After clinical evaluation, especially clinical prediction rules, appropriately ordered venous duplex has become the standard test for evaluating and excluding deep vein thrombosis (DVT). Ultrasound is useful for lower- and upper-extremity veins. Protocols include grayscale, color Doppler, and spectral Doppler. Recommended lower-extremity protocols include central leg and calf veins. Duplex Doppler is widely used to evaluate patients with chronic venous disease, especially with suspected venous reflux. Mapping to identify adequate veins before surgery is another widely used indication for venous ultrasound. Ultrasound for thrombosis can be characterized as normal, acute DVT, superficial thrombosis, or chronic postthrombotic changes in most patients.

The need for safe and effective methods to manage deep vein thrombosis (DVT), given the risks associated with anticoagulants and thrombolytic agents, motivated research into innovative approaches to resolve blood clots. In response to this challenge, sonothrombolysis is being explored as a technique that combines microbubbles, ultrasound, and thrombolytic agents to facilitate the aggressive dissolution of thrombi. Prior studies have indicated that relatively large microbubbles accelerate the dissolution process, either in an in vitro or an arterial model. However, sonothrombolysis using large microbubbles must be evaluated in venous thromboembolism diseases, where blood flow velocity is not comparable. In this study, the efficacy of sonothrombolysis was validated in a murine model of pre-existing DVT. During therapy, microfluidically produced microbubbles of 18 μm diameter and recombinant tissue plasminogen activator (rt-PA) were administered through a tail vein catheter for 30 min, while ultrasound was applied to the abdominal region of the mice. Three-dimensional ultrasound scans were performed before and after therapy for quantification. The residual volume of the thrombi was 20% in animals post sonothrombolysis versus 52% without therapy ( p = 0.012 < 0.05 ), indicating a significant reduction in DVT volume. Histological analysis of tissue sections confirmed a reduction in DVT volume post-therapy. Therefore, large microbubbles generated from a microfluidic device show promise in ultrasound-assisted therapy to address concerns related to venous thromboembolism.

The optimal treatment approach for patients with active venous leg ulcers (VLUs) and post-thrombotic syndrome (PTS) associated with great saphenous vein (GSV) reflux remains unclear. To address this gap, we retrospectively compared the outcomes of patients with post-thrombotic VLU with an intact GSV vs those with a stripped or ablated GSV.

We retrospectively analyzed data from 48 patients with active VLUs and documented PTS, who were treated at a single center between January 2018 and December 2022. Clinical information, including ulcer photographs, was recorded in a prospectively maintained digital database at the initial and follow-up visits. Two patient groups-group A (with an intact GSV) and group B (with a stripped or ablated GSV)-were compared in terms of time to complete healing, proportion of ulcers achieving complete healing, and ulcer recurrence during the follow-up period.

There were no significant differences in age, gender, initial ulcer size, or ulcer duration between the two groups. All included patients had femoropopliteal post-thrombotic changes. Group A had significantly more completely healed ulcers (33 of 34 ulcers, 97%) compared with group B (10 of 14 ulcers, 71%) (P = .008). Group A also exhibited a significantly shorter time to complete ulcer healing (median: 42.5 days, interquartile range [IQR]: 65) compared with group B (median: 161 days, IQR: 530.5) (P = .0177), with a greater probability of ulcer healing (P = .0084). Long-term follow-up data were available for 45 of 48 patients (93.7%), with a mean duration of 39.6 months (range: 5.7-67.4 months). The proportion of ulcers that failed to heal or recurred during the follow-up period was significantly lower in group A (9 of 32 ulcers, 27%) compared with group B (11 of 13 ulcers, 85%) (P = .0009). In addition, in a subgroup analysis, patients with an intact but refluxing GSV (12 of 34) had a significantly shorter time to heal (median: 34 days, IQR: 57.25) (P = .0242), with a greater probability of ulcer healing (P = .0091) and significantly fewer recurrences (2 of 12, 16%) (P = .006) compared with group B.

Our findings suggest that removal of the GSV through stripping or ablation in patients with post-thrombotic deep venous systems affecting the femoropopliteal segment may result in delayed ulcer healing and increased ulcer recurrence. Patients with an intact GSV had better outcomes, even when the refluxing GSV was left untreated. These findings emphasize the potential impact of GSV treatment on the management of VLUs in individuals with PTS. Further investigation is needed to validate these results and explore alternative therapeutic strategies to optimize outcomes for this patient population.

Venous thromboembolism (VTE), notably deep venous thrombosis (DVT), represents a significant cardiovascular disease with high morbidity from post-thrombotic syndrome (PTS). Recent advancements in early thrombus removal technologies have prompted randomized controlled trials (RCT) to assess their efficacy and safety, particularly for iliofemoral DVT (IF-DVT), which carries the greatest risk of developing PTS. This narrative review summarizes these trials and introduces upcoming innovations to evaluate acute intervention for IF-DVT. Specific technologies discussed include catheter-directed thrombolysis, pharmacomechanical catheter-directed thrombolysis, ultrasound-accelerated catheter-directed thrombolysis, and non-lytic mechanical thrombectomy. This review underscores the importance of patient selection, with those presenting with extensive, symptomatic IF-DVT likely to benefit most.

