Author(s): Ady Correa-Mendoza, MD, Rosalynn Conic, MD, PhD
Originally published: September 20, 2014 Last updated: June 14, 2023
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Disease/ Disorder

Definition

Chronic venous disorders (CVDs): this term includes the full spectrum of morphologic and functional abnormalities of the venous system.1

Chronic venous disease: (Any) morphological and functional abnormalities of the venous system of long duration manifested either by symptoms and/or signs indicating the need for investigation and/or care.1

Chronic venous insufficiency (CVI): A term reserved for advanced CVD, which is applied to functional abnormalities of the venous system producing edema, skin changes, or venous ulcers.1

Post-thrombotic syndrome (PTS): Chronic venous symptoms and/or signs secondary to proximal deep vein thrombosis and its sequelae.1 It is the most common sequelae of deep venous thrombosis (DVT), occurring in approximately 20 to 50% of patients with a history of DVT in the past two years.2,3

Epidemiology including risk factors and primary prevention

Chronic Venous Insufficiency

The prevalence of chronic venous insufficiency ranges from less than 1% to 17% in men and less than 1% to 40% in women based on the different populations studied.3   In the United States, it is estimated that more than 25 million adults have a diagnosis of CVI and >20% of them have severe disease.4 Additionally, more than 20,000 adults are diagnosed with venous ulcers each year.5Approximately 2% of annual healthcare spending in the United States is related to the management of CVI.6

Established risk factors for venous insufficiency include intrinsic venous or valvular defects, family history, older age, female sex, pregnancy, obesity, occupations with prolonged sitting or standing, tobacco use, diet, phlebitis, and previous leg trauma.7,8

Data regarding primary prevention of CVI is limited. However, mitigating modifiable risk factors such as avoiding sitting/standing for prolonged periods of time, avoiding smoking/tobacco use, and maintaining a healthy weight and diet may contribute to decreasing risks of CVI.

Post-thrombotic syndrome

The incidence of PTS is about 20-50% in the first two years following a DVT, and 5-10% of patients will develop severe disease, including ulcers.9

Risk factors for PTS include DVT location (proximal > distal), especially involving iliac or common femoral arteries, previous or recurrent ipsilateral DVT, premorbid venous insufficiency, obesity (body mass index higher than 30kg/m2), older age, severity of the symptoms at the onset of DVT, subtherapeutic anticoagulation used to treat acute DVT in the first three months after diagnosis of DVT, persistent venous sign and symptoms at 3 months after acute DVT, residual thrombosis 3 to 6 months after acute DVT, and persistently elevated D-dimer levels. Inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6, IL-8, IL-10, and ICAM-1 and higher level of certain metalloproteinases are associated with PTS as well. Overall, the most important risk factor for PTS is the development of recurrent ipsilateral DVT.2,9

Primary prevention of PTS includes the following:

  • Thromboprophylaxis to prevent DVT in high-risk hospitalized patients.
  • Reduce risk of recurrent DVT by appropriate anticoagulation after acute DVT.
  • Thrombolysis of acute DVT followed by standard anticoagulant therapy in patients with extensive thrombosis, and low risk of bleeding.6
  • May consider use of elastic compression stockings (ECS) with ankle pressure gradient of 30 to 40 mm Hg for at least 2 years if the patient is symptomatic has a proximal DVT and/or symptoms of PTS; however, supporting data is conflicting.

Patho-anatomy/physiology

The venous network in the lower extremities is divided into superficial, deep, and perforating veins. The deep veins within the calf muscles are the main conduit for venous blood to return to the heart. The superficial compartment is a low-pressure chamber. The deep compartment is a high-pressure chamber because of the calf muscle pump. The perforator veins connect the deep and superficial veins. When the calf muscles (muscular systole) contract, the perforator valves close, preventing transmission of high pressure to the superficial veins. When the calf muscles relax (muscular diastole) the pressure in the superficial compartment is higher than the deep veins causing a reversal of blood flow.5

