Incidence and predictors of post-thrombotic syndrome in patients with proximal DVT in a real-world setting: findings from the GARFIELD-VTE registry.

Although substantial progress has been made in the pathophysiology and management of the post-thrombotic syndrome (PTS), several aspects still need clarification. Among them, the incidence and severity of PTS in the real world, the risk factors for its development, the value of patient's self-evaluation, and the ability to identify patients at risk for severe PTS. Eligible participants (n = 1107) with proximal deep-vein thrombosis (DVT) from the global GARFIELD-VTE registry underwent conventional physician's evaluation for PTS 36 months after diagnosis of their DVT using the Villalta score. In addition, 856 patients completed a Villalta questionnaire at 24 months. Variable selection was performed using stepwise algorithm, and predictors of severe PTS were incorporated into a multivariable risk model. The optimistic adjusted c-index was calculated using bootstrapping techniques. Over 36-months, 27.8% of patients developed incident PTS (mild in 18.7%, moderate in 5.7%, severe in 3.4%). Patients with incident PTS were older, had a lower prevalence of transient risk factors of DVT and a higher prevalence of persistent risk factors of DVT. Self-assessment of overall PTS at 24 months showed an agreement of 63.4% with respect to physician's evaluations at 36 months. The severe PTS multivariable model provided an optimistic adjusted c-index of 0.68 (95% CI 0.59-0.77). Approximately a quarter of DVT patients experienced PTS over 36 months after VTE diagnosis. Patient's self-assessment after 24 months provided added value for estimating incident PTS over 36 months. Multivariable risk analysis allowed good discrimination for severe PTS.

Treatment Strategies for Proximal Deep Vein Thrombosis: A Network Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To investigate the outcomes of treatment strategies for proximal and iliofemoral deep vein thrombosis (DVT). METHODS: Randomised controlled trials (RCTs) investigating outcomes of catheter directed thrombolysis (CDT), ultrasound assisted CDT (USCDT), percutaneous aspiration thrombectomy (PAT), and best medical therapy (BMT) for proximal DVT from 2000 onwards were considered. MEDLINE, EMBASE, and CINAHL were searched using the Healthcare Databases Advanced Search interface developed by the National Institute for Health and Care Excellence. The primary outcome was the rate of post-thrombotic syndrome (PTS), which was defined using the Villalta scoring system (score of ≥5). Secondary outcomes included vessel patency, recurrence, bleeding, and mortality. The network of evidence was summarised using network plots, and random effects network meta-analyses were performed. The certainty of evidence was assessed using the Certainty In Network Meta-Analysis (CINeMA) approach. RESULTS: Seven RCTs meeting the inclusion criteria were identified. There were direct comparisons between medical therapy, CDT, and USCDT across outcomes, except for patency. There were no direct comparisons between medical therapy and PAT (except for patency), and USCDT and PAT. There was no significant difference observed in PTS between the treatment modalities for proximal and iliofemoral DVT (low certainty). There was a significant difference in patency rates between medical therapy and USCDT (odds ratio [OR] 9.46, 95% confidence interval [CI] 3.05 - 29.35; low certainty) and CDT (OR 2.03, 95% CI 1.46 - 2.80; low certainty) in favour of USCDT and CDT, respectively, for proximal DVT. USCDT significantly improved patency rates compared with CDT (OR 4.67, 95% CI 1.58 - 13.81; very low certainty) for proximal DVT. There was no significant difference in DVT recurrence, bleeding, or mortality between treatment groups for proximal and iliofemoral DVT (low to moderate certainty for most comparisons). CONCLUSION: USCDT may improve patency rates compared with BMT and the other interventional treatment modalities used for the management of proximal DVT. However, no treatment modality showed superiority with regard to a reduction in PTS, and overall, the quality of available evidence is poor.

[Risk of post-thrombotic syndrome following direct oral anticoagulant intake: a systematic review and meta-analysis]. / Risk razvitiya posttromboticheskoi bolezni pri ispol'zovanii pryamykh oral'nykh antikoagulyantov: sistematicheskii obzor literatury i metaanaliz.

