How to predict and diagnose postthrombotic syndrome.

Postthrombotic syndrome (PTS) is the most frequent complication of deep vein thrombosis (DVT). From 20% to 50% of the patients will develop PTS after DVT, and from 5% to 10%, severe PTS. PTS is diagnosed on clinical grounds, based on the presence of signs and symptoms of venous insufficiency in the leg ipsilateral to DVT. The Villalta scale, a clinical scale that incorporates venous symptoms and signs, is a recommended standard for the diagnosis of PTS. 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. Clinical predictors of PTS have been progressively characterized, but the ability to predict which patient with DVT is likely to develop PTS remains limited. A number of risk factors for PTS have been identified; of these, proximal location of DVT and a previous ipsilateral DVT are the most important. This review discusses the knowledge gained over the last decade on the diagnosis and predictors of PTS.  

Post-thrombotic syndrome: prevention is better than cure.

Post-thrombotic syndrome (PTS) can be debilitating to patients and have a major economic impact on health-care services. It arises after deep venous thrombosis (DVT) due to residual venous obstruction or valvular reflux, leading to increased venous pressure in the microcirculation. While the inflammatory process at the time of DVT may aid thrombus resolution, it may also promote destruction of venous valves. The diagnosis of PTS is principally clinical and patients typically complain of leg heaviness, swelling, pain, itching, cramps, ulcer and signs of lipodermatosclerosis. Several clinical scales or classifications have been used but it is recommended that Villalta scale is the most suitable. Risk factors for PTS include a proximal DVT and recurrent thrombosis as well as obesity and prior varicose veins. Poor quality of anticoagulation control may also be a factor. Established PTS is usually managed along the same lines as chronic venous hypertension with compression therapy and leg elevation. Surgery has only a limited role but may benefit some patients. Further trials are desperately needed to define the role of acute thrombolysis and mechanical thrombectomy, which seem to be promising treatments in the studies to date. For patients who have had a DVT more attention should be given to prescribing and using compression hosiery.

[Treatment of postoperative thrombosis]. / Therapie der postoperativen Thrombose.

For the treatment of deep vein thrombosis (DVT), rapid diagnosis and prompt therapy are crucial to minimize the risk of fatal pulmonary embolism and long-term complications, including the postthrombotic syndrome and recurrent thromboembolism. The treatment of acute DVT remains controversial. In this review, treatment options in relation to exposing and predisposing risk factors are discussed. Evidence-based data and recommendations from official guidelines are presented.

Contemporary issues in the prevention and management of postthrombotic syndrome.

OBJECTIVE: To provide an evidence-based review and clinical summary of postthrombotic syndrome (PTS). DATA SOURCES: A literature review was performed via MEDLINE (1950-July 1, 2009) and International Pharmaceutical Abstracts (1970-June 2009) searches using the terms post-thrombotic syndrome, post-phlebitic syndrome, deep vein thrombosis, and compression stockings. DATA SYNTHESIS: PTS is best characterized as a chronic syndrome of clinical signs and symptoms including pain, swelling, parasthesias, and ulceration in the affected limb following deep vein thrombosis (DVT). It occurs in up to half of patients with symptomatic DVT, usually within the first 2 years. Although the pathophysiology of PTS is not well understood, a thrombus may cause venous hypertension and valvular incompetence resulting in edema, tissue hypoxia, and in severe cases, ulceration. Risk factors for PTS include recurrent ipsilateral DVT, obesity, and poor quality of anticoagulant therapy. PTS diagnosis is based on the presence of typical signs and symptoms and may be made using one of several clinical scoring systems. Prevention of PTS should focus on DVT prevention and the use of elastic compression stockings following DVT, while fibrinolysis remains under investigation as an effective method for PTS prevention. The treatment of PTS may include either pharmacologic or mechanical modalities, although none of these regimens has been rigorously tested. Pharmacists have the opportunity to provide more comprehensive antithrombotic management by educating patients and providers on PTS, recommending appropriate preventive therapy, assisting patients in obtaining and adhering to this therapy, and assisting providers with the management of PTS. CONCLUSIONS: Providers should be proactive in preventing PTS, with pharmacists taking an active role in optimal DVT prevention, identifying patients at risk for PTS, and counseling and directing preventive therapies.

