Relationship between deep venous thrombosis and the postthrombotic syndrome

The postthrombotic syndrome (PTS) is a frequent complication of deep venous thrombosis (DVT). Clinically, PTS is characterized by chronic, persistent pain, swelling, and other signs in the affected limb. Rarely, ulcers may develop. Because of its prevalence, severity, and chronicity, PTS is burdensome and costly. Preventing DVT with the use of effective thromboprophylaxis in high-risk patients and settings and minimizing the risk of ipsilateral DVT recurrence are likely to reduce the risk of development of PTS. Daily use of compression stockings after DVT might reduce the incidence and severity of PTS, but consistent and convincing data about their effectiveness are not available. Future research should focus on standardizing diagnostic criteria for PTS, identifying patients at high risk for PTS, and rigorously evaluating the role of thrombolysis in preventing PTS and of compression stockings in preventing and treating PTS. In addition, novel therapies should be sought and evaluated.     

Management of the postthrombotic syndrome: the Rotterdam approach

The postthrombotic syndrome (PTS) affects the deep venous system, and may also extend to the superficial venous system of the legs in patients with a documented history of deep vein thrombosis. Clinical symptoms of PTS may vary considerably and range from scarcely visible skin changes to changes in pigmentation, pain, discomfort, venous ectasia, edema, and ulceration. Our view based on standard investigations and the proper place of advanced investigations regarding the etiology and pathophysiology of PTS has lead to the Rotterdam approach, incorporating the evidence-based diagnostics and treatments available for PTS. High-quality duplex sonography is mandatory in all patients, providing anatomical and functional (reflux) information on both the deep and superficial venous systems, and non- or partially recanalized veins (occlusion) can also be detected using this technique. If the results of duplex sonography are not clear or a venous desobstruction procedure is to take place, phlebography will be the investigation of choice. There is a lot of evidence that medical elastic stockings (MECS) are effective in the prevention of PTS with documented reflux, obstruction, or both. When prescribing MECS, it is important to examine both elasticity and hysteresis of the fabric of the stockings to apply the correct dynamic pressure for each individual patient. Patients with documented PTS should receive life-long follow-up.     

Frequency and determinants of the postthrombotic syndrome after venous thromboembolism

PURPOSE OF REVIEW: Postthrombotic syndrome (PTS) is the most common complication of deep venous thrombosis (DVT). Identifying which patients are at high risk of developing PTS would help improve the management of patients with DVT and allow physicians to provide patients with individualized information on their expected prognosis. This review discusses the knowledge gained from key studies over the last decade on the incidence and determinants of PTS, with special emphasis on published studies from the last 2 years. RECENT FINDINGS: About a third to half of DVT patients will develop PTS, in most cases within 1-2 years of acute DVT. Important risk factors for PTS appear to be ipsilateral recurrence of DVT, poor quality of initial anticoagulation for the treatment of DVT and increased body mass index. SUMMARY: Preventing DVT recurrence by providing adequate intensity and duration of anticoagulation for the initial DVT and using effective thromboprophylaxis in high-risk settings is likely to reduce the frequency of PTS. Despite some advances in identifying risk factors for PTS, however, it is still not possible to reliably predict an individual patient's risk of developing PTS after an episode of DVT. Further studies of clinical determinants and biological markers of increased risk of PTS are needed to ultimately improve long-term prognosis after DVT.     

Clinical course of postthrombotic syndrome in children with history of venous thromboembolism