When the calf muscle pumping is ineffective or does not occur, it can lead to venous blood pooling and subsequent venous hypertension which in turn results in leukocyte infiltration, inflammation, endothelial dysfunction, venous dilation and progressively worsening venous insufficiency.10 Normally, leukocytes roll along the lumen of the vein; however with changes in shear stress, cell adhesion molecules (ex. intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), along with inflammatory factors (ex. monocyte chemoattractant protein 1, bone morphogenic protein 4), leading to leukocyte adhesion and migration.11 Endothelial cells are similarly activated and start producing growth factors (vascular endothelial growth factor (VEGF), platelet-derived growth factor, angiotensin 2, endothelin 1, fibroblast growth factor β (FGF-β)) leading to proliferation of vascular smooth muscle cells (VSMCs) which in turn increases vein rigidity and disrupts vein wall structure.12 The extracellular matrix is further disrupted by transforming growth factor-β1 (TGF- β1) and its stimulation of tissue inhibitors of metalloproteinase production, which may trigger a prothrombotic process.13

Pathophysiology of PTS starts with an obstructive thrombus causing damage to the vein wall, initiating an inflammatory response. A phenotypic change of the vascular smooth muscle cell occurs, which promotes collagen and other matrix accumulation, vein wall fibrosis, leading to functional obstruction and resulting in reflux, and stiffness.8 The combination of obstruction and reflux produces ambulatory venous hypertension, meaning that the venous pressure cannot be reduced with exercise. Prolonged venous hypertension results in dilation of the vessels, increased permeability of proteins and red blood cells, which translates into skin changes that may include hyperpigmentation, edema, fibrosis and ulcers.2 The presence of mast cells suggests a regulatory role in ulcer formation.14

Genetic predisposition and various candidate genes and their polymorphisms and environmental factors (obesity and standing posture) are also important in the development of chronic venous disease.15

Specific secondary or associated conditions and complications

Chronic Pain

Aching, or cramping pain is present in 15-70% of patients with CVI and can severely impact quality of life.16It is thought to be due to sensitization of venous nociceptors or due to venous stasis resulting in venous microangiopathy and increased endoneurial pressure. The severity of pain is not associated with the severity of CVI.

Phlebolymphedema

When there is excessive fluid load in the tissues due to CVI, the capillary system does not function properly and places additional load to the lymphatic system, which is also responsible for draining excess fluid and proteins from the tissues back to the bloodstream. When the lymphatic system exceeds its capacity to compensate for excess fluid in CVI, the valves of the lymph vessels may become insufficient (lymphostasis), which may lead to chronic lymphatic insufficiency. The dysfunction of both systems (venous and lymphatic) secondary to CVI results in phebolymphedema.17

Cellulitis

Bacterial cellulitis is a common complication of CVI and can occur in the presence of dermatitis or open ulcers or in the absence of skin breakdown (spontaneously).18The patient would experience sudden pain, redness and new or increased leg swelling. Fever and leukocytosis are often absent. Differential diagnosis includes superficial thrombophlebitis and DVT.

Venous Ulceration

Progression of venous insufficiency can lead to ulceration over time. Venous leg ulcers affect 3-5% of patients 65 or older.19 The ulcers are typically in the supramalleolar region and vary in size.19,20 The majority of these wounds heal within 12 weeks with lower leg compression; however, depending on vasculature they can persist or never heal. Furthermore, the wounds may recur if CVI is not treated and the same factors persist. The ulcers may be complicated by infection.

DVT/PE

Of patients with DVT, 5% to 10% develop severe PTS, including ulcers, which is precipitated by trauma to the gaiter area (perimalleolar).21

Essentials of Assessment

History

Medical history should include the following:

  • Current symptoms, their duration, worsening and alleviating factors
    • Pain in the upper or lower extremities, pelvis, flank, back
    • Skin changes in the extremities: discoloration/hyperpigmentation/redness/cold/pallor/numbness/hair loss/ulcers22
    • Edema in the calves or feet
    • Symptoms of intermittent claudication
    • Redness or tenderness
  • Prior treatments/compression therapy23
  • Pregnancies
  • Age
  • Previous DVT/thrombophlebitis
  • Medications/oral contraceptives
  • Smoking
  • Family history

A thorough history should consider other potential causes of edema, including systemic conditions such as heart failure, liver failure, nephrosis, or endocrine dysfunction; medication side effects; lymphedema or lipedema; and local tissue trauma such as ruptured popliteal cyst, hematoma, gastrocnemius tear, or compartment syndrome.  Physical exam findings, as discussed below, may also help to inform the differential diagnosis in patient’s presenting with edema.7

Physical examination

Examine patients in a warm, well-lit room while standing to allow physiologic distention of the veins.

