The vast majority of PS patients has a history of DVT, most likely of recurrent DVT. In most cases, DVT has been diagnosed a few months ago, but latency periods of several years have also been reported. Idiopathic PS, i.e., manifestation of PS-related symptoms without previous diagnosis of DVT, has been described but most likely results from undiagnosed DVT and subsequent CVI.

Patients normally present with unilateral lesions of ankles or calfs. PS-associated symptoms largely resemble those of DVT and CVI. Patients generally claim their legs to feel heavy and tire easily. Their skin is tender, in many cases even painful. If the ankles are affected, pain may be provoked by calf compression since this measure increases venous pressure in more distal regions. Cramps are commonly experienced. Pruritus and paresthesias indicate dermatological lesions and may precede or accompany stasis dermatitis. Leg ulcers are long-term complications of DVT and will not be observable in patients presenting with acute thromboembolism [4]. Further dermatological symptoms that may be observed in PS patients are lipodermatosclerosis, hyperpigmentation and induration.

Patients commonly find relief in elevating their legs while long periods of standing or walking cause an exacerbation of symptoms. Consequently, symptoms tend to worsen over the course of the day.

• Disability

  The postphlebitic syndrome was identified in 13 patients and was disabling in 6. The syndrome was present in 9 of the 11 patients with a venographically proven deep vein thrombosis (DVT) and in 4 of the 32 without DVT. [ncbi.nlm.nih.gov]

  Despite standard care, 25%-50% of patients with clots in the deep veins of the arms and legs progress to chronic post-clot problems resulting in significant disability, loss of productivity, and healthcare costs. [clinicaltrials.gov]

  The postphlebitic syndrome can last for a very long time (more than a year) and can be very disabling. [vasculardoc.com]

• Weakness

  It also tackles the surgical treatment of superficial vein incompetence; the functional phlebography in venous disorders of the lower limbs; and valveless syndrome and weak vein syndrome. [books.google.de]

  The AHA gives a weak recommendation for endovascular treatment (recommendation class IIb, evidence level B) ( 17 ). [aerzteblatt.de]

  The association of IL‐6 and CRP with PTS was weak using the CEAP classification with a RR of 1.2 (0.7–2.2) and 1.8 (0.9–3.3) and absent according to the Villalta scale 0.6 (0.2–1.4) and 1.2 (0.6–2.5), respectively. [doi.org]

• Short Stature

  She was of a short stature, heavy built, with a prominent malar flush, dark eyes, colored hair, and deeply scarred right face and trunk (due to burns). [ijrh.org]

• Falling

  Bleeding will be defined as major if it is clinically overt and associated with a fall in hemoglobin of 20 g/L or a need for transfusion of ≥ 2 units of red blood cells; if it was intracranial or retroperitoneal; or if it warranted the permanent discontinuation [bmccardiovascdisord.biomedcentral.com]

• Cough

  If you have any of these symptoms, call 911 or go to the emergency room right away: Sudden cough, which may be bloody Rapid breathing or sudden shortness of breath, even while resting Chest pain : sharp or stabbing, burning, aching, or dull (might get [webmd.com]

• Nausea

  […] that horse chestnut seed extract is efficacious for the short-term treatment of symptoms of chronic venous insufficiency such as leg pain and edema and that adverse events were mild and infrequent and included gastrointestinal complaints, dizziness, nausea [bloodjournal.hematologylibrary.org]

• Thrombosis

  Thrombosis Research, 10.1016/j.thromres.2018.11.002, (2018). [doi.org]

  There does not seem to be any convincing evidence that heparin exerts a favorable influence on pulmonary embolism in situ or on portal vein thrombosis. [ncbi.nlm.nih.gov]

• Heart Disease

  Body weight and weight gain during adult life in men in relation to coronary heart disease and mortality. A prospective population study. Eur Heart J 1999; 20: 269-77. 14 Ham TS, van Reel EM, Seidell JC, Lean MEJ. [doi.org]

• Chest Pain

  If it's medium-sized, it can cause chest pain and breathing difficulties. A large clot can cause the lungs to collapse, resulting in heart failure, which can be fatal. About 1 in 10 people with an untreated DVT develops a severe pulmonary embolism. [nhs.uk]

