Postthrombotic Syndrome: A Scientific Statement Calling for More Data

Postthrombotic syndrome (PTS) is a common long-term consequence of deep vein thrombosis (DVT). It is prevalent, affecting as many as 60% of patients after a proximal DVT. The most common clinical manifestations of PTS include swelling, skin changes and limb pain. Approximately 1 in 10 of patients will suffer from severe PTS, manifesting with skin ulcerations.¹ These outcomes result in increased medical costs and marked reduction in quality of life in many patients. Therefore, strategies to promote prevention, early detection and effective treatment are greatly needed. However, to date, PTS has been largely ignored in the peer-reviewed medical literature, with barely over one hundred original studies, most of which were flawed and subsequently criticized. It is in this setting that Kahn and colleagues have compiled a long overdue document that summarizes the epidemiology, pathophysiology, methods of diagnosis, clinical manifestations and treatment options of PTS. They should be congratulated on a concise and clear representation of currently available data, highlighting their obvious clinical expertise, especially in this poorly understood disease state.

The postthrombotic syndrome is a frustrating condition to diagnose and treat. First, it can manifest long after an initial deep venous thrombosis (DVT). Intermittent symptoms may become chronic without warning. Adding to the frustration is the fact that in some patients no history of DVT can be elicited, raising the question of primary venous valvular incompetence as an etiology.² Notwithstanding, despite the high prevalence, the pathophysiology of PTS is unclear. Factors that probably play a role include venous hypertension that is the result of venous obstruction, valve dysfunction, and an inflammatory process.

The scientific statement identifies multiple studies that have highlight both patient-related and thrombosis-related factors that help predict the likelihood of a patient developing PTS. However, even in patients in whom risk is high, there is no proven method for prevention of PTS. In fact, primary and secondary prevention of DVT are probably the most effective means of PTS prevention.³ Unfortunately, the level of evidence regarding the effectiveness of various options to prevent PTS after an initial DVT has occurred is low. While graded compression stockings are commonly prescribed in clinical practice for the prevention of PTS post DVT, data concerning their efficacy has been conflicting. Most recently the SOX trial, the most rigorously performed study on the topic, concluded that such stockings were ineffective.⁴ Another modality to resolve venous hypertension, thought to contribute to PTS formation, is early resolution of the thrombus with thrombolysis. Catheter directed thrombolysis (CDT) or pharmacomechanical techniques are sometimes offered in specialized centers to patients who present with an ilio-femoral DVT. The Catheter-directed Venous Thrombolysis trial (CaVeNT) compared anticoagulation with or without CDT.⁵ This study identified a high incidence of PTS, but highlighted a 26% reduction in the treatment group after 24 months. This study has been criticized for a number of factors including inconsistencies in anticoagulant therapy and underutilization of post-CDT stenting. More encouraging results came from the Thrombus Obliteration by Rapid Percutaneous Endovenous Intervention in Deep Venous Occlusion (TORPEDO) trial, albeit also criticized for several limitations.⁶ Perhaps the most anticipated study in this regard is the ATTRACT trial, which will be the largest prospective, randomized study to address the role of CDT in PTS prevention.⁷

Furthermore, once PTS develops, treatment is often ineffective. The current document discusses the various treatment modalities that are at clinicians’ disposal, however the lack of high level evidence to support conclusive recommendations is evident. Graduated compression stockings are arguably the most common form of treatment offered to PTS patients to control swelling and venous hypertension.⁸ Problematic are two issues, including the absence of convincing evidence regarding their efficacy, and the lack of patient compliance due to many factors including difficulty applying and removing them, aesthetics, and discomfort, as any clinician who prescribes them soon learns. Intermittent compression devices, while safe, also lack high-level evidence to support their use, are not as readily available as graduated compression, and are expensive. Exercise, which is easy to recommend and appears to be safe following DVT, is understudied and underutilized. The level of evidence regarding several pharmacological therapies is low as well, resulting in low clinical use. Once venous stasis ulcers develop, compression is the mainstay of therapy, however in many cases ulcer healing is protracted and a cause for added morbidity and cost.⁹ More heroic treatment modalities including percutaneous venous valves (which are purely experimental and remain unproven) and surgical venous valve reconstruction have been performed in patients with severe PTS. Again, data quality has been low and results have been mixed and highly operator dependent.

In summary, PTS is a common disorder, is difficult to anticipate and prevent, contributes to patient morbidity and reduced quality of life, results in increased health care expenses, with an absence of effective treatments. Kahn et al have done a marvelous job summarizing the current evidence and outlining the open questions in the field, which are still numerous. One must hope that the future will hold better prevention strategies for DVT and PTS and better evidence based solutions for this often ignored patient population.