Post-thrombotic syndrome after total hip arthroplasty is uncommon.

BACKGROUND: Deep vein thrombosis (DVT), usually asymptomatic, is common after total hip arthroplasty (THA). Post-thrombotic syndrome (PTS) is a potential late complication of DVT, but there is limited data on its occurrence. PATIENTS AND METHODS: This was a prospective cohort study of subjects at one hospital who had participated in a trial of thromboprophylaxis for THA and who had postoperative venography. Data were collected at baseline and 2-4 years later to ascertain symptoms of PTS using a modification of a validated scoring system. Outcomes were collected without knowledge of baseline characteristics or venogram results. Potential predictors of PTS were explored using exact logistic regression analyses. RESULTS: The cohort (n=188) had a mean age of 63 years, 51% were male, 35% had a BMI of>30, and 4% had a prior history of DVT. 25 patients (13%) had DVTs on venography. 12 patients (6%, 95% CI: 3-11) subsequently developed symptoms consistent with PTS, 7 with bilateral symptoms. Most affected limbs (15 of 19) had no postoperative DVT. No statistically significant predictors of PTS were found. INTERPRETATION: Symptoms of PTS are infrequent after THA in patients who receive some form of thromboprophylaxis. Our findings, which are consistent with the existing literature, suggest that there is a potential benefit to giving thromboprophylaxis for reduction of symptomatic PTS.

New anticoagulants for treatment of venous thromboembolism.

Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into 2 stages: Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This article (1) reviews the pharmacology of these agents, (2) outlines their potential strengths and weaknesses, (3) describes the results of clinical trials with these new drugs, and (4) identifies the evolving role of new anticoagulants in the management of VTE.

Effectiveness of compression stockings to prevent the post-thrombotic syndrome (the SOX Trial and Bio-SOX biomarker substudy): a randomized controlled trial.

BACKGROUND: Post thrombotic syndrome (PTS) is a burdensome and costly complication of deep venous thrombosis (DVT) that develops in 20-40% of patients within 1-2 years after symptomatic DVT. Affected patients have chronic leg pain and swelling and may develop ulcers. Venous valve disruption from the thrombus itself or thrombus-associated mediators of inflammation is considered to be a key initiating event for the development of venous hypertension that often underlies PTS. As existing treatments for PTS are extremely limited, strategies that focus on preventing the development of PTS in patients with DVT are more likely to be effective and cost-effective in reducing its burden. Elastic compression stockings (ECS) could be helpful in preventing PTS; however, data on their effectiveness are scarce and conflicting. METHODS/DESIGN: The SOX Trial is a randomized, allocation concealed, double-blind multicenter clinical trial. The objective of the study is to evaluate ECS to prevent PTS. A total of 800 patients with proximal DVT will be randomized to one of 2 treatment groups: ECS or placebo (inactive) stockings worn on the DVT-affected leg daily for 2 years. The primary outcome is the incidence of PTS during follow-up. Secondary outcomes are severity of PTS, venous thromboembolism (VTE) recurrence, death from VTE, quality of life and cost-effectiveness. Outcomes will be evaluated during 6 clinic visits and 2 telephone follow ups. At baseline, 1 and 6 months, blood samples will be obtained to evaluate the role of inflammatory mediators and genetic markers of thrombophilia in the development of PTS (Bio-SOX substudy). DISCUSSION: The SOX Trial will be the largest study and the first with a placebo control to evaluate the effectiveness of ECS to prevent PTS. It is designed to provide definitive data on the effects of ECS on the occurrence and severity of PTS, as well as DVT recurrence, cost-effectiveness and quality of life. This study will also prospectively evaluate the predictive role of biomarkers that are reflective of putative underlying pathophysiological mechanisms in the development of clinical PTS. As such, our results will impact directly on the care of patients with DVT. TRIAL REGISTRATION: NCT00143598 and ISRCTN71334751.

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.

Late results of catheter-directed recombinant tissue plasminogen activator fibrinolytic therapy of iliofemoral deep venous thrombosis.

