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Background: While anticoagulation therapy is highly effective at treating venous thromboembolism, some patients can develop rapidly progressive thrombosis in multiple organs or sites despite therapeutic anticoagulation. Effective strategies to manage life-threatening thrombosis in these patients are elusive. Objectives: We describe our experience using dual direct oral anticoagulant (DOAC) therapy with a factor (F)Xa inhibitor (such as rivaroxaban or apixaban) and a FIIa inhibitor (dabigatran) for refractory cases of thrombosis. Methods: A retrospective chart review of all patients treated with simultaneous dabigatran and an oral FXa inhibitor at our institution was conducted. We included all patients over the age of 18. The study was approved by the University of British Columbia Research Ethics Board (REB number: H23-02575). Results: Eight patients were included. All patients initiated standard therapeutic anticoagulation upon diagnosis of acute venous thromboembolism with a median of 3 breakthrough thrombotic events prior to dual DOAC use. Five patients had a positive heparin-induced thrombocytopenia screen, but only 2 had heparin-induced thrombocytopenia confirmed on serotonin release assay testing. There were no recurrent deep vein thrombosis, pulmonary embolism, or bleeding events during dual DOAC use. Most patients ultimately transitioned to a single oral FXa inhibitor. Conclusion: Dual DOAC therapy may be a useful strategy for managing challenging thrombosis cases resistant to conventional anticoagulation. Further research is warranted to validate these findings and explore the broader applicability of dual DOAC therapy in challenging thrombotic scenarios.

Background: Critically ill medical patients face a heightened risk of developing venous thromboembolism. In Thailand, routine thromboprophylaxis is not employed. The incidence of deep vein thrombosis (DVT) in the medical intensive care unit (ICU) has not been elucidated in the Thai population. Objectives: The aims were to evaluate the incidence of DVT and identify associated risk factors in critically ill medical patients. Methods: A single-center, prospective cohort study was conducted from 2019 to 2020. Consecutive patients underwent screening for proximal DVT by duplex ultrasound of both legs. Results: A total of 200 patients were enrolled, with 115 being male (57%). The mean (SD) age was 66.5 (16.4) years. The mean (SD) Acute Physiology and Chronic Health Evaluation II score was 27 (8). The cumulative incidence of DVT over 5 days was 7% (95% CI, 3.4%-10.6%). No clinically or radiologically diagnosed pulmonary embolism occurred in patients with DVT. No independent risk factor associated with DVT was identified. Hospital mortality in those with and those without DVT was 42.9% and 32.3%, respectively. There was no significant difference in the length of ICU or hospital stay or inpatient mortality between those with and those without DVT. Conclusion: Without thromboprophylaxis, the incidence of DVT in the Thai population remains low. A strategy of screening ultrasound 5 to 7 days after admission to the ICU may be a suitable alternative to anticoagulant prophylaxis in critically ill Thai patients without symptoms of venous thromboembolism.

Abstract Background Hand grip strength (HGS), a common proxy of whole‐body muscular strength, is associated with a wide range of adverse health outcomes and mortality. However, there are limited data on the association between HGS and risk of venous thromboembolism (VTE). Objectives We aimed to investigate the association between HGS and risk of incident VTE in a population‐based cohort. Methods Participants (n = 13,704) from the fourth to seventh surveys of the Tromsø study (Tromsø4–Tromsø7, enrollment: 1994–2016) were followed throughout 2020, and all incident VTEs were recorded. HGS of the nondominant hand was measured using a Martin Vigorimeter (Tromsø4–Tromsø6) and a Jamar Digital Dynamometer (Tromsø7). Hazard ratios (HRs) for VTE with 95% confidence intervals (CIs) according to weak HGS (less than 25th percentile) versus normal HGS (25th percentile or greater) were estimated using Cox regression models and adjusted for age, sex, body height, body mass index, physical activity, cardiovascular disease, and cancer. Results During a median of 6.5 years of follow‐up, 545 incident VTEs occurred. Participants with weak HGS had a 27% higher risk of VTE (HR, 1.27; 95% CI, 1.03–1.57) compared to those with normal HGS. Subgroup analyses revealed that the point estimates were higher for unprovoked VTE (HR, 1.35; 95% CI, 0.96–1.91) and deep vein thrombosis (DVT; HR, 1.52; 95% CI, 1.14–2.01). Similar results were found in analyses restricted to men, women, and elderly (aged greater than 75 years). Conclusion A weak HGS was associated with increased risk of VTE, and particularly unprovoked VTE and isolated DVT. Our findings suggest that weak muscle strength may be a risk factor for VTE.

Abstract Introduction Postthrombotic syndrome (PTS) remains associated with significant clinical and economic burden. This study aimed to investigate known and novel predictors of the development of PTS in participants of the ATTRACT (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter‐Directed Thrombolysis) trial. Methods We used multivariable logistic regression to identify baseline and postbaseline factors that were predictive of the development of PTS during study follow‐up, as defined by a Villalta score of 5 or greater or the development of a venous ulcer from 6 to 24 months after enrollment. Results Among 691 patients in the study cohort (all had proximal deep vein thrombosis [DVT] that extended above the popliteal vein, of which 57% had iliofemoral DVT), 47% developed PTS. Further, we identified that Villalta score at baseline (odds ratio [OR], 1.09 [95% confidence interval [CI], 1.05–1.13] per one‐unit increase) and employment status (unemployed due to disability: OR, 3.31 [95% CI, 1.72–6.35] vs. employed more than 35 hours per week) were predictive of PTS. In terms of postbaseline predictors, leg pain severity at day 10 (OR, 1.28 [95% CI, 1.13–1.45] per 1‐point increase in a 7‐point scale) predicted PTS. Also, patients receiving rivaroxaban on day 10 following randomization had lower rates of PTS (OR, 0.53 [95% CI, 0.33–0.86]) than patients on warfarin. Conclusions Novel predictors for PTS identified in our study include baseline Villalta score, leg pain severity at 10 days, and unemployed due to disability. Our findings also suggest that the