OBJECTIVE: To perform a systematic review and meta-analysis of data devoted to the risk of post-thrombotic syndrome (PTS) following direct oral anticoagulant (DOAC) intake. MATERIAL AND METHODS: A systematic review and meta-analysis of trials available in the PubMed database were performed in March 2021. Analysis included the reports with known Villalta score for PTS in patients receiving DOACs or alternative anticoagulation. We analyzed the incidence and risk of any form of PTS. RESULTS: We found 10 comparative studies comprising 3161 patients. Incidence of PTS under DOAC therapy was 30.8% (95% confidence interval (CI) 22.2-39.3%), severe PTS - 2.2% (95% CI 1.0-3.4%). DOACs were associated with significantly less risk of any form of PTS (odds ratio (OR) 0.57; 95% CI 0.48-0.68; p<0.001) and severe PTS (OR 0.56; 95% CI 0.36-0.87; p=0.010) compared to vitamin K antagonists. Among various DOACs, specified data were available only for rivaroxaban (OR 0.54, 95% CI 0.42-0.71, p<0.001 for any PTS; OR 0.49, 95% CI 0.27-0.89, p=0.019 for severe PTS). The use of flavonoids in adjunction to rivaroxaban was associated with additional risk reduction for PTS (OR 0.14; 95% CI 0.06-0.31; p<0.001). CONCLUSION: Moderate quality evidence suggests that DOACs are associated with significant less risk of any PTS and severe PTS compared to VKA in patients with deep vein thrombosis. Among all DOACs, only rivaroxaban has clear data confirming PTS risk reduction. The use of flavonoids in adjunction to rivaroxaban can further improve treatment outcomes.

The natural history of asymptomatic central venous catheter-related thrombosis in critically ill children.

Asymptomatic central venous catheter (CVC)-related thrombosis in children varies in incidence from 5% to 69%. The rate of acute and long-term complications, such as postthrombotic syndrome (PTS), from asymptomatic CVC-related thrombosis is unknown. This article reports the outcomes of a prospective study of 189 children in pediatric intensive care that aimed to determine the frequency of asymptomatic CVC-related thrombosis during hospital admission, and the incidence of residual CVC-related thrombosis and clinically significant PTS 2 years later. Risk factors associated with CVC-related thrombosis were also identified. This study is distinct from previous work as children identified to have asymptomatic CVC-related thrombosis were not treated (clinical team kept blinded) and the entire cohort was followed for 2 years to determine the natural history of asymptomatic thrombosis. Ultrasounds of 146 children determined a 21.9% incidence of acute CVC-related thrombosis. Two children were symptomatic. No radiological thrombosis extension or clinical embolization occurred in the 126 children assessed at follow-up. Using 2 recognized PTS scales, clinically significant PTS was reported in 2 children (1 symptomatic, 1 asymptomatic CVC-related thrombosis), however, neither had functional impairment. Cardiac arrest was a risk factor for CVC-related thrombosis during admission and femoral CVC placement was predictive of residual thrombosis 2 years later. This study challenges the notion that critically ill children with asymptomatic CVC-related thrombosis require anticoagulant treatment, as the results demonstrate that the incidence of acute or long-term complications is low. A larger confirmatory study of nontreatment of CVC-related thrombosis in critically ill children is justified.

Thrombolytic strategies versus standard anticoagulation for acute deep vein thrombosis of the lower limb.

