PATHOPHYSIOLOGY

AND TREATMENT OF VARICOSE VEINS

Group 11 of 2018 A

Jean Adi Bactie 17700103

Putu Septia Kartika Putri 15700057

Lintang Fajar Parahiyangan 15700102

FAKULTAS KEDOKTERAN

UNIVERSITAS WIJAYA KUSUMA SURABAYA

2021/2022
 PREFACE

First of all, thanks to God because of the help of God, writer finished
writing the paper entitled "Pathophysiology and Treatment of Varicose Veins"
right in the calculated time. The purpose in writing this paper is to fulfill the
assignment that given by surgical.

In arranging this paper, the writer trully get lots challenges and
obstructions but with help of many indiviuals, those obstructions could passed.
Writer also realized there are still many mistakes in process of writing this paper.

Because of that, the writer says thank you to all individuals who helps in
the process of writing this paper. Hopefully God replies all helps and bless you
all. The writer realized tha this paper still imperfect in arrangment and the content.
Then the writer hope the criticism from the readers can help the writer in
perfecting the next paper. Last but not the least hopefully, this paper can help the
readers to gain more knowledge about Pathophysiology and Treatment of
Varicose Veins.

Surabaya, December 7th, 2021

The writer
 TABLE OF CONTENTS

CHAPTER I INTRODUCTION...........................................................................1

CHAPTER II CONTENTS...................................................................................2

2.1 Definition.......................................................................................................2

2.2 Pathophysiology...........................................................................................3

2.3 Treatment.....................................................................................................8

CHAPTER III CONCLUSION..........................................................................13

REFERENCE.......................................................................................................17
 CHAPTER I
INTRODUCTION

Varicose veins are twisted, dilated veins most commonly located on the
lower extremities. Risk factors include chronic cough, constipation, family history
of venous disease, female sex, obesity, older age, pregnancy, and prolonged
standing. The exact pathophysiology is debated, but it involves a genetic
predisposition, incompetent valves, weakened vascular walls, and increased
intravenous pressure. A heavy, achy feeling; itching or burning; and worsening
with prolonged standing are all symptoms of varicose veins. Potential
complications include infection, leg ulcers, stasis changes, and thrombosis. Some
conservative treatment options are avoidance of prolonged standing and straining,
elevation of the affected leg, exercise, external compression, loosening of
restrictive clothing, medical therapy, modification of cardiovascular risk factors,
reduction of peripheral edema, and weight loss. More aggressive treatments
include external laser treatment, injection sclerotherapy, endovenous
interventions, and surgery. Comparative treatment outcome data are limited.
There is little evidence to preferentially support any single treatment modality.
Choice of therapy is affected by symptoms, patient preference, cost, potential for
iatrogenic complications, available medical resources, insurance reimbursement,
and physician training (Jones and Carek, 2008)
 CHAPTER II
CONTENTS
2.1 Definition
Varicose veins are lengthening, widening accompanied by a tortuous
venous system and the presence of impaired blood circulation in it. Varicose veins
arise as a result of the decreased ability of the leg muscles to contract due to
increasingly hard and flat roads and the use of inappropriate shoes/footwear
(Puruhito, 2016).

Varicose veins and spider veins occur in the lower limbs because of
upright position and hydrostatic pressure. Differentiation among spider veins,
reticular veins, and varicose veins is related to size, with a varix being at least 3
mm in diameter. Valvular dysfunction does not need to be present in either the
GSV or small saphenous vein (SSV) (FIGURE 1) for large varicosities to
develop; it can happen because of local incompetence alone. Definition of
varicose veins is expanded to include cosmetic telangiectasias, they are present in
79% of men and 88% of women (Hamdan, 2012).