  • Inspection: Note the distribution of abnormal spider veins, telangiectasias, ankle or malleolar flare, size, location, and distribution of varicose veins, skin changes, edema, location of active or healed ulcers, and inflammatory changes, trophic changes on the skin, hair distribution/loss, hyper or hypopigmentation of the skin, auscultation for bruits
  • Palpation: distal pulses to assess for underlying arterial disease, venous cord, calf muscle consistency, assess for tenderness
  • Measure bilateral calf and ankle circumference at a consistent time of day
  • Range of motion: assess upper and lower extremities
  • Neurologic exam

Note that, in contrast to other causes of peripheral edema, the forefoot is often spared of pitting edema which may be seen in the dependent lower leg.  In more chronic cases, skin may become more resilient to pitting.  There are numerous scales available for grading edema, but none is universally agreed-upon.7

Functional assessment

Patients with CVD and venous leg ulcers have poorer quality of life (QOL) in all aspects of daily living compared with the general population. Pain is the main factor that impacts QOL. The presence, size, and duration of ulcers also has a significant and substantial association with decreased QOL, as does decreased mobility. Age has been shown to have a strong negative association with QOL.  Other factors, such as social and emotional isolation, socioeconomic status, comorbidities, feeling of uncleanliness, and problems finding appropriate footwear have also been implicated but findings are mixed. Loss of employment has a significant social impact.24,25

Imaging

  • Duplex ultrasound [DUS] is recommended as the first diagnostic test for all patients with suspected CVD. Additionally, it has an important role in identifying patients at risk of PTS, as two important parameters for development of PTS are residual vein thrombosis and venous reflux (valve incompetence).
  • Air plethysmography (APG) is used for assessing severity of disease. APG can evaluate calf muscle pump function and quantify global venous reflux and outflow obstruction.
  • Computed Tomographic Venography [CTV] and Magnetic Resonance Venography [MRV] are helpful in more complex disease and preoperatively a it provides more detail than duplex ultrasonography. It is especially useful for the evaluation of more proximal veins and their surrounding structures and may help in the assessment of post-thrombotic obstruction, venous compression or stenosis.4,13 However, evidence of its efficacy for evaluating venous system is mixed, for which these studies are not routinely recommended.2
  • Contrast venography is an invasive test that involves the injection of contrast from either an ascending or descending pathway to delineate venous anatomy prior to surgical intervention or to identify reflux, usually in cases where venous duplex imaging is unable to give sufficient information to guide venous reconstruction.
  • Intravascular ultrasound is an invasive technique that uses a catheter-based ultrasound probe to assess for stenosis or venous obstruction and has been gaining popularity as a tool to help guide interventions, as it seems to give more detailed and curate information regarding the morphology of vessels in comparison to venography.

Photoplethysmography, strain gauge plethysmography, and foot volumetry are additional available techniques; the latter two may better correlate with clinical disease severity than venous duplex imaging but are not routinely used.7

Supplemental assessment tools

The Brodie-Trendelenberg Percussion Test can be performed at the bedside to help differentiate superficial reflux from deep venous disease. To perform the test, place your finger over the distal part of the vein being examined, and tap the proximal part of the vein. The test is positive if the percussion is felt at the distal portion and indicates valvular incompetence. The Brodie- Trendelenburg Tourniquet test is used specifically to identify venous insufficiency at the saphenofemoral junction. The affected leg is raised, and a tourniquet is applied tightly to constrict the saphenous vein, and the subject then stands up for 30 seconds, then the tourniquet is removed. The test is positive if once the tourniquet is removed the internal saphenous vein rapidly fills, indicating that saphenous valves are incompetent. It is doubly positive if the veins rapidly fill on standing and worsen when the tourniquet is removed indicating incompetency of saphenous valves, and those of the communicating veins.