Herein, we review the current processes that govern experimental deep vein thrombus (DVT) resolution. How the human DVT resolves at the molecular and cellular level is not well known due to limited specimen availability. Experimentally, the thrombus resolution resembles wound healing, with early neutrophil-mediated actions followed by monocyte/macrophage-mediated events, including neovascularization, fibrinolysis, and eventually collagen replacement. Potential therapeutic targets are described, and coupling with site-directed approaches to mitigate off-target effects is the long-term goal. Similarly, timing of adjunctive agents to accelerate DVT resolution is an area that is only starting to be considered. There is much critical research that is needed in this area.

To analyze the first 250 patients from the prospective, multicenter, industry-sponsored ClotTriever Outcomes (CLOUT) registry, assessing the safety and effectiveness of mechanical thrombectomy for acute, subacute, and chronic deep vein thrombosis (DVT).

Real-world patients with lower extremity DVT were treated with the ClotTriever System (Inari Medical, Irvine, California). Adjuvant venoplasty, stent placement, or both were performed at the physician's discretion. Thrombus chronicity was determined by visual inspection of removed thrombus, categorizing patients into acute, subacute, and chronic subgroups. Serious adverse events (SAEs) were assessed through 30 days. Clinical and quality-of-life (QoL) outcomes are reported through 6 months.

Thrombus chronicity was designated for 244 of the 250 patients (acute, 32.8%; subacute, 34.8%; chronic, 32.4%) encompassing 254 treated limbs. Complete or near-complete (≥75%) thrombus removal was achieved in 90.8%, 81.9%, and 83.8% of the limbs with acute, subacute, and chronic thrombus, respectively. No fibrinolytics were administered, and 243 (99.6%) procedures were single sessions. One (0.4%) patient in the subacute group experienced a device-related SAE, a fatal pulmonary embolism. On comparing baseline and 6-month data, improvements were demonstrated in median Villalta scores (acute, from 10 to 1; subacute, from 9 to 1; chronic, from 10 to 3; for all, P < .0001) and mean EuroQol group 5-dimension (EQ-5D) self-report questionnaire scores (acute, 0.58 to 0.89; subacute, 0.65 to 0.87; chronic, 0.58 to 0.88; for all, P < .0001). There were no significant differences in outcomes across the subgroups.

Mechanical thrombectomy using the ClotTriever System with adjunctive venoplasty and stent placement is safe and similarly effective for acute, subacute, and chronic DVT.

Deep venous thrombosis and residual thrombus burden correlates with circulating IL-6 levels in humans. To investigate the cellular source and role of IL-6 in thrombus resolution, Wild type C57BL/6J (WT), and IL-6-/- mice underwent induction of VT via inferior vena cava (IVC) stenosis or stasis. Vein wall (VW) and thrombus were analyzed by western blot, immunohistochemistry, and flow cytometry. Adoptive transfer of WT bone marrow derived monocytes was performed into IL6-/- mice to assess for rescue. Cultured BMDMs from WT and IL-6-/- mice underwent quantitative real time PCR and immunoblotting for fibrinolytic factors and matrix metalloproteinase activity. No differences in baseline coagulation function or platelet function were found between WT and IL-6-/- mice. VW and thrombus IL-6 and IL-6 leukocyte-specific receptor CD126 were elevated in a time-dependent fashion in both VT models. Ly6Clo Mo/MØ were the predominant leukocyte source of IL-6. IL-6-/- mice demonstrated larger, non-resolving stasis thrombi with less neovascularization, despite a similar number of monocytes/macrophages (Mo/MØ). Adoptive transfer of WT BMDM into IL-6-/- mice undergoing stasis VT resulted in phenotype rescue. Human specimens of endophlebectomized tissue showed co-staining of Monocyte and IL-6 receptor. Thrombosis matrix analysis revealed significantly increased thrombus fibronectin and collagen in IL-6-/- mice. MMP9 activity in vitro depended on endogenous IL-6 expression in Mo/MØ, and IL-6-/- mice exhibited stunted matrix metalloproteinase activity. Lack of IL-6 signaling impairs thrombus resolution potentially via dysregulation of MMP-9 leading to impaired thrombus recanalization and resolution. Restoring or augmenting monocyte-mediated IL-6 signaling in IL-6 deficient or normal subjects, respectively, may represent a non-anticoagulant target to improve thrombus resolution.

The objective of this study was to determine the pathologic features of venous in-stent stenosis over time occurring in bare metal stents.

