Catheter-Directed Thrombolysis Protocols for Deep Venous Thrombosis of the Lower Extremities-A Systematic Review and Meta-analysis.

OBJECTIVE: To summarize characteristics, complications, and success rates of different catheter-directed thrombolysis (CDT) protocols for the treatment of lower extremity deep venous thrombosis (LE-DVT). METHODS: A systematic review using electronic databases (MEDLINE, Scopus, and Web of Science) was performed to identify randomized controlled trials and observational studies related to LE-DVT treated with CDT. A random-effects model meta-analysis was performed to obtain the pooled proportions of early complications, postthrombotic syndrome (PTS), and venous patency. RESULTS: Forty-six studies met the inclusion criteria reporting 49 protocols (n = 3,028 participants). In studies that addressed the thrombus location (n = 37), LE-DVT had iliofemoral involvement in 90 ± 23% of the cases. Only four series described CDT as the sole intervention for LE-DVT, while 47% received additional thrombectomy (manual, surgical, aspiration, or pharmacomechanical), and 89% used stenting.Definition of venogram success was highly variable, being the Venous Registry Index the most used method (n = 19). Among those, the minimal thrombolysis rate (<50% lysed thrombus) was 0 to 53%, partial thrombolysis (50-90% lysis) was 10 to 71%, and complete thrombolysis (90-100%) was 0 to 88%. Pooled outcomes were 8.7% (95% confidence interval [CI]: 6.6-10.7) for minor bleeding, 1.2% (95% CI: 0.8-1.7%) for major bleeding, 1.1% (95% CI: 0.6-1.6) for pulmonary embolism, and 0.6% (95% CI: 0.3-0.9) for death. Pooled incidences of PTS and of venous patency at up to 1 year of follow-up were 17.6% (95% CI: 11.8-23.4) and 77.5% (95% CI: 68.1-86.9), respectively. CONCLUSION: Assessment of the evidence is hampered by the heterogeneity of protocols, which may be reflected in the variation of PTS rates. Despite this, CDT is a low-risk treatment for LE-DVT.

A systematic review and meta-analysis of the incidence of post-thrombotic syndrome, recurrent thromboembolism, and bleeding after upper extremity vein thrombosis.

BACKGROUND: Data on complications after upper extremity vein thrombosis (UEVT) are limited and heterogeneous. METHODS: The aim of the present study was to evaluate the pooled proportions of venous thromboembolism (VTE) recurrence, bleeding, and post-thrombotic syndrome (PTS) in patients with UEVT. A systematic literature review was conducted of PubMed, Embase, and the Cochrane Library databases from January 2000 to April 2023 in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. All studies included patients with UEVT and were published in English. Meta-analyses of VTE recurrence, bleeding, and of PTS after UEVT were performed to compute pooled estimates and associated 95% confidence intervals (CIs). Subgroup analyses of cancer-associated UEVT and catheter-associated venous thrombosis were conducted. Patients with Paget-Schroetter syndrome or effort thrombosis were excluded. RESULTS: A total of 55 studies with 15,694 patients were included. The pooled proportions for VTE recurrence, major bleeding, and PTS were 4.8% (95% CI, 3.8%-6.2%), 3.0% (95% CI, 2.2%-4.0%), and 23.8% (95% CI, 17.0%-32.3%), respectively. The pooled proportion of VTE recurrence was 2.7% (95% CI, 1.6%-4.6%) for patients treated with direct oral anticoagulants (DOACs), 1.7% (95% CI, 0.8%-3.7%) for patients treated with low-molecular-weight heparin (LMWH), and 4.4% (95% CI, 1.5%-11.8%) for vitamin K antagonists (VKAs; P = .36). The pooled proportion was 6.3% (95% CI, 4.3%-9.1%) for cancer patients compared with 3.1% (95% CI, 2.1%-4.6%) for patients without cancer (P = .01). The pooled proportion of major bleeding for patients treated with DOACs, LMWH, and VKAs, was 2.1% (95% CI, 0.9%-5.1%), 3.2% (95% CI, 1.4%-7.2%), and 3.4% (95% CI, 1.4%-8.4%), respectively (P = .72). The pooled proportion of PTS for patients treated with DOACs, LMWH, and VKAs was 11.8% (95% CI, 6.5%-20.6%), 27.9% (95% CI, 20.9%-36.2%), and 24.5% (95% CI, 17.6%-33.1%), respectively (P = .02). CONCLUSIONS: The results from this study suggest that UEVT is associated with significant rates of PTS and VTE recurrence. Treatment with DOACs might be associated with lower PTS rates than treatment with other anticoagulants.

Effect of exercise after a deep venous thrombosis: A systematic review.