For hemodynamic assessment in CVI, ambulatory venous pressure monitoring remains the gold standard. However, for practical reasons it is seldom used in clinical practice.7 In practice, venous duplex imaging is typically a preferred modality for noninvasive testing.7

Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification was established in 1993 and is the international standard for describing chronic venous disease, and takes into account the clinical factors, etiologic factors, anatomic location, and pathophysiologic mechanisms that, together, play a role in CVD. It is used routinely in clinical practice as a standardized tool designed to clearly define a patient’s disease at any given moment in time in a reliable and reproducible fashion, and yet provide the flexibility to change as a patient’s disease changes over time.26 The clinical, etiologic, and anatomic sections were updated in 2020 for more accurate representation of current disease findings.27

Venous-Insufficiency-Table-1-2020-CEAP-ClassificationDownload

The Villalta score was constructed to diagnose and categorize PTS. Points are given to the following symptoms: pain, cramps, heaviness, paresthesia, and pruritus. Clinical signs scored are pretibial edema, skin induration, hyperpigmentation, redness, venous ectasia, and pain on calf compression. Points ranging from 0 to 3 for each of these elements are recorded. PTS is diagnosed if the Villalta score is greater than 4 and the disease is considered severe if the score is greater than 14 or if an ulcer is present.

Venous-Insufficiency-Table-2-Villalta-ScoreDownload

The score has also been used on follow-up to assess the effectiveness of treatment.15 There are several other scoring mechanisms including the Ginsberg, Brandjes, Widmer and Venous Clinical Severity Score; however only the Villalta score can reliably diagnose, categorize severity and be used for follow-up disease progression. On the other hand, Ginsberg scale is more likely to identify the most severe disease cases.2,28

Environmental

Environmental and behavioral factors associated with CVI include an unhealthy weight and diet, prolonged sitting, and standing at work, and inappropriate skin care.

Social role and social support system

The socioeconomic impact of CVI is significant because it is the seventh leading cause of chronic disability in the United States.14 This results in impaired ability to engage in social and occupational activities, reducing QOL and imposing financial constraints. Costs of treating venous ulcers average $2,400/month, not including any surgical interventionand the financial burden on the health care system for treatments of CVI and venous ulcers in the United States surpasses $3 billion annually.5,29,30Disability related to venous ulcers leads to loss of productive work hours (estimated at 2 million workdays per year). Of workers with venous ulcers, 12% will retire prematurely.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Lifestyle modifications

Weight loss, diet, exercise, leg elevation, ECS are recommended. Compression therapy is the mainstay of management. However, a 2016 meta-analysis which consisted of 6 RCTs with 1465 patients with acute DVT was unable to draw a conclusion as to whether or not compression therapy prevented PTS.31

Exercise has a role in patients with acute or previous DVT. It has been suggested an exercise program for 6 months or more consisting of leg strengthening and aerobic exercise is reasonable for patients who can tolerate it.17 Early walking and habitual physical activity do not worsen symptoms in DVT and improve calf-muscle pump and QOL.8,21

Compression therapy

  • Graduated ECS with higher pressure at the ankle are the cornerstone of CVD management.
  • Knee-length stockings are as effective as thigh-length stockings, easier to apply, more comfortable, have better compliance, and are cheaper.31
  • Stockings with 30 to 40 mm Hg compression pressure are recommended for C5-6 CVI; 20 to 30 mm Hg are recommended for symptomatic varicose veins and mixed venous and arterial disease.
  • Unna boot (50-60 mm Hg pressure) is used for ambulatory patients unable to tolerate graduated ECS.
  • Multilayer bandages (40 mm Hg pressure) are more effective in healing ulcers.
  • Indications for intermittent pneumatic compression are nonambulatory patients, need for higher compression, patients not responding to stockings/wraps, or patients with very large legs who cannot tolerate stockings/wraps.26

