Continuing Education Activity

Varicose veins in the lower extremities involve the great and small saphenous veins and their tributaries between the fascia and the skin. Varicose veins are characterized by subcutaneous dilated, tortuous veins greater than or equal to three millimeters, involving the saphenous veins, saphenous tributaries, or non-saphenous superficial leg veins with age and family history considered important risk factors. For several reasons, including cosmetic complaints and complications with thrombosis formation, varicose veins should be treated. This activity reviews the evaluation and management of varicose veins. It highlights the role of interprofessional team members in collaborating to provide well-coordinated care and enhance outcomes for affected patients.

Objectives:

• Describe the etiology of varicose veins.
• List the factors associated with an increased risk of developing varicose veins.
• Describe exam findings consistent with varicose veins.
• Employ interprofessional team strategies for improving care coordination and communication to enhance outcomes for patients affected by varicose veins.

Introduction

Varicose veins are characterized by subcutaneous dilated, tortuous veins greater than or equal to three millimeters, involving the saphenous veins, saphenous tributaries, or non-saphenous superficial leg veins with age and family history considered important risk factors.[1] Varicose veins are considered a common clinical manifestation of chronic venous disease.[2] Notwithstanding the cosmetic challenges with varicose veins, the associated superficial axial venous reflux should be evaluated. Accordingly, great and small saphenous vein reflux exclusion is part of the primary diagnostic management.[3] Varicose vein entity includes a vast majority of clinical and pathological manifestations, from limited leg discomfort to swelling and non-healing ulcers.[4][5][6]

Etiology

The risk factors for varicose veins include female sex, multiparity, body weight, constipation, and history of venous thrombosis.[3][4][5] Prolonged standing or walking at work has been suggested to be a cause of VVs. Varicose veins are considered C2 in the clinical classification of clinical, etiologic, anatomic, and pathophysiological (CEAP) for chronic venous disorders.[3] Despite the multifactorial pathogenesis of varicose veins, the contributing genetic and environmental factors are understudied.[7] 

In one of the recent studies, researchers applied machine learning to probe the potential risk factors of varicose veins in almost 500,000 individuals in the UK Biobank.[7] Consequently, a genome-wide association study of varicose veins and expression quantitative loci and pathway analysis were performed among unrelated individuals of white British descent.[8] Linkage disequilibrium score regression (LDSC), a tool to estimate single nucleotide polymorphisms (SNP) heritability, genetic correlation, and genomic inflation, was applied to a genome-wide association study (GWAS) summary data sets of the UK biobank.[9] Interestingly, height has emerged as a new potential risk factor, and several mendelian randomization analyses examined height's causal role in varicose vein development and severity.[7][10] 

Recent mendelian randomization studies unveiled the positive and inverse association of genetically-predicted factors. Accordingly, it has been demonstrated that height, body mass index, smoking, and circulating iron levels were positively associated with the risk of varicose veins. However, circulating minerals, including calcium and zinc levels, showed an inverse association with varicose veins development. Several putative predictors that have been variably reported in the literature, including hypertension, age at menopause, and smoking, were not reported among the top predictors with machine learning approaches.[7] Indeed, the associations were further adjusted, and the results were against the association for genetically predicted systolic blood pressure after adjustment for height.[10] Moreover, the following genetically predicted factors were reported to have a positive association with the development of varicose veins; 1. coffee consumption, 2. circulating vitamin B12, and 3. magnesium levels.[10][11] 

Some uncertain risk factors, including oral contraceptive pills use, are less likely to correlate independently.[7] Additionally, height and varicose veins were correlated in almost 16% of the reviewed patients. The correlation was stronger than the estimated correlation between the varicose vein and body mass index. Moreover, the history of DVT had the greatest genetic correlation with varicose vein disease. More than 850 new SNPs associated with varicose veins were evaluated, and 30 independent putative genetic variants were assessed. The strongest association was located on chromosome 1 in the CASZ1 gene, a well-established blood pressure locus.[7][12] 

