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: 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: Chronic venous symptoms and/or signs secondary to deep vein thrombosis and its sequelae.1 It is the most common sequelae of DVT, occurring in approximately 40% of patients presenting with a DVT.2
Epidemiology including risk factors and primary prevention
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 Approximately 2% of annual healthcare spending in the United States is related to management of CVI.3
Established risk factors for venous insufficiency include family history, older age, sex, pregnancy, obesity, occupation, diet, phlebitis, and previous leg trauma.4,5
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. 6
Risk factors for PTS include DVT location (proximal > distal), previous or recurrent ipsilateral DVT, premorbid venous insufficiency, obesity, older age, adequacy of anticoagulation used to treat acute DVT, persistent venous sign and symptoms 1 month after acute DVT, residual thrombosis 3 to 6 months after acute DVT, and persistently elevated D-dimer levels.6
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.
- Use elastic compression stockings (ECS) with ankle pressure gradient of 30 to 40 mm Hg for at least 2 years if patients have symptomatic, proximal DVT and symptoms of PTS.
- Thrombolysis of acute DVT followed by standard anticoagulant therapy.6
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.4
Chronic venous insufficiency (CVI) results from venous hypertension caused by valvular incompetence leading to extravasation of macromolecules and red blood cells, microvascular endothelial cell activation, and leukocyte diapedesis. Alteration of the extracellular matrix produces intense collagen deposition. Microcirculatory changes are mediated by increased levels of transforming growth factor-β1 and its effect on matrix metalloproteins and tissue inhibitors of metalloproteinase production. The presence of mast cells suggests a regulatory role in ulcer formation.7
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, and stiffness.8
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.9
Specific secondary or associated conditions and complications
Of patients with DVT, 5% to 10% develop severe PTS, including ulcers, which is precipitated by trauma to the gaiter area (perimalleolar).6
Essentials of Assessment
Medical history should include the following:
- Family history
- Previous DVT/thrombophlebitis
- Medications/oral contraceptives
- Pain in the limbs/pelvis
- Skin changes/ulcers
- Prior treatments/compression therapy10
A thorough history should take into account 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.4
Examine patients in a warm, well-lit room while standing to allow physiologic distention of the veins.
- 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
- Palpation for venous cords and for calf muscle consistency
- Measure bilateral calf and ankle circumference at a consistent time of day
- Pedal pulses for underlying arterial disease
- Ulcer description
- Ankle mobility
- Auscultation for bruits
- 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.4
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 main factor that impacts QOL. The presence, size, and duration of ulcers also has 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.11, 12
Duplex scanning is recommended as the first diagnostic test for all patients with suspected CVD.
- 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 or Magnetic Resonance Venography is indicated in more complex disease and preoperatively because it provides more detail than duplex ultrasonography; it is especially useful for the evaluation of more proximal veins and their surrounding structures.4,13
- 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.4
Supplemental assessment tools
The Brodie-Trendelenberg tourniquet test can be performed at the bedside to help differentiate superficial reflux from deep venous disease, however in practice venous duplex imaging is typically a preferred modality for noninvasive testing.4
For hemodynamic assessment in CVI, Ambulatory venous pressure monitoring remains the gold standard, however for practical reasons it is seldom used in clinical practice.4
CEAP Classification of Chronic Venous Disease 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.14
The Villalta score is the only scale that is specific for the diagnosis and categorization of 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. The score has also been used on follow-up to assess the effectiveness of treatment.15
Environmental and behavioral factors associated with CVI include prolonged sitting and standing at work.4
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.7 This results in impaired ability to engage in social and occupational activities, reducing QOL and imposing financial constraints. Disability 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. The financial burden on the health care system is estimated at $3 billion annually for the treatment of venous ulcers.4
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.16
Venoactive drugs are not recommended for PTS and diuretics are not recommended for PTS-related edema.17
- 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.16
- 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.14
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.5,6
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.14
- 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 (eg, 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 phlebectactica, 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 is subfascial endoscopic perforator surgery. Newer, less invasive techniques (eg, percutaneous ablation of perforators, EVLA, ultrasound-guided sclerotherapy) are less well studied.13,18
Surgical repair of incompetent valves have 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.7
Lifelong ECS with 30 to 40 mm Hg compression is recommended to prevent recurrence of ulceration.13,18
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.12
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.19 Home-based exercises to improve calf-muscle pump function is recommended.19 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.20
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.13
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.21
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 for venous system.8
Gaps in the Evidence- Based Knowledge
Lack of QOL measures in current disease-specific scales.22
1. Eklof B, Perrin M, Delis KT et al. Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document. J Vasc Surg. 2009 Feb;49(2):498-501.
