The post-thrombotic syndrome: current knowledge, controversies, and directions for future research
Introduction
The post-thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT) that is characterized by leg swelling and pain and occasionally venous ulceration.[1], [2] Despite enormous efforts that have led to major advances in the diagnosis, prevention and treatment of acute venous thromboembolism (VTE),[3], [4], [5] PTS, a chronic consequence of DVT, has been grossly understudied and underappreciated for a number of reasons. First, there is no accepted “gold standard” test or even uniform definition for the diagnosis of PTS. Second, because of its latency and chronicity, it is difficult and costly to study PTS prospectively because such studies require years of follow-up of patients with DVT. Third, despite its morbidity and high prevalence, like most chronic conditions, the evaluation and management of PTS holds less interest for researchers and clinicians than that of acute VTE, which is more dramatic.
Recent studies have shed light on the incidence of PTS, risk factors for its occurrence, clinical scales and quality of life measures to diagnose and quantify PTS, and the effectiveness of various treatments for PTS. In this article, we critically review the evidence on the epidemiology, pathophysiology, diagnosis, prevention and treatment of PTS, and discuss the impact of PTS on healthcare costs and quality of life. Controversies in the field and key areas for future research are underlined.
Section snippets
Incidence of venous thromboembolism
Since PTS is a direct consequence of DVT, its prevalence is influenced by the incidence of DVT. Despite advances in the prevention and treatment of VTE, population-based studies from Europe and North America performed in each of the last three decades consistently show that the overall annual incidence of VTE is 1.0–1.6 per 1000 persons per year, with a per-person lifetime incidence of 2–5%.[6], [7], [8], [9], [10] The apparent lack of decrease in VTE incidence over time could be the result of
Clinical presentation and pathophysiology of PTS
Patients with PTS complain of pain, heaviness, swelling, cramps, itching or tingling in the affected limb. Typically, symptoms are aggravated by standing or walking and improve with rest and recumbency. On physical examination, edema, telangiectasiae, hyperpigmentation, eczema, and varicose superficial (collateral) veins may be present (Table 2). In severe cases, there may be thickening and induration of the subcutaneous tissue around the ankle (lipodermatosclerosis) and evidence of healed or
General approach to diagnosis
There is no `gold standard' test to diagnose PTS. Because of the poor specificity of objective tests of valvular incompetence for symptomatic PTS, the diagnosis of PTS should be based primarily on the presence of typical clinical features. The vast majority of patients with symptomatic PTS have valvular incompetence, but many with valvular incompetence do not have symptoms. However, objective evidence of venous valvular reflux can help to confirm the diagnosis in symptomatic patients,
Risk factors for the development of PTS
While numerous risk factors for acute DVT have been identified, far less is understood about factors that predict the development of PTS after DVT.
Thromboprophylaxis and optimal duration of anticoagulation
The best way to prevent PTS is by prevention of the initial DVT. This can be achieved with the judicious use of thromboprophylaxis in high-risk patients and settings, as recommended in consensus guidelines3. Although proven to be safe and effective, thromboprophylaxis is still underutilized, particularly among non-orthopedic surgery patients and medical in-patients.[77], [78], [79], [80]
Since ipsilateral recurrence is a risk factor for PTS,13 preventing recurrent DVT is an important goal. This
Costs of PTS
Because of its prevalence and chronicity, PTS incurs high direct medical costs, as well as indirect costs such as loss of productivity at work and in the home. A Swedish study estimated that over a 15 year follow-up, the average cost of treating DVT complications such as recurrent events, venous ulcers and chronic venous insufficiency was ∼$4700US, which was 75% of the cost of treating the primary DVT.111 A US study estimated that 1/4 of cases of venous stasis syndrome were attributable to
Summary
PTS is a common, frequently overlooked, chronic complication of DVT that is burdensome and costly. PTS is likely to become more prevalent since the incidence of DVT does not appear to be decreasing over time. About 20–50% of patients with symptomatic DVT will develop PTS, usually by 1–2 years after the initial DVT. In most cases PTS is mild or moderate in severity, but severe PTS, which includes venous ulcers, occurs in 5–10% of cases. Physicians should actively screen DVT patients for PTS
Future research
There is much work to be done to address gaps in our understanding of PTS. The true frequency of PTS in different DVT patient subpopulations (asymptomatic vs. symptomatic, proximal vs. distal, provoked vs. unprovoked, with vs. without thrombophilia) requires evaluation. This can only be accomplished with rigorously designed prospective studies of consecutive DVT patients, and a systematic approach to PTS diagnosis that focuses on patient symptoms and clinical signs. Potential predictors of PTS
Acknowledgements
Dr. Kahn is a recipient of a Clinical Research Scientist Award from the Fonds de la Recherche en Santé du Québec. Dr. Ginsberg is a recipient of a Career Investigator Award from the Heart and Stroke Foundation of Ontario and a Research Chair from the Canadian Institutes of Health Research/Astra Zeneca.
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