PURPOSE: To evaluate the efficacy of catheter-directed low-dose recombinant tissue-type plasminogen activator infusion in the treatment of iliofemoral deep venous thrombosis and prevention of post-thrombotic syndrome. METHOD: Eighteen patients (out of 260 evaluated) with acute iliofemoral deep venous thrombosis and no previous evidence of venous insufficiency were prospectively selected for thrombolytic therapy. Catheter-directed low-dose recombinant tissue-type plasminogen activator (1 mg/h) was infused into the thrombotic segments. RESULTS: Effective fibrinolysis was achieved in 14 of 18 cases, with correlation between effective fibrinolysis and major/complete resolution of acute signs and symptoms (P <.01). There were no episodes of major complications. Four patients presented with early rethrombosis (1 to 8 weeks). Individuals were followed for a period up to 131 weeks (average, 85.2). The incidence of clinical signs and symptoms of venous insufficiency and duplex-scan findings of valvular reflux was significantly lower in the patients in which lytic therapy succeeded and patency was kept, compared with patients experiencing acute therapeutic failure or rethrombosis (P <.01). CONCLUSIONS: Low-dose recombinant tissue-type plasminogen activator fibrinolytic therapy is safe and effective in the treatment of acute iliofemoral venous thrombosis. The late evolution as revealed clinically and by ultrasound was superior in patients for whom lytic therapy was effective.

Diagnóstico y tratamiento de la trombosis venosa profunda / No disponible

La trombosis venosa profunda (TVP) es un proceso frecuente que causa complicaciones como el síndrome postfl ebítico y el embolismo pulmonar, que puede ser mortal. En la actualidad un algoritmo que combina la probabilidad clínica, el dímero D y la ecografía venosa permite una estimación adecuada y no invasiva de la TVP. La base del tratamiento inicial de la TVP es la anticoagulación, fundamentalmente con heparinas de bajo peso molecular o pentasacárido (fondaparinux) que permiten el manejo ambulatorio de forma efi caz y segura. La duración del tratamiento depende de si la TVP es idiopática o secundaria a un factor de riesgo transitorio. La trombolisis y el empleo de fi ltro en la vana cava se reservan para situaciones especiales

Deep-vein thrombosis (DVT) is a common condition that can lead to complications such as postphlebitic syndrome, pulmonary embolism and death. Currently, an algorithm strategy combining pretest probability, D-dimer testing and compression ultrasonography imaging allows for safe and convenient estimation of suspected lower-limb thrombosis. The mainstay of treatment is anticoagulation therapy. The use of lowmolecular- weight heparin or pentasaccharide (fondaparinux) allows for outpatient management of most patients with DVT. The duration of anticoagulation depends on whether the primary event was idiopathic or secondary to a transient risk factor. Interventions such as thrombolysis and placement of inferior vena cava fi lter are reserved for special situations

Late results of catheter-directed recombinant tissue plasminogen activator fibrinolytic therapy of iliofemoral deep venous thrombosis

PURPOSE: To evaluate the efficacy of catheter-directed low-dose recombinant tissue-type plasminogen activator infusion in the treatment of iliofemoral deep venous thrombosis and prevention of post-thrombotic syndrome. METHOD: Eighteen patients (out of 260 evaluated) with acute iliofemoral deep venous thrombosis and no previous evidence of venous insufficiency were prospectively selected for thrombolytic therapy. Catheter-directed low-dose recombinant tissue-type plasminogen activator (1 mg/h) was infused into the thrombotic segments. RESULTS: Effective fibrinolysis was achieved in 14 of 18 cases, with correlation between effective fibrinolysis and major/complete resolution of acute signs and symptoms (P <.01). There were no episodes of major complications. Four patients presented with early rethrombosis (1 to 8 weeks). Individuals were followed for a period up to 131 weeks (average, 85.2). The incidence of clinical signs and symptoms of venous insufficiency and duplex-scan findings of valvular reflux was significantly lower in the patients in which lytic therapy succeeded and patency was kept, compared with patients experiencing acute therapeutic failure or rethrombosis (P <.01). CONCLUSIONS: Low-dose recombinant tissue-type plasminogen activator fibrinolytic therapy is safe and effective in the treatment of acute iliofemoral venous thrombosis. The late evolution as revealed clinically and by ultrasound was superior in patients for whom lytic therapy was effective.