Epidemiology

Varicose veins are reported in up to 30 percent of the general population, with significantly increased rates in the older population.[13] Varicose veins are seen globally and are influenced by activity and lifestyle. Overall, varicose veins are more common in women than in men. The Framingham Study examined the presence of varicose veins every two years for a 16-year duration. Accordingly, twenty-three and thirty percent of the male and female population developed varicose veins during the mentioned follow-up. However, the presence or absence of venous reflux was not evaluated. The two-year incidence of varicose veins was 39.4 to 51.9 per 1000. The incidence was highest in women in their 40s.[12] There is an obvious racial correlation with the prevalence of varicose veins. Accordingly, the prevalence of chronic venous insufficiency and varicose veins in Asians is lower than non-Hispanic whites.[14]

Pathophysiology

A myriad of intrinsic and extrinsic factors contribute to the formation of varicose veins, including age, gender, pregnancy, obesity, height, race, diet, occupation, history of deep vein thrombosis (DVT), and genetics. The primary pathologies related to varicose veins are; 1) elevated venous pressure in the extremities and 2) defective or incompetent valves resulting in reflux and, thus, elevated venous pressure in the extremity. Whether venous hypertension and valvular incompetence occur before the irreversible alterations of venous wall development or the reverse is still inconclusive.[15] Several pathophysiological mechanisms, including hypoxia, cellular hyperplasia, and dysregulated apoptosis, might affect and change the combination of the extracellular matrix in the involved vein at the cellular level.[13] 

Incompetent venous valves result in the backward transmission of the pressure gradient. The pressure gradient would be transmitted from the deep to the superficial venous system via the saphenofemoral junction (SFJ) and perforator veins. The most common site for the incompetent venous valve is the below-knee great saphenous vein.[16] Moreover, venous hypertension has been correlated with the severity of the disease.[15] Any conditions with increased intraabdominal pressure, including pregnancy and obesity in individuals with incompetent lower leg valves, might impose a higher risk for varicose veins. 

A limited number of genetic disorders have been correlated with varicose veins disease. Accordingly, the correlation between Klippel-Trenaunay syndrome and varicose vein disease has been well established.[17] Moreover, mutations in FOXC2, thrombomodulin (THBD), and desmuslin (SYNM) may alter vein function and impose the risk of varicose vein development.[18]

Histopathology

In varicose vein pathology, two main index events are involved: venous hypertension and valvular incompetence. The mentioned events induce a cascade of immune cells and pro-inflammatory signaling pathways resulting in the consequent venous wall remodeling. However, the opponent's school of thought argues that the venous wall alteration is the index event. Collectively, venous arterialization, smooth muscle cell hypertrophy, and hyperplasia are the histopathological findings in varicose vein disease. Insulin receptor substrate (IRS)-4 may be involved in the mentioned changes.[19] 

The mentioned insulin receptor, similar to other receptor proteins of the IRS substrate family, mediates cell signaling from the insulin receptor (IR) and insulin-like growth factor (IGF)-1 receptor (IGF-1R). Accordingly, insulin and IGF-1 regulate IRS-4 expression. The regulation occurs via the activation of IR/IGF-1R. Consequently, altered IRS-4 expression may be associated with impaired cellular growth and glucose dysmetabolism. Thus, histopathological evaluation of IRS-4 elucidated that IRS-4 overexpression could be served as a prognostic measure and a potential therapeutic target.[20] 

History and Physical

The clinical-etiology-anatomy-pathophysiology (CEAP) classification system of venous reflux is used to assess the clinical severity of symptoms:

• C0 no visible or palpable signs of venous disease
• C1 telangiectasies or reticular veins
• C2 varicose veins
• C3 edema
• C4a pigmentation and eczema
• C4b lipodermatosclerosis and atrophie blanche
• C5 healed venous ulcer
• C6 active venous ulcer[3] However, as the evidence related to these aspects of venous disorders, specifically the subject of this topic, varicose veins (C2), continues to develop, the CEAP classification should be periodically analyzed and revised. Accordingly, in May 2017, the American venous forum CEAP task force introduced several changes, including Corona phlebectatica as the C4c clinical subclass and "r" for recurrent varicose veins and venous ulcers.[3] Among the most critical revisions, additional assessments of chronic vascular disease (CVD) regarding the functional status and sub-categorical anatomical involvement significantly improved the comprehensive evaluation of CVD with CEAP.[21]

Initial diagnosis is by clinical evaluation of swelling, discoloration, and skin ulcerations.