Endovascular biopsy samples were obtained prospectively from venous bare metal stents implanted in 2009 through 2018. All samples were formalin-fixed, paraffin-embedded and stained with hematoxylin and eosin. Samples were examined by a cardiovascular pathologist to estimate the amount of its constituent components, which included fresh thrombus, organizing thrombus, old thrombus, or diffuse intimal thickening (DIT), and pathologic features including calcification, neovascularization, and hemosiderin deposition. This pathologic characterization was correlated with time following stent implantation to discern time-dependence of pathologic evolution of in-stent stenosis using both descriptive statistics and binary logistic regression.

A total of 254 post-stent venograms with biopsies of in-stent contents from 148 unique patients were studied. Fresh thrombus and organizing thrombus were both present across all studied time intervals. Old thrombus was seen beginning at approximately 2 weeks and DIT at approximately 4 weeks. Calcification was a rare finding encountered at later time intervals. The prevalence of each component varied with time: the probability of encountering fresh thrombus (P = .010) and organizing thrombus (P = .008) decreased over time. By contrast, the probability of finding DIT (P = .002) and calcifications (P < .001) increased over time. The presence of old thrombus, neovascularization, or hemosiderin did not demonstrate time dependence. Diffuse intimal thickening was frequently seen along with organizing thrombus as well as independently, and in many instances, these two features were directly merged.

The evolution of human venous in-stent restenosis appears to follow a time-dependent course, suggesting a possible progressive evolution from fresh and organizing thrombus to DIT. Contrasted with the literature on arterial in-stent restenosis, vein in-stent restenosis may have an increased thrombus prevalence (both organizing and old thrombus). DIT is a primary feature of late in-stent stenosis and may explain in part why many of these lesions may not respond to thrombolytic or anticoagulant treatment alone.

The all-comer ClotTriever Outcomes registry assessed indicators of thrombus chronicity in patients with acute, subacute, and chronic lower extremity deep vein thrombosis (DVT). The effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) by chronicity subgroup was also assessed and reported here in this subanalysis.

All-comer patients with lower extremity DVT were enrolled, with no limitation based on the patients' symptom duration. Chronicity was assessed three times and compared: before the procedure based on symptom duration, during the procedure based on available pre-thrombectomy imaging, and visual inspection of the extracted thrombus morphology after thrombectomy. Patients were grouped into acute, subacute, and chronic subgroups according to their post-thrombectomy thrombus chronicity based on thrombus morphology. Analyses on baseline and procedural characteristics along with thrombus removal were performed across subgroups. The effectiveness of thrombus removal was determined by Marder scores adjudicated by an independent core laboratory, with a prespecified primary effectiveness end point of complete or near-complete (≥75%) thrombus removal.

Of the 260 treated limbs from 250 patients, using symptom duration alone, 70.7% were considered acute, 20.9% subacute, and 8.4% chronic. Upon visual inspection, the extracted thrombus chronicity was approximately one-third in each subgroup: 32.7% had acute thrombus, 35.4% subacute thrombus, and 31.9% chronic thrombus. Chronicity assessed using symptom duration alone mismatched the post-thrombectomy chronicity in 55.1% of limbs (P < .0001) with 49.0% being more chronic than suggested by the patients' duration of symptoms. Chronicity assessed using pre-thrombectomy imaging mismatched the post-thrombectomy chronicity in 17.5% of limbs (P < .0001). No patients received thrombolytics and 99.6% were treated in a single session. Complete or near-complete thrombus removal was achieved in a high percentage of limbs regardless of thrombus chronicity: 90.8%, 81.9%, and 83.8% in limbs with acute, subacute, and chronic thrombus, respectively.

This subanalysis from the all-comer ClotTriever Outcomes registry demonstrates that extracted thrombus in DVT may be more chronic than suggested by the patients' duration of symptoms. The addition of imaging is helpful to determine the ability of thrombus to respond to therapy. Irrespective of thrombus chronicity, the ClotTriever system can be effective at removing acute, subacute, and chronic thrombus in a single-session procedure without the need for thrombolytics.

Deep vein thrombosis (DVT) and its sequela, post-thrombotic syndrome (PTS), remain a clinically significant problem. Interleukin-6 (IL-6) is a proinflammatory cytokine that is elevated in patients who develop PTS. We hypothesized that genetic deletion of IL-6 and the use of anti-IL-6 pharmacologic agents would be associated with decreased late vein wall injury.

Wild-type C57BL/6J (WT) and IL-6-/- mice underwent induction of stasis venous thrombosis by ligation of the infrarenal IVC. Vein wall inferior vena cava and thrombus were harvested at 21 days after ligation and analyzed by Western blot and immunohistochemistry of the vein wall using monocyte markers CCR2 and arginase 1, the endothelial marker CD31, and fibroblast markers DDR2 and FSP-1. Two anti-IL-6 pharmacologic agents (gp130 [glycoprotein 130] and tocilizumab) were tested and compared with low-molecular-weight heparin (LMWH) as the reference standard in WT mice. Plasma was collected at 4 and 48 hours to confirm the pharmacologic agents' effects.