OBJETIVOS: Avaliar a eficácia da infusão seletiva por cateter do ativador de plasminogênio tecidual recombinante em baixas doses no tratamento da trombose venosa iliacofemoral e na prevenção da síndrome pós-trombótica. MÉTODO: Dezoito pacientes (de 260 avaliados) portadores de trombose venosa profunda iliacofemoral sem evidência prévia de insuficiência venosa foram selecionados para terapia fibrinolítica e submetidos a infusão seletiva por cateter do ativador de plasminogênio tecidual recombinante na dose de 1mg/dl nos segmentos venosos trombóticos. RESULTADOS: Quatorze pacientes apresentaram fibrinólise efetiva; observamos correlação entre o grau de melhora clínica observado e a redução percentual do volume trombótico (P<.01). Não houve episódios de complicações graves. Quatro pacientes apresentaram retrombose precoce (1 a 8 semanas). Os pacientes foram seguidos por um período de até 131 semanas (média 85.2). A incidência de sinais e sintomas clínicos de insuficiência venosa e os achados ecográficos de refluxo valvular foram significativamente menores nos pacientes em que a terapia fibrinolítica foi efetiva e a perviedade mantida ao longo do período de seguimento, na comparação com os casos de falha aguda ou de retrombose precoce (P<.01). CONCLUSÕES: A terapia fibrinolítica da trombose venosa iliacofemoral com ativador de plasminogênio tecidual recombinante seletivo em baixas doses demonstrou-se eficaz e segura. A evolução clínica e ecográfica tardia foi superior nos pacientes em que a terapia lítica foi efetiva.

New technology applications: thrombolysis of acute deep vein thrombosis.

Treatment of deep vein thrombosis traditionally has focused on preventing the potentially life-threatening complication of pulmonary embolism rather than on removing or reducing the thrombus. Although treatment with anticoagulants may prevent thrombus propagation, the body's intrinsic thrombolytic system is left to attempt clot dissolution. Because this natural process is generally ineffective in its ability to fully recanalize a proximal vein, the risks of recurrent thrombosis as well as the disabling complication of postthrombotic syndrome increase. Moreover, the long-term consequences of postthrombotic syndrome include pain, disability, and, for many, a significant decrease in the quality of life. Recent technology using high-frequency, low-power ultrasound, or mechanical thrombectomy with catheter-directed delivery of a thrombolytic drug directly into the clot is available and showing promise. Nurses are caring for patients who receive endovascular interventions with lytic infusions. The nursing challenge is to provide safe and effective patient care.

Review on the value of graduated elastic compression stockings after deep vein thrombosis.

Graduated elastic compression stockings (GECS) are commonly used in the primary prevention of deep vein thrombosis (DVT); however, their role in preventing recurrent DVT and also post-thrombotic syndrome is less well established. The aim of this review was to investigate the effect of GECS after DVT. A literature search was performed by two independent searchers in order to identify randomised controlled trials on the effect of GECS in preventing recurrent DVT and post-thrombotic syndrome. Four randomised trials, including 537 patients, were identified. Two of the studies demonstrated that below-knee GECS significantly reduced post-thrombotic syndrome during follow-up, while a smaller study showed equivocal results. GECS reduced the incidence of post-thrombotic syndrome from 54% to 25.2% [relative risk (RR) 0.47, 95% confidence interval (CI) 0.36-0.61] with the number needed to treat (NNT) being 4 (95% CI 2.7-5.0). The rate of recurrent asymptomatic DVT was also significantly reduced by GECS (RR 0.20, 95% CI 0.06-0.64; NNT 5); the reduction in symptomatic DVT was not significant (RR 0.79, 95% CI 0.50-1.26; NNT 34). In conclusion, there is level Ia evidence to suggest that GECS can significantly reduce the incidence of post-thrombotic syndrome (PTS) after DVT, and therefore these should be routinely prescribed. The evidence for recurrent DVT is less conclusive. Further research is needed towards standardising PTS diagnostic criteria and evaluating more effective preventive measures after DVT.

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.

The post-thrombotic syndrome: progress and pitfalls.