  If you have any of these symptoms, call 911 or go to the emergency room right away: Sudden cough, which may be bloody Rapid breathing or sudden shortness of breath, even while resting Chest pain : sharp or stabbing, burning, aching, or dull (might get [webmd.com]

• Fracture

  The non-fractured limb was used as a control. Postphlebitic symptoms were present in 51% and signs in 49% of fractured limbs compared with 4% and 24% respectively in the control limbs. [ncbi.nlm.nih.gov]

  In contrast, surgery and recent trauma or fracture were associated with a decreased risk for recurrent venous thromboembolism (hazard ratios, 0.36 [CI, 0.21 to 0.62] and 0.51 [CI, 0.32 to 0.87], respectively). [doi.org]

  […] for long periods of time, such as in a plane or car During and after pregnancy Not having enough water in the body (dehydration) Taking birth control pills or estrogen hormones (especially in women who smoke) Using an intravenous catheter long-term Fractures [lymphedemablog.com]

• Leg Cramp

  He now has a swollen leg, cramping pain and discolouration, all the usual symptoms of PTS. We have recently found that Guy's hospital is the only UK NHS hospital which is treating these symptoms with great success. [patient.info]

  […] in the leg (which can be worse after walking or standing for a long time and better after resting or raising the leg) Leg heaviness Leg itching Leg tingling Leg cramping An ulcer (sore) on the leg If you have any of these symptoms, you should see your [circ.ahajournals.org]

• Ulcer

  Excision of perforators and ulcer care are effective but are associated with a high rate of ulcer recurrence. [ncbi.nlm.nih.gov]

  or tingling in the affected limb and is a chronic complication of deep venous thrombosis Postphlebetic syndrome with inflammation Postphlebetic syndrome with ulcer Postphlebetic syndrome with ulcer and inflammation postphlebitic syndrome venous stress [wikidata.org]

  Patients may develop leg ulcers and skin fibrosis, claim pain, swelling and paresthesias. Ulcers may become infected and lead to even more severe dermatological lesions. [symptoma.com]

  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. [now.aapmr.org]

• Eczema

  The complications after DVT may include persistent edema (swelling), pain, purpura (bleeding into the skin), increased skin pigmentation, eczematoid ( eczema -like) dermatitis, pruritus (itchiness), ulceration, and cellulitis (bacterial infection just [medicinenet.com]

  Post-thrombotic syndrome symptoms include: Pain or aching Leg or arm swelling Heaviness Cramping Redness Skin discoloration or dark pigmentation Bluish fingers or toes Dry skin or eczema Varicose veins If a vein is completely blocked, smaller veins nearby [everydayhealth.com]

  Tiredness, heaviness and cramping of leg Diffuse aching Tingling sensation Capability of leg become diminished Post-thrombotic pigmentation leads to pigmented dark patches in the leg skin Toes or foot of the affected leg develops bluish discoloration Eczema [medicalfoxx.com]

  […] swelling Chronic (or waxing and waning) pain Unspecific discomfort of the extremity Diffuse aching Heaviness, tiredness and cramping of extremity Dark skin pigmentation Bluish discoloration of toes/fingers, foot/hand or diffusely of leg/arm Skin dryness Eczema [bloodclotrecovery.net]

  […] waning) pain unspecific discomfort of the extremity diffuse aching heaviness, tiredness and cramping of extremity dark skin pigmentation (=post-thrombotic pigmentation) bluish discoloration of toes/fingers, foot/hand or diffusely of leg/arm skin dryness eczema [stoptheclot.org]

• Pruritus

  The complications after DVT may include persistent edema (swelling), pain, purpura (bleeding into the skin), increased skin pigmentation, eczematoid ( eczema -like) dermatitis, pruritus (itchiness), ulceration, and cellulitis (bacterial infection just [medicinenet.com]

  A clinical score developed by Villalta and colleagues has been proven very helpful to this end: Patients are queried for a feeling of heavy legs, pain, cramps, pruritus and paresthesias. [symptoma.com]

  Pruritus may accompany skin changes. [merckmanuals.com]

  […] seed extract is efficacious for the short-term treatment of symptoms of chronic venous insufficiency such as leg pain and edema and that adverse events were mild and infrequent and included gastrointestinal complaints, dizziness, nausea, headache, and pruritus [bloodjournal.hematologylibrary.org]

