Severe Post-thrombotic Syndrome Research Articles

An uncommon clinical condition: chronic thrombosis of the inferior vena cava. A case report and review of literature

The lifetime incidence of deep vein thrombosis (DVT) is approximately 0.1% in general population and even more uncommon in subjects below 40 years of age. Thrombosis of the inferior vena cava (IVC) is an exceptionally rare clinical condition, with etiological factors similar to lower limb DVT. We present a case of post-traumatic chronic obstruction of the IVC in 41 years-old man, caused by a prolonged squatted position, while he was working as a bricklayer. We visited the patient fifteen years after the onset of the first clinical setting showing a severe post thrombotic syndrome, as a consequence of the already diagnosticated thrombosis, involving predominantly the right inferior leg. Thrombophilia screening tests showed patient to be a heterozygous carrier of methylenetetrahydrofolate reductase (MTHFR) gene mutation. Computed tomography (CT) scan confirmed the thrombotic obstruction of the infrahepatic IVC, both common iliac veins, right external and internal iliac veins, with multiple collateral pathways. Because of thrombosis extension, inherited prothrombotic condition and the young age of the patient, we decided to continue life-long oral anticoagulant therapy.

Clinical and Ultrasonographic Evaluation of Lower-extremity Vein Thrombosis in Behcet Syndrome

Vascular involvement can be seen in up to 40% of patients with Behcet syndrome (BS), the lower-extremity vein thrombosis (LEVT) being the most common type. The aim of the current study was to compare venous Doppler findings and clinical features between BS patients with LEVT and control patients diagnosed as having LEVT due to other causes.All consecutive 78 patients (71 men, 7 women; mean age 38.6 ± 10.3 years) with LEVT due to BS and 50 control patients (29 men, 21 women; mean age 42.0 ± 12.5 years) who had LEVT due to other causes, or idiopathic, were studied with the help of a Doppler ultrasonography after a detailed clinical examination. Patterns of venous disease were identified by cluster analyses. Clinical features of chronic venous disease were assessed using 2 classification systems. Venous claudication was also assessed.Patients with BS were more likely to be men, had significantly earlier age of onset of thrombosis, and were treated mainly with immunosuppressives and less frequently with anticoagulants. Furthermore, they had significantly more bilateral involvement, less complete recanalization, and more frequent collateral formation. While control patients had a disorganized pattern of venous involvement, BS patients had a contiguous and symmetric pattern, involving all deep and superficial veins of the lower extremities, with less affinity for crural veins. Clinical assessment, as measured by the 2 classification systems, also indicated a more severe disease among the BS patients. In line, 51% of the BS patients suffered from severe post-thrombotic syndrome (PTS) and 32% from venous claudication, whereas these were present in 8% and 12%, respectively, among the controls. Among BS patients, a longer duration of thrombosis, bilateral femoral vein involvement, and using no anticoagulation along with immunosuppressive treatment when first diagnosed were found to be associated independently with severe PTS.Lower-extremity vein thrombosis associated with BS, when compared to LEVT due to other causes, had distinctive demographic and ultrasonographic characteristics, and had clinically a more severe disease course.

Excellent long-term results with iliac stenting in local anesthesia for post-thrombotic syndrome.

BackgroundOnly 20% of iliac veins will recanalize on anticoagulation (AC) treatment alone and may, therefore, develop venous obstruction after iliofemoral deep venous thrombosis (DVT). A considerable number of these patients will suffer from post-thrombotic syndrome (PTS) leading to impaired quality of life in more than 50%. Endovascular treatment for iliac vein obstruction using stents is known to alleviate PTS symptoms in selected patients.PurposeTo report the Danish long-term results of endovascular treatment with iliac stenting.Material and MethodsFrom 2000 to 2013 consecutive patients were evaluated and 19 patients with severe venous claudication were identified and subsequently underwent angioplasty and stenting. AC treatment was prescribed for 6 months, and knee-high class II compression stocking recommended for 1 year. Scheduled follow-up was done in the outpatient clinic at 6 weeks, 3 months, and annually thereafter.ResultsNineteen patients, all women, all with left-sided iliac vein obstruction, and all with severe PTS symptoms were included. The median follow-up time was 81 months (range, 1–146 months; mean, 69 months). Primary patency rate of the inserted iliac stent was 89% (17/19) and 16 patients (84 %) had almost or total symptom relief at follow-up.ConclusionEndovascular stenting of iliac obstruction in local anesthesia is minimally invasive and shows excellent long-term outcomes for patients suffering from PTS.