Symptoms associated with varicose veins include:

• Leg heaviness
• Itching
• Cramps
• Mild tenderness
• Skin discoloration
• Exercise intolerance
• Leg fatigue[22][14]

The physical exam may reveal visibly distended veins from the thigh to the ankle. The discoloration is usually most prominent around the ankle and calf. The Trendelenburg test is often used to assess the competency of the deep venous valves. The leg is elevated until all the superficial veins have collapsed. With the hand, the groin area is compressed to occlude the saphenofemoral junction, and the patient is asked to stand up. If the deep valves are incompetent, the leg's superficial veins will start filling up. If distal varicosity remains empty, the point of entry is most likely at the saphenofemoral junction. This patient can benefit from ligation of the saphenous vein at this junction.[23]

Evaluation

If venous reflux is suspected based on symptomatology and clinical evaluation, the practitioner should obtain a color duplex venous ultrasound exam. This study is an objective assessment of the anatomy of the veins as well as valvular function. During the ultrasound, evaluation for deep vein thrombosis should also be performed to confirm that DVT/obstruction is not contributing to the clinical scenario.[24][25] 

Several Duplex sonography markers have been proposed to identify the preferred index for varicose vein grading study. Accordingly, the peak reflux velocity and reflux time in cases of varicose veins and non-varicose veins were compared. The results demonstrated that quantifying peak reflux velocity is more consistent than reflux time in cases of superficial venous reflux. Moreover, an optimal peak reflux velocity cut-off point of 27.4 cm/sec had the discriminatory power to differentiate the diseased limbs.[26] 

Contrast venography is rarely done today. Pulsed-wave Doppler images of varicose veins in axial projection will demonstrate retrograde blood flow after the release of manual calf compression. In the varicose vein with reflux, the reflux can be easily quantified with an ultrasound probe angled steeply upward while imaging in axial projection.[27]

Treatment / Management

Injection Sclerotherapy

Utilizes chemical irritants to obliterate unwanted superficial veins. Sclerotherapy primarily applies to small nonaxial varicose veins with less than 6 mm diameter. For aesthetic reasons, sclerotherapy might be indicated in symptomatic and even asymptomatic varicose veins.[28] Several sclerosing agents have been introduced in the management of varicose veins. Polidocanol is widely used to manage reticular and spider veins with 1 to 3 and equal to or less than 1 mm diameter. The spider veins are treated with higher concentrations. (0.5 % versus 1 %), and the injections should be repeated in 1 to 2 weeks.[29] 

Recently, the cyanoacrylate glue application has been the popular and preferred way to treat chronic venous insufficiency with varicose veins. This technique has several advantages, including the short duration of a minimally-invasive procedure lack of need for anesthesia induction.[28]

Conservative Treatments

Most patients obtain adequate symptom relief using long-term graduated compression stockings, leg elevation, and oral pain medications. For compression rates, the recommended graduation is 20-30 mmHg and, in more severe cases, can be elevated to 30-40 mmHg.[30][31][32] Stockings, when worn daily, are the ideal treatment for patients who do not want surgery. They do work, but the heat and hot weather can reduce compliance.

Surgical Treatment

Traditional surgical treatment consisted of ligation and stripping the greater saphenous vein with the avulsion of tributary veins.  

Surgical techniques involve ligation and/or removal of the veins; however, the method selection is based on the location, size, and extent of the venous involvement with or without venous reflux. Unilateral surgery in bilateral limb involvement is recommended to avoid the risk of post-operative limitations and intolerance. 