• Stroke

  Altogether we’re covering Introduction DVT, Deep Vein Thrombosis Post-thrombotic syndrome PE, Pulmonary Embolism Pulmonary hypertension AF, Atrial Fibrillation Heart Valve conditions – aortic and mitral Thrombophilia Stroke heart attack Introduction Post [coagulationconversation.com]

  Although the life expectancy of PS patients may be reduced, this is likely due to comorbidities predisposing for thromboembolic events like stroke, myocardial or renal infarction. [symptoma.com]

  Start off at the top of your legs and work in long smooth strokes down your leg towards your ankles. Then, once your reach the bottom go back up to the top and work down again in small circular motions. [hubpages.com]

  Dr Ginsberg is a recipient of a Career Investigator Award from the Heart and Stroke Foundation of Ontario, Toronto, and a Research Chair from the Canadian Institutes of Health Research/AstraZeneca, Ottawa, Ontario. [doi.org]

  Declarations Acknowledgements The SOX Trial is funded by the Canadian Institutes of Health Research (MCT# 63142) and the BioSOX Study is funded by the Heart and Stroke Foundations of Quebec and Ontario (HSFO#5629). [bmccardiovascdisord.biomedcentral.com]

PS diagnosis is based on the patient's medical history, physical examination and visualization of deep veins draining the affected area.

Both medical history and physical examination may, however, not allow for a clear distinction between DVT, CVI and PS if leg ulcers are not present. A clinical score developed by Villalta and colleagues has been proven very helpful to this end [5]:

• Patients are queried for a feeling of heavy legs, pain, cramps, pruritus and paresthesias. They are requested to estimate the severity of these complaints and to assign scores ranging from 0 (not perceived) to 3 (intense complaints).
• The physician revises the patient for local erythema, edema, fibrotic skin induration, hyperpigmentation, venous ectasia and pain upon increasing venous pressure. These signs are similarly scored.
• Scores have to be ascertained repeatedly, ideally in six-month intervals.

Repeated scores of >5 indicate PS, whereby the achieved score correlates with disease severity. Scores >15 indicate severe PS. This also applies to patients who suffer from stasis ulcers.

Duplex ultrasonography may be applied to rule out DVT and to confirm symptomatic CVI. This technique yields reliable and reproducible results, is of low cost and readily available. Typical findings are venous reflux and lack of compressibility due to fibrotic reorganization of vein walls. Detailed protocols are described elsewhere [6].

• Dyslipidemia

  Levels of soluble cell adhesion molecules in patients with dyslipidemia. Circulation 1996; 93: 1334-1338. 29 Hartge MM, Unger T, Kintscher U. The endothelium and vascular inflammation in diabetes. [doi.org]

  She was also diagnosed with hypothyroidism and dyslipidemia during routine investigations about 6 years back for which she is taking Thyronorm 50 mcg (thyroxine sodium) and Storvas (atorvastatin). [ijrh.org]

Causative treatment is not available; therapy of PS aims at cure of dermatological lesions, reduction of venous pressure and prevention of relapses. Patients may achieve a state of largely asymptomatic CVI, but the functionality of defective venous valves cannot be restored. Remodeling processes that led to fibrotic remodelling of the vessel's wall is only partially reversible.

The following measures may be taken:

• Usage of graduated elastic compression stockings is advised for up to two years after DVT [7]. This period covers the time of highest risks of CIV and PS. And even though it seems plausible that the reduction of venous pressure facilitates venous return and reduces blood stasis, scientific evidence for the effectivity of that measure remains scarce. Recently published studies even argue against that hypothesis [8].
• Intermittent pneumatic compression may be considered as an alternative to compression stockings.
• Patients should be advised to regularly elevate their legs above heart level and to avoid prolonged periods of standing. They should be encouraged to practice regular exercise. These measures contribute to resolution of blood stasis and edema.
• Topical wound care is required if the patient suffers from stasis dermatitis and ulcers. Very good results have been achieved with Unna boots and interactive dressings.
• The application of a venocuff locally compensates for venous function impairment [9], but more extensive studies are required to assess its short- and long-term efficacy.

PS is related with significant morbidity and reduces the life quality of affected individuals. Although the life expectancy of PS patients may be reduced, this is likely due to comorbidities predisposing for thromboembolic events like stroke, myocardial or renal infarction.