Figure 1
 Common Pattern of Major Superficial and Deep Veins of the Lower Extremity

(Hamdan, 2012)

Figure 2

Schematic of Venous Reflux

(Hamdan, 2012)

2.2 Pathophysiology
One of several pathologic processes along a continuum of chronic lower
extremity venous disease, varicose veins ectatic, tortuous vessels of the superficial
venous system that are at least 3 mm in sizedare a common problem with
significant impact on the patient’s quality of life. They are more than a simple
cosmetic issue; the presence of varicosities carries an increased risk for the
development of superficial vein thrombosis and venous thromboembolic disease.
Varicose veins pose a sizable cost burden on the health care system and are one of
the most common reasons for appointments with primary care providers. Despite
their prevalence, little is known about the biologic mechanisms underlying their
development (Jacobs et al, 2017).
 Figure 3
Pathophysiology of Varicose Veins
(Jacobs et al, 2017)
a. HEMODYNAMIC FACTORS
Blood flow in the venous system is dependent on intact valves and muscle
pumps to allow return of blood to the heart against gravity. Under normal
physiologic conditions, venous flow is transmitted from the superficial system to
the deep system and proximally to the central veins in a caudal to cranial
direction. Superficial, deep, and perforating veins contain valves that, when fully
competent, maintain cranial flow and prevent reflux. Dilation of varicosities may
be due to failure of these valves in the lower extremity, allowing backward
transmission of the pressure gradient from the deep system to the superficial
through the saphenofemoral junction (SFJ) and perforating collaterals (Jacobs et
al, 2017).
Anatomic, ultrasound, and plethysmographic studies have demonstrated that
the presence of valvular incompetence is widely distributed throughout the leg in
affected individuals. The most common location for incompetence is caudal in the
branch vessels, with the most common site in the below-knee great saphenous
vein. Increased venous pressures have been shown to correlate with increased
severity of disease. Engelhorn et al conducted ultrasound investigation in 590
extremities with Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) class
2 disease8; 77% of patients demonstrated great saphenous vein reflux, with a
segmental reflux pattern in 58%, with only 12% demonstrating reflux at the SFJ.
However, the contribution of SFJ reflux is unclear, as another study showed that
half of patients had incompetence at the SFJ (Jacobs et al, 2017).
Supportive of the hypothesis are data that obesity, multiparity, and
occupations requiring prolonged standing are strong risk factors for the
development of lower extremity varicosities; increased intra-abdominal pressure
is transmitted caudally, causing distention of extremity veins and rendering valves
incompetent. This is further supported by clinical improvement in symptoms seen
with compression stockings and with surgical ligation or ablation of incompetent
axial veins (Jacobs et al, 2017).
The descending theory, initially described by Trendelenburg, has been the
dominant hemodynamic theory for many years. It is from this theory that the
practice of ligation of the SFJ and radiofrequency and laser ablation of the
saphenous vein derive. The ascending theory of varicose vein development
suggests that rather than arising from incompetence located in more cranial
segments of the superficial system, caudal venous shunts and reflux entry points
allow filling of varicosities and the creation of an ascending column of hydrostatic
pressure and consequent inability to drain the superficial system (Jacobs et al,
2017).
The conservative hemodynamic correction for venous insufficiency and
ambulatory selective varices ablation under local anesthesia techniques are based
on this ascending theory. In the conservative hemodynamic correction for venous
insufficiency technique, venovenous shunts and reflux entry points are
interrupted, interrupting the column of hydrostatic pressure and allowing
varicosities to drain into the deep system through perforators.16 Ambulatory
selective varices ablation under local anesthesia involves the removal of epifascial
varicosities without interruption of the great saphenous vein (Jacobs et al, 2017).
Hemodynamic factors do not fully explain the pathogenesis of varicose
veins. There is clearly a heritable component as the number one risk factor for the
development of varicosities is a first-degree relative with the disease, and wall
dilation and varicosities have been seen below entirely competent valves (Jacobs
et al, 2017).
b. VEIN WALL FACTORS
The weak wall hypothesisdthat local vein wall factors precede valvular
incompetencedis based in part on the observation that areas of greatest histologic
abnormality are often just caudal to the venous valve rather than just cranial, as
would be expected if venous hypertension was the primary process. The Table
presents the findings of selected studies of varicose vein pathophysiology.
Dilation distal to the valve over time separates the cusps, rendering them
insufficient (Jacobs et al, 2017).
Varicose vein walls demonstrate a significantly altered histopathologic
