Guidance for the prevention and treatment of the post-thrombotic syndrome

J Thromb Thrombolysis (2016) 41:144–153 DOI 10.1007/s11239-015-1312-5 Guidance for the prevention and treatment of the post-thrombotic syndrome Susan R. Kahn1,5 • Jean-Philippe Galanaud2 • Suresh Vedantham3 • Jeffrey S. Ginsberg4 Published online: 16 January 2016  The Author(s) 2016. This article is published with open access at Springerlink.com Abstract The post-thrombotic syndrome (PTS) is a frequent, potentially disabling complication of deep vein thrombosis (DVT) that reduces quality of life and is costly. Clinical manifestations include symptoms and signs such as leg pain and heaviness, edema, redness, telangiectasia, new varicose veins, hyperpigmentation, skin thickening and in severe cases, leg ulcers. The best way to prevent PTS is to prevent DVT with pharmacologic or mechanical thromboprophylaxis used in high risk patients and settings. In patients whose DVT is treated with a vitamin K antagonist, subtherapeutic INRs should be avoided. We do not suggest routine use of elastic compression stockings (ECS) after DVT to prevent PTS, but in patients with acute DVTrelated leg swelling that is bothersome, a trial of ECS is reasonable. We suggest that selecting patients for catheterdirected thrombolytic techniques be done on a case-by-case basis, with a focus on patients with extensive thrombosis, recent symptoms onset, and low bleeding risk, who are seen at experienced hospital centers. For patients with established PTS, we suggest prescribing 20–30 mm Hg knee-length ECS to be worn daily. If ineffective, a stronger & Susan R. Kahn 1 McGill University, Montreal, QC, Canada 2 Department of Internal Medicine, Montpellier University Hospital, Montpellier, France 3 Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MD, USA 4 5 Department of Medicine, McMaster University, Hamilton, ON, Canada Division of Internal Medicine & Center for Clinical Epidemiology, Jewish General Hospital, 3755 Cote Ste. Catherine Room H420.1, Montreal, QC H3T 1E2, Canada 123 pressure stocking can be tried. We suggest that intermittent compression devices or pneumatic compression sleeve units be tried in patients with moderate-to-severe PTS whose symptoms are inadequately controlled with ECS alone. We suggest that a supervised exercise training program for 6 months or more is reasonable for PTS patients who can tolerate it. We suggest that management of postthrombotic ulcers should involve a multidisciplinary approach. We briefly discuss upper extremity PTS and PTS in children. Keywords Post-thrombotic syndrome
Venous thromboembolism
Deep venous thrombosis
Direct oral anticoagulants (DOAC)
New oral anticoagulants (NOAC) Introduction The post-thrombotic syndrome (PTS) is a chronic condition that develops in *20–50 % of patients after deep venous thrombosis (DVT) [1]. It adversely affects health and quality of life, and is costly as measured by health care costs, out of pocket expenditures, and lost productivity. The objective of this chapter is to provide guidance for the general practitioner, internist, nurse practitioner, pharmacist, and other healthcare professionals on best current practices for the prevention and treatment of PTS. Background Traditionally, clinical trials investigating new therapies or management approaches to treat DVT have focused on their effectiveness to prevent recurrent venous thromboembolism (VTE) in the short (3 months) to medium term Guidance for the prevention and treatment of the post-thrombotic syndrome (12 months) after DVT, while their effectiveness to prevent PTS has been ignored. Over the last 10–15 years, however, PTS has been increasingly recognized as a frequent and important outcome of DVT. Recent studies have improved understanding of the epidemiology, risk factors, and health and economic impact of PTS. Recommendations for standardization of the definition of PTS for clinical studies have been published [2], and rigorous clinical trials are underway to evaluate new approaches to preventing and treating PTS. Recently, the first evidence-based guidelines focused solely on PTS were published by the American Heart Association [3]. Methods To provide guidance on the management of the postthrombotic syndrome, we first developed a number of pivotal practical questions pertaining to the PTS (Table 1). Questions were developed by consensus from the authors. The literature addressing the questions below was reviewed by searching electronic databases (PubMed, Medline) and the authors’ personal libraries, with a focus on high quality cohort studies and randomized controlled trials published in the last 10 years, where available. For each question, a brief summary and interpretation of pertinent literature and existing guidelines, where available, are provided, followed by guidance for the reader. Guidance (1) What is PTS and why is it important (i.e. epidemiology, impact on quality of life, cost)? PTS is a clinical disorder of pain and disability resulting from chronic venous insufficiency following DVT. PTS is Table 1 Guidance questions to be considered (1) What is PTS and why is it important (i.e. epidemiology, impact on quality of life, cost)? (2) What are the clinical manifestations of PTS and what is its underlying pathophysiology? (3) How is PTS diagnosed? (4) What are known risk factors for PTS? (5) Is there a best anticoagulant to treat DVT that influences the occurrence of PTS? (6) What are current best approaches to preventing PTS after DVT? (7) What are current best approaches to treating PTS? (8) Does PTS occur after upper extremity DVT? (9) Does PTS occur after DVT in children? (10) What are the most pressing research needs in the field? 145 the most frequent complication of DVT. It develops in *20–50 % of patients within 2 years of DVT diagnosis [4, 5], even when patients are adequately treated with anticoagulants, and is severe in 5–10 % of cases. Hence on average, about 6 of 10 DVT patients recover without any residual symptoms, 3 of 10 have some degree of PTS, and *1 of 10 to 1 of 20 develop severe PTS that can include pain leg ulcers. The overall estimated incidence of VTE is 0.7–2 per 1000 person-years and increases with age [6, 7] so that more than one-third of cases occur in persons older than 60 years of age [8]. VTE is a growing public health problem due to increased life expectancy, an increasing proportion of elderly individuals and an expected increase in the prevalence of PTS. Due to its high prevalence and chronicity, PTS is a costly condition. A Canadian study estimated that the total per-patient cost of PTS over a two-year period was almost 50 % higher than for DVT patients without PTS [9]. Costs were largely attributable to frequent healthcare visits and prescription medications. In the United States, annualized median total costs for DVT patients who developed PTS was $20,569 compared with $15,843 in matched controls with DVT and no PTS [10]. Costs are highest in (...truncated)