Post-thrombotic syndrome (PTS) is a common complication after deep vein thrombosis (DVT) and has a major impact on physical symptoms, quality of life (QoL) and economic costs. Relatively simple lifestyle interventions as physical exercise might reduce PTS severity and increase QoL. To evaluate the direct and long-term effects of physical activity in patients with an acute or previous DVT. We conducted a systematic review through an additional search from 2007 up to March 2022, to complement the comprehensive systematic review of Kahn et al. Articles evaluating the effect of exercise after a DVT including symptoms, QoL and the incidence and severity of PTS, were included. Quality of the studies was assessed using a GRADE-like checklist and results were reported according to the PRISMA Statement. Ten studies were included, seven randomized controlled trials and three cohort studies. We identified three types of physical activity based on timing and duration; (1) early mobilisation in the acute phase of the DVT; (2) short duration exercise 1 year after DVT and (3) prolonged exercise during follow-up after a previous DVT. Early mobilisation showed improvement in QoL and pain reduction and after 2 years it resulted in a significant reduction of PTS severity. Prolonged supervised exercise resulted in improvement of QoL. In addition, positive effects on symptoms of venous insufficiency and muscle functions were observed. None of the included studies reported an increased risk of PTS or worsening of symptoms due to physical activity. Physical exercise after a DVT is safe, improves QoL, reduces pain and decreases PTS severity. Lifestyle intervention such as guided individualized training programs can be a useful supplementary therapy for patients after a DVT or for PTS patients. Optimal training programs may be identified by further studies that improve patient-oriented outcomes for both adults and children after a DVT.

Biomarkers in pediatric venous thromboembolism: a systematic review of the literature.

BACKGROUND: Accurate prediction of the individual risk of venous thromboembolism (VTE) remains suboptimal in children, and biomarkers are currently not used to stratify the risk of VTE in children. OBJECTIVES: This study aimed to assess which biological or radiological biomarkers may predict VTE or VTE complications in children. PATIENTS/METHODS: A literature search was performed for peer-reviewed publications (1990-2022). We included studies addressing the use of biomarkers for patients aged 29 days to 18 years to predict VTE or its complications, including but not limited to TE-related death, VTE recurrence, or postthrombotic syndrome. Given the heterogeneity of the study designs, populations, and outcomes, no quantitative data synthesis was performed. RESULTS: Forty studies were included, totaling 10,987 participants (median age: 4.7 years). Reports were often lacking critical methodological data, including blood collection method (68% of studies) and timepoints, laboratory testing technique (41%), or primary outcome definition (20%). Forty-six individual biomarkers were assessed for VTE prediction (32 studies, 9525 participants), including d-dimers, fibrinogen, platelet count, white blood cell count, and factor VIII. Albumin, C-reactive protein, d-dimers, factor VIII, and thrombin-antithrombin levels showed promising results for VTE prediction. In 9 studies (1606 participants), no biomarker was consistently predictive of postthrombotic syndrome, VTE persistence, or VTE recurrence in children. CONCLUSIONS: Several candidate biomarkers were promising in the prediction of VTE in children. Still, discrepancies between different studies and the high risk of bias from the current literature prevent their widespread use in the clinical setting. Further prospective research in various pediatric subpopulations is required.

Residual Venous Obstruction as an Indicator of Clinical Outcomes following Deep Vein Thrombosis: A Management Study.

BACKGROUND: Residual venous obstruction (RVO) is considered a risk factor of recurrence and possibly other clinical outcomes following deep vein thrombosis (DVT). Current guidelines do not support an RVO-tailored duration of anticoagulant therapy; contemporary data of such management strategies are scarce. We aimed to evaluate an RVO-based management strategy and to assess associations of RVO with recurrence, post-thrombotic syndrome (PTS), arterial events and cancer. To gain further insight, D-dimer levels were measured 1 month after stopping anticoagulant therapy. METHODS: Consecutive patients with symptomatic, proximal DVT were treated in a 2-year clinical care pathway (CCP) at Maastricht University Medical Center and were followed up to 5 years. RVO was assessed at the end of regular duration of anticoagulant therapy, which was extended once if RVO was detected. The study was approved by the medical ethics committee. RESULT: From a total of 825 patients, 804 patients (97.5%) completed the CCP and 755 (93.9%) were available for extended follow-up. Most patients (76.5%) stopped anticoagulant therapy. Incidence rates of recurrence, PTS, arterial events, and cancer were 4.4, 11.9, 1.7, and 1.8 per 100 patient-years, respectively. RVO was independently associated with PTS (hazard ratio [HR]: 1.66 [1.19-2.32]) and arterial events (HR: 2.07 [1.18-3.65]), but not with recurrence or cancer. High D-dimer was associated with recurrence (HR: 3.51 [2.24-5.48]). CONCLUSION: Our RVO-based management strategy might have attenuated the association of RVO with recurrence. In addition, RVO identified patients at increased risk of PTS and arterial events, which might be used to identify patients in need of alternative treatment strategies.

