to the endothelium by disrupting
cell membranes, resulting in sustained vasospasm and denu-
dation of the venous monolayer. The end result is a brous
obliteration of the vessel lumen. Currently available
evidence suggests the mechanism is the same whether the
physical phase of the inciting agent is liquid or foam. Physical
properties of foam may afford a more prolonged contact
with the venous endothelium, and the efciency of sclerosis
is increased, allowing a smaller volume of agent to be given.
There are few local and systemic complications of sclerother-
apy. The results of randomized control trials using foam scle-
rotherapy are presented in Table IV. Contraindications to
foam sclerotherapy are essentially the same as those for liquid
sclerotherapy (Table V).
Reux ablation has been reported to range from 68%
to 100%. However, differences do occur in the denition
of a successful procedure as well as the use of surrogate
markers of success, for example, occlusion of the treated
vein (resolution of reux), different primary outcome
markers (resolution of symptoms), improved quality of
life scores, recurrent varices, and ulcer healing. The number
of ultrasound-guided foam sclerotherapy sessions needed
to achieve success confounds the analysis of the results.
Follow-up periods may range from 1 to 10 years, although
studies reporting over a 3-year interval have demonstrated
success rates of 81% to 92%.47,48 After the highest point of
reux is treated, sclerotherapy and ambulatory phlebec-
tomy may be used to eliminate further areas of insuf-
ciency, including spider veins and telangiectasias or
branch vessel varicosities. Controversy exists whether the
various treatment modalities should be staged or sequen-
tially applied. A great deal of this depends on the motiva-
tion and convenience of the patient.
The primary limitation of sclerotherapy is the vein diam-
eter. The sclerosing agent must make contact with the vein
wall to cause endothelial damage. Blood ow within larger
veins may also dissipate the agent and prevent it from effec-
tively interacting with the vein wall. Different types of scle-
rosing agents are grouped by categories by their mechanism
of action for producing endothelial damage. Currently avail-
able solutions include osmotic, alcohol, or detergent cate-
gories. Each agent has a category and each specic agent
has its own advantage and disadvantage. When choosing an
agent, these need to be considered carefully. The concentra-
tion also needs to be selected carefully. The vessel size and
solution concentration need to be matched. Too high
a concentration may result in matting and pigmentation
and too low a concentration may result in failure.

44S Lohr and Bush
Table V. Contraindications to foam sclerotherapy
Contraindications
Known allergy to local anesthetic
Known allergy to sclerosant agent
Acute deep vein thrombosis
Coagulopathy
Peripheral vascular disease (ankle-brachial index <0.8)
Pregnancy
Relative contraindications
Patient foramen ovale
History of severe migraines
May-Thurner syndrome
Klippel-Trnaunay syndrome
Four agents are currently approved by the U.S. Food
and Drug Administration (FDA) for sclerotherapy. These
include sodium tetradecyl sulfate, polidocanol, sodium
morrhuate, and ethanolamine oleate. Agents cause the
dehydration of the endothelial cells through osmosis,
which leads to endothelial cell destruction. The two
primary agents used for lower extremity varicosities include
hypertonic saline, 23.4% sodium chloride, or a hypertonic
saline-dextrose mixture. Alcohol agents are a weak sclero-
sant and cause irreversible destruction of the endothelial
cells upon contact.
Detergent agents are strong sclerosants that produce
destruction of the target vein by aggregating on the endo-
thelial wall to cause thrombosis. Three agents that are
FDA-approved at this time for lower extremity venous insuf-
ciency treatment: sodium morrhuate, sodium tetradecyl,
and polidocanol. Sodium morrhuate has a high incidence
of skin necrosis and is not widely used for this indication.49
The contraindications for sclerotherapy include known
allergy to the sclerosant, acute cellulitis, acute respiratory or
skin diseases, severe systemic disease, acute supercial phle-
bitis, pregnancy, hypothyroidism, and bed rest. Relative
contraindications include asthma, late complications of dia-
betes, a known hypercoagulable state, leg edema, advanced
peripheral arterial occlusive disease, and chronic renal insuf-
ciency.50,51 The complications arising from sclerotherapy
include pigmentation changes, telangiectasia matting,
allergic reactions, anaphylaxis, ulcerations, cutaneous
necrosis, venous thrombosis, inadvertent arterial injection
(most common location is the posterior or medial malleolar
region), nerve damage (saphenous and sural nerve), super-
cial phlebitis, DVT, and pulmonary embolism.51,52 As
a staged procedure, the sclerotherapy should follow the
endovenous ablation or saphenectomy of the great and
small saphenous veins. This method allows existing truncal
varicosities to decrease in size or disappear before further
procedures are performed.53
Depending on the number and severity of the diseased
veins and the goals of the patient, several sclerotherapy treat-
ment sessions may be necessary to eliminate the veins and
achieve the stated goals. It is necessary that the patient
and the treating physician have the same expectation and
that the treating physician clearly explain this before under-
taking any treatment of venous insufciency. Compression
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JOURNAL OF VASCULAR SURGERY
April Supplement 2013
improves the comfort and results of sclerotherapy54 and
may also decrease the incidence of matting.55 Early liberal
use of microthrombectomy will also reduce the incidence
of pigmentation.56 Treatment choices need to be individu-
alized for each patient and centered around the patients
goals and anatomy. Minimally invasive treatment options
continue to expand.
AUTHOR CONTRIBUTIONS
Conception and design: JL, RB
Analysis and interpretation: JL, RB
Data collection: JL, RB
Writing the article: JL, RB
Critical revision of the article: JL, RB
Final approval of the article: JL, RB
Statistical analysis: Not applicable
Obtained funding: Not applicable
Overall responsibility: JL, RB
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Submitted Jan 10, 2012; accepted Oct 26, 2012.