Less fibrosis but no increase in luminal endothelialization was found in IL-6-/- mice compared with WT mice at 21 days. The IL-6-/- mice had fewer DDR2- and arginase 1-positive cells in the vein wall compared with the WT mice. However, no difference was found in the CCR2+ cells. Despite documented in vivo activity, exogenous gp130 and tocilizumab were not associated with decreased vein wall fibrosis or increased endothelial luminal coverage at 21 days. LMWH therapy, both before and after treatment, was not associated with decreased vein wall fibrosis at 21 days.

IL-6 genetic deletion was associated with less fibrotic vein wall injury at a late time point, consistent with the PTS timeframe. However, neither the standard of care LMWH nor two available anti-IL-6 agents showed antifibrotic biologic effects in this model.

Characterize an ovine endovascular radiofrequency ablation based venous stenosis and thrombosis model for studying venous biomechanics and response to intervention.

Unilateral short-segment (n= 2) or long-segment (n = 6) iliac vein stenoses were created in eight adult sheep using an endovenous radiofrequency (RF) ablation technique. Angiographic assessment was performed at baseline, immediately after venous stenosis creation, and after 2-week (n = 6) or 3-month (n = 2) survival. Stenosed iliac veins and contralateral healthy controls were harvested for histological and biomechanical assessment.

At follow-up, the short-segment RF ablation group showed stable stenosis without occlusion. The long-segment group showed complete venous occlusion/thrombosis with formation of collateral veins. Stenosed veins showed significant wall thickening (0.28 mm vs 0.16 mm; p = 0.0175) and confluent collagen deposition compared to healthy controls. Subacute non-adherent thrombi were apparent at 2 weeks, which were replaced by fibrous luminal obliteration with channels of recanalization at 3 months. Stenosed veins demonstrated increased longitudinal stiffness (448.5 ± 5.4 kPa vs. 314.6 ± 1.5 kPa, p < 0.0001) and decreased circumferential stiffness (140.8 ± 2.6 kPa vs. 246.0 ± 1.6 kPa, p < 0.0001) compared to healthy controls.

Endovenous radiofrequency ablation is a reliable technique for creating venous stenosis and thrombosis in a large animal model with histological and biomechanical attributes similar to those seen in humans. This platform can facilitate understanding of venous biomechanics and testing of venous specific devices and interventions.

The accuracy of non-contrast MRI in diagnosing acute deep vein thrombosis (DVT) of the lower extremities is different. To explore the application of high-resolution non-contrast 3D CUBE T1-weighted MRI in the lower extremities DVT. We recruited 26 patients suspected DVT of the lower extremities from Hebei General Hospital in China. All patients underwent high-resolution non-contrast 3D CUBE T1-weighted MRI. We evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of diagnosing thrombosis. And we divided thrombi into two parts: filling thrombus (FT) and non-filling thrombus (NFT), compared the agreement between MRI and Ultrasound (US) and analysed the locations of thrombi. Compared with US, MRI yielded a sensitivity of 79%, a specificity of 94.2% in mean value, a sensitivity of 85.7%, 97.4%, and 51.7% in iliac, femoral-popliteal, and calf segments respectively, a specificity of 97.6%, 88.3%, and 98.2% in iliac, femoral-popliteal, and in calf segments respectively. The accuracy of MRI in the diagnosis of lower extremity DVT was in very good agreement (κ = 0.711, 95% CI 0.627, 0.795). The FT was the most part in US and CUBE (68/56), CUBE can detect more NFT in femoral vein than US (22/4). 3D CUBE T1-weighted MRI can be used to accurately diagnose acute DVT and detect more NFT. It has the potential of follow-up at the end of treatment to establish a new baseline to stop anticoagulant drug.

This review aims to summarise the efficacy and safety of dedicated venous stenting for the treatment of obstructive chronic deep venous disease. The approaches to stenting and post-procedural management of different vascular units are also highlighted.

MEDLINE and Embase were searched to identify relevant literature on dedicated venous stents published from January, 2010 to May, 2020. The patient population and study characteristics; procedural characteristics; and outcomes related to post-stenting symptoms, health-related quality of life, patency and complications were analysed.

Sixteen single-arm observational studies were included from 2,366 studies identified from key-word searches. In total, 1,688 patients were included, of which 70.5% had post-thrombotic syndrome and the remainder had non-thrombotic iliac vein lesions. Nine studies (n = 848), stated whether lesions were stenotic (36.6%) or occlusive (63.4%). Seven studies did not report the lesion characteristics (n = 840). Eight different dedicated venous stent brands were employed. 73.4% of ulcers healed at last follow-up. The remaining symptomatic changes were described narratively; sustained improvements in pain, venous claudication and oedema following stenting were observed. Significant post-stenting improvements in health-related quality of life were noted, as measured by the Chronic Venous Insufficiency Questionnaire-20 instrument. Overall, the most frequently reported complications were in-stent occlusion (n = 204), in-stent stenosis (n = 149) and minor bleeding (n = 77). At 12 months, the primary patency ranged from 59% to 94%, whilst the secondary patency ranged 87% to 100%. The pooled-primary and secondary stent patency rates at 12 months were 74.0% and 90.4%, respectively. The incidence of major and minor bleeding was 1.9% and 4.7%, respectively; bleeding complications were more common in patients undergoing hybrid intervention.