In the case of saphenous vein stripping, complete skin exposure and meticulous hygiene concerns are respected. The lower extremity is prepared and draped circumferentially from the anterior superior iliac spine to the ankle. Since several skin markings are needed, alcohol-containing skin preparation is discouraged. In the presence of venous ulceration, skin preparation for the skin overlying the ulcer should be undertaken in the last step. The ulcers should be excluded from the sterile surgical field with drapes. According to the potential for significant blood loss during the surgery, specifically in the large tortuous veins, tourniquet application has been recommended.[33] The blood loss with a tourniquet application was up to 16 ml compared to almost 133 ml without the tourniquet.[34] Moreover, long-term complications, including nerve injury, were not reported. However, improper tourniquet application might cause further complications with bleeding due to venous hypertension or deep vein thrombosis due to prolonged stasis.[35] 

Saphenous vein inversion and removal A transverse incision of up to 2 cm is made over the saphenofemoral junction, preferably marked with a Duplex scan, 3 cm peripheral to the pubic tubercle.[36] The saphenofemoral junction is identified and isolated. However, only the anteromedial and posterolateral tributaries are ligated; the abdominal wall branches are preserved. The latter is recommended to minimize varicose vein recurrence.[37] The greater end of the greater saphenous vein (GSV) is ligated adjacent to the GSV-CFV (common femoral vein ) confluence.[38] 

Consequently, a retrograde vein stripper is passed caudally. Smooth passage regarding the incompetent venous valve is expected. The distal end of the vein stripper is pulled out adjacent to the patella, while the proximal end is secured in the groin. Mushroom tips are discouraged due to the potential for extensive tissue damage and bleeding. Venous marsupialization and removal would be followed consequently. The procedure is completed with the disruption of the tributary veins followed by precise hemostasis with direct pressure and groin incision closure in multiple layers. Inversion and removal are also indicated in the small saphenous varicose vein. However, potential neurovascular bundle complications during popliteal fossa dissection and sural nerve injury should be considered.

High saphenous ligation  Albeit the ligation of the saphenous vein at the saphenofemoral junction is introduced, the technique is less encouraged due to the higher recurrence rate, persistent symptoms, and occurrence of distal superficial thrombophlebitis.[36][39] The High ligation of the saphenous vein is indicated for patients with proximal superficial phlebitis that creeps on the saphenofemoral junction with a contraindication to anticoagulation.

Ambulatory Phlebectomy 

The procedure implies the excision and avulsion of the involved superficial vein with multiple skip incisions. Multiple options exist for managing varicose veins, including a combination of the procedure with saphenous inversion. Punctures are made with an 18 gauge needle or an 11-blade scalpel. Punctures are made adjacent to the target vein. Sequential venous sections are ligated and avulsed. Post-procedural hemorrhage is controlled with direct pressure application and limb elevation.[40]

Transilluminated Powered Phlebectomy

The technique is less commonly used compared to the other minimally-invasive procedures for venous ablation. The procedure is undertaken in three discrete steps under general or regional anesthesia with a mixture of saline, lidocaine, and epinephrine. The procedure starts with hydrodissection of the involved veins, followed by the introduction of the illumination device and vein maceration and aspiration through the second incision. The procedure relies on applying a mechanical aspirator labeled transilluminated powered phlebectomy (TIPP).[41] Transilluminated powered phlebectomy is considered a minimally-invasive procedure with fewer incisions. However, a significantly higher range of post-operative pain and hematoma of a more expensive procedure is inevitable.[42]

Endovascular Management

Catheter-based endovenous ablations have been extensively used for EVTL, either via laser or radiofrequency. The procedure is preferably undertaken with local anesthetics. However, oral anxiolytics might be added for apprehensive patients. A catheter is introduced in an antegrade fashion for a few centimeters away from the saphenofemoral or saphenopopliteal junction. The catheter course within the saphenous vein is completely anesthetized. Next, the saphenous vein would be ablated by either heat energy or radiofrequency during the catheter withdrawal.[43][44]

Differential Diagnosis

• Lymphedema
• Deep vein thrombosis
• Cellulitis
• Stasis dermatitis

Prognosis

There is no cure for varicose veins. Even after surgical removal, recurrences are common. Those who develop venous ulcers have the highest morbidity and a poor quality of life. Unlike the deep venous system, clots in superficial veins rarely embolize, and hence the risk of pulmonary embolism is rare. Untreated varicose veins reflect poor aesthetics, and this is the key reason why most people seek treatment.