A Multicenter, Retrospective Study of the Effectiveness of the Trellis-8 System in the Treatment of Proximal Lower-Extremity Deep Vein Thrombosis

Deep vein thrombosis (DVT) occurs in up to 600,000 patients in the United States annually and can lead to long-term morbidity because of the post-thrombotic syndrome. The multicenter isolated-pharmacomechanical thrombolysis device (ISOL-8) study was designed to determine the safety and efficacy of the Trellis™-8 peripheral infusion system when used as the primary intervention to achieve DVT thrombolysis in patients with proximal lower-extremity occlusive DVT, and track the incidence and severity of the post-thrombotic syndrome (PTS) symptoms in patients 2 years after treatment. Data were collected retrospectively from 6 centers on patients treated with the Trellis-8 system, an isolated-pharmacomechanical thrombolysis device (IPMTD). Patients with occlusive lower-extremity DVT involving at least the iliac and/or common femoral vein were included. Patient demographics, medical history, procedure outcomes, complications, and follow-up venous duplex and Venous Clinical Severity Score (VCSS) were collected through 24 months. Data analysis of outcomes were performed at 1 and 12 months. A 24-month analysis was not performed because of the small number of patients for whom 24-month data could be collected. A total of 151 limbs in 139 patients were treated with IPMTD. The mean ± standard deviation (SD) procedure time was 122.6 ± 63.4 min. Single session treatment was delivered in 69.9% (93 of 133) of cases. Occlusive DVT extended from the femoral into the external and/or common iliac vessel segments in most of the cases (113 of 151 limbs; 74.8%). Before treatment, 23.2% (35 of 151) of the treated limbs, based on a history of prior ipsilateral DVT or preoperative imaging revealing chronic venous scar, were expected to have some chronic venous disease despite presenting with acute symptoms. After treatment, 43.7% (66 of 151) of the limbs showed evidence of chronic thrombus. The average amount (mean ± SD) of thrombolysis, as determined by venogram, was highest in patients who had acute thrombus (81 ± 19.7%), compared with subacute thrombus (61 ± 22.5%) and complex cases involving acute and/or subacute thrombus on chronic scar (56 ± 26.5%). VCSS scoring showed the number of patients with none and/or mild pain, varicose veins, and skin changes at 1-month remained stable at 12 months whereas the percent of patients with none and/or mild venous edema improved from 71.7% at 1 month (38 of 53) to 86.8% (46 of 53) at 12 months. Twenty-four-month follow-up data were available for only 15% (23 of 151) of patients. No clinically significant pulmonary emboli or major periprocedural bleeding events were reported. Patients with acute lower-extremity DVT involving the proximal veins can be safely and successfully treated with IPMTD. Major procedural bleeding was absent. The occurrence of severe PTS after primary treatment with Trellis-8 system IPMTD is low. Further long-term follow-up data are needed to confirm the benefit of intervention for thrombus removal compared with standard medical management.

Compression Therapy in the Prevention of Postthrombotic Syndrome: A Systematic Review and Meta-Analysis.

Although compression therapy has been widely used after deep vein thrombosis (DVT), its efficacy in prevention of postthrombotic syndrome (PTS) remains disputable. We aimed to update the meta-analysis to comprehensively evaluate the effect of compression therapy on the prevention of PTS in adult patients after DVT.PubMed, Embase, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) evaluating the preventive effect of compression therapy on PTS in adult patients after DVT were included. The primary outcome was the incidence of PTS. All meta-analyses were performed using random-effects models regardless of the heterogeneity. Subgroup and sensitivity analysis were also performed to examine the robustness of the pooled effects according to our predesigned plan. Potential publication bias was assessed.Eight RCTs with 1598 patients were included. Overall, compression therapy could significantly reduce the incidence of PTS (estimate 0.68, 95% confidence interval [CI] 0.52-0.90; P = 0.007). However, it was only associated with a reduction in the incidence of mild/moderate PTS (relative risk [RR] 0.66, 95% CI 0.46-0.93; P = 0.019) but not in the incidence of severe PTS (RR 0.64, 95% CI 0.27-1.50; P = 0.31). Additionally, compression therapy failed to reduce the incidence of recurrent venous thromboembolism (RR 0.91, 95% CI 0.65-1.27; P = 0.58), the incidence of ulceration (RR 0.74, 95% CI 0.36-1.53; P = 0.42), or mortality (RR 0.99, 95% CI 0.72-1.37; P = 0.96). No publication bias was observed.Current evidence still supports compression therapy to be a clinical practice for prophylaxis of PTS in adult patients after DVT. However, our findings should be cautiously interpreted because of heterogeneity and hence more large-scale and well-designed RCTs are still warranted.