Venoactive drugs are not recommended for PTS and diuretics are not recommended for PTS-related edema.32 

Pharmacologic Therapy

  • Venoactive drugs (saponins, flavonoids, pentoxifylline, acetylsalicylic acid): used in the management of pain and swelling at initial stages of CVI. Not recommended for PTS or venous ulcers.32,33
  • Sulodexide: Antithrombotic agent proven to be beneficial for symptoms of CVD including cramps, heaviness and edema.34
  • Anticoagulation therapy: Has been shown to be beneficial in the prevention of PTS and venous ulcers after acute DVT. However, prolonged treatments after the recommended length of therapy for DVT is not proven to provide further benefits.35

*Data on pharmacologic treatments for CVD is heterogenous and further studies are needed to evaluate its efficacy.

Surgical Treatment

  • Vein stripping: Consists of ligating and physically removing the affected vein. However, there is heterogenous data on the long-term benefits of this procedure and there is a risk of recurrence for which the procedure is considered only when conservative treatments do not resolve symptoms of CVD.35
  • Sclerotherapy: Includes the use of different chemicals such as polidocanol, glycerin or sodium tetradecyl sulfate, which works as a type of chemical ablation of varicose veins in CVD. Additionally, this procedure may have a role in accelerating venous ulcer healing but it’s considered as a second line of treatment in fragile patients or those who cannot undergo surgical treatments.36,37
  • Endovenous thermal ablation (EVLA): This procedure has been recommended as first line of therapy for patients with CVD and reflux of the great saphenous vein (varicose vein- VV). There are two types of ablation: Endovenous Laser Therapy (EVLT) and Radiofrequency Ablation (RFA). In both techniques, thermal injury is induced to the affected varicose vein, leading to occlusion and eventual fibrosis of the saphenous vein. EVLT has been proven to have higher efficacy versus RFA.38
  • Subfascial endoscopic perforator surgery: Small studies have assessed the efficacy of ligating and clamping perforator veins to disrupt the connection between deep and superficial veins. The goal is to interrupt the venous flow in those veins where there is increased congestion and potentially decrease the risk of developing venous ulcers. However, further studies are needed to better assess the efficacy of these procedures.39
  • Bioprosthetic veno-valve implantation in the femoral vein: bioprosthesis that contains porcine cardiac valve and is implanted in cases of deep venous valvular disease with the goal to improve venous reflux. It has been proven to be efficient at 1-year post-implantation in patients with severe deep CVI.40
  • Percutaneous transluminal angioplasty + stenting: utilized in cases where conservative therapy does not provide relief, specifically persistent CVI symptoms in patients with pathology of the iliac veins.

At different disease stages

The clinical, etiology, anatomy, pathophysiology (CEAP) classification is a useful guide for treatment at different stages of the disease. Changes in the 2020 update include adding Corona phlebectatica as the C4c clinical subclass, introducing the modifier “r” for recurrent varicose veins and recurrent venous ulcers, and replacing numeric descriptions of the venous segments by their common abbreviations.26

  • In CEAP class 1, patients display spider veins and telangiectasias.
  • In class 2, patients have varicose veins. They have mild symptoms and no venous insufficiency. No treatment is recommended. For cosmetic concerns, vein stripping, Endovenous thermal ablation (EVLA), or foam sclerotherapy may be prescribed, along with ECS of 20 to 30 mm Hg. Class 2r is recurrent varicose veins.
  • CEAP class 3 displays edema. Treatment is similar to CEAP classes 1 and 2.
  • CEAP class 4 was further subdivided in the 2020 update:
    • CEAP class 4a displays edema and early skin changes (e.g., pigmentation, eczema). This is indicative of venous reflux, which is sufficiently severe to cause venous hypertension. Daily compression and/or correction of venous hypertension by venous ablation or other techniques are recommended.
    • CEAP class 4b has severe skin changes, lipodermatosclerosis, significant tissue inflammation, or induration. These patients are at a higher risk to progress to ulceration. They need a corrective venous procedure.
    • CEAP class 4c is corona phlebectatica, or abnormally dilated veins around the ankle.
  • CEAP classes 5 (healed ulcer) and 6 (active ulcer) should undergo correction of venous hypertension to speed the healing of the ulcer and prevent recurrence. Class 6r is a recurrent active venous ulcer. The preferred procedure for correction of reflux in the perforator veins