phenotype, characterized by architectural and structural remodeling of the vein
wall. Development of intimal and smooth muscle cell hyperplasia is common. The
abnormal vessel of the varicosity is invariably ectatic, and luminal diameter is
larger than in normal vein. Importantly, varicose vein disease is characterized by
skip lesions, areas of normal vein between varicosities. Histologic study of
varicose veins has shown that they are alternately thickened and fibrotic in some
areas and thin and collapsed in others (Jacobs et al, 2017).
Alterations in the normal ratio and function of extracellular matrix (ECM)
components and smooth muscle cells may contribute to the development of
dilation in varicosities. Varicose veins may have intrinsic reductions in elastic
recoil, decreasing their ability to pump blood forward and resulting in venous
pooling and dysfunctional coaptation of valve cusps. Some studies have found
increases in collagen, whereas others have found it decreased. Similarly
conflicting findings have been shown with elastin. This variability may be due to
previously mentioned skip lesions and consequent difficulty in comparing exactly
the same section of vein across and within studies. In one study, decreased levels
of elastin and type III collagen in the great saphenous vein vessel wall correlated
with abnormal vein diameter at rest and with abnormal distensibility on Valsalva
maneuver (Jacobs et al, 2017).
Disorganization of the ECM in relation to smooth muscle fibers is likely
more important than total content of collagen and elastin. Multiple studies have
shown disorganization of collagen fibers in varicose veins that inappropriately
invade and intercalate with smooth muscle layers. This disorganization affects
smooth muscle contractile function, although overall numbers of smooth muscle
cells remain normal for vessel size. Differential responsiveness to vasoconstrictive
stimuli in sections from varicosities and from cranial and caudal segment of vein.
Angiotensin II responsiveness was reduced in all three segments compared with
control vein, and responsiveness to phenylephrine was reduced in vein segments
cranial to the varix segment. Relaxin-2, which has effects on both venodilation
and ECM turnover, has been shown to be reduced in varicose veins (Jacobs et al,
2017).
Local hypoxia in the luminal blood from pooling and from compression of
the vasa vasorum by distended wall may induce phenotypic changes. Data are
conflicting as to whether oxygen tension is in fact lower in varicose vein blood.
Many of these conflicting studies have been conducted in supine patients. One
study found no difference in oxygen tension in the supine position, but after a 30-
minute period of sitting, oxygen tension in varicosities dropped significantly
lower than that in brachial artery blood. Activation of hypoxiainducible factor, a
nuclear transcription factor regulated by intracellular oxygenation, has been
implicated in angiogenesis, ECM metabolism, and apoptosis. Upregulation of
hypoxia-inducible factors and their target genes in varicose vein. Dysregulation of
hypoxia-inducible factor pathways may also affect apoptosis in the cell wall and
consequent fibrosis and abnormality of the ECM (Jacobs et al, 2017).
Matrix metalloproteinases (MMPs), which are known to be involved in
arterial aneurysmal disease, have been shown to be similarly abnormal in varicose
veins. MMP-9 plasma levels drawn from lower extremity varicosities after a 30-
minute period of postural stasis had significant increases in plasma pro-MMP-9
compared with controls. The main source of MMP-9 in diseased veins is
neutrophils, suggesting a role for neutrophil activation in the development of
varicosities. It has been hypothesized that vascular adhesion molecule
upregulation in hypoxic conditions in varicose veins increases inflammatory cell
infiltration and consequent disordered ECM turnover. Correspondingly increased
levels of inflammatory markers interleukin 6, interleukin 8, and monocyte
chemotactic protein are found in blood drawn from varicose veins. D-dimer, a
fibrin degradation product, has been found to be locally elevated in varicosities
compared with blood drawn from the arm of the same patient; from this, the
conjecture has been made that there is increased thrombosis and thrombus
turnover in the pooling, hypoxic blood of the varicose veins; this may precede
endothelial activation and infiltration of inflammatory cells (Jacobs et al, 2017).
Again, these findings do not necessarily indicate a local primary pathologic
process. One can make the inference from these that hypoxia, local
thrombogenesis, and inflammatory cell infiltration are all secondary to venous
distention and valvular incompetence. One promising target of investigation is the
FoxC2 regulatory element. Genetic polymorphisms in FoxC2 have been identified
in patients with varicose veins. These thickened areas of vein appear arterialized
in some respects; arterialspecific markers have been found to be upregulated in
varicosities. Surendran et al illustrated that activation of angiogenic pathways
through Delta-like ligand 4 induces uncontrolled smooth muscle cell hyperplasia
and a consequent arterialization of the wall of the varicosity (Jacobs et al, 2017).