Unraveling the pathophysiology of lower-limb postthrombotic syndrome in adolescents: a proof-of-concept study.

A better understanding of the pathophysiology of pediatric postthrombotic syndrome (PTS) is needed to develop strategies to treat this condition. We investigated calf pump function, exercise capacity, balance in power output, and changes in limb muscle oxygen saturation (SmO2) and fluid content during exercise in 10 pediatric patients with unilateral lower-limb PTS, and in age- and sex-matched controls (1:1-1:2 ratio). Outcomes were investigated using bioimpedance spectroscopy, torque-sensing pedals, and near-infrared spectroscopy during incremental- and constant-load cycling tests. The median age at participation was 17 years (25th-75th percentile, 15-18 years); 68% of participants were females. The median CAPTSure score in the affected leg of affected participants was 35 points (25th-75th percentile, 24-46 points), indicating moderate/severe PTS; 20% of patients had a history of central venous catheter-related thrombosis. Increasing PTS severity was associated with higher calf pump venous volume and higher ejection volume, leading to compensated calf pump performance. We found no evidence of PTS impact on exercise capacity. Leg contribution to power output was similar in affected and unaffected legs. However, the PTS-affected legs showed lower SmO2 during active cycling and recovery with increasing PTS severity, indicating impaired microvascular function in the muscle. These findings suggest that PTS severity is associated with impaired blood flow, presumably from elevated venous pressure during and after exercise. The fact that microvascular function is impaired in young patients with PTS underscores the relevance of developing strategies to mitigate the effects of this chronic vascular disease to minimize its deleterious effects as children grow older.

Exploring phenotypes of deep vein thrombosis in relation to clinical outcomes beyond recurrence.

BACKGROUND: Deep vein thrombosis (DVT) is a multifactorial disease with several outcomes, but current classifications solely stratify it based on recurrence risk. OBJECTIVES: We aimed to identify DVT phenotypes and assess their relation to recurrent venous thromboembolism (VTE), postthrombotic syndrome, arterial events, and cancer. PATIENTS/METHODS: Hierarchical clustering was performed on a DVT cohort with a follow-up of up to 5 years using 23 baseline characteristics. Phenotypes were summarized by discriminative characteristics. Hazard ratios (HRs) were calculated using Cox regression; the recurrence risk was adjusted for the anticoagulant therapy duration. The study was carried out in accordance with the Declaration of Helsinki and approved by the medical ethics committee. RESULTS: In total, 825 patients were clustered into 4 phenotypes: 1. women using estrogen therapy (n = 112); 2. patients with a cardiovascular risk profile (n = 268); 3. patients with previous VTE (n = 128); and 4. patients without discriminant characteristics (n = 317). Overall, the risks of recurrence, postthrombotic syndrome, arterial events, and cancer were low in phenotype 1 (reference), intermediate in phenotype 4 (HR: 4.6, 1.2, 2.2, 1.8), and high in phenotypes 2 (HR: 6.1, 1.6, 4.5, 2.9) and 3 (HR: 5.7, 2.5, 2.3, 3.7). CONCLUSIONS: This study identified 4 distinct phenotypes among patients with DVT that are not only associated with the increasing recurrence risk but also with outcomes beyond recurrence. Our results thereby highlight the limitations of current risk stratifications that stratify based on the predictors of the recurrence risk only. Overall, risks were lowest in women using estrogen therapy and highest in patients with a cardiovascular risk profile. These findings might inform a more personalized approach to clinical management.

Functional impact of pediatric postthrombotic syndrome.

BACKGROUND: Postthrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT) in children. OBJECTIVES: We aimed to assess the impact of pediatric PTS on functioning as assessed by movement ability, mobility, functional disability, and physical activity levels in children after diagnosis of limb DVT. METHODS: Patients aged 8-21 years in follow-up care after objectively documented limb DVT were prospectively recruited in this cross-sectional study. Measures of functioning (outcomes) included self-reported questionnaires that assessed: 1) movement ability, measured with the Movement Ability Measure-Computer Adaptive Test version; 2) mobility, evaluated with the Computer Adaptive Test version of the Patient-Reported Outcomes Measurement Information System Pediatric Physical Functioning, Mobility domain; 3) functional disability, evaluated with the Functional Disability Inventory; and 4) physical activity levels, evaluated with the Godin Leisure-Time Exercise Questionnaire. The main predictor was PTS severity, which was assessed using the index for the Clinical Assessment of PTS in children. The association between PTS and outcomes was analyzed using linear models. RESULTS: Eighty-seven patients (median age, 16 years; 25th-75th percentile, 15-18 years; 56% boys) were enrolled. Adjusted for age, sex, and underlying condition, increasing PTS severity was associated with lower current movement ability, a wider gap between current vs preferred movement ability, lower mobility, and slightly higher functional disability scores. There was a nonsignificant effect of PTS severity on moderate-strenuous physical activity. CONCLUSION: In children, increased PTS severity is associated with lower movement ability and impaired mobility. Reducing the gap between the patients' current vs preferred movement ability is a relevant aspect of PTS management in children.

