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Postthrombotic Syndrome
Introduction
Postthrombotic syndrome describes the signs and symptoms of chronic venous insufficiency following an episode of acute deep vein thrombosis (DVT). This condition is characterized by leg discomfort and heaviness, as well as vein dilatation, edema, skin discoloration, and venous ulcers. DVT occurs around 1 in 1000 individuals yearly. Despite adequate anticoagulation therapy, the postthrombotic syndrome can still develop, affecting 20% to 50% of patients with DVT.[1][2]
Postthrombotic syndrome is a significant public health concern due to its profound impact on quality of life and healthcare costs. The socioeconomic repercussions of the condition are expected to increase in the next few years. While notable advances have been made in understanding postthrombotic syndrome, numerous unresolved questions remain. Currently, efficacious and validated treatment options for postthrombotic syndrome are limited. The best management approach involves DVT avoidance, prompt identification, and recurrence prevention.[3]
Etiology
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Etiology
The etiology of postthrombotic syndrome remains partially elucidated. However, the condition is thought to arise from venous hypertension secondary to venous valvular impairment and restriction of venous outflow due to persistent thrombosis and fibrosis of the vessel wall. Acute DVT results in partial or complete venous flow restriction. Failure to recanalize, usually seen as early as 6 weeks after diagnosis, determines persistent flow obstruction that leads to fibrotic damage to the venous wall.[4] The inflammatory cascade also contributes to direct venous valve damage.[5] The postthrombotic alterations elevate venous pressures transmitted to the capillary beds, leading to tissue swelling, lipodermatosclerosis, and, ultimately, tissue oxygen deprivation and venous ulcer formation.[6]
Epidemiology
Comprehensive epidemiological data on postthrombotic syndrome are insufficient, but some studies show an incidence of 20% to 50% in patients with previous DVT.[7] Approximately 8% to 10% of cases are severe, significantly diminishing these patients' quality of life.[8] A systematic review of 16 cohort studies showed variations in occurrence rates among different countries, with an overall 2-year incidence of postthrombotic syndrome found to be 37.5%.[9] Moreover, a registry of 1107 patients with proximal DVT revealed a 3-year incidence rate of 27.8%, with older patients having an increased incidence and a higher prevalence of persistent DVT risk factors. Studies have also shown that the overall occurrence of postthrombotic syndrome plateaus between 1 and 2 years after an acute DVT. However, symptoms can develop within 6 years in approximately one-third of patients.[10]
History and Physical
Postthrombotic syndrome can present with a range of symptoms, from mild, such as skin pigmentation, telangiectasia, mild discomfort, and edema, to severe, including chronic pain, severe edema, and skin ulceration. Symptoms may appear within weeks or months after a DVT episode or persist from an acute DVT.[11] Edema occurs in about two-thirds of individuals with postthrombotic syndrome and may be accompanied by limb heaviness and discomfort, typically after prolonged standing or walking, and relieved by resting or elevating the limb.
Approximately one-third of individuals experience skin changes, including discoloration, telangiectasia, eczema, varicose veins, or lipodermatosclerosis. Ulceration occurs in less than 5% of patients. Dermatologic alterations often manifest 2 to 4 years after an acute DVT.[12]
Evaluation
The diagnosis of postthrombotic syndrome is primarily based on clinical evaluation, as no gold standard test is currently recommended. Additional diagnostic testing is typically unnecessary. The condition should be suspected in a patient with a history of DVT.[13]
Several clinical scores are available to aid in diagnosing and characterizing postthrombotic syndrome. The Villalta scale was developed in 1994 to diagnose postthrombotic syndrome and classify the condition according to severity. The score is determined based on 6 subjective symptoms, 6 objective signs, and the presence of venous ulceration (see Table. The Villalta Scale).[14] The presence of a venous ulcer or a score greater than 5 establishes the diagnosis of postthrombotic syndrome. The disease is considered mild if the score is between 5 and 10. Scores of 10 to 14 indicate moderate postthrombotic syndrome, whereas scores of 15 and above indicate severe disease.[15][16] The International Society on Thrombosis and Haemostasis recommends using the Villalta score during the first visit to establish the diagnosis of postthrombotic syndrome and 3 months later to assess its grade and severity.[17]
The Villalta scale is the primary clinical score to evaluate for lower extremity postthrombotic syndrome. However, postthrombotic syndrome may also occur in the upper extremities.[18] Instead of the Villalta scale, the upper-extremity postthrombotic syndrome (UE-PTS) score is used to evaluate upper-extremity involvement. This score is based on the presence and severity of 5 symptoms (edema, heaviness, fatigue upon use, pain, and functional arm limitations) and 3 clinical signs (asymmetrical circumference of upper and lower arms, discoloration at rest, and presence of collateral veins around shoulder, torso, or breast). By using the Villalta scale, postthrombotic syndrome is graded as absent, mild, moderate, or severe.[19]
The shortened Disabilities of the Arm, Shoulder, and Hand Questionnaire (QuickDASH) is a concise 11-item questionnaire that assesses physical function and symptoms in individuals with upper-extremity musculoskeletal disorders. The questionnaire covers daily activities, house/yard work, shopping, recreation, self-care, food, sleep, friends, job, pain, and tingling or numbness.[20] The international Delphi consensus recommends including the QuickDASH questionnaire in the evaluation of UE-PTS.