Postthrombotic syndrome (PTS) is a chronic morbidity of venous thromboembolism (VTE) in children. Information about the evolution of PTS is lacking in children. Present study was aimed to evaluate the time-course of extremity PTS in children who were serially followed in a hematology clinic. This retrospective cohort study included 69 consecutive children with documented VTEs that presented with symptoms of extremity VTE: 67 extremity VTEs with or without extension to vena cava, 2 inferior vena cava VTEs. Severity of PTS was assessed using modified Villalta scale. Median age of the cohort was 12.6 years (interquartile range 1.6-15 years) while median follow-up was 28.7 months (interquartile range 13.3-33.4 months. PTS prevalence was 46.8% [95% confidence interval (CI) 37.9-57.7%]. Lower extremity VTE was associated with development of PTS compared to upper extremity VTE regardless of catheter use (P = 0.002). The time-course of PTS fluctuated in 11 of 33 children (33%; 95% CI 20-47%) at a median interval of 12 months from diagnosis of VTE (range 4-14 months): three progressed from mild/moderate to severe, one improved from moderate to mild, seven fluctuated between mild and moderate. Recurrence and incomplete resolution of VTE were associated with variability in PTS severity (P < 0.05). In summary, this study suggested that almost 50% of study cohort developed PTS, and the time-course of PTS was not static in one third of children. Future research should focus on identifying the predictors contributing to the worsening of PTS and developing risk-stratified treatment interventions so as to improve the outcome of children with VTE.     

Effect of postthrombotic syndrome on health-related quality of life after deep venous thrombosis

BACKGROUND: Postthrombotic syndrome (PTS) is a frequent chronic complication of deep venous thrombosis, yet its impact on health-related quality of life has not been well characterized. We compared generic and venous disease-specific quality of life in patients with and without PTS, and assessed whether quality of life correlated with severity of PTS. METHODS: Subjects with previous deep venous thrombosis were participants in a study of the effects of exercise after deep venous thrombosis. We ascertained PTS and its severity using a validated clinical scale. Subjects completed generic (the 36-Item Short-Form Health Survey) and disease-specific (Venous Insufficiency Epidemiologic and Economic Study quality-of-life questionnaire [VEINES-QOL] and its validated subscale of 10 items on venous symptoms [VEINES-Sym]) quality-of-life measures. Age- and sex-adjusted mean quality-of-life scores were compared in patients with and without PTS, and by severity of PTS. RESULTS: Of the 41 subjects (mean age, 51.2 years), 19 (46%) had PTS. Subjects with PTS had significantly worse disease-specific quality-of-life scores than those without PTS (mean +/- SD VEINES-QOL score, 44.5 +/- 11.6 vs 54.8 +/- 5.4, respectively [P<.001]; mean +/- SD VEINES-Sym score, 45.6 +/- 11.4 vs 54.1 +/- 6.7, respectively [P =.003]), which worsened significantly with increasing severity of PTS. We found no differences in generic quality-of-life scores between subject groups. CONCLUSIONS: Postthrombotic syndrome has a significant impact on disease-specific quality of life that may not be captured by generic quality-of-life measures. Patient-based quality-of-life measures correlated well with physician-assessed PTS. Further research is indicated to assess the value of including quality of life as a routine measure of outcome in clinical studies of patients with deep venous thrombosis and PTS.     

Acute effects of exercise in patients with previous deep venous thrombosis: impact of the postthrombotic syndrome

BACKGROUND: The postthrombotic syndrome (PTS) occurs frequently after deep venous thrombosis (DVT) and is believed to worsen with upright posture and physical activity. However, the effects of exercise in patients with previous DVT have not been studied. STUDY OBJECTIVES: To determine whether previous DVT and PTS limit the ability to exercise, and whether exercise increases the severity of venous symptoms and signs. DESIGN AND SETTING: A repeated-measures cohort study that was conducted at a university-affiliated teaching hospital, 1999-2000. PARTICIPANTS: Subjects with a first episode of unilateral DVT at least 1 year earlier were recruited from the Thrombosis Clinic (total, 41 subjects; with PTS, 19 subjects). INTERVENTION: Treadmill exercise session. Measurements and results: Venous symptoms, calf muscle fatigability, flexibility, and leg volume before and after treadmill exercise were measured and compared. Exercise did not worsen venous symptoms, despite a higher gain in affected leg volume in subjects with PTS vs subjects without PTS (mean difference: affected leg, 53 mL; unaffected leg, -15 mL; p = 0.018). Calf flexibility significantly improved after exercise in subjects with PTS (gastrocnemius: affected-unaffected, PTS vs no PTS + 4.5 degrees, p = 0.0029; soleus: affected-unaffected, PTS vs no PTS + 5.7 degrees, p = 0.0011). CONCLUSIONS: Exercise did not acutely exacerbate symptoms and, in subjects with PTS, resulted in improved flexibility in the affected leg. Our findings suggest that treadmill or similar exercise is unlikely to make symptoms of PTS worse, and may improve flexibility. Further study is indicated to determine whether a regular exercise-training program might have a role in the management of patients with PTS, since, to date, the treatment options for this condition are limited.     