Does prescription of medical compression prevent development of post-thrombotic syndrome after proximal deep venous thrombosis?

The aim of this review is to try to explain the controversy by critical analysis of previously published randomized controlled trials on the value of elastic compression stockings in the treatment of acute proximal deep vein thrombosis in prevention of post-thrombotic syndrome, which forms the scientific basis for our present management. A research was made through Medline and Embase databases to identify relevant original articles, not abstracts, with the following keywords: post-thrombotic syndrome, deep venous thrombosis, venous thromboembolism, compression stockings, prevention and compliance. We identified five randomized controlled trials (RCTs) before the SOX trial including 798 patients with acute proximal deep vein thrombosis. Brandjes (1997): at two years' follow-up, elastic compression stockings reduced post-thrombotic syndrome by 50%;Ginsberg (2001): no difference in post-thrombotic syndrome with or without elastic compression stockings after more than two years' follow-up;Partsch (2004): elastic compression stockings with routine above knee and early ambulation reduced the incidence and severity of post-thrombotic syndrome after two years' follow-up;Prandoni (2004) showed significantly less post-thrombotic syndrome after elastic compression stockings for two years with a five-year follow-up;Aschwanden (2008) showed no difference with elastic compression stockings after three years' follow-up. Prescription of elastic compression stockings for the prevention of post-thrombotic syndrome is now in doubt. Immediate compression after diagnosis of acute deep vein thrombosis to prevent swelling and reduce pain, permitting early ambulation in combination with adequate anticoagulation has proven benefit, although a secondary analysis of the SOX trial refutes this belief. Continued long-term compression treatment is questioned. Two major questions remain:Is the lack of positive outcome on the development of post-thrombotic syndrome after proximal deep vein thrombosis due to the fact that there were a few patients with iliofemoral extension in the quoted randomized controlled trials who may benefit from prolonged medical compression treatment?Compliance is the major issue, and the two randomized controlled trials with excellent control of compliance showed significant reduction in the rate of post-thrombotic syndrome, but we know that in daily practice the adherence is closer to Kahn's data.

Clinical Assessment of Endovascular Stenting Compared with Compression Therapy Alone in Post-thrombotic Patients with Iliofemoral Obstruction

The study aimed to evaluate the clinical results of stent placement in post-thrombotic patients with iliofemoral obstruction compared with results in those treated with elastic compression stockings (ECS). A retrospective analysis of post-thrombotic patients with iliofemoral obstruction was conducted in a single institution from January 2007 to December 2012. Duplex ultrasound and selective phlebography were performed in patients with chronic venous disease and previous deep venous thrombosis (DVT). Post-thrombotic syndrome (PTS) with iliofemoral vein obstruction (Villalta score ≥10) was diagnosed in 216 patients. Among these, 122 patients were treated by stent placement, and the remaining 94 patients were treated conservatively with 30-40 mmHg ECS therapy. Technical success, stent patency rates, and complications were recorded after the interventions. Results including Villalta score, pain, edema, ulcer, and popliteal vein reflux were assessed in both groups. Percutaneous iliofemoral venous stenting was successful in 116 of 122 patients (95.1%) without major complications. Follow up periods ranged from 3 to 58 months (median 21 months). Cumulative primary, assisted primary, and secondary stent patency rates at 3 years were 68.9%, 79.0%, and 91.6%, respectively. Among patients with severe PTS, the Villalta score decreased significantly with endotreatment, compared to the score of those treated by ECS therapy (16.12 ± 4.91 vs. 10.98 ± 5.89, p < .01). However, there was no significant score improvement between the two therapies in patients with moderate PTS (6.59 ± 2.37 vs. 5.75 ± 3.03, p = .22). There was a significantly higher 24 month recurrence free ulcer healing rate in the endotreatment groups (86.6% vs. 70.6%, p < .01). Both edema and pain improved significantly in the two groups. The popliteal vein reflux rate showed no significant change after endotreatment. Endovascular treatment is a safe, effective, and feasible method to correct the iliofemoral obstruction of PTS. Only post-thrombotic patients with severe PTS as assessed by the Villalta score appear to benefit from the endovascular treatment.