For patients experiencing severe symptoms, exploring any venous abnormalities that may warrant intervention, such as a remaining blockage or proximal venous reflux, is advisable. The main imaging techniques used for this purpose are venous duplex, intravascular ultrasonography, and venography.[21] Patients with a history of DVT who are asymptomatic, despite exhibiting persistent venous obstruction or venous hypertension on imaging, do not meet the criteria for a diagnosis of postthrombotic syndrome.[22]
Table. The Villalta Scale
| None | Mild | Moderate | Severe | |
| Symptoms | ||||
| Pain | 0 | 1 | 2 | 3 |
| Cramps | 0 | 1 | 2 | 3 |
| Heaviness | 0 | 1 | 2 | 3 |
| Paresthesia | 0 | 1 | 2 | 3 |
| Pruritus | 0 | 1 | 2 | 3 |
| Clinical Signs | ||||
| Pretibial edema | 0 | 1 | 2 | 3 |
| Skin induration | 0 | 1 | 2 | 3 |
| Redness | 0 | 1 | 2 | 3 |
| Hyperpigmentation | 0 | 1 | 2 | 3 |
| Venous stasis | 0 | 1 | 2 | 3 |
| Pain in calf compression | 0 | 1 | 2 | 3 |
| Venous ulcer | Absent | Present |
Treatment / Management
The main pillars for postthrombotic syndrome management include exercise, limb elevation, and compression therapy. However, more in-depth interventional studies are needed to determine the best approach.[23](A1)
Exercise enhances venous blood flow, decreasing venous stasis and hypercoagulability, variables that contribute to thrombosis development.[24] Recent studies have found that exercise does not raise the risk of pulmonary embolism in patients with DVT. An inferior vena cava filter is an option in high-risk patients.[25] Physical activity aids with symptom reduction, and resistance training has been shown to improve muscle strength and enhance walking performance by reducing the size of the thrombus and accelerating its dissolution.[26]
Compression-based therapies help reduce symptoms and enhance daily functionality. Compression-based therapies aid in symptom reduction and enhance daily functionality. Depending on the severity of symptoms and the presence of edema, skin abnormalities, or ulceration, compression socks, short stretch bandages, multilayer compression, or zinc paste bandages may be utilized.[27] For patients with moderate-to-severe postthrombotic syndrome who do not experience symptom relief from elastic compression stockings alone, a portable intermittent compression device is a therapeutic option.[28][29] However, most of the evidence for this intervention comes from unblinded trials. Thus, observational bias may have been present. (A1)
Pharmacologic therapy, including venoactive drugs such as diosmin and rutosides, has been used to aid with lower extremity symptoms. Nevertheless, high-quality data from randomized trials are insufficient to support the use of pharmacologic interventions in postthrombotic syndrome.