Deep venous stenting using dedicated venous stents is a safe technique to treat obstructive chronic deep venous disease and within the limitations of this study, is associated with good patency outcomes and symptomatic improvement.

Up to 50% of patients with proximal deep vein thrombosis (DVT) will develop the postthrombotic syndrome characterized by limb swelling and discomfort, hyperpigmentation, skin ulcers, and impaired quality of life. Although catheter-based interventions enabling the restoration of blood flow (RBF) have demonstrated little benefit on postthrombotic syndrome, the impact on the acuity of the thrombus and mechanisms underlying this finding remain obscure. In experimental and clinical studies, we examined whether RBF has a restricted time window for improving DVT resolution.

First, experimental stasis DVT was generated in C57/BL6 mice (n=291) by inferior vena cava ligation. To promote RBF, mice underwent mechanical deligation with or without intravenous recombinant tissue plasminogen activator administered 2 days after deligation. RBF was assessed over time by ultrasonography and intravital microscopy. Resected thrombosed inferior vena cava specimens underwent thrombus and vein wall histological and gene expression assays. Next, in a clinical study, we conducted a post hoc analysis of the ATTRACT (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) pharmacomechanical catheter-directed thrombolysis (PCDT) trial (NCT00790335) to assess the effects of PCDT on Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores for specific symptom-onset-to-randomization timeframes.

Mice that developed RBF by day 4, but not later, exhibited reduced day 8 thrombus burden parameters and reduced day 8 vein wall fibrosis and inflammation, compared with controls. In mice without RBF, recombinant tissue plasminogen activator administered at day 4, but not later, reduced day 8 thrombus burden and vein wall fibrosis. It is notable that, in mice already exhibiting RBF by day 4, recombinant tissue plasminogen activator administration did not further reduce thrombus burden or vein wall fibrosis. In the ATTRACT trial, patients receiving PCDT in an intermediate symptom-onset-to-randomization timeframe of 4 to 8 days demonstrated maximal benefits in Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores (between-group difference=8.41 and 1.68, respectively, P<0.001 versus patients not receiving PCDT). PCDT did not improve postthrombotic syndrome scores for patients having a symptom-onset-to-randomization time of <4 days or >8 days.

Taken together, these data illustrate that, within a restricted therapeutic window, RBF improves DVT resolution, and PCDT may improve clinical outcomes. Further studies are warranted to examine the value of time-restricted RBF strategies to reduce postthrombotic syndrome in patients with DVT.

The severity, course, and outcomes of thrombosis are determined mainly by the size and location of the thrombus, but studying thrombus structure and composition has been an important but challenging task. The substantial progress in determination of thrombus morphology has become possible due to new intravital imaging methodologies in combination with mechanical thrombectomy, which allows extraction of a fresh thrombus from a patient followed by microscopy. Thrombi have been found to contain various structural forms of fibrin along with platelet aggregates, leukocytes, and red blood cells, many of which acquire a polyhedral shape (polyhedrocytes) as a result of intravital platelet-driven contraction. The relative volume fractions of thrombus components and their structural forms vary substantially, depending on the clinical and pathogenic characteristics. This review summarizes recent research that describes quantitative and qualitative morphologic characteristics of arterial and venous thrombi that are relevant for the pathogenesis, prophylaxis, diagnosis, and treatment of thrombosis.

Post-thrombotic syndrome (PTS) is an end stage manifestation of deep vein thrombosis. This is an inherently inflammatory process, with consequent fibrosis. Multiple cellular types are involved, and are likely driven by leukocytes. Herein, we review the current gaps in therapy, and insights from rodent models of venous thrombosis that suggest possible targets to treat and prevent PTS.

The risk factors obesity and reduced mobility are not well known in the development of a Venous Leg Ulcer (VLU). The aim of this scoping review is to explore the mechanisms by which obesity and reduced mobility contribute the development of a VLU in patients with Chronic Venous Disease (CVD).

For this scoping review a search was performed in May 2019 in the Cochrane Library and Pubmed to identify studies on the working mechanisms of obesity and mobility in developing a VLU. Hand searches were performed to find additional studies explaining the working mechanisms (indirectly related to the VLU). Two reviewers independently reviewed the abstracts and full-text articles.

Twenty-eight studies met our eligibility criteria. Disturbed range of ankle motion and gait can lead to a reduced Calf Muscle Pump (CMP) function which leading to a venous outflow disorder. Increased abdominal pressure due to obesity can lead to a venous outflow obstruction and increased adipose tissue mass results in an increase in adipokine secretion. The venous outflow disorder, outflow obstruction and increased adipokine secretion can all lead to chronic systemic inflammation, increased endothelial permeability and hence microcirculatory dysfunction. This alone can result in a VLU.