Clinical study of late-stage postthrombotic lower extremities

Through clinical and venographic study of 353 diseased limbs, the authors advocate a new classification for the postthrombotic syndrome of the deep veins of the lower extremity. The postthrombotic lower extremities may be divided into two types: (1) lesions of the whole lower extremity, consisting of the completely obstructed, partially recanalized, and completely recanalized types; (2) local lesions, such as segmental obstruction of the iliac, iliofemoral, superficial femoral, femoropopliteal veins, and the tibioperoneal venous trunk and the venous plexus in calf muscles. Each type has its characteristics related to the duration of symptoms and clinical features, and their management is not the same at all. The authors suggest that clinically this new classification may be of great help in estimating the status of the diseased limb and in selecting proper method of treatment.     

A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of postthrombotic syndrome in children

Important predictors of adverse outcomes of thrombosis in children, including postthrombotic syndrome (PTS), have recently been identified. Given this knowledge and the encouraging preliminary pediatric experience with systemic thrombolysis, we sought to retrospectively analyze our institutional experience with a thrombolytic regimen versus standard anticoagulation for acute, occlusive deep venous thrombosis (DVT) of the proximal lower extremities in children in whom plasma factor VIII activity and/or D-dimer concentration were elevated at diagnosis, from within a longitudinal pediatric cohort. Nine children who underwent the thrombolytic regimen and 13 who received standard anticoagulation alone were followed from time of diagnosis with serial clinical evaluation and standardized PTS outcome assessments conducted in uniform fashion. The thrombolytic regimen was associated with a markedly decreased odds of PTS at 18 to 24 months compared with standard anticoagulation alone, which persisted after adjustment for significant covariates of age and lag time to therapy (odds ratio [OR] = 0.018, 95% confidence interval [CI] = < 0.001-0.483; P = .02). Major bleeding developed in 1 child, clinically judged as not directly related to thrombolysis for DVT. These findings suggest that the use of a thrombolysis regimen may safely and substantially reduce the risk of PTS in children with occlusive lower-extremity acute DVT, providing the basis for a future clinical trial.     

Thigh-length versus below-knee compression elastic stockings for prevention of the postthrombotic syndrome in patients with proximal-venous thrombosis: a randomized trial

Although below-knee compression elastic stockings (CES) are effective for the prevention of the postthrombotic syndrome (PTS), a substantial number of patients with deep venous thrombosis still develop PTS. In the present open-label, randomized clinical trial, we compared thigh-length with below-knee CES for the prevention of PTS. A total of 267 patients with the first episode of proximal deep venous thrombosis were randomized to wear either thigh-length or below-knee CES for 2 years. After 3, 6, 12, 18, 24, and 36 months, they were assessed for PTS manifestations according to the Villalta scale. PTS developed in 44 (32.6%) of the 135 patients randomized to thigh-length CES and in 47 (35.6%) of the 132 allocated to below-knee CES, for an adjusted hazard ratio of 0.93 (95% confidence interval, 0.62-1.41). Severe PTS developed in 3 patients in each group. CES-related side effects developed in 55 (40.7%) of the 135 patients allocated to thigh-length CES and in 36 (27.3%) of those randomized to the below-knee group (P = .017), and led to premature discontinuation of their use in 29 (21.5%) and 18 (13.6%) patients, respectively. We conclude that thigh-length CES do not offer a better protection against PTS than below-knee CES and are less well tolerated.     