Developing and optimizing a machine learning predictive model for post-thrombotic syndrome in a longitudinal cohort of patients with proximal deep venous thrombosis.

BACKGROUND: Post-thrombotic syndrome (PTS) is the most common chronic complication of deep venous thrombosis (DVT). Risk measurement and stratification of PTS are crucial for patients with DVT. This study aimed to develop predictive models of PTS using machine learning for patients with proximal DVT. METHODS: Herein, hospital inpatients from a DVT registry electronic health record database were randomly divided into a derivation and a validation set, and four predictive models were constructed using logistic regression, simple decision tree, eXtreme Gradient Boosting (XGBoost), and random forest (RF) algorithms. The presence of PTS was defined according to the Villalta scale. The areas under the receiver operating characteristic curves, decision-curve analysis, and calibration curves were applied to evaluate the performance of these models. The Shapley Additive exPlanations analysis was performed to explain the predictive models. RESULTS: Among the 300 patients, 126 developed a PTS at 6 months after DVT. The RF model exhibited the best performance among the four models, with an area under the receiver operating characteristic curves of 0.891. The RF model demonstrated that Villalta score at admission, age, body mass index, and pain on calf compression were significant predictors for PTS, with accurate prediction at the individual level. The Shapley Additive exPlanations analysis suggested a nonlinear correlation between age and PTS, with two peak ages of onset at 50 and 70 years. CONCLUSIONS: The current predictive model identified significant predictors and accurately predicted PTS for patients with proximal DVT. Moreover, the model demonstrated a nonlinear correlation between age and PTS, which might be valuable in risk measurement and stratification of PTS in patients with proximal DVT.

Postthrombotic Syndrome and Chronic Pulmonary Embolism after Obstetric Venous Thromboembolism.

OBJECTIVE: While the majority of venous thromboembolism (VTE) during pregnancy events resolve with anticoagulation, long-term complications may occur including (1) postthrombotic syndrome and (2) chronic pulmonary embolism. The objective of this study was to determine risk of these two complications. STUDY DESIGN: A retrospective cohort study using the MarketScan databases was performed on deliveries from 2008 to 2014. We identified women aged 15 to 54 years diagnosed with acute VTE during pregnancy, the delivery hospitalization, or ≤60 days postpartum who received at least one prescription postpartum for anticoagulants. Risks of (1) chronic PE and (2) postthrombotic syndrome were evaluated for women at 6, 12, 24, and 60 months after delivery hospitalization through 2017 via the International Classification of Diseases, 9th/10th Revision, Clinical Modification codes. RESULTS: Of 4,267 of 4,128,900 pregnancies complicated by VTE, the majority had DVT alone (61.8%, n = 2,637), while 25.8% had PE alone (n = 1,103) and 12.4% (n = 527) had both DVT and PE. Of the entire cohort, 3,328 retained insurance coverage at 6 months, 2,823 at 12 months, 2,161 at 24 months, and 831 at 60 months. Restricted to DVT, risk of postthrombotic syndrome was 0.7% at 6 months (n = 17), 1.1% at 12 months (n = 22), 1.7% at 24 months (n = 26), and 2.7% at 60 months (n = 16). Among women with PE diagnoses, the risk of chronic PE was 2.4% at 6 months (n = 30), 3.3% at 12 months (n = 36), 4.2% at 24 months (n = 36), and 7.2% at 60 months (n = 24). CONCLUSION: In comparison to the general population, the risk of postthrombotic syndrome was lower. In comparison, the risk of chronic PE was similar to the estimates in the general population at comparable time points after PE events. For women with obstetric PE, it may be appropriate to be vigilant for findings and symptoms associated with chronic PE. KEY POINTS: · Risk of postthrombotic syndrome after obstetric deep vein thrombosis is low.. · Risk of chronic pulmonary embolism may approximate that in the general population.. · Overall risk of chronic complications after obstetric VTE was relatively low..

Venous thromboembolic screening in pediatric trauma: A prospective cohort study of risk-stratified ultrasonography.