Local management of skin alterations and venous ulcers is crucial in treating postthrombotic syndrome. Moisturizers and midpotency topical corticosteroids are used to treat dry skin, itching, and eczematous changes. Additionally, dressings are used to cover ulcers and facilitate moist wound healing.[30]
In a randomized clinical trial involving 208 patients with acute DVT of the lower extremity, distributed equally among 4 groups (warfarin alone, warfarin plus rosuvastatin, rivaroxaban alone, and rivaroxaban plus rosuvastatin), those taking rosuvastatin experienced a greater decrease in inflammatory marker levels compared to those on anticoagulants alone (P <.0001). A significant change in lower limb size was observed in 3 groups 3 months after DVT. However, the groups taking rosuvastatin experienced a more significant decrease in lower limb size than those receiving anticoagulation alone (P <.0001 versus P <.05).[31](A1)
Vascular procedures may be necessary if severe symptoms persist and venous obstruction or reflux is evident. Interventions such as percutaneous angioplasty with or without stenting, venous bypass, and endophlebectomy can reduce ulcer recurrence and skin alterations, thereby enhancing patients' quality of life.[32] In addition, some studies show that eliminating the source of retrograde flow can improve venous hemodynamics.[33][34] (B2)
Ultimately, the prompt treatment of acute DVT is crucial in preventing postthrombotic syndrome. A meta-analysis comparing different anticoagulants indicated that edoxaban was more effective in preventing postthrombotic syndrome compared to rivaroxaban.[35](A1)
Differential Diagnosis
Postthrombotic syndrome manifestations, such as lower extremity pain, heaviness, and edema, are also present in various conditions, including primary venous insufficiency, increased body mass index, lipedema, lymphedema, soft tissue masses, and posttraumatic changes. A prior history of DVT can help distinguish postthrombotic syndrome from primary venous insufficiency. Signs and symptoms of postthrombotic syndrome are typically isolated to the limb where the DVT occurred, whereas primary venous insufficiency tends to occur bilaterally.
Masses causing venous obstruction, such as arterial aneurysms, Baker cysts, and soft tissue tumors, may be readily noticeable during physical examination of the groin and popliteal fossa. However, they can be challenging to detect in obese patients or those with significant limb swelling. Ultrasound or cross-sectional imaging techniques can aid in identifying and distinguishing these masses.
Prognosis
Despite recent advancements, postthrombotic syndrome remains one of the more prevalent, chronic, and debilitating complications of acute DVT with limited treatment options. Over 50% of patients prescribed elastic compression stockings and receiving proper follow-up maintain stability or show improvement, regardless of the initial severity of the syndrome.[36] However, some studies present mixed evidence supporting the benefits of elastic compression stockings. For instance, the SOX study, the largest placebo-stocking controlled trial, failed to show a significant interventional effect, with 14.2% of patients who used elastic compression stockings developing postthrombotic syndrome compared to 12.7% in the placebo group. Nonetheless, these results might be influenced by the low compliance rate due to barriers such as discomfort, cost, and difficulty putting on the stockings.
Complications
A proximal DVT is associated with a greater occurrence risk and more intense postthrombotic syndrome symptoms than a distal DVT.[37] However, complications in both cases mainly occur in patients who continue to experience the initial venous symptoms linked to DVT.
Leg ulceration represents a significant complication of postthrombotic syndrome and a substantial cause of disability and financial burden on both individuals and healthcare systems. Venous ulcers are usually painless, superficial lesions with irregular borders, red granulation tissue, yellow fibrin at the base, and exudates. Indicators of poor prognosis for ulcer healing include duration longer than 3 months, initial size of 10 cm or greater, the presence of arterial disease, advanced age, and an elevated body mass index.
Deterrence and Patient Education
The following measures are recommended for preventing postthrombotic syndrome:
- Regular ambulation
- Frequent physical activity
- Use of compression stockings
- Adherence to anticoagulation therapy after an acute DVT
By emphasizing these practical strategies, healthcare providers can better support patients adopting and adhering to these preventive measures.
Enhancing Healthcare Team Outcomes
Collaboration among healthcare providers, including physicians, nurses, and physical therapists, is essential for delivering patient-centered treatment for postthrombotic syndrome. Healthcare personnel must possess clinical skills and expertise to effectively diagnose, evaluate, and treat this condition. Competencies include accurately identifying postthrombotic syndrome symptoms, recognizing potential complications, and implementing complex management strategies. Consultation with a vascular surgery specialist may be necessary, depending on symptom severity. A strategic methodology that incorporates personalized care plans tailored to each patient's specific circumstances is crucial for mitigating postthrombotic syndrome complications, such as venous ulcers.
Interprofessional healthcare team members need a comprehensive understanding of their responsibilities and must actively contribute their distinct areas of expertise to the patient's care plan. Effective interprofessional communication is crucial for smooth information delivery and collaborative decision-making among healthcare teams and patients. By adopting best practices in interprofessional communication and care coordination, healthcare professionals can enhance patient outcomes and improve team performance in managing postthrombotic syndrome.
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