Severe Post Thrombotic Syndrome Is Associated to Lower Echogenicity of the Residual Venous Thrombosis

Introduction: The post-thrombotic syndrome (PTS) is a common chronic complication of deep venous thrombosis (DVT) of the lower limbs and may occur even after an appropriate anticoagulant treatment. PTS may develop in the first two years after DVT in about 20-50% of patients; 5–10% of those may present severe manifestations of the disease. PTS is associated to an increased risk for DVT recurrence, morbidity, poor quality of life and significant cost to public health. The diagnosis of PTS is performed by clinical evaluation; particularly, the Villalta scale is recommended by the ISTH for PTS diagnosis and severity evaluation. The PTS-associated medical conditions are poorly understood, and it seems that hypercoagulability and inflammation, after the first episode of DVT, may play an important role in the disease development. Therefore, we performed a comprehensive analysis of clinical parameters, inflammation and ultrasound (US) examination of the affected limb in patients with history of previous DVT and PTS.Objective: The aim of this study was to evaluate possible medical conditions associated to PTS and its severity.Material and Methods: Between February 2013 and October 2013, consecutive patients with history of previous unprovoked DVT of lower limbs (> 6 months from the diagnosis), attended at the Hematology Center of the University of Campinas, Brasil, were included. Patients were submitted to physical evaluation for body mass index (BMI) determination and PTS diagnosis, by Villalta scale. Levels of the IL-8, IL-6 and TNF-α were performed by ELISA, D-dimer by turbidimetry and CRP by nephelometry. US examination was performed by duplex. In patients with residual venous thrombosis (RVT), the thrombus echogenicity was determined by grayscale median (GSM) evaluation, as described for atherosclerotic plaques. The GSM analysis was performed by a computer based US using specific software. Only the region containing the thrombus was analyzed, the image was depicted manually point by point to trace the line surrounding the thrombus, the final GSM values were automatic calculated and translated the thrombus echogenicity. A low GSM value (<25) suggests acute thrombosis and a high GSM vlaue (> 25) suggest subacute thrombosis.. Continuous variables were analyzed by Kruskal-Wallis test and categorical variables were compared using the Fisher´ s exact test.Results: From the 56 patients included, 15 did not present PTS, 23 were classified as mild, 11 as moderate and 7 as severe PTS. Serum levels of CRP was significantly higher in patients with severe PTS when compared to patients with mild+moderate PTS and to those without PTS (respectivelly 0.64mg/dL, 0.31mg/dL and 0.13mg/dL; P=0.02).Serum levels of IL-6 and TNF-α were higher in patients with severe PTS compared to patients with mild/moderate PTS and without PTS (IL-6= 2.81pg/mL vs. 1.48pg/mL vs. 0.80pg/mL respectively, and TNF 1.68pg/mL vs. 1.33pg/mL vs 1.17pg/mL respectively), however the differences did not reach statistical significance. Levels of IL-8 and DD were similar between severe PTS and the other two groups. The presence of RVT was similar between groups, however US-generated GSM was significantly lower in patients with severe PTS compared to patients with mild+moderate PTS and patients without PTS (GSM= 22, 31 and 28.5, respectively; P=0.04). As predicted, the BMI was also higher in patients with severe PTS when compared to mild+moderate PTS and no PTS group (BMI= 34,8 vs. 29,3 vs. 25,9, respectively P=0.007).Conclusion: Our results suggest that severe PTS may be associated with a chronic inflammatory response, characterized by obesity and higher levels of CRP. Besides, we could also observe that severe PTS may be associated with the persistence of a hypoechoic residual thrombus, determined by lower US-generated GSM values. The finding about the persistence of a hypoechoic thrombus in patients with severe PTS, even long time after the acute thrombosis event, is new and may possibly suggest that an adequate thrombus organization process is required to avoid the development of PTS. DisclosuresNo relevant conflicts of interest to declare.