2.3 Treatment
Modalities for Management of Varicose Veins :
a. Conservative Management
Lifestyle changes. Patients who have varicose veins can manage and prevent
symptoms with the use of lifestyle changes, and the NP’s role in patients’
education is paramount in helping patients understand the importance of lifestyle
changes. Education should be given regarding daily skin care, the types of
clothing to avoid, the need to elevate the legs, and the need for lower extremity
exercises. Recommended daily skin care should involve the use of a mild soap
and lukewarm water followed by the application of a petrolatum-based
moisturizer (Zhang, et al. 2014)
Patients should also be educated on the need to avoid wearing constrictive
clothing, such as knee-high or panty hose stockings, that can restrict the flow of
blood in the lower extremities. The NP should educate patients on the need to
elevate the legs above the level of the heart for about 30 minutes 4 times each day.
Patients can be told to avoid having the legs in the dependent position for
prolonged periods of time to avoid the pooling of blood in the legs (Zhang, et al.
2014)
The NP should also teach the patient about different leg exercises that can be
performed to aid the calf muscles in the return of blood to the heart. Leg exercises
that can be done include walking (slightly uphill if possible), tiptoe movements
that involve standing and rising up on the tips of the toes while holding onto a bar
or other form of support, and dorsiflexion and plantar flexion of the feet several
times each day. Patients can also be educated on the use of compression stockings
to help with blood return from the legs to the heart (Zhang, et al. 2014).
b. Support hosiery
Compression hosiery improves both symptoms and venous haemodynamics
among patients with varicose veins and reduces oedema24 with grade II
compression (20–30 mmHg) conferring maximal relief. However, benefit is
restricted to the period during which the stocking is worn. Compliance is variable
(Rachmat et al. 2018)
and difficult to assess. It has been reported, however, that only 37–47%
patients continue to wear them 1 year after DVT or for the long term prevention
of venous ulceration. Poor compliance has been attributed to both the cost of
stockings, and lack of patient education, but may also be due to poor cosmesis. In
general, grade II stockings are tolerated better than grade III stockings and
compliance also varies depending on the manufacturer. A small nonblinded
randomised controlled trial of compression stockings (class I and II) in pregnancy
showed that the development of LSV reflux and symptoms were less common in
the treated group (pZ0.047) as compared to controls, but that there was no
difference in development of varicose veins. Compression therapy may also be
facilitated with a variety of proprietary bandages although with the exception of
Setopressw (half strength 30 mmHg; full strength 40 mmHg) the pressure exerted
by these is uncertain and difficult to control (Beale, 2005).
c. Conventional surgical stripping
All management modalities for varicose veins are safe and effective at short-
term and midterm followup. The methods to manage great saphenous veins
traditionally include ligation and division of the saphenofemoral junction and its
tributaries in the groin, stripping the great saphenous veins from groin to knee
level. The incompetent small saphenous veins are ligated and divided, rather than
stripped, close to the popliteal vein in the knee pit, because stripping small
saphenous veins may potentially damage the sural nerve. It is not rare for
recurrence, hematoma, and skin infection to occur after surgical procedure. And
massive bleeding due to injury to femoral veins, or even to femoral artery during
surgery, and mortality from pulmonary embolism and DVT can happen, even
though these are rarely reported.
d. Endovenous thermoablation
Endovenous thermoablation approaches include EVLA and radiofrequency
ablation; these belong to the category of minimally invasive catheter-based
procedures. In this procedure, a catheter is inserted and positioned at 2 cm below
the saphenofemoral or saphenopopliteal junction. Local anesthesia is used with
perivenous tumescent technique to prevent neural damage and skin burn.
Alternatively, venous sedation can be used. The thermal energy is delivered onto
the diseased venous wall and induces inflammation response and subsequent
fibrosis and closure of the vein.
Thermal ablation destroys damaged veins using an external laser or via
endovenous catheter using a laser (endovenous laser ablation) or radio waves
(radiofrequency ablation). External laser thermal ablation works best for
telangiectasias. In this therapy, hemoglobin absorbs the laser light leading to
thermocoagulation. Endovenous thermal ablation can be used for larger vessels,
including the great saphenous vein. Under ultrasound guidance, a laser optical
fiber or radiofrequency catheter electrode is inserted into the vein in a distal to
proximal direction. Heat from the laser or radio waves coagulates the blood in the
vein, resulting in closure of the vein and redirection of blood flow to functional
veins (Raetz et al. 2019).