BACKGROUND: Standard treatment for deep vein thrombosis (DVT) aims to reduce immediate complications. Use of thrombolytic clot removal strategies (i.e. thrombolysis (clot dissolving drugs), with or without additional endovascular techniques), could reduce the long-term complications of post-thrombotic syndrome (PTS) including pain, swelling, skin discolouration, or venous ulceration in the affected leg. This is the fourth update of a Cochrane Review first published in 2004. OBJECTIVES: To assess the effects of thrombolytic clot removal strategies and anticoagulation compared to anticoagulation alone for the management of people with acute deep vein thrombosis (DVT) of the lower limb. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries to 21 April 2020. We also checked the references of relevant articles to identify additional studies. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) examining thrombolysis (with or without adjunctive clot removal strategies) and anticoagulation versus anticoagulation alone for acute DVT. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. We assessed the risk of bias in included trials with the Cochrane 'Risk of bias' tool. Certainty of the evidence was evaluated using GRADE. For dichotomous outcomes, we calculated the risk ratio (RR) with the corresponding 95% confidence interval (CI). We pooled data using a fixed-effect model, unless we identified heterogeneity, in which case we used a random-effects model. The primary outcomes of interest were clot lysis, bleeding and post thrombotic syndrome. MAIN RESULTS: Two new studies were added for this update. Therefore, the review now includes a total of 19 RCTs, with 1943 participants. These studies differed with respect to the thrombolytic agent, the doses of the agent and the techniques used to deliver the agent. Systemic, loco-regional and catheter-directed thrombolysis (CDT) strategies were all included. For this update, CDT interventions also included those involving pharmacomechanical thrombolysis. Three of the 19 included studies reported one or more domain at high risk of bias. We combined the results as any (all) thrombolysis interventions compared to standard anticoagulation. Complete clot lysis occurred more frequently in the thrombolysis group at early follow-up (RR 4.75; 95% CI 1.83 to 12.33; 592 participants; eight studies) and at intermediate follow-up (RR 2.42; 95% CI 1.42 to 4.12; 654 participants; seven studies; moderate-certainty evidence). Two studies reported on clot lysis at late follow-up with no clear benefit from thrombolysis seen at this time point (RR 3.25, 95% CI 0.17 to 62.63; two studies). No differences between strategies (e.g. systemic, loco-regional and CDT) were detected by subgroup analysis at any of these time points (tests for subgroup differences: P = 0.41, P = 0.37 and P = 0.06 respectively). Those receiving thrombolysis had increased bleeding complications (6.7% versus 2.2%) (RR 2.45, 95% CI 1.58 to 3.78; 1943 participants, 19 studies; moderate-certainty evidence). No differences between strategies were detected by subgroup analysis (P = 0.25). Up to five years after treatment, slightly fewer cases of PTS occurred in those receiving thrombolysis; 50% compared with 53% in the standard anticoagulation (RR 0.78, 95% CI 0.66 to 0.93; 1393 participants, six studies; moderate-certainty evidence). This was still observed at late follow-up (beyond five years) in two studies (RR 0.56, 95% CI 0.43 to 0.73; 211 participants; moderate-certainty evidence). We used subgroup analysis to investigate if the level of DVT (iliofemoral, femoropopliteal or non-specified) had an effect on the incidence of PTS. No benefit of thrombolysis was seen for either iliofemoral or femoropopliteal DVT (six studies; test for subgroup differences: P = 0.29). Systemic thrombolysis and CDT had similar levels of effectiveness. Studies of CDT included four trials in femoral and iliofemoral DVT, and results from these are consistent with those from trials of systemic thrombolysis in DVT at other levels of occlusion. AUTHORS' CONCLUSIONS: Complete clot lysis occurred more frequently after thrombolysis (with or without additional clot removal strategies) and PTS incidence was slightly reduced. Bleeding complications also increased with thrombolysis, but this risk has decreased over time with the use of stricter exclusion criteria of studies. Evidence suggests that systemic administration of thrombolytics and CDT have similar effectiveness. Using GRADE, we judged the evidence to be of moderate-certainty, due to many trials having small numbers of participants or events, or both. Future studies are needed to investigate treatment regimes in terms of agent, dose and adjunctive clot removal methods; prioritising patient-important outcomes, including PTS and quality of life, to aid clinical decision making.

Comparison of Pharmacomechanical Catheter-Directed Thrombolysis versus Catheter-Directed Thrombolysis for the Treatment of Acute Iliofemoral Deep Vein Thrombosis: Measures of Long-Term Clinical Outcome and Quality of Life.