Cirugía de la trombosis venosa profunda iliofemoral: postura en contra

The iliofemoral location of a deep vein thrombosis (DVT) is particularly serious, as it affects the single drainage stem of the lower limb. Treatment with anticoagulatants alone is often insufficient in preventing severe post-thrombotic syndrome, due to frequent incomplete thrombus resolution. While new thrombectomy techniques are capable of achieving patency of the iliofemoral venous system in a higher percentage of cases than previous techniques, they have not been compared with the current standard of treatment, which is the catheter-directed thrombolysis. This catheter-directed thrombolysis also can be combined with mechanical thrombolysis, increasing its effectiveness. A clinical trial is currently in the recruiting phase and it will assess the most efficient dose of alteplase in catheter-directed thrombolysis in patients with iliofemoral DVT, and the possibility of increasing its effectiveness with mechanical methods.

Tratamiento recanalizador de las trombosis venosas del sector iliofemoral

Patients with DVT affecting the iliac veins develop a more severe post-thrombotic syndrome. This has been traditionally treated with anticoagulation alone, based on outdated experiences.Contemporary venous thrombectomy, intrathrombus thrombolysis, and pharmaco-mechanical thrombolysis can be offered with increasing safety.Thrombus removal offers better long-term outcomes than anticoagulation alone.In the literature, including our own experience, venous stenting techniques have zero mortality and low complication rates. In stenosis or thrombotic stent occlusions it is almost zero. Patency is almost 100% in non-post thrombotic lesions, 74-89% in post-thrombotic non-occlusive lesions, and 66-90% in chronic occlusions.In patients with iliofemoral DVT without contraindication, thrombus removal should be attempted.Surgical thrombectomy should be considered when lytic therapy is contraindicated, and in phlegmasia.Thrombolytic therapy, mechanical thrombectomy, and angioplasty and stenting are the treatments of choice of iliac vein DVT. They are safe and can be performed with high long-term patency rates, especially if used in the acute phase.

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.

Efficacy of a short course of complex lymphedema therapy or graduated compression stocking therapy in the treatment of post-thrombotic syndrome

Treatment options for established post-thrombotic syndrome (PTS) are limited. Complex lymphedema therapy (CLT), a non-invasive treatment that improves lymphatic flow, may have the potential to improve PTS. We conducted a single-center, investigator-blind, randomized controlled trial of 31 patients with a clinically established diagnosis of PTS and compared the efficacy of graduated compression stockings alone (30-40 mmHg) with CLT, a treatment that includes compression stockings, exercise, patient education, skin care and lymphatic drainage. Primary outcomes were the 1- and 3-month changes in PTS severity by the Villalta score and disease-specific quality of life using the VEINES-QOL (Venous Insufficiency Epidemiological and Economic Study Quality of Life) questionnaire. Analysis was by intent-to-treat. We found from a baseline average score of 9.9 points, CLT reduced mean PTS severity scores by -2.4 points (p=0.02) at the 1-month and -2.3 points (p=0.05) at the 3-month follow-up. Score reductions with stockings only were similar at -2.1 (p=0.03) and -3.3 points (p=0.03) at 1 and 3 months. The differences in score between treatments were not significant. Neither treatment significantly changed the VEINES-QOL score except in patients with severe disease. Patients with moderate to severe PTS derived the greatest benefit from either therapy and the two therapies differentially impacted PTS signs and symptoms. We found a short course of lymphedema therapy and compression stockings offer similar benefit in patients with PTS; however, larger studies are needed to further explore the potential use of CLT in PTS, particularly in patients with more severe disease. ClinicalTrials.gov Identifier: NCT00633971.