The post-thrombotic syndrome (PTS) develops in up to one half of patients after symptomatic deep venous thrombosis (DVT) and is the most common complication of DVT. Typical features of PTS include chronic pain, swelling, heaviness, oedema and skin changes in the affected limb. In severe cases, venous ulcers may develop. The frequency of PTS is likely to be reduced by preventing DVT with the use of effective thromboprophylaxis in high-risk patients and settings and by minimising the risk of ipsilateral DVT recurrence. Use of compression stockings for 2 years after DVT appears to reduce the incidence and severity of PTS but issues remain regarding their use and effectiveness. Future research should focus on elucidating the pathophysiology and risk factors for PTS, assessing the safety and effectiveness of catheter-directed thrombolysis to prevent PTS and evaluating the optimal use of compression stockings to prevent and treat PTS. In addition, new therapies to treat PTS should be sought and evaluated.

A new method for aggressive management of deep vein thrombosis: retrospective study of the power pulse technique.

Failure to treat deep vein thrombosis (DVT) is associated with significant morbidity and mortality. Anticoagulation, although effective at preventing clot progression, is not able to prevent postthrombotic syndrome. Catheter-directed thrombolysis is a more aggressive alternative, with some small studies suggesting a better long-term outcome, but the associated risks are significant, and the treatment can require 2-3 days in a monitored setting. This report describes the power pulse technique, in which mechanical thrombectomy is combined with thrombolytic agents to maximize the effectiveness of the treatment and reduce the need for prolonged infusion and its associated risks. A 24-patient retrospective study showed complete thrombus removal (>90%) in 12 patients, substantial thrombus removal (50%-90%) in seven patients, and partial thrombus removal (<50%) in five patients. All 24 patients had resolution of presenting symptoms. Only two patients required blood transfusion, and one patient experienced temporary nephropathy.

Compression with or without early ambulation in the prevention of post-thrombotic syndrome: a systematic review.

INTRODUCTION: The aim of this study was to assess whether there is enough evidence to suggest that compression with or without early ambulation after proximal DVT reduces the risk of post-thrombotic syndrome (PTS). METHODS: Systematic review based on electronic and hand searching of the relevant literature. RESULTS: Four randomized studies were identified and despite the fact that there was lack of uniformity in reporting standards all but one showed significant risk reduction of PTS using compression. No difference in recurrent thromboembolic events (DVT or pulmonary embolism) was observed between the compression and control group. In one study the early outcome from the combination of early ambulation with compression was faster reduction of swelling with better well-being without increased risk of PE compared to the control group. Pooled analysis of all studies showed that PTS developed in 24% (61/254) in the compression group and in 46% (110/239) in the control group (chi2=25.36, p=0.0001; OR: 0.37, 95%CI: 0.25, 0.54; RR: 0.52, 95%CI: 0.40, 0.67; and RRR: 0.48, 95%CI: 0.33, 0.60) with a 48% risk reduction from the use of compression. CONCLUSION: Despite the fact that compression with or without early ambulation appears to be safe and it is more often associated with a decreased rate of PTS, the four existing studies do not permit meaningful data comparison due to lack of uniformity in reporting standards.

A cost analysis of the treatment of patients with post-thrombotic syndrome in Brazil.

INTRODUCTION: Post-thrombotic syndrome (PTS) occurs in 15-50% of patients with deep vein thrombosis (DVT), and is associated with substantial medical costs. This prospective observational study investigated the costs associated with the treatment of PTS in Brazil. MATERIALS AND METHODS: A total of 157 patients diagnosed with PTS and with a history of DVT were recruited from nine centers in Brazil. The costs of investigations and treatment for PTS over a 1-year follow-up period were analyzed. Ninety patients were available for this analysis. RESULTS: Of the 90 patients, 17 had mild-to-moderate PTS, and 73 had severe PTS. The patients with severe PTS tended to undergo more investigations and hospitalizations for PTS than those with mild-to-moderate PTS, although the differences between the two groups did not reach statistical significance. The mean annual cost of treating PTS in Brazilian Reais was 1214 R dollars (426 US dollars) for mild-to-moderate PTS and 3386 R dollars (1188 US dollars) for severe PTS. The difference was mainly due to significantly higher hospitalization costs in patients with severe PTS (704 R dollars/247 US dollars vs. 0 R dollars; p=0.044). CONCLUSION: These results suggest that PTS imposes substantial demands on health care resources in Brazil. The implementation of effective thromboprophylactic strategies could significantly reduce the incidence of DVT, and hence of PTS, potentially resulting in significant cost savings.