BACKGROUND: We studied the occurrence of post-thrombotic syndrome (PTS) in patients with either Pharmacomechanical Catheter-Directed Thrombolysis (hereafter "pharmacomechanical thrombolysis"; PT) or Catheter-Directed Thrombolysis (CDT) for the treatment of acute iliofemoral deep vein thrombosis (DVT). METHODS: This retrospective study of data archived between September 2013 and September 2015 was surveyed. Two separate patient populations were identified and analyzed: patients were separated into PT group or CDT group. For up to 5 years post-treatment, the incidence, severity of PTS, and chronic venous insufficiency questionnaire (CIVIQ) score difference were compared. RESULTS: The study identified 131 patients divided into PT group (65) and CDT group (66). Within the 5-year follow-up period, there was no significant difference in the incidence of PTS (45.0% PT vs. 57.6% CDT; odds ratio (OR) = 0.602; 95% confidence interval (CI), 0.291-1.242; P = 0.201), but there was reduced severe PTS in the PT group (Villalta scale ≥15 or ulcer:11.7% PT vs. 27.1% CDT; OR 0.355; 95%CI 0.134-0.941, P = 0.039; and Venous Clinical Severity Score (VCSS) ≥8: 13.3%PT vs. 28.8% CDT; OR 0.380; 95% CI 0.149-0.967, P = 0.045). There was also a larger improvement of venous disease-specific quality of life (QOL) in the PT group at 5 years [(62.89 ± 14.19) vs (56.39 ±15.62), P = 0.036] compared to the CDT group. CONCLUSION: In patients with acute iliofemoral DVT treated with PT, PT significantly reduced PTS severity scores, and resulted in greater improvement in venous disease-specific QOL. However, the incidence of was not significantly different from that measured in the CDT.

Can we predict and prevent the postthrombotic syndrome?

Postthrombotic syndrome (PTS) remains one of the major late complications of deep vein thrombosis (DVT) with a reported prevalence from 10 to 50%. Many factors were found to be related with the development and severity of PTS such as ipsilateral recurrent DVT, advanced age, obesity, ilio-femoral DVT and primary chronic venous disease presence. Some PTS prediction models have been proposed based on risk factor weight. However, it is still difficult to predict which patient with DVT will develop PTS and thus, the clinical application of these models remains limited. Among the identified problems the heterogeneity of the DVT patient population together with the variety of PTS clinical presentations and difficulties concerning PTS severity assessment should be mentioned. Difficulties on the implementation of the specific and objective PTS identification method have also the significant influence on the research focusing on PTS prevention modalities including risk factor modification, compression treatment, anticoagulation and invasive DVT treatment. In this review, the current approach and knowledge on PTS prediction and prevention are presented, including the conservative and invasive DVT treatment possibilities.

Incidence and severity of postthrombotic syndrome after iliofemoral thrombosis - results of the Iliaca-PTS - Registry.

Background: Deep venous thrombosis (DVT) and in particular, iliofemoral thrombosis (IFT) can lead to recurrent thrombosis and postthrombotic syndrome (PTS). Data on the prevalence, predictors and outcome of IFT are scarce. Patients and methods: We retrospectively searched our database of outpatients who had presented with DVT and IFT including the iliac veins from 2014 until 2017. In addition, we performed a prospective registry in a subgroup of patients with IFT. These patients received duplex ultrasound, magnetic resonance venography and measurement of symptom-free walking distance using a standardized treadmill ergometry. The severity of PTS was analyzed using the Villalta-Scale (VS) and quality of life was assessed using the VEINES-QOL/Sym Questionnaire. Results: 847 patients were retrospectively identified with DVT and 19.7% (167/847) of these presented with IFT. 50.9% (85/167) of the IFT-patients agreed to participate in the prospective registry. The majority of these patients (76.5%: 65/85) presented with left-sided IFT. In 53.8% (35/65) May-Thurner syndrome was suspected. 27.1% (23/85) underwent invasive therapy. Moderate or severe PTS (VS ≥ 10) occurred in 10.6% (9/85). The severity of PTS is correlated with a reduced quality of life (ρ (CI 95%) = -0.63 (-0.76; -0.46); p < 0.01). None of the patients presented with a venous ulcer at any time. A high body mass index was a significant predictor (OR (CI 95%) = 1.18 (1.05; 1.33), p = 0.007) for the development of clinically relevant PTS (VS ≥ 10) and venous claudication. Conclusions: Every fifth patient with DVT presented with an IFT. The majority developed left sided IFT. Every 10th patient developed moderate or severe PTS (VS ≥ 10). A high body mass index was predictive for the development of PTS and venous claudication.

Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis.