Health-related quality of life in children and young adults with post-thrombotic syndrome: Results from a cross-sectional study

While post-thrombotic syndrome (PTS) is increasingly recognized in children with a history of deep vein thrombosis (DVT), its impact on the health-related quality of life (HRQoL) is unknown. Our objective was to evaluate the association between the PTS and HRQoL by surveying a cohort of patients treated at our institution for DVT. All unique pediatric patients (0-18 years) treated for a DVT at the Mayo Clinic during the 15-year period, 1995-2009 were identified. A previously validated PTS survey instrument and age appropriate Pediatric Quality of Life inventory, version 4 (PedsQL 4.0) were mailed to eligible patients. Linear regression models were fit to compare the HRQoL scores between PTS groups (none, mild, moderate/severe), after adjusting for the presence of potential covariates. Of the 90 respondents, 65 (72%) reported signs and/or symptoms of PTS. Mean age (± SD) at DVT diagnosis and survey completion were 12.8 (± 6.1) and 19.3 (± 7.7) years, respectively. Self-report PedsQL 4.0 module was completed by 79 patients, and 34 guardians completed the parent-proxy module. Patients with moderate to severe PTS reported significantly worse total HRQoL score (mean ± SD, 71.3 ± 13.4) as compared to patients with mild PTS (84.8 ± 14.2) and no PTS (83.4 ± 14) (P = 0.001). Moderate to severe PTS has a significant impact on self-reported HRQoL as measured using the generic PedsQL 4.0. Further research is warranted to develop a venous disease-specific quality of life measure for children with a history of DVT.

Biomarkers for post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is a serious condition that occurs in 20%-50% of patients following deep venous thrombosis (DVT). Biomarkers can be of use in further exploring the etiology as well as in developing risk stratification tools for PTS. The relationship between PTS and specific biomarkers may help guide prevention and therapy based on a patient's individual risk profile. This review gives an overview of the current knowledge on biomarkers in relation to PTS. A systematic search was executed in three databases (Pubmed, Embase/Medline, Cochrane) to identify all publications on biomarkers in relation to PTS. Where possible, results of studies were pooled and a meta-analysis was performed using Review Manager 5.1 (The Cochrane Collaboration). Twenty-four papers were included in this review. Inpatients after DVT, increased D-dimer appeared to be associated with the development of PTS (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.02-4.08; P= .04). Neither prothrombin G20210A (OR, 0.95; 95% CI, 0.53-1.69; P= .86, nor increased factor VIII (OR, 1.78; 95% CI, 0.88-3.57; P= .11) were associated with PTS. For factor V Leiden (FVL), conflicting results were found. FVL was not associated with PTS within a population of patients with a history of DVT (OR, 0.98; 95% CI, 0.74-1.29; P= .88), but FVL was positively associated with post-thrombotic ulceration in severe PTS, inpatients compared with healthy individuals without a history of DVT (OR, 11.42; 95% CI, 6.37-20.48; P<.00001). A meta-analysis could not be performed for markers of inflammation and tissue remodelling in relation to PTS. Increased D-dimer levels are associated with a twofold increased risk for PTS. Inherited hypercoagulability, including FVL is not associated with PTS in general. In contrast, FVL is strongly associated with post-thrombotic ulceration in severe PTS. The role of inflammation in the etiology of PTS still has to be elucidated.

Endovascular treatment of iliofemoral chronic post-thrombotic venous flow obstruction.

Patients with deep vein thrombosis affecting the iliac and vena cava veins develop a more severe post-thrombotic syndrome than those with femoropopliteal disease. It has been traditionally treated only with medical therapy. During the last decade, endovascular repair has become the treatment of choice. The aim of this study is to report our midterm results using this technique. From 2009 to 2012, 41 limbs in 36 patients with post-thrombotic chronic flow obstruction of iliofemoral vein secondary to stenotic or occlusive lesions and with a clinical CEAP class 3 or higher or venous pain underwent percutaneous treatment. Stent-related outcome (patency and thrombotic events), clinical outcome (improvement of revised Venous Clinical Severity Score [VCSS] and Villalta score) were evaluated after intervention. The procedure was successful in 39 limbs (95%) withno mortality and low morbidity. Thrombotic events occurred in nine limbs (23%) during the follow-up period. At33 months, primary, assisted-primary, and secondary cumulative patency rates were 74%, 87%, and 89%, respectively. The main risk factor associated with stent occlusion was the severity of thrombotic disease. All postoperative thrombotic events occurred in occluded veins; no previously stenotic veins presented any complication (P= .04). Presence of thrombophilia, stent brand, and stent extension into the common femoral vein were not significantly associated with stent thrombosis. After surgery, the mean revised VCSS and Villalta scores improved substantially (P< .0001). The cumulative rate of revised VCSS improvement was 89% at 33months. Clinical improvement was observed despite deep venous system reflux remaining uncorrected. Percutaneous treatment of post-thrombotic venous flow obstruction is an excellent therapeutic option withlow morbidity and no mortality. It can be performed with high midterm patency rates and midterm clinical improvement.