BACKGROUND: This prospective observational cohort study evaluates risk-stratified venous thromboembolism (VTE) screening in injured children. While the reported incidence of VTE is 6% to 10% among critically injured children, there is no standard for screening. Venous thromboembolism may have long-term sequelae in children, including postthrombotic syndrome. METHODS: Patients admitted to a level 1 pediatric trauma center were risk stratified for VTE using a validated prediction algorithm. Children at high risk (risk scores ≥523; i.e., ≥1% risk) received screening duplex ultrasonography. Children at moderate risk (risk scores 410-522; i.e., 0.3-0.99% risk) were screened as a comparison/control. RESULTS: Three-hundred fifty-five children were consecutively risk stratified from October 2019 to May 2021. Forty-seven children received screening duplex ultrasounds: 21 from a high-risk cohort and 26 from a moderate-risk cohort. Four children were diagnosed with VTE in the high-risk cohort compared with seven in the moderate-risk cohort ( p = 0.53). Total incidence of VTE among screened children was 23.4% (11 of 47). Asymptomatic VTE accounted for 81.8% of all events (9 of 11). Fifty-four percent (6 of 11) of VTE were central venous catheter associated. Venous thromboembolism in surviving children resolved by 3 to 6 months with no symptoms of postthrombotic syndrome after 1 year. No cases of VTE were identified in unscreened children, yielding an institutional VTE incidence of 3.1% (11 of 355). DISCUSSION: Risk-stratified screening demonstrates a significant incidence of asymptomatic VTE in injured children. These results may guide reevaluation of prediction algorithms developed from symptomatic VTE risk and longitudinal study of the sequelae of asymptomatic VTE. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Specific management of lipodermatosclerosis (sclerotic hypodermitis) in acute and chronic phase.

Lipodermatosclerosis or sclerotic hypodermitis is presented as a complication of venous insufficiency and in particular of post-thrombotic syndrome with a high risk of progression to leg ulcers. However, it has also been described in obese patients without venous insufficiency, and even in the course of various systemic diseases including scleroderma. It most often affects middle-aged women and is usually bilateral, with a typically "inverted champagne bottle" leg appearance. The pathogenic role of venous hypertension explains why compression with bands or stockings is the basis of treatment. In acute phase, which may precede or complicate chronic forms, the pain is so severe that compression is not tolerated. In acute phase, non-steroidal anti-inflammatory drugs, intra-lesional use of triamcinolone, and capsaicin transdermal patches indicated for neuropathic pain have been proposed. In chronic forms, the treatment of superficial venous insufficiency and/or incontinent perforating veins, documented during a Duplex ultrasound scan, is usually proposed, whenever possible. In association with elastic compression, pentoxifylline and colchicine have been used without clear evidence of clinical efficacy. Finally, in the most advanced clinical presentation with the appearance of a sclerotic gaiter associated with ulcerations, surgical treatment with excision-cutaneous grafting associated or not with perforating veins ligation and a fasciotomy may be discussed as a last resort for treatment.

Clinical Presentation and Short- and Long-term Outcomes in Patients With Isolated Distal Deep Vein Thrombosis vs Proximal Deep Vein Thrombosis in the RIETE Registry.

Importance: Insufficient data exist about the clinical presentation, short-term, and long-term outcomes of patients with isolated distal deep vein thrombosis (IDDVT), that is, thrombosis in infrapopliteal veins without proximal extension or pulmonary embolism (PE). Objective: To determine the clinical characteristics, short-term, and 1-year outcomes in patients with IDDVT and to compare the outcomes in unadjusted and multivariable adjusted analyses with patients who had proximal DVT. Design, Setting, and Participants: This was a multicenter, international cohort study in participating sites of the Registro Informatizado Enfermedad Tromboembólica (RIETE) registry conducted from March 1, 2001, through February 28, 2021. Patients included in this study had IDDVT. Patients with proximal DVT were identified for comparison. Patients were excluded if they had a history of asymptomatic DVT, upper-extremity DVT, coexisting PE, or COVID-19 infection. Main Outcomes and Measures: Primary outcomes were 90-day and 1-year mortality, 1-year major bleeding, and 1-year venous thromboembolism (VTE) deterioration, which was defined as subsequent development of proximal DVT or PE. Results: A total of 33 897 patients were identified with isolated DVT (without concomitant PE); 5938 (17.5%) had IDDVT (mean [SD] age, 61 [17] years; 2975 male patients [50.1%]), and 27 959 (82.5%) had proximal DVT (mean [SD] age, 65 [18] years; 14 315 male patients [51.2%]). Compared with individuals with proximal DVT, those with IDDVT had a lower comorbidity burden but were more likely to have had recent surgery or to have received hormonal therapy. Patients with IDDVT had lower risk of 90-day mortality compared with those with proximal DVT (odds ratio [OR], 0.47; 95% CI, 0.40-0.55). Findings were similar in 1-year unadjusted analyses (hazard ratio [HR], 0.52; 95% CI, 0.46-0.59) and adjusted analyses (HR, 0.72; 95% CI, 0.64-0.82). Patients with IDDVT had a lower 1-year hazard of VTE deterioration (HR, 0.83; 95% CI, 0.69-0.99). In 1-year adjusted analyses of patients without an adverse event within the first 3 months, IDDVT was associated with lower risk of VTE deterioration (adjusted HR, 0.48; 95% CI, 0.24-0.97). By 1-year follow-up, symptoms or signs of postthrombotic syndrome were less common in patients with IDDVT (47.6% vs 60.5%). Conclusions and Relevance: Results of this cohort study suggest that patients with IDDVT had a less ominous prognosis compared with patients with proximal DVT. Such differences were likely multifactorial, including the differences in demographics, risk factors, comorbidities, particularly for all-cause mortality, and a potential association of thrombus location with VTE deterioration and postthrombotic syndrome. Randomized clinical trials are needed to assess the optimal long-term management of IDDVT.