BACKGROUND: The ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) previously reported that pharmacomechanical catheter-directed thrombolysis (PCDT) did not prevent postthrombotic syndrome (PTS) in patients with acute proximal deep vein thrombosis. In the current analysis, we examine the effect of PCDT in ATTRACT patients with iliofemoral deep vein thrombosis. METHODS: Within a large multicenter randomized trial, 391 patients with acute deep vein thrombosis involving the iliac or common femoral veins were randomized to PCDT with anticoagulation versus anticoagulation alone (No-PCDT) and were followed for 24 months to compare short-term and long-term outcomes. RESULTS: Between 6 and 24 months, there was no difference in the occurrence of PTS (Villalta scale ≥5 or ulcer: 49% PCDT versus 51% No-PCDT; risk ratio, 0.95; 95% CI, 0.78-1.15; P=0.59). PCDT led to reduced PTS severity as shown by lower mean Villalta and Venous Clinical Severity Scores ( P<0.01 for comparisons at 6, 12, 18, and 24 months), and fewer patients with moderate-or-severe PTS (Villalta scale ≥10 or ulcer: 18% versus 28%; risk ratio, 0.65; 95% CI, 0.45-0.94; P=0.021) or severe PTS (Villalta scale ≥15 or ulcer: 8.7% versus 15%; risk ratio, 0.57; 95% CI, 0.32-1.01; P=0.048; and Venous Clinical Severity Score ≥8: 6.6% versus 14%; risk ratio, 0.46; 95% CI, 0.24-0.87; P=0.013). From baseline, PCDT led to greater reduction in leg pain and swelling ( P<0.01 for comparisons at 10 and 30 days) and greater improvement in venous disease-specific quality of life (Venous Insufficiency Epidemiological and Economic Study Quality of Life unit difference 5.6 through 24 months, P=0.029), but no difference in generic quality of life ( P>0.2 for comparisons of SF-36 mental and physical component summary scores through 24 months). In patients having PCDT versus No-PCDT, major bleeding within 10 days occurred in 1.5% versus 0.5% ( P=0.32), and recurrent venous thromboembolism over 24 months was observed in 13% versus 9.2% ( P=0.21). CONCLUSIONS: In patients with acute iliofemoral deep vein thrombosis, PCDT did not influence the occurrence of PTS or recurrent venous thromboembolism. However, PCDT significantly reduced early leg symptoms and, over 24 months, reduced PTS severity scores, reduced the proportion of patients who developed moderate-or-severe PTS, and resulted in greater improvement in venous disease-specific quality of life. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00790335.

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

BACKGROUND: The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS: We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS: Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS: Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).

Incidence of deep vein thrombosis from screening by venous ultrasonography in Japanese patients.

The aim of the present study was to investigate the incidence of deep vein thrombosis (DVT) patients in a Japanese population by screening them with venous ultrasonography. This retrospective, single-center analysis examined 963 patients who underwent venous ultrasonography in 2015. The primary outcome was the incidence of DVT, and secondary outcomes were predictive factors of DVT in patient characteristics, treatment strategy for DVT patients, and proportion of post thrombotic syndrome (PTS). The overall incidence rate of DVT was 10.3% (100/963). The location of thrombus was the iliac vein in 3.6% (n = 35), the femoral vein in 4.4% (n = 43), and the calf vein in 8.2% (n = 79) of the patients. The main complaint or purpose of examination was perioperative screening in 37% of the patients, leg edema and/or limb swelling in 27% of the patients, and skin disease in 8% of the patients. In a multivariate analysis, the incidence of DVT was significantly higher in the hospitalization group and the "having symptoms" group. Fifty percent of DVTs received treatment, and almost all therapies were medical treatment with oral anticoagulants (OAC). Within a three-year follow-up period, the proportion of PTS was 27% with no significant difference between anticoagulation or non-anticoagulation patients; the risk of PTS was in concomitant varicose veins. In conclusion, of the patients, 10.3% were diagnosed with DVT, and only half received treatment with only anticoagulation.

Ultrasound Aspects and Recanalization Rates in Patients with Lower-Limb Deep Venous Thrombosis Treated with Rivaroxaban.