Currently available treatment options generally provide symptom relief. If patients are willing to take certain lifestyle decisions, e.g., if they are able to reduce weight and take care of their legs, life quality and possible life expectancy will further improve. However, CVI is largely irreversible and venous function may not be restored. Thus, patients may be cured from PS but will continue to suffer from CVI; they will most likely experience symptomatic periods throughout life. An overall improvement can be expected in most cases, though.

PS is the medical term for symptomatic CVI and CVI most commonly results from DVT. Thus, any condition predisposing for DVT should also be considered a risk factor for PS. In this context, the following pathologies should be contemplated as possible etiologic factors:

• Genetic disorders associated with thrombophilia, e.g., protein C deficiency, protein S deficiency, hereditary deficiency of antithrombin III, factor V Leiden mutation
• Autoimmune disease like antiphospholipid syndrome
• Any pathological condition predisposing for thromboembolism, e.g., atherosclerosis, hypertension, hypercholesterolemia, diabetes mellitus

Patients presenting with recurrent DVT have particularly high risks of CVI and PS.

Additionally, obesity and tobacco consumption have been identified as risk factors for CVI [1]. Traumatic lesions of vessels may also interfere with vein function, particularly if patients are forced to maintain the affected limb immobilized during convalescence.

DVT is a rather common disease and it has been estimated that 20 to 50% of DVT patients develop CVI and PS despite being adequately treated. This results in annual incidence rates of PS of 1 to 3 per 1,000 inhabitants [2]. The individual risk of developing DVT, CVI and PS increases with age.

Gender predilection has been reported differently by various authors.

Venous thrombosis interferes with blood drainage and, consequently, with oxygen and nutrient supply to dependent areas. Ischemia, cell death and an acute inflammatory response occur in those tissues. These events result in edema formation and pressure enhancement. Furthermore, the vessel's wall and valves are damaged. In healthy individuals, venous valves impede reflux and blood stasis, but these structures cannot fulfill their functions in patients suffering from CVI. Blood stasis occurs and leads to pressure-induced fibrotic remodeling of venous walls, surrounding soft tissues and skin. These processes further impede venous return and lead into a vicious circle.

As can be deducted from the aforegiven description of pathophysiological events, venous hypertension in the lower limbs play a major role in PS pathogenesis [3]. In CVI and PS patients, venous return becomes highly dependent on leg elevation and exercise, because both mediate a reduction of venous pressure. However, calf muscle function is increasingly impaired by inflammatory processes taking place in surrounding tissues. Thus, symptoms aggravate over the course of the day and patients only find relieve when elevating their legs over heart level.

Since the majority of PS patients is older than 60 years, prevalence rates of cardiovascular disorders in that patient group is high. Unfortunately, cardiac insufficiency further aggravates disturbance of venous return, edema formation and loss of venous function.

This chain of events can only be interrupted by recanalization - preferentially before irreversible tissue damage occurs - and, if need be, drug therapy of cardiac insufficiency.

Prevention of PS consists in prevention of venous thromboembolism by avoidance of the above mentioned risk factors, and adequate treatment of DVT and CVI. Recent studies suggest that catheter-directed thrombolysis and venous thrombectomy may be superior to conventional anticoagulant therapy of DVT with regards to the conservation of venous function [10]. Long-term drug therapy may still be indicated to avoid relapses. Additionally, DVT and CVI patients should be advised to use compression stockings and to elevate their legs regularly in order to facilitate venous return.

Deep vein thrombosis (DVT) refers to the formation of a blood clot in determined vessels, most commonly in deep veins draining the lower limbs. Preference for these vessels is generally explained by the fact that a human's upright posture complicates venous return from anatomical structures situated far below the heart. Of note, DVT may also affect the upper limbs. DVT is associated with tenderness, pain, swelling and erythema. Patients presenting with DVT often receive anticoagulants, but catheter-directed thrombolysis and venous thrombectomy may also be considered.

Although the aforementioned therapeutic approaches cause significant symptom relief in most patients, affected individuals may continue to experience minor complaints. Their legs may still feel heavy and tire easily, and in some cases pain and swelling persist or reappear intermittently. Such observations suggest chronic venous insufficiency (CVI). Patients suffering from CVI may be asymptomatic at times, but functional impairment of venous valves and venous walls don't resolve spontaneously.