Obesity and reduced mobility can lead to a reduction of the CMP function, an increase in abdominal pressure and an increase in adipose tissue mass. This can simultaneously lead to haemodynamic changes in the macro- and microcirculation of the lower extremities and eventually in a VLU. In patients with obesity and reduced mobility the microcirculation alone can lead to skin changes and eventually a VLU. Therefore, early recognition of CVD symptoms in patients with obesity and reduced mobility is crucial to diagnose and treat CVD to prevent a VLU.

Venous thromboembolism (VTE) is a pathology encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with high morbidity and mortality. Because patients often present after a thrombus has already formed, the mechanisms that drive DVT resolution are being investigated in search of treatment. Herein, we review the current literature, including the molecular mechanisms of fibrinolysis and collagenolysis, as well as the critical cellular roles of macrophages, neutrophils, and endothelial cells. We propose two general models for the operation of the immune system in the context of venous thrombosis. In early thrombus resolution, neutrophil influx stabilizes the tissue through NETosis. Meanwhile, macrophages and intact neutrophils recognize the extracellular DNA by the TLR9 receptor and induce fibrosis, a complimentary stabilization method. At later stages of resolution, pro-inflammatory macrophages police the thrombus for pathogens, a role supported by both T-cells and mast cells. Once they verify sterility, these macrophages transform into their pro-resolving phenotype. Endothelial cells both coat the stabilized thrombus, a necessary early step, and can undergo an endothelial-mesenchymal transition, which impedes DVT resolution. Several of these interactions hold promise for future therapy.

Background Postthrombotic syndrome is a common complication of deep vein thrombosis, with limited treatment options. Methods and Results ACCESS PTS (Accelerated Thrombolysis for Post-Thrombotic Syndrome Using the Acoustic Pulse Thrombolysis Ekosonic Endovascular System) is a multicenter, single-arm, prospective study evaluating patients with chronic deep vein thrombosis and postthrombotic syndrome (Villalta score ≥8) who received minimum 3 months of anticoagulation. Patients underwent percutaneous transluminal venoplasty and ultrasound-accelerated thrombolysis, with data collected on clinical characteristics, postthrombotic syndrome, imaging, and quality of life to 1 year. The primary efficacy outcome was a reduction of ≥4 points in the Villalta score 30 days after procedure. The primary safety outcomes were major bleeding episodes within 72 hours and symptomatic pulmonary embolism during the index hospitalization. A total of 82 limbs (78 patients) were treated (age, 54.6±12.7 years; 32.1% women; mean Villalta score, 15.5±5.2). The primary end point was met in 64.6% (51/79). At 1 year, 77.3% (51/66) of limbs continued with a Villalta reduction ≥4. At 365 days, >90% of segments had patency with ultrasound flow present. Baseline to 1-year Physical Component Summary mean score of the Short Form-36 increased from 38.9±9.5 to 45.2±9.8 (P≤0.0001), and mean VEINES-QOL (Venous Insufficiency Epidemiological and Economic Study-Quality of Life) increased from 61.9±19.7 to 82.6±20.8 at 1 year (P<0.0001). Iliofemoral venous stenting was performed in 42 patients, with similar improvements seen in all outcomes, regardless of stenting status. One patient developed severe bleeding within 72 hours of the intervention and died at 32 days after procedure (1.3% mortality rate). Conclusions Percutaneous transluminal venoplasty and ultrasound-accelerated thrombolysis resulted in successful recanalization of chronic venous obstruction with improved postthrombotic syndrome severity and quality of life. Results were sustained at 1-year after procedure. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02159521.

Chronic, post-thrombotic iliofemoral and inferior vena caval obstruction is associated with debilitating morbidity. Venoplasty and stenting are often successful; however, in the presence of a diseased or occluded common femoral vein (CFV), failure is common. A hybrid operative procedure of open surgical CFV endovenectomy and endoluminal recanalization or bypass of the obstructed iliofemoral and vena caval segments has been developed and modified. The purpose of this report was to assess the technical evolution of this procedure on operative complications.

Thirty-one patients undergoing CFV endovenectomy and proximal ipsilateral endoluminal reconstruction (iliac, inferior vena caval) or contralateral outflow were analyzed. The initial techniques of patient management were compared with the present contemporary techniques, evaluating procedural complications and failures. The contemporary procedure evolved to include routine axial imaging, preoperative venography through the popliteal vein, preoperative passage of a guidewire or catheter into the patent vena cava, placement of an ipsilateral popliteal vein sheath for intraoperative and postoperative anticoagulation, routine patch closure, routine arteriovenous fistulas, routine completion intravascular ultrasound, and long-term anticoagulation with warfarin to a target international normalized ratio of 3.0 to 4.0. Procedure-related complications were compared between the initial and contemporary techniques.