Complications

• Venous ulcers
• Pain
• Poor cosmesis
• Deep vein thrombosis (DVT) and pulmonary embolism (PE), a Taiwanese database study, mentioned that the propensity for DVT in individuals with varicose veins compared to matched control patients without varicose veins was (6.6 versus 1.2 per 1000 person-years; hazard ratio, 5.30) and (0.48 versus 0.28 per 1000 person-years; hazard ratio, 1.73).[45] Still, further complementary studies are mandatory to confirm this claimed association and to enclose that it is not affected by confounding variables, including smoking and obesity.[8]
• Superficial thrombophlebitis might be complicated with prolonged bleeding and pain.[14]
• Superficial vein thrombosis[46]

Postoperative and Rehabilitation Care

One of the important aspects of care in varicose vein surgical management is the compression dressing application following the surgery. Notwithstanding the significance of compression therapy in the management of varicose veins, still, the recommendation is equivocal. Accordingly, in venous ulceration treatment, 40 and less than 20 mmHg pressure in peri-malleolar and below the knee are recommended.[47]

The prescription of compression stockings after surgical or laser ablation interventions for varicose vein disease is standard practice; however, the consensus regarding the necessity and preferred duration of compression therapy is lacking. [48][49]

The optimal duration of compression therapy after endo-venous laser ablation (EVLA) with a 1470-nm diode dual-ring radial fiber laser was evaluated.[50] The authors concluded that long-term compression stocking for more than two days following EVLA would not significantly change the outcomes.[50] The results were against the traditional recommendation for equal to or longer than 1-week compression therapy. However, it should be highlighted that the mentioned prospective studies reviewed the less-applicable low wavelength of 810 nm.[51]

Deterrence and Patient Education

• Graduated compression hose
• Healthy weight
• Exercise

Pearls and Other Issues

Venous reflux disease is a common condition that results in a considerable lifestyle impact due to the symptoms of leg pain and swelling, and that has the potential to cause more significant morbidity by eventual venous ulcer formation. Treatment with endovenous ablation with a period of compression therapy is usually effective in reducing the associated symptoms.

Enhancing Healthcare Team Outcomes

Varicose veins are very common and often lead to poor cosmesis and fatigue. However, most patients seek medical assistance because of poor cosmesis. Today, general and vascular surgeons perform several different types of procedures to treat varicose veins, but recurrence is a problem. More important, varicose vein surgery is considered cosmetic and not covered by most health plans, so the patient is left to pay for the entire cost. Each year, consumers spend millions of dollars on the care of varicose veins. In view of the fact that recurrences are common and that surgical procedures also have complications, prevention is critical. The primary care provider, pharmacist, and nurse are in a primary position to educate the patient on preventing varicose veins.

Most people can prevent varicose veins by wearing compression stockings, maintaining a healthy weight, and exercising. In addition, the patient should be educated that if the varicose vein is untreated, it can lead to a venous ulcer that is very difficult to cure and costs the healthcare system millions of dollars annually. Finally, when evaluating a patient with a varicose vein, suspicion of a DVT should be high, and the patient should be referred for a duplex ultrasound. Before referring any patient for surgery, the primary care provider, nurse, and pharmacist should advise the patient to change lifestyle, stop smoking, elevate the legs at bedtime and wear stockings- for those who comply; there is no need for surgery.[52][53][54] [Level 5]

Evidence-based Outcomes

Every surgical procedure has good to excellent outcomes for varicose veins, but each is associated with recurrence. For those who develop a venous ulcer, the morbidity is very high as there is no cure. It is also important to note that patients with varicose veins are also at high risk for deep vein thrombosis, which requires prolonged treatment with an anticoagulant which carries further morbidity from the side effects like bleeding. [Level 5] Hence, an interprofessional team approach to varicose veins is recommended to achieve good outcomes.[31][6][55] [Level 5]