BACKGROUND: In this article, we report the ultrasound aspects and recanalization rates of patients with deep venous thrombosis (DVT) in the lower limbs treated with the rivaroxaban, focusing on the recanalization rate and the ultrasonographic aspects. METHODS: This was a prospective and consecutive cohort study of patients admitted with DVT who were submitted to treatment with rivaroxaban for 6 months at the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual, São Paulo, Brazil, between March 2016 and July 2018. RESULTS: Fifty-one patients with DVT were admitted to the Vascular Surgery Department and received rivaroxaban for 6 months. The follow-up time was 360 days. Analyses were performed at 180 and 360 days. The rate of total venous recanalization at 360 days was 76.4% (39 patients). The incidence of partial venous recanalization was 23.5% (12 patients). At the first month, 11 patients (21.7%) continued with total occlusion of the vein, with 4 patients (6.5%) with no residual thrombi. However, at 6 months, only 2 patients (2.2%) continued with total occlusion of the vein, with 26 patients (47.8%) with no residual thrombi. At 12 months, there were 39 patients (76.4%) with no residual thrombi. Univariate and multivariate logistic regression identified the following factors related to total venous recanalization: the absence of popliteal vein reflux (odds ratio [OR], 0.386; P = 0.007), no residual thrombi (OR, 3.213; P = 0.008), femoropopliteal clot length at 1 month (OR, 3.021; P = 0.016), femoropopliteal clot length at 6 months (OR, 2.234; P = 0.008). The incidence of post-thrombotic syndrome (PTS) at 12 months was 8.3%. CONCLUSIONS: In this study, patients who received oral rivaroxaban displayed satisfactory total vein recanalization rate after 6 months and 12 months. The factors associated with better total recanalization rates were the absence of popliteal vein reflux, the absence of residual thrombi in the veins, femoropopliteal clot length at 1 month (OR, 3.021; P = 0.016), and femoropopliteal clot length at 6 months (OR, 2.234; P = 0.008). Moreover, the incidence of PTS at 12 months was 8.3%.

Risk factors for post-thrombotic syndrome in patients with deep vein thrombosis: from the COMMAND VTE registry.

Post-thrombotic syndrome (PTS) is the most common chronic complication of deep vein thrombosis (DVT). Identifying high-risk patients for the development of PTS might be useful for its prevention. The COMMAND VTE Registry is a multicenter registry that enrolled 3027 consecutive patients with acute symptomatic venous thromboembolisms (VTEs) in Japan between January 2010 and August 2014. The current study population consisted of 1298 patients with lower extremities DVTs who completed 3-year follow-up for those who developed PTS and those without PTS. We investigated risk factors for the development of PTS at the time of DVT diagnosis, using a multivariable logistic regression analysis. Of the entire 1298 study patients, 169 (13%) patients were diagnosed with PTS within 3 years. The rate for anticoagulation discontinuation during follow-up was not significantly different between those with and without PTS. Chronic kidney disease (OR 2.21, 95% CI 1.45-3.39, P < 0.001), leg swelling (OR 4.15, 95% CI 2.25-7.66, P < 0.001), absence of transient risk factors for VTEs (OR 2.39, 95% CI 1.55-3.67, P < 0.001), active cancer (OR 3.66, 95% CI 2.30-5.84, P < 0.001), and thrombophilia (OR 2.07, 95% CI 1.06-4.04, P = 0.03) were independent risk factors for the development of PTS. In this real-world Japanese DVT registry, we could identify several important risk factors for the development of PTS at the time of DVT diagnosis.

Endovascular Management of Acute Lower Limb Deep Vein Thrombosis: A Systematic Review and Meta-analysis.