CATCH: a randomised clinical trial comparing long-term tinzaparin versus warfarin for treatment of acute venous thromboembolism in cancer patients

BackgroundLow-molecular-weight heparin (LMWH) is recommended and commonly used for extended treatment of cancer-associated thrombosis (CAT), but its superiority over warfarin has been demonstrated in only one randomised study. We report here the rationale, design and a priori analysis plans of Comparison of Acute Treatments in Cancer Haemostasis (CATCH; NCT01130025), a multinational, Phase III, open-label, randomised controlled trial comparing tinzaparin with warfarin for extended treatment of CAT.Methods/DesignThe primary objective is to assess the efficacy of tinzaparin in preventing recurrent venous thromboembolism (VTE) in patients with active cancer and acute, symptomatic proximal deep vein thrombosis and/or pulmonary embolism. The secondary objectives are to determine: safety of tinzaparin given over 6 months; clinical and laboratory markers for recurrent VTE and/or major bleeding; 6-month overall mortality; incidence and severity of post-thrombotic syndrome; patient-reported quality of life; and healthcare resource utilisation. Nine hundred patients are randomised to receive tinzaparin 175 IU/kg once daily for 6 months or initial tinzaparin 175 IU/kg once daily for 5–10 days and dose-adjusted warfarin (target INR 2.0–3.0) for 6 months. The primary composite outcome is time to recurrent VTE, including incidental VTE and fatal pulmonary embolism. All patients are followed up to 6 months or death, whichever comes sooner. Blinded adjudication will be performed for all reported VTE, bleeding events and causes of death. Efficacy will be analysed using centrally adjudicated results of all patients according to intention-to-treat analysis. An independent Data Safety Monitoring Board is reviewing data at regular intervals and an interim analysis is planned after 450 patients have completed the study.DiscussionThe results will add significantly to the knowledge of the efficacy, safety and cost effectiveness of tinzaparin in the prevention of recurrent VTE in patients with cancer and thrombosis. Prospective data will emerge on the clinical significance of incidental VTE and risk stratification in patients with CAT. Results on post-thrombotic syndrome, quality of life and healthcare resource utilisation will inform decision makers on how to secure better patient care. If tinzaparin is shown to be more effective than warfarin, CATCH will provide valuable confirmatory data to support the use of the LMWH tinzaparin for extended treatment of CAT.

Catheter-directed thrombolysis for deep venous thrombosis might be cost-effective, but for whom?

Catheter-directed thrombolysis for deep venous thrombosis might be cost-effective, but for whom?

Our early experience with iliofemoral vein stenting in patients with post-thrombotic syndrome

Venous balloon dilation and stent therapy have been proposed as effective treatments for chronic iliofemoral thrombosis. In this study, we report our experience and describe the one-year outcome and efficacy of balloon angioplasty and stenting for the treatment of post-thrombotic syndrome (PTS) in iliofemoral vein segments. From June 2011 to June 2012, 52 consecutive patients with chronic PTS (59 limbs; 75% women; median age 58 years; range: 23-76 years) referred to our unit for interventional assessment were included in the study. Treatment effects were assessed using Villalta scale, Venous Clinical Severity Score (VCSS) and Chronic Venous Insufficiency Questionnaire (CIVIQ)-20 for PTS, CEAP (clinical, aetiological, anatomical and pathological elements) grading and measurement of leg circumference, before and after intervention. Stenting was successfully accomplished in all patients. Coagulation abnormality was identified in 21 subjects (40.3%). CEAP grades were as follows: C3 in 19 patients, C4 in 24 patients, C5 in one patient and C6 in eight patients. According to Villalta scores, three patients were mild, seven patients were moderate and 42 patients were severe PTS. VCSS, Villalta scale and CIVIQ-20 showed a significant decrease in the severity of PTS signs and symptoms (P < 0.001). The calf and middle thigh circumferences decreased significantly on both sides (P < 0.001). Treatment of iliac venous obstruction with balloon angioplasty and stenting appears to be a minimally invasive and safe therapeutic approach in patients with PTS offering quick symptomatic relief, good patency and minimal morbidity.