Of 17 patients treated with the early techniques, 15 (88%) had major complications: 5 iliofemoral thromboses, 4 major wound bleeds, 4 wound infections, and 2 CFV stenoses requiring reintervention. One iliac vein rupture treated with a stent graft thrombosed. Of 14 patients treated with the contemporary techniques, 2 (14%; P = .006) had major complications: 1 bleed and 1 infected seroma. One intraoperative iliac vein rupture, treated with a second stent relining the first, remains patent.

Contemporary hybrid operative techniques for incapacitating post-thrombotic iliofemoral and vena caval obstruction increase procedural success and reduce complications compared with the initial approach. The contemporary techniques are recommended for patients undergoing hybrid operative management of post-thrombotic iliofemoral and vena caval occlusion involving the CFV.

The surgical treatment of deep venous thrombosis (DVT) has significantly evolved and is focused on different strategies of early thrombus removal in the acute phase and deep venous recanalization or bypass in the chronic phase. Along with the use of anticoagulation agents, endovascular techniques based on catheter-directed thrombolysis and pharmacomechanical thrombectomy have been increasingly used in patients with acute extensive DVT. Patient selection is crucial to provide optimal outcomes and minimize complications.

Patients with iliofemoral deep venous thrombosis are at risk for development of post-thrombotic syndrome. Iliac vein stenting has been shown to significantly improve clinical outcomes in patients with venous outflow obstruction, although many studies include a heterogeneous population with several different venous pathologic processes. Our objective was to evaluate the results of iliocaval and infrainguinal venous intervention for venous outflow obstruction due to post-thrombotic chronic venous occlusive disease.

All patients treated at a single institution for symptomatic iliocaval venous occlusive lesions with and without infrainguinal extension between 2008 and 2015 were retrospectively analyzed. Nonthrombotic iliac vein lesions were excluded from analysis. All patients with symptomatic post-thrombotic occlusion of the iliac vein or inferior vena cava (IVC) and a Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) score of 3 or greater were included. Demographics of the patients, presence of IVC filters at presentation, presenting CEAP score, postintervention CEAP score, primary and secondary patency, wound healing and subjective clinical improvement outcomes, and procedural details were recorded in a database.

There were 105 patients with symptomatic iliocaval venous occlusive lesions identified, of which 31 patients (42 limbs) met inclusion criteria. Presenting symptoms included pain or swelling (100%); venous claudication (81%); and CEAP class 3 (76%), 4 or 5 (14%), or 6 (10%). All patients presented with either subacute (>30 days [35%]) or chronic (>90 days [65%]) iliocaval venous thrombosis. Procedural technical success with venous recanalization was achieved in 100% of cases and in 46% of IVC filter retrieval attempts. Overall clinical improvement was achieved in 84% of patients; complete clinical resolution was obtained in 42% and a decrease in CEAP score in 65%. At a mean follow-up of 14.7 months (range, 2-49 months), primary and secondary 1-year patency was 66% and 75% overall, and primary patency was equivalent between patients requiring isolated iliac venous stenting and those requiring infrainguinal stent extension (68% vs 65%, respectively; P = .74, not significant). Patients who presented with IVC filters had a higher rate of complete clinical resolution if the filter could be removed (100%) compared with those patients in whom the filter could not be removed (17%; P < .01).

Treatment of chronic venous occlusive disease with iliocaval and infrainguinal venous stenting is associated with acceptable 1-year patency rates, healing of venous ulcers, and a significant reduction in symptoms and CEAP score. Patients who underwent successful removal of indwelling IVC filters showed improved clinical outcomes compared with those in whom the IVC filter could not be removed.

May-Thurner syndrome (MTS) is a condition in which the left common iliac vein is compressed by the right common iliac artery, which may cause swelling, pain or deep venous thrombosis of the left lower extremity.¹ Postthrombotic syndrome, nonthrombotic chronic venous insufficiency, and recurrence after venous thrombosis are also possible complications. Although MTS combined with left iliac arteriovenous fistula is rarely reported, we treated 3 such cases in the past year.

Macrophages are involved in venous thrombus (VT) resolution and vein wall remodeling. This study was undertaken to identify variations in macrophage phenotypes in thrombi and vein wall in multiple models of VT to clarify the natural history of macrophage polarization in clearance of VT. We also sought to demonstrate the feasibility of macrophage phenotyping in human VT.