Feasibility of Endovascular Recanalization in Post-Thrombotic Syndrome of Intentionally Interrupted Inferior Vena Cava.

PURPOSE: Surgical plication of inferior vena cava was commonly used until the 1980s for prevention of pulmonary embolism, associated with high incidence of post-thrombotic syndrome (PTS). This study aims to assess the feasibility and safety of endovascular iliocaval recanalization after intentionally surgically interrupted inferior vena cava by external plicating clip. MATERIALS AND METHODS: Endovascular iliocaval recanalizations in relation to previous vena cava clip plication were extracted from the retrospective French multicentre database and further analysed. All procedure data were retrospectively reviewed, including technical aspects, technical success and outcomes (clinical response and ultrasound stent patency). RESULTS: From 2016 to 2018, 8 patients from 4 different centres underwent endovascular iliocaval recanalization for PTS in relation to previous caval interruption by clip. Recanalization of iliocaval occlusion through the clip and stent reconstruction were successfully performed for all of them without complications. After angioplasty, plicating clip was opened in U shape (n = 3) or ovalized without significant residual stenosis (n = 5). Patency of the inferior vena cava was maintained for all patients with a mean follow-up of almost two years after stenting. All patients clinically improved. CONCLUSIONS: In this small cases series, endovascular recanalization and stenting of surgical vena cava clip plication seem technically feasible without morbidity. Restoration of blood flow through the iliocaval occlusion, using non-invasive endovascular technique, even as late treatment may be durable, with improvement of patient's venous symptoms. LEVEL OF EVIDENCE: 4, Short Communication.

Management of Post-thrombotic Syndrome: A Comprehensive Review.

BACKGROUND: Post-thrombotic syndrome (PTS) is the most common long-term complication of acute deep venous thrombosis (DVT). The cumulative incidence of PTS in the first two years after the first acute DVT diagnosis approximates 25%. OBJECTIVE: This study aims to summarize the most recent updates and provide a comprehensive review of the current management of PTS. METHODS: We searched MEDLINE/PMC/NCBI Bookshelf (PubMed), Cochrane, Embase, Scopus, ClinicalTrials, and OpenGrey databases for relevant articles in English published from the establishment of each separate database until February 9, 2021. CONCLUSION: PTS constitutes the most frequent long-term complication of lower limb deep venous thrombosis (DVT). Lifestyle changes and compression treatment represent an integral part of PTS management and have a clear benefit to offer in PTS patients. Pharmacological treatment with phlebotonic and non-phlebotonic medications, such as micronized purified flavonoid fraction (MMPF) and sulodexide, respectively, may have a more central and significant role in PTS management than previously thought. The introduction of percutaneous transluminal venoplasty (PTV) and stenting has again raised our expectations with the field, along with new concerns and considerations. There is a growing number of studies that report promising results on patientoriented outcomes on PTS patients who were treated with PTV and stenting. Moreover, hybrid (endovascular/ surgical) interventions may also represent a safe and efficacious treatment option for a subset of patients with PTS. Patient selection criteria for endovascular and hybrid interventional treatment should be carefully set and standardized. Post-operative care after venoplasty is an important field of future research with potential clinical impact. Management of deep and superficial reflux remains controversial. Hopefully, future prospective studies shall provide more robust evidence on the management of PTS.

Effect of body mass index on initial presentation and outcomes after stenting for quality of life-impairing chronic iliofemoral venous obstruction.