Faster recovery from EVLA, no need for hospital admission, no surgical
incision, and early resumption of daily activity or work are advantages of this
procedure. However, like other surgeries, EVLA still can cause operative or
postoperative complications, such as hematoma, infection, skin burn, bruising,
and catheter stabbing by laser fiber, or the broken catheter can be left in the body.
Many clinical studies and randomized controlled trials of high quality compared
EVLA and conventional surgical procedures and showed no differences in
postoperative pain, recurrence rates, or returning to work or normal activity.
Clinical experience shows that the pain after laser ablation contributes to
the skin contusion caused between skin and uneven bandages used after the
procedure, blisters induced by skin burn, and endovenous thermal–induced
thrombosis and thrombophlebitis; all of these problems can be prevented with
careful manipulation during the procedure. Using proper compression stocking
rather than bandage may reduce the risk of skin contusion. In addition, early
ambulation is always critical to preventing DVT.
e. Radiofrequency ablation
The technique of endovenous RFA has been available since 1998; it delivers
thermal energy from a bipolar catheter to the insufficient veins. RFA is an
effective and safe treatment modality for incompetent veins, and it can be
performed in-office as a minimally invasive procedure. The advantages of RFA
include low complication rate, reduced pain, high vein occlusion rates, and early
return to work and normal activities. Currently available clinical trial evidence
suggests RFA and EVLA are at least as effective as surgery in the treatment of
great saphenous varicose veins (Brar et al. 2010)
f. Foam sclerotherapy
Sclerosing foam is injected through a cannula in the vein under duplex
ultrasound guidance; it can be undertaken in the outpatient clinic, and a
compression stocking should be used immediately after FS. Observational studies
found that success rates vary from 82% to 100%,5 and the recovery was faster
following FS than following conventional surgical stripping. It takes
approximately 1 hour to perform FS, patients do not need to take medicine or stay
in the hospital, and patients can go home or continue to work immediately after
the procedure. The efficacy of FS is obvious in comparison with conventional
surgical stripping. Complications after FS are rare, including bruising,
thrombophlebitis, skin pigmentation, and visual disturbance.
 In this large, multicenter trial comparing surgery, laser ablation, and foam
sclerotherapy for the treatment of primary varicose veins, quality of life was better
at 5 years than at baseline in all groups. Five years after treatment, there were
significant differences between the treatments with respect to disease-specific
quality of life (Brittenden et al. 2019).
g. Ambulatory phlebectomy
Ambulatory phlebectomy is an outpatient procedure that removes superficial
veins through small 2- to 3-mm incisions in the skin overlying the varicose veins
and is performed under local anesthesia. The accepted indications for this
technique are side branch varicose veins, and varicose veins of the foot, around
the ankle, and the knee pit. The most important instrument for this technique is the
vein retractor or phlebectomy hook. There are two ways by which the veins can be
grasped. The phlebectomy hook is inserted through an incision and the varicose
vein is hooked, extracted, and subsequently fixed with a clamp; the vein is finally
pulled out by turning the exteriorized part of the vein. Graded compression
stockings or compression bandages are usually used for 1 to 2 weeks after the
procedure. This procedure is often used as an adjunct to EVLA or RFA, either
concomitantly or in the sequential management of tributaries for symptomatic
varicose veins. The complications are uncommon but include paresthesia,
bruising, hemorrhage, and hematoma. EVLA with with both treatments achieves
excellent results at 5 years. Concomitant treatment of varicosities is associated
with optimal improvement in both clinical disease severity and quality of life (Lin
et al. 2015).
 CHAPTER III
CONCLUSION
The pathogenesis of varicose veins remains poorly understood. In the past
decade, there has been a shift from the initial theories that were based on purely
mechanical factors to hypotheses focusing on complex molecular and
histopathologic alterations in the vessel wall and the ECM. Pathologic mechanical
factors such as valvular incompetence and venous hypertension are not found in
all cases of varicose veins, and the histopathologic alterations are uniformly
present. However, because valvular incompetence and venous hypertension are
present in the majority of cases, these mechanical factors are likely to modulate
the severity of disease. Increased venous pressure causes stretching of the
endothelium, which can in turn promote expression of cytokines and adhesion
molecules, activation of extracellular signal–related kinases, and free radical
production. These mechanical and valvular factors may therefore be an alternate
mechanism for the activation of the molecular changes that are now seen to be
central to varicose vein development (Oklu et al., 2012).