Established murine models of VT were used to mimic the clinical spectrum of human VT (stasis and nonstasis models). Vein wall and thrombi were isolated at acute (2 days) or chronic (6-21 days) time points and analyzed by Bio-Plex assay (Bio-Rad, Carlsbad, Calif) for cytokines (interleukin [IL]-1β, IL-6, IL-10, IL-12), by immunohistochemistry for "M1-like" (IL-12) or "M2-like" (arginase 1 [Arg-1]) markers, and by histology for intimal thickness and collagen content (Sirius red staining). Bone marrow was harvested from animals 2 days after undergoing sham, stasis, or nonstasis surgery. Macrophages were skewed toward M1 using lipopolysaccharide, and RNA analysis was done for inflammatory cytokine genes (IL-1β, IL-12). Human blood samples were similarly analyzed with reverse transcription polymerase chain reaction for macrophage polarization markers (CD206, inducible nitric oxide synthase, CCR2) and thrombi with immunohistochemistry (inducible nitric oxide synthase, Arg-1).

Stasis (chronic) and nonstasis (acute and chronic) thrombi were characterized by a predominance in anti-inflammatory (M2) macrophages (n = 4-5/group; P < .05). Larger thrombi were found in the stasis model at both time points (n = 3; P < .01), correlating with decreased intrathrombus inflammatory (M1) cytokines (IL-1β, P = .03; IL-12, P = .17; n = 4) and diminished inflammatory response of bone marrow-derived macrophages to lipopolysaccharide (IL-1β, P = .03; IL-12, P = .04; n = 4) compared with nonstasis model. Anti-inflammatory (M2 [Arg-1]) macrophage cell counts were elevated in the post-thrombotic vein wall of stasis mice compared with nonstasis mice (acute: n = 4, P < .05; chronic: n = 5, P < .01), consistent with increased intimal thickness (P < .01; n = 4-6) and collagen deposition chronically (P = .005; n = 12). M2-like thrombi (Arg-1, P < .05; n = 4-7) and circulating markers (CD206, P < .05; n = 9-17) decreased over time in human VT.

Experimental VT is characterized by an anti-inflammatory predominant macrophage phenotype, possibly impairing thrombus resolution, and is model dependent. Altering the M1/M2 macrophage balance may accelerate thrombus resolution and allow the development of translatable novel therapies to treat VT and to prevent post-thrombotic syndrome.

Essentials This study examined vein wall remodeling in acute thrombosis and postthrombotic syndrome (PTS). Thrombus-wall interface was measured using ultrasound real-time high definition zoom. Experimental cohorts demonstrated increased vein wall thickness localized to affected segments. Presence of thrombus or PTS are the most important factors affecting wall thickening.

Introduction A few studies have investigated venous wall remodeling after venous thrombosis by using rodent models. Such information is lacking in humans. This study was designed to determine the acute and chronic effects of thrombus on the vein wall. Methods Patients aged > 16 years with deep vein thrombosis diagnosed by duplex ultrasound were assessed by the use of case-control methodology. Those with recurring thrombotic episodes, cardiorespiratory disease, terminal cancer, morbid obesity, penetrating trauma or significant inflammation were excluded. High-resolution ultrasound was employed to determine wall thickness, with strict quality criteria and inclusion of only technically adequate ultrasound images. Results Data were collected from patients with acute thrombosis (35), patients with chronic postthrombotic changes (15), and unaffected controls (32), with 853 total vein segments being analyzed. As compared with controls (mean 0.37 mm; 95% confidence interval [CI] 0.37-0.38 mm), venous wall thickness was increased in acute (mean 0.63 mm; 95% CI 0.61-0.64 mm) and postthrombotic (mean 0.85 mm; 95% CI 0.80-0.91 mm) venous segments. Ipsilateral, contralateral and unaffected control vein segments were not different. Ipsilateral segments were thicker than controls in postthrombotic syndrome (PTS) patients, but not in acute patients. Multiple regression analyses demonstrated small impacts of age and sex on vein wall thickness. Conclusions Wall thickness increases in all lower-tcglimb venous segments of patients with acute and postthrombotic disease. Age and sex may affect wall thickness, although further investigation is required to clarify their impact. The equivalence of ipsilateral and unaffected control segments suggests that acute vein wall remodeling is mediated through direct interaction with the thrombus, whereas remodeling in PTS patients may be affected by other factors.

Post thrombotic syndrome (PTS) is a very common chronic complication of deep venous thrombosis (DVT), as three out of ten patients with lower extremity DVT will develop PTS. The possibility to identify patients at risk is limited. Diagnosis is challenging, because there is no gold standard diagnostic method. Progress in diagnostic options may therefore change future diagnostic strategies. The better understanding of pathophysiologic processes that underlie PTS may stimulate the development of treatment modalities and improve and diversify management options. The quest for adequate preventive strategies and treatment is important because PTS has a detrimental effect on patients' quality of life and is associated with increased healthcare as well as societal costs. The problem of PTS prevention is therefore clearly relevant to patients, doctors as well as policy makers.

Acquired arteriovenous malformations, such as is the case with dural arteriovenous fistulae (DAVF), are the consequence of a pathological new arterial ingrowth into venous spaces that reaches directly the venous lumen, without interposition of a capillary network, thereby creating an AV-shunt.The following concise text will provide elements in regards to diagnosis, indication for treatment discussion and choice of endovascular treatment (EVT) method.