OBJECTIVE: The incidence of obesity has been increasing, with recent data indicating that the age-adjusted mean body mass index (BMI) is close to 30 kg/m2 in the United States. Prior studies have raised concerns for an increased incidence of chronic venous insufficiency in the obese population. We aimed to build on current knowledge by assessing the effects of BMI on the initial presentation and outcomes after intravascular ultrasound (IVUS) luminal area-guided stenting in patients presenting with quality of life (QOL)-impairing chronic iliofemoral venous obstruction (CIVO). METHODS: A retrospective analysis of contemporaneously entered electronic medical record data on 464 continuous patients (464 limbs) with initial iliofemoral stents (2014-2017) for QOL-impairing CIVO was performed. The characteristics evaluated and compared included the degree of iliofemoral compression, CEAP (clinical, etiologic, anatomic, pathophysiologic) clinical class, venous clinical severity score (VCSS), grade of swelling (GOS), visual analog scale (VAS) for pain score, ulcer healing, reflux (venous segmental disease score; venous filling index-90), calf pump function (ejection fraction; residual volume fraction), and quality of life (CIVIQ-20 [chronic lower limb venous insufficiency 20-item questionnaire]) for those with a BMI <30 kg/m2 (group I) and a BMI ≥30 kg/m2 (group II). Paired and unpaired t tests were used for comparisons of the clinical variables and a Kaplan-Meier analysis was used to evaluate stent patency. RESULTS: Of the 464 limbs in the study cohort, 122 were in group I and 342 in group II. The median BMI was 26.3 kg/m2 (interquartile range, 19.6-29.9 kg/m2) in group I and 38.9 kg/m2 (interquartile range, 30.0-66.9 kg/m2) in group II. The IVUS luminal area-determined degree of compression was higher in group I than in group II across the common iliac, external iliac, and common femoral segments (P < .01). The supine foot venous and femoral venous pressures were higher in group II than in group I (P < .001). The ejection fraction was higher (57.4% vs 45.6%; P = .0008) and residual volume fraction was lower (27.5% vs 40.5%; P = .0008) in group II than in group I. Although the baseline VCSS and GOS were lower in group I than in group II (P < .05), no differences were found in the VAS for pain scores or ulcer prevalence. The median follow-up was 22 months. At 24 months after stenting, improvement was found in the VCSS, GOS, and VAS for pain score in both groups. The CIVIQ-20 QOL score had improved from 58.1 to 18.8 in group I (P = .0002) and from 60 to 37.5 in group II (P < .0001). At 5 years, primary patency was 70% in group I and 73% in group II (P = .6) and primary assisted patency was 100% in both groups (P = .99) without a significant difference in the reintervention rate (P = .5). CONCLUSIONS: Obese patients with CIVO-impairing QOL have a lesser degree of iliofemoral venous stenosis, more severe venous hypertension, and better calf pump function than their nonobese counterparts. After stenting, no differences were found in the clinical, stent patency, or QOL-related outcomes between the two groups.

Protein S Deficiency with Recurrent Deep Vein Thrombosis and Post Thrombotic Syndrome: A Case Report.

Protein S is a vitamin K-dependent protein that acts as a break in secondary hemostasis by inactivating activated factor V and activated factor VIII. We report a case of a 40 years old male who had the first episode of deep vein thrombosis of the left lower limb 10 years back, which despite treatment, reoccurred 3 months later in the bilateral lower limb. Thrombophilic screening showed severe protein S deficiency. The patient then developed deep vein thrombosis of both upper limbs. The patient was advised to place an inferior vena cava filter, which he denied. The patient is now presenting with multiple episodes of post-thrombotic syndrome. Such attacks are treated with elastic compression stockings, rivaroxaban, and morphine. However, despite medication, the pain has not yet subsided. Hence, even though protein S deficiency is the rare cause of deep vein thrombosis when recurrent should be considered despite its rare occurrence. Keywords: deep vein thrombosis; protein S deficiency; rivaroxaban.

Performance of two clinical scales to assess quality of life in patients with post-thrombotic syndrome.

OBJECTIVE: We directly compared the Villalta scale and the Venous Clinical Severity Score (VCSS) to determine which of the two measures would be better at capturing clinically important cases of post-thrombotic syndrome (PTS) and PTS severity compared with patient-reported quality of life (QOL) scores. METHODS: We performed a secondary analysis of the ATTRACT (acute venous thrombosis: thrombus removal with adjunctive catheter-directed thrombolysis) trial study population. We calculated the correlations of the Villalta scores and VCSSs with QOL scores (short-form 36-item health survey [SF-36] physical component summary [PCS] and mental component summary [MCS]; and VEINES [venous insufficiency epidemiological and economic study]-QOL/symptom [VEINES-QOL/Sym] questionnaire) at each study visit (6, 12, 18, and 24 months of follow-up). The correlation of the random intercept (mean scores) and random slope (rate of change of the scores) among the Villalta scores, VCSS, and VEINES-QOL/Sym scores was assessed using a multivariate longitudinal model. RESULTS: The median correlation between Villalta scores and VCSSs was 0.72. The median correlation between the Villalta scores and VEINES-QOL and VEINES-Sym scores at all follow-up visits was -0.68 and -0.71, respectively. The median correlation between the Villalta scores and SF-36 PCS and MCS scores was -0.51 and -0.31, respectively. For the VCSSs, the median correlation with the VEINES-QOL and VEINES-Sym scores at all follow-up visits was -0.39 and -0.41, respectively. The median correlation between the VCSSs and SF-36 PCS and MCS scores was -0.32 and -0.13, respectively. The correlations between the random effects in the multivariate longitudinal models showed a similar pattern. The effect of covariate adjustment by age, sex, and body mass index was minor. CONCLUSIONS: The Villalta scores and VCSSs correlated strongly. The Villalta scale showed a substantially greater correlation with venous disease-specific and general QOL scores compared with the correlation with the VCSS. Our findings suggest that when a single scale is used to assess for clinically meaningful PTS, the Villalta scale will better capture the effects of PTS on patient-reported QOL.

