An update on etiology, prevention, and therapy of postthrombotic syndrome

Henke PK, Comerota AJ. J Vasc Surg. 2011;53:500-509.

Reviewed by
Gillet Jean-Luc, Bourgoin, France

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Postthrombotic syndrome (PTS) is a common sequela of deep vein thrombosis (DVT). It has been reported to occur in 25% to 46% of patients treated by anticoagulation (AC) alone for acute DVT ¹. In this article, the authors review the definition, epidemiology, basic pathology, and preventive management of PTS. They highlight the current primary medical and interventional treatment modalities used to decrease the occurrence of PTS.

PTS is difficult to quantify. The best agreed upon tool is the Villalta score ², which is designed to grade limb symptoms and signs in patients with PTS.

Duplex ultrasound imaging is essential for quantifying venous reflux and location, as well as documenting thrombotic obstruction, but imaging is not correlated with severity. Other imaging methods, such as computed tomography venography or magnetic resonance venography, can delineate thrombotic obstruction but are not routinely used outside of planning for interventions or defining proximal iliac or caval thrombosis.

The underlying pathophysiology leading to PTS is ambulatory venous hypertension. The onset of PTS can be progressive, but the severity of venous symptoms at 1 month has been identified as a risk factor for PTS ³. Iliofemoral location, recurrent ipsilateral DVT, high body mass index, older age, and female gender are also variables predicting the worst postthrombotic morbidity ³. Conversely, calf vein thrombosis is not often associated with PTS.

Prevention of DVT is the primary intervention. Prophylaxis is often underprescribed in surgical patients ⁴. Recurrent ipsilateral DVT is associated with more severe postthrombotic morbidity. The quality of early anticoagulation (AC) for acute DVT significantly affects the likelihood of recurrence. The duration of AC is also closely associated with recurrence. Studies confirm that the longer the duration of AC, the lower the risk of recurrence with generally acceptable bleeding risk.

Identifying patients at risk of recurrent DVT is a crucial issue. Two options to consider at 3 to 6 months after the initial DVT include ¹ imaging the deep venous system for residual thrombus or wall abnormality, and ² identifying patients with elevated D-dimer levels. Prandoni et al ⁵ demonstrated a nearly threefold increase in recurrent DVT in patients with residual abnormality compared with those with a normal result on venous duplex ultrasound. Studies demonstrated that elevated D-dimer levels after the termination of oral AC identified patients with a threefold increased risk of recurrence during the next 2 years.

Randomized trials ⁶ have demonstrated the value of 30 to 40 mm Hg ankle-gradient stockings in the management of acute DVT. When applied early in the course of therapy and continued for at least 2 years, postthrombotic morbidity was reduced by about 50%. Whether stockings can be worn for a shorter period of time than 2 years after DVT is not yet definitively answered. Ambulation early in the course of treatment is also an essential measure.

Active thrombus removal- An ongoing multi-institutional trial will answer the question: Is active thrombus removal plus best medical therapy superior to best medical therapy for iliofemoral DVT? Beside venous thrombectomy, catheter-directed thrombolysis is now the most common form of intervention for extensive DVT. Several studies ⁷ have reported success rates of 80% to 85%. Recent reports demonstrated bleeding complications of < 5%. According to Comerota et al (unpublished data), patients treated with catheter-directed thrombolysis have reduced postthrombotic morbidity. This reduction was directly related to the volume of thrombus lysed.

Interventions for PTS sequelae – Occluded or stenotic segments, in properly selected patients, seem well served by percutaneous angioplasty and stenting. According to the authors, valve reconstruction procedures rarely seem efficacious in patients with PTS. Their recommendations are an expanded role for angioplasty and stenting and a reduced role for valve reconstruction. However, the authors did not discuss Maleti’s valve reconstruction procedure which could to be a promising approach ⁸. Prosthetic valves have undergone limited experimental evaluation, and the risk of thrombosis and durability is still uncertain.

Pharmacologic interventions must also be considered. Some drugs, such as micronized purified flavonoid fraction and pentoxifylline, have been shown to be of value in chronic venous insufficiency.

An attractive area of research involves biomarkers to stratify patients at risk of PTS after DVT. Several biomarkers correlate with less complete thrombus resolution in humans. Larger studies will be necessary to determine their sensitivity and specificity in relation to clinical PTS.

Finally, the authors recall that a recent trial ⁹ suggests that statins in patients at modest cardiac risk are also helpful in reducing incident DVT.

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