The Post-Thrombotic Syndrome: A 2012 Therapeutic Update

Post-thrombotic syndrome (PTS) refers to chronic manifestations of venous insufficiency following a deep-vein thrombosis (DVT). It is a frequent, chronic, burdensome and costly disease for which therapeutic options are limited. Above all, the optimal management of PTS consists of preventing its occurrence: first, by preventing DVT, and second, by preventing development of PTS after a DVT. Prevention of DVT is challenging, particularly in the case of nonsurgical hospital inpatients, where physician's adherence to recommended thromboprophylaxis is often low. In our opinion, this adherence should be improved by generalizing the use of multi-component approaches, including that of automatic reminders. For prevention of PTS after an acute DVT, our recommendations are as follows. After a proximal (popliteal and above) DVT we recommend early ambulation with daily use of 30-40mmHg graduated elastic compression stockings (ECS) for two years, in addition to careful monitoring of anticoagulant therapy. Below-knee ECS are preferred to thigh-length ECS, as they have similar efficacy in preventing PTS and are better tolerated. To improve compliance with ECS, patient education is important, and use of lighter strengths of compression in patients not tolerating traditional strengths should be considered. Catheter-directed thrombolysis of acute DVT was recently shown to be effective in preventing PTS, but we believe that confirmatory studies are needed before recommending its general use. The cornerstone of management of established PTS relies on patient education and use of compression therapy. We encourage ambulation, use of ECS to manage symptoms, and participation in an exercise training program, which has the potential to improve patients' quality of life (QOL) and PTS scores. In the absence of symptom relief, ECS that provide a higher strength (40-50mmHg) should be tried. In case of moderate to severe PTS, intermittent compressive devices can be used to improve PTS symptoms. Surgery and endovascular procedures, including balloon angioplasty, stent placement, endovenectomy or valve reconstruction should be considered only in specialized centers, and only for patients with severe PTS for whom previous conservative treatment has failed. These techniques are still under evaluation and the level of evidence supporting their use is low.

Post-thrombotic syndrome 3 years after deep venous thrombosis in the Thrombosis and Pulmonary Embolism in Out-Patients (TULIPA) PLUS Registry.

Reported post-thrombotic syndrome (PTS) rates may be confounded by including patients with a history of deep venous thrombosis (DVT) before the index event, varicose veins, or chronic venous insufficiency independent of PTS. We were interested in assessing PTS incidence rates of patients without these pre-existing disease conditions. A prospective registry with a 3-year follow-up after an initial DVT was assessed. Available for analysis were 135 ambulatory patients without a history of DVT (before the index DVT), signs of varicose veins, or chronic venous insufficiency affecting the ipsilateral or contralateral leg, and Villalta score. PTS was detected in 24.5% of patients, with 17.0% having mild (Villalta score, 5-9), 6.0% moderate (score, 10-14), and 1.5% severe PTS (score ≥15) after a first DVT. Of these, 52.6% had proximal and 47.4% distal DVT; 63.7% were provoked and 35.6% unprovoked (one patient missing). Patients with proximal DVT (32.4%) significantly more often developed any PTS compared with patients with distal DVT (15.6%; P= .024); however, groups were similar with regard to severity of PTS by the four-level Villalta score (P= .109). In univariate analysis, PTS was more frequent (odds ratio, 95% confidence interval) with higher age (1.06 per year; 1.02-1.09), a body mass index of 25 to 30 kg/m(2) (2.38; 0.71-7.97) and ≥30 kg/m(2) (6.08; 1.75-21.14), proximal vs distal DVT (2.59; 1.12-5.98), and calf swelling ≥3 cm larger than the asymptomatic leg (3.77; 1.66-8.55). In a multivariate analysis, age (1.05; 1.01-1.09) and calf swelling ≥3 cm larger than the asymptomatic leg (2.94; 1.20-7.20) remained predictive for PTS. Compression therapy was used by 78.5% of patients at the 1-year follow-up and by 46.7% at the 3-year follow-up. Both rates were higher in patients with PTS (93.9%) vs no PTS (66.7%). This prospective survey demonstrates a low rate of PTS in patients with a first DVT and no pre-existing DVT, varicose veins, or chronic venous insufficiency, and a high adherence rate to compression therapy, within the first 3 years of follow-up. Age and marked calf swelling were independent predictors of PTS.