Iliocaval vein stenting: Long term survey of postthrombotic symptoms and working capacity

To evaluate the long term effect on lower extremity function and working capacity after stenting of iliocaval vein segments for acute deep venous thrombosis (DVT) or chronic venous occlusive disease. During a 14 year period from November 1994 to October 2008, 114 patients with median age 36 (interquartile range [IQR], 27–48) years, 72 (63%) women, 72 (63%) with hypercoagulable disorders, with acute DVT (n = 44, 39%), or chronic occlusions (n = 70, 61%) in the iliocaval vein segment were treated with venous stent placement after catheter-directed thrombolysis, angioplasty or recanalization. The long term impact on lower extremity function and working capacity was evaluated through retrospective evaluation of a prospectively registered database in combination with a questionnaire sent to all 108 surviving patients. The questionnaire was returned by 91/108(84%) patients, 37 (86%) with acute DVT, and 54(83%) with chronic venous occlusions. After a median follow-up of 6.2 (IQR 3.8–10.5) years, 38 (42%) patients were without anticoagulation therapy. Among patients with acute DVT 29 (78%) reported no lower extremity pain, 31 (84%) reported no ulcerations, and 26 (70%) were without lower extremity swelling, and 33(89%) without pelvic or genital pain. In summary, 22 (59%) were free from any symptomatic postthrombotic symptoms (PTS). Among patients with chronic occlusions, corresponding figures were 22 (41%), 45 (80%), 13 (24%), 39 (72%), and 7 (13%). Among patients treated for acute DVT 27 (73%) were working full- or part time, and 2 (5%) were above retirement age. Corresponding figures among patients treated for chronic venous occlusions were 31 (57%), and 10 (19%). Stenting of iliocaval vein segments with or without catheter-directed thrombolysis is a promising treatment of both acute thrombosis and chronic iliocaval vein occlusion that requires further study in comparison to non-interventional treatment concerning long time effects on postthrombotic symptoms and working capacity.     

Appropriate level and length of postthrombotic warfarin treatment: an evaluation of recent developments

Current treatment and secondary prophylaxis of venous thromboembolism has two major drawbacks. During vitamin K antagonist therapy, patients need to be monitored closely to maintain efficacy and minimize the bleeding risk due to fluctuations of the prothrombin time (international normalized ratio, INR), and after cessation of therapy there is the problem of recurrent thrombosis, ie, the catch-up phenomenon. Recent studies indicate that for most patients, vitamin K antagonist therapy aimed at an INR of 2.0 to 3.0 is optimal. For patients with thrombosis due to a temporary risk factor, extending treatment beyond 3 months is not needed, whereas for other patients a minimal duration of 1 year can be advocated. For patients with cancer, it is beneficial to postpone therapy with vitamin K antagonists and prolong initial low-molecular-weight therapy for 3 to 6 months. New developments are aimed at further individualization of the duration of treatment and at the introduction of agents that are suitable for long-term treatment and do not require monitoring.     

The metabolic syndrome in polycystic ovary syndrome

Much overlap is present between the polycystic ovary syndrome (PCOS) and the metabolic syndrome. This article reviews the existing data regarding the prevalence, characteristics, and treatment of the metabolic syndrome in women with PCOS. The prevalence of the metabolic syndrome in PCOS is approximately 43-47%, a rate 2-fold higher than that for women in the general population. High body mass index and low serum HDL cholesterol are the most frequently occurring components of the metabolic syndrome in PCOS. The pathogenic link between the metabolic syndrome and PCOS is most likely insulin resistance. Therefore, the presence of the metabolic syndrome in PCOS suggests a greater degree of insulin resistance compared to PCOS without the metabolic syndrome. Obesity, atherogenic dyslipidemia, hypertension, impaired fasting glucose/impaired glucose tolerance, and vascular abnormalities are all common metabolic abnormalities present in PCOS. Lifestyle modification has proven benefit and pharmacological therapy with insulin-sensitizing agents has potential benefit in the treatment of the metabolic syndrome in women with PCOS.