Effect of thrombophilia on clinical outcomes of chronic post-thrombotic patients after iliofemoral stenting with nitinol venous stents.

OBJECTIVE: Thrombophilia is a prothrombotic condition that increases the risk of venous thromboembolism. It is unclear whether the presence of thrombophilia alters the clinical outcomes after deep venous stenting. The aim of the present study was to examine the relationship between thrombophilia and outcomes after stenting for post-thrombotic syndrome. METHODS: Consecutive patients (2012-2017) receiving a nitinol venous stent for chronic post-thrombotic venous occlusive disease with a minimum of 18 months of follow-up in one center using the same anticoagulation protocol were included. The clinical history and thrombophilia testing results were reviewed. The outcomes were stent patency, which was assessed using duplex ultrasonography at 24 hours, 2 and 6 weeks, 3 months, 6 months, and annually thereafter; and reinterventions, which were performed when the stent diameter was <50% or occluded. RESULTS: Of the 136 patients who had undergone intervention, 55 (40%) had had a provoked deep vein thrombosis (DVT) and 81 (60%) had had an unprovoked DVT and had therefore undergone thrombophilia testing. Of the 81 patients, 38 (47%) had had either inherited (n = 19; 50%) or acquired (n = 19; 50%) thrombophilia. Of the 136 patients who had undergone stenting, 68 had required reintervention (50%) during follow-up to maintain stent patency. Of the 55 patients with a provoked DVT, 29 (53%) had required reintervention. Of the 81 patients with an unprovoked DVT, 39 (48%) had required reintervention (P = .420). Of the 38 patients with unprovoked DVT and thrombophilia, 17 (45%) had required reintervention. Of the 43 patients with unprovoked DVT and no thrombophilia, 22 (51%) had required reintervention (P = .766). The cumulative patency rate was 80% for patients with provoked DVT and 88% for those with unprovoked DVT (P = .193). The presence of thrombophilia was not associated with patency loss (92% cumulative patency for patients with thrombophilia and 84% for patients without thrombophilia; P = .307). CONCLUSIONS: Using our anticoagulation protocol, patients with and without thrombophilia had similar clinical outcomes after deep venous stenting and should not be excluded from iliofemoral venous stenting. We found no significant differences in outcomes in conjunction with appropriate postoperative anticoagulation therapy.

Incidence of Stent Thrombosis after Endovascular Treatment of Iliofemoral or Caval Veins in Patients with the Postthrombotic Syndrome.

BACKGROUND: Patients with postthrombotic syndrome (PTS) treated with stents are at risk of stent thrombosis (ST). The incidence of ST in the presence and absence of anticoagulation therapy (AT) is unknown. Risk factors are not well understood. PATIENTS AND METHODS: From the prospective Swiss Venous Stent registry, we conducted a subgroup analysis of 136 consecutive patients with PTS. Incidence of ST was estimated from duplex ultrasound or venography, and reported for the time on and off AT. Baseline, procedural, and follow-up data were evaluated to identify factors associated with ST. RESULTS: Median follow-up was 20 (interquartile range [IQR] 9-40) months. AT was stopped in 43 (32%) patients after 12 (IQR 6-14) months. Cumulative incidence of ST was 13.7% (95% confidence interval [CI] 7.8-19.6%) and 21.2% (95% CI 13.2-29.2%) during the first 6 and 36 months, respectively. The time-adjusted incidence rate was 11.2 (95% CI 7.7-16.2) events per 100 patient-years, 11.3 (95% CI 7.3-17.3) for the period on, and 11.2 (95% CI 5.3-23.6) for the period off AT. May-Thurner syndrome (MTS) was associated with decreased incidence of ST (hazard ratio [HR] 0.37, 95% CI 0.15-0.91), whereas age < 40 years (HR 2.26, 95% CI 1.03-4.94), stents below the common femoral vein (HR 3.03, 95% CI 1.28-7.19), and postthrombotic inflow veins (HR 2.92, 95% CI 1.36-6.25) were associated with increased incidence. CONCLUSION: The 6-month incidence of ST was considerably high. Beyond 6 months, consecutive annual incidence rates persisted at 4.1 and 3.4% per year thereafter. Patients with higher incidence of ST were younger, had stents below the common femoral vein, postthrombotic leg inflow veins, and less often MTS. Incidence rates for the period on and off AT must be interpreted with caution. CLINICAL TRIAL REGISTRATION: The study is registered on the National Institutes of Health Web site (ClinicalTrials.gov; identifier NCT02433054).