There is clearly a genetic component that leads to the histologic and

molecular alterations within the varicose vessel wall, as evidenced by the FOXC2
studies,with the degree of clinical severity then further compounded by lifestyle
and demographic factors. As the full cascade of the pathophysiologic changes that
lead to vessel wall and ECM changes in varicose veins is characterized and
understood, genetic screening and gene-targeted therapy may play pivotal roles in
the clinical management of what has become one of the most commonly
encountered vascular problems in modern clinical practice (Oklu et al., 2012).

Overall, all management modalities appear to be safe and effective in the

short term and midterm, and it is equally true that no procedures for varicose
veins have no side effects during or after the procedure. Current studies showed
that FS and RFA were associated with less pain and faster recovery than EVLA
and surgical stripping; EVLA and RFA have shown faster recovery and earlier
return to work in comparison with conventional high ligation and stripping. FS
was associated with the highest failure rate (Lin et al. 2015).
 REFERENCE
Beale RJ; M.J. Gough (2005). Treatment Options for Primary Varicose Veins—A
Review. , 30(1), 83–95. doi:10.1016/j.ejvs.2005.02.023

Brar, R.; Nordon, I. M.; Hinchliffe, R. J.; Loftus, I. M.; Thompson, M. M. (2010).
Surgical Management Of Varicose Veins: Meta-analysis. Vascular, 18(4),
205–220. doi:10.2310/6670.2010.00013

Brittenden, Julie; Cooper, David; Dimitrova, Maria; Scotland, Graham; Cotton,

Seonaidh C.; Elders, Andrew; MacLennan, Graeme; Ramsay, Craig R.;
Norrie, John; Burr, Jennifer M.; Campbell, Bruce; Bachoo, Paul; Chetter, Ian;
Gough, Michael; Earnshaw, Jonothan; Lees, Tim; Scott, Julian; Baker, Sara
A.; Tassie, Emma; Francis, Jill; Campbell, Marion K. (2019). Five-Year
Outcomes of a Randomized Trial of Treatments for Varicose Veins. New
England Journal of Medicine, 381(10), 912–922.
doi:10.1056/NEJMoa1805186

Hamdan A., (2012). Management of Varicose Veins and Venous Insufficiency.

American Medical Association. Vol 308. No 24

Jacobs, Benjamin N.; Andraska, Elizabeth A.; Obi, Andrea T.; Wakefield,
Thomas W. (2017). Pathophysiology of varicose veins. Journal of Vascular
Surgery: Venous and Lymphatic Disorders, 5(3), 460–467.
doi:10.1016/j.jvsv.2016.12.014

Jones R. H., Carek P J. (2008) Management of Varicose Veins. American Family

Physician. Vol. 78. No 11. Pp : 1-6

Lin, Fan; Zhang, Shiyi; Sun, Yan; Ren, Shiyan; Liu, Peng (2015). The
Management of Varicose Veins. International Surgery, 100(1), 185–189.
doi:10.9738/intsurg-d-14-00084.1

Oklu, Rahmi; Habito, Roy; Mayr, Manuel; Deipolyi, Amy R.; Albadawi, Hassan;
Hesketh, Robin; Walker, T. Gregory; Linskey, Katy R.; Long, Chandler A.;
Wicky, Stephan; Stoughton, Julianne; Watkins, Michael T. (2012).
Pathogenesis of Varicose Veins. Journal of Vascular and Interventional
Radiology, 23(1), 33–39. doi:10.1016/j.jvir.2011.09.010
Puruhito. (2016). Bedah Varises Tungkai dalam Buku Ilmu Bedah Toraks,
Kardiak dan Vaskular. Airlangga University Press dengan LP3 UNAIR. Pp :
397

Rachmat J., Puruhito, Tahalele P., Dahlan M., Hakim T., Jusi D., (2018) Jantung
Pembuluh Darah dan Limfe dalam Buku Ilmu Bedah De Jong. Pp 583-585.

Raetz J., Wilson M., Collins K., (2019). Varicose Veins : Diagnosis and
Treatment.. American Family Physician. Vol 99. No 11. Pp : 683-691

Zhang S., Melander S., (2014). Varicose Veins : Diagnosis, Management, and
Treatment. The Journal for Nurse Practitioners. Pp : 1-8