Over prolonged periods of time, CVI-associated symptoms may aggravate significantly. Patients may develop leg ulcers and skin fibrosis, claim pain, swelling and paresthesias. Ulcers may become infected and lead to even more severe dermatological lesions. The entirety of symptoms is referred to as postphlebitic syndrome (PS) or postthrombotic syndrome. Thus, PS describes symptomatic CVI.

Clinically, it is not always easy to distinguish between DVT, CVI and PS. Patients who present with PS have suffered from DVT and CVI previously and these diseases have most likely been triggered by systemic pathologies causing thrombophilia and/or thromboembolism. Genetic disorders, autoimmune diseases and atherosclerosis shall be mentioned as examples at this point. The majority of these disorders persists and thus, it is not unlikely that someone who suffered from DVT once will present with this condition again. In fact, recurrent DVT is a major risk factor for PS. Diagnostic imaging, namely Duplex sonography, is very helpful in diagnosing DVT or ruling out the latter in case of PS.

Causative treatment is not available and compression stockings are still the mainstay of PS therapy. Topical wound care is of utmost importance if patients present ulcers. Even though venous function cannot be restored, the prognosis for symptomatic relief is favorable.

Postphlebitic syndrome (PS), sometimes also referred to as postthrombotic syndrome, is the medical term for a symptom complex that may manifest in patients who previously suffered from deep vein thrombosis (DVT) and chronic venous insufficiency (CVI).

DVT occurs when a blood clot forms within determined vessels or is carried there. Most commonly, the lower legs are affected. The thrombus interferes with blood drainage and oxygen supply to dependent tissues. This leads to ischemia, cell death and an acute inflammatory response that does, in turn, provoke damage to the vessel's wall, venous valves, surrounding soft tissues and skin. Unfortunately, these pathophysiological events further hamper venous function, favor renewed thrombus formation, blood stasis and increased venous pressure.

If this vicious cycle cannot be interrupted, patients develop CVI. In general, CVI-associated symptoms wax and wane. However, severe vascular and dermatological lesions may manifest during symptomatic episodes - and in their entirety, they constitute PS:

• Sensation of fullness or heaviness, legs tire easily
• Swelling
• Tenderness and pain
• Cramps
• Reddened skin, itching, tingling sensations
• Skin induration
• Hyperpigmentation
• Leg ulcers

Therapy of PS is challenging and the best treatment of this complicated condition is an early, adequate therapy of DVT and CVI. If PS manifests, patients are recommended to wear graduated elastic compression stockings, and to regularly elevate their legs above heart level. Wound care is of utmost importance to cure ulcers and other dermatological lesions.

However, venous function cannot fully be restored and although patients may be cured from PS, they will continue to suffer from CVI and will most likely experience symptomatic periods throughout life.

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2. Kahn SR, Comerota AJ, Cushman M, et al. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2014; 130(18):1636-1661.
3. Schmitt BP. Review: After lower-extremity DVT, compression stockings do not reduce postthrombotic syndrome or recurrence. Ann Intern Med. 2016; 164(10):JC53.
4. Walker N, Rodgers A, Birchall N, Norton R, MacMahon S. Leg ulceration as a long-term complication of deep vein thrombosis. J Vasc Surg. 2003; 38(6):1331-1335.
5. Villalta S, Bagatella P, Piccioli A, et al. Assessment of validity and reproducibility of a clinical scale for the post-thrombotic syndrome. Hemostasis. 1994; 24:158a.
6. Zygmunt JA. Duplex ultrasound for chronic venous insufficiency. J Invasive Cardiol. 2014; 26(11):E149-155.
7. Brandjes DP, Buller HR, Heijboer H, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997; 349(9054):759-762.
8. Schmitt BP. Review: After lower-extremity DVT, compression stockings do not reduce postthrombotic syndrome or recurrence. Ann Intern Med. 2016; 164(10):JC53.
9. Yavuz C, Demirtas S, Guclu O, et al. An alternative therapy for recurrent stasis ulcers in chronic venous insufficiency: venocuff. Case Rep Vasc Med. 2012; 2012:315147.
10. Plate G, Eklof B, Norgren L, Ohlin P, Dahlstrom JA. Venous thrombectomy for iliofemoral vein thrombosis--10-year results of a prospective randomised study. Eur J Vasc Endovasc Surg. 1997; 14(5):367-374.