Surgical repair of incompetent valves has resulted in 65% to 80% healing of stasis ulcers at 5 years and some even at 15 to 20 years. Venous stenting is minimally invasive and a much easier procedure. Two thirds of patients with venous stasis ulcers have healed following stent placement. However, a third will have recalcitrant ulcers and require valve reconstruction.14

Lifelong ECS with 30 to 40 mm Hg compression is recommended to prevent recurrence of ulceration.41,42

Contraindications for compression therapy: Ankle=brachial index <0.6, severe heart failure, allergy to materials used for compression therapy, severe diabetic neuropathy at risk of necrosis.43

Coordination of care

Multidisciplinary care of patients with CVD includes medical practitioners, vascular surgeons, dermatologists, wound care specialists, and psychologists. Nursing is the most important discipline; they are the leaders in this field and are responsible for the continuum of care in the home and clinics. Patients treated in nurse-led leg ulcer clinics experienced better QOL.25

Patient & family education

Education should focus on life-long use of ECS, leg elevation, smoking cessation, exercise, avoiding trauma to the legs, weight management, and nutrition.44 Home-based exercises to improve calf-muscle pump function is recommended.44 It has been suggested that stretching, leg strengthening/flexibility, and walking for 45 to 60 minutes 3 times per week for 6 months improves overall fitness, disease-specific QOL measures, and severity of PTS.45 Leg elevation, use of insoles, cooling therapy and avoiding exposure may improve pain symptoms and improve QoL.46

In terms of diet, a low carb diet, high fiber, vitamins and polyunsaturated acids (PUFA) promotes adequate function of the immune system. Additionally, the Mediterranean diet has anti-inflammatory and cardioprotective effects, which could have a potentially positive effect in decreasing risk of CVD and PTS.33

Emerging/unique interventions

Commonly used generic QOL measures include the Medical Outcomes Study 36-Item Short-Form Health Survey and visual analog scale. Disease-specific scales include the Venous Insufficiency Epidemiologic and Economic Study of Quality of Life and Charing Cross Venous Ulceration Questionnaire.41

Electrical calf stimulation in PTS treatment has been shown to reduce recurrent DVT rates, increase the speed of deep vein recanalization, and improve clinical PTS outcomes.47

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  • Lifestyle modification is important in prevention and management of CVI.
  • Compression therapy is the mainstay of management.

Cutting Edge/ Emerging and Unique Concepts and Practice

  • The association of circulating biomarkers with CVI.
  • Use of statins in the prevention of DVT and PTS.
  • Prosthetic valves and stenting for venous system.40,43,48

Gaps in the Evidence-Based Knowledge

Current QOL measures in disease-specific scales [i.e., Aberdeen Varicose Veins Questionnaire (AVVQ), Chronic Venous Insufficiency Questionnaire (CIVIQ), Venous Insufficiency Epidemiological and Economic Study quality of life/symptoms (VEINES-QOL/Sym)] are limited and time-consuming, for which further studies are needed to establish patient-reported outcome measures (PROMs).43,49

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Original Version of the Topic:

Sikha Guha, MD, Eathar Saad, MD. Venous Insufficiency: Rehabilitation Management of Venous Stasis and Postphlebitic Syndrome. 9/20/2014

Previous Revision(s) of the Topic:

Laurentiu Dinescu, MD, Rebecca Sussman, MD, Michael Mosier, MD, Amarin Suriyakhamhaengwongse, MD. Venous Insufficiency: Rehabilitation Management of Venous Stasis and Postphlebitic Syndrome. 12/10/2020

Author Disclosures

Ady Correa-Mendoza, MD
Nothing to Disclose

Rosalynn Conic, MD, PhD
Nothing to Disclose