BACKGROUND: Deep vein thrombosis (DVT) is associated with significant complications, including the development of post-thrombotic syndrome (PTS). Traditional management is with oral anticoagulation, but the endovascular techniques of catheter-directed thrombolysis (CDT), pharmacomechanical thrombolysis, and venous stenting are now increasingly used. This study aims to review the evidence for these endovascular techniques in the management of acute lower limb DVT, and their role in the reduction of complications such as PTS. METHODS: A systematic review and meta-analysis was carried out, with studies that compared CDT, pharmacomechanical thrombolysis, and/or venous stenting with oral anticoagulation included. Primary outcome measure was the incidence of PTS; secondary outcome measures were the incidence of recurrent venous thromboembolism (VTE) and bleeding complications. Treatment effects were calculated as risk ratios (RR) with their 95% confidence interval (CI). RESULTS: Five studies met the final inclusion criteria. CDT reduced the incidence of PTS (RR 0.56, 95% CI 0.43-0.73), whereas pharmacomechanical thrombolysis had only a minor effect on the incidence of PTS that did not achieve statistical significance (RR 0.87, 95% CI 0.75-1.01). Recurrent VTE following CDT was reduced compared to oral anticoagulation (RR 0.62, 95% CI 0.34-1.13), while bleeding complications were more likely following CDT (RR 5.11, 95% CI 2.16-12.08). CONCLUSIONS: CDT decreases the incidence of PTS when treating iliofemoral DVT, but pharmacomechanical thrombolysis does not. CDT also reduces the incidence of recurrent VTE, but leads to more bleeding complications when compared to oral anticoagulation. Further randomized controlled trials are needed to determine the role of endovascular management of DVT occurring below the iliofemoral level, and the role of venous stenting.

Incidence and Risk Factors for Post-Thrombotic Syndrome in Patients With Deep Vein Thrombosis Following Total Knee and Hip Arthroplasty.

BACKGROUND: Deep vein thrombosis (DVT) is common after total joint arthroplasty (TJA), and can cause the sequela of post-thrombotic syndrome (PTS), which is associated with decreased quality of life and increased treatment cost. The purpose of this study is to determine the incidence and risk factors for PTS in patients with DVT following primary unilateral total knee and hip arthroplasty. METHODS: We conducted this follow-up study involving patients developing DVT after primary unilateral total knee arthroplasty or total hip arthroplasty at our institution between April 2010 and March 2017. Each patient received a follow-up clinical interview regarding PTS-related symptoms and signs. We introduced demographic, clinical, and surgical data into the analysis to identify the risk factors for PTS. RESULTS: A total of 182 patients with postoperative DVT were enrolled with a mean follow-up time of 3.6 years. The incidence of PTS was 9.3% in patients developing DVT after TJA. Malignancy (P = .033), previous surgery in ipsilateral lower extremity (P = .013), and blood transfusion (P = .022) appeared to be the risk factors for PTS. CONCLUSION: We determined the incidence and risk factors for PTS in patients with DVT following TJA. Preventive measures should be used for patients at high risk of PTS.

Percutaneous mechanical thrombectomy in the treatment of acute iliofemoral deep vein thrombosis: a systematic review.

BACKGROUND: Conventional treatment of deep vein thrombosis (DVT) of the lower extremities by anticoagulation alone has been proven to be insufficient to prevent recurrence and post-thrombotic syndrome (PTS). Early restoration of venous patency and preservation of valvular function by endovascular surgery has been advocated. The aim of this study was to review the efficacy and safety of percutaneous mechanical thrombectomy (PMT) against catheter-directed thrombolysis (CDT) in the treatment of acute iliofemoral DVT. METHODS: Three hundred sixty-nine articles were identified through screening of the PubMed, EMBASE, and Cochrane databases from January 2006 to December 2016. RESULTS: Fifteen retrospective studies and one prospective registry, totalling 1170 patients, were recruited for qualitative synthesis. The venous patency rate ranged from 75% to 100% with mean follow-up of 12.3 months. The rates of PTS and recurrent DVT were less than 17% and 15%, respectively. The overall mortality rate was 0.26%. Compared with CDT, PMT was shown to reduce PTS at 1 year (Villalta score: 2.1 ± 3.0 in the PMT group and 5.1 ± 4.1 in the CDT group, P=0.03) and bleeding complications (packed cells transfused: 0.2 ± 0.3 units in the pharmacomechanical thrombectomy group and 1.2 ± 0.7 units in the CDT group, P<0.05). CONCLUSION: Percutaneous mechanical thrombectomy is a safe and effective treatment for acute iliofemoral DVT in terms of restoration of venous patency, prevention of DVT recurrence, and PTS. Compared with CDT alone, PMT offers a lower risk of PTS and bleeding complications.