2. Metz AK, Diaz JA, Obi AT, Wakefield TW, Myers DD, Henke PK. Venous Thrombosis and Post-Thrombotic Syndrome: From Novel Biomarkers to Biology. Methodist Debakey Cardiovasc J. 2018 Jul-Sep;14(3):173-181.
3. Patel SK, Surowiec SM. Venous Insufficiency. 2020 Aug 15. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–.
4. Eberhardt RT, Raffetto JD. Chronic venous insufficiency. Circulation. 2014 Jul 22;130(4):333-46.
5. Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld D. The epidemiology of chronic venous insufficiency and varicose veins.Ann Intern Med. 2008;149(10):698-707.
6. Kahn SR. The post-thrombotic syndrome. Hematology Am Soc Hematol Educ Program. 2016 Dec 2; 2016(1): 413–418
7. Meissner MH, Gloviczki P, Bergan J, et al. Primary chronic venous disorders.J Vasc Surg.2007;46 Suppl S:54S-67S.
8. Henke PK, Camerota AJ. An update on etiology, prevention, and therapy of post thrombotic syndrome.J Vasc Surg. 2011;53(2):500-509.
9. Raffetto JD. Pathophysiology of Chronic Venous Disease and Venous Ulcers. Surg Clin North Am. 2018 Apr;98(2):337-347.
10. Mowatt-Larssen E, Desai SS, Dua A, et al. Phlebology, Vein Surgery and Ultrasonography: Diagnosis and Management of Venous Disease. Switzerland: Springer; 2014.
11. Hopman WM, VanDenKerkhof EG, Carly ME, et al. Factors associated with health-related quality of life in chronic leg ulceration. Qual Life Res. 2014 Aug;23(6):1833-40
12. Gonzalez-Consuegra RV, Verdu J. Quality of life in people with venous leg ulcers: an integrative review.J Adv Nurs. 2011;67(5):926-944.
13. Gloviczki P, Camerota AJ, Dalsing MC, et al. The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum.J Vasc Surg. 2011;53(5 Suppl):2S-48S.
14. Lurie F, Passman M, Meisner M, et al. The 2020 update of the CEAP classification system and reporting standards. J Vasc Surg: Venous and Lym Dis 2020;8:342-52.
15. Utne KK, Ghanima W, Foyn S, et al. Development and validation of a tool for patient reporting of symptoms and signs of the post-thrombotic syndrome. Thromb Haemost. 2016;115(2):361-367.
16. Jin YW, Ye H, Li FY, Xiong XZ, Cheng NS. Compression Stockings for Prevention of Postthrombotic Syndrome: A Systematic Review and Meta-Analysis. Vasc Endovascular Surg. 2016 Jul;50(5):328-34.
17. Kahn SR, Galanaud JP, Vedantham S, Ginsberg JS. Guidance for the prevention and treatment of the post-thrombotic syndrome. J Thromb Thrombolysis. 2016;41(1):144-153.
18. Marston WA. Evaluation of varicose veins: what do the clinical signs and symptoms reveal about the underlying disease and need for intervention.Semin Vasc Surg. 2010;23(2):78-84.
19.Wound, Ostomy, and Continence Nurses Society (WOCN). Guidlines for Management of Wounds in Patients With Lower Extremity Venous Disease: WOCN Clinical Practice Guidline Series No. 4. 2011.
20. Kahn SR, Shrier I, Shapiro S, et al. Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial.CMAJ. 2011;183(1):37-43.
21. Lobastov K, Ryzhkin V, Vorontsova A, et al. Electrical calf muscle stimulation in patients with post-thrombotic syndrome and residual venous obstruction after anticoagulation therapy. Int Angiol. 2018 Oct;37(5):400-410.
22. Soosainathan A, Moore HM, Gohel MS, Davies AH. Scoring systems for the post thrombotic syndrome.J Vasc Surg. 2013;57(1):254-261.
Original Version of the Topic:
Sikha Guha, MD, Eathar Saad, MD. Venous Insufficiency: Rehabilitation Management of Venous Stasis and Postphlebitic Syndrome. Published 9/20/2014
Laurentiu Dinescu, MD
Nothing to Disclose
Rebecca Sussman, MD
Nothing to Disclose
Michael Mosier, MD
Nothing to Disclose
Amarin Suriyakhamhaengwongse, MD
Nothing to Disclose