ABO blood group and the risk of post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) has been associated to DVT recurrence, increased FVIII, inflammatory biomarker plasma levels, and persistence of vein obstruction. These same features have also been widely reported in non-O blood type subjects. Our aim was to investigate the correlation between the incidence of PTS and ABO blood types. Consecutive patients referred to the Department of Medicine of University of Padua between January 2004 and January 2012 following the diagnosis of a first episode of proximal DVT were enrolled. The presence of PTS was assessed via the Villalta scale at predefined time points (3, 6, 12, 18, 24, 36 months). Hazard ratio (HR) for PTS development was calculated in non-O (exposed) vs O blood (unexposed) type patients. Out of 671 eligible patients, 606 were enrolled. Overall, 192 (31.7%) patients developed PTS: 142 (34.5%) non-O and 50 (25.6%) O blood type patients. Individuals with non-O blood group were associated with a significantly higher risk to develop PTS (HR 1.53, 95% CI, 1.05-2.24; p = 0.028) than O group. Non-O blood type might be a risk factor for the development of PTS.

Standards for recanalisation of chronic venous outflow obstructions.

Postthrombotic syndrome (PTS) is the most common complication after iliofemoral deep vein thrombosis. It reduces quality of life and increases deep vein thrombosis (DVT)-related costs. The clinical symptoms and severity of PTS may vary; the most common symptoms include edema, pain (venous claudication), hyperpigmentation, lipodermatosclerosis, and ulceration. PTS is based on the principle of outflow obstruction, which may be caused by venous hypertension and may lead to valvular damage and venous reflux or insufficiency. Recent technical developments and new stent techniques now allow recanalisation of even complex venous outflow obstructions within the iliac vein and the inferior vena cava. This manuscript gives an overview on the latest standards for venous recanalisation.

Symptoms Associated With Chronic Venous Disease in Response to a Cooling Treatment Compared to Placebo: A Randomized Clinical Trial.

PURPOSE: The purpose of this study was to examine the efficacy of a self-administered cooling treatment on clinically meaningful differences (CMDs) in symptom changes in patients with chronic venous disease. DESIGN: Blinded, prospective, randomized controlled trial. SUBJECTS AND SETTING: Two hundred seventy-six community-dwelling adults 21 years and older with skin changes and/or a healed venous leg ulcer (Clinical-Etiologic-Anatomic-Pathologic [CEAP] 4 and 5 classification) completed the 6-month active treatment period. METHODS: Participants were recruited from wound and medicine clinics and from the general population through referrals or advertisements. Participants were randomly allocated to a sham control cuff or interventional cooling cuff group. Demographic and symptom-specific data were collected at baseline and at months 1, 3, and 6 with the 11-item symptom Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom (VEINES QOL/Sym) questionnaire subscale for heavy legs, aching legs, swelling, night cramps, heating or burning sensation, restless legs, throbbing, itching, tingling sensation (pins and needles), pain, and irritability. Participants in the intervention group received a cooling gel cuff and those in the control group received a cotton-filled cuff to be place around the most affected lower leg during leg elevation. Both groups received standard of care for their chronic venous disease with compression wraps and skin hygiene. Dosing consisted of daily 30-minute treatment for 1 month, twice weekly for 2 months, and then thrice weekly for 3 months. To analyze and compare data, a mixed percentage clinically meaningful percentage change was used to assess CMDs in symptoms between groups for treatment modality, sex, and age group. RESULTS: All symptoms showed improvement, with throbbing, aching, itching, and pain demonstrating the greatest CMD in response to the cooling treatment. For throbbing and aching, similar improvements were noted in response to cooling; 50% in the cooling group showed improvement, whereas 60% in both groups responded favorably to pain. More than 50% of females and males reported improvements in throbbing; both males and females reported 60% improvements in pain in response to cooling. In contrast, far fewer females reported worsening of aching in the treatment group as compared to male participants (8% vs 20%). Age differences were noted for throbbing in the younger group (<65 years of age); older individuals 65 years or older saw CMDs in aching in response to cooling. CONCLUSIONS: Of the 11 symptoms, aching, throbbing, itching, and pain had greater clinically meaningful improvements in response to a cooling cuff applied to lower leg skin affected by chronic venous disease. These CMDs inform evidence-based practice by enhancing clinician understanding of which symptoms, physical, physiological, and behavioral outcomes, respond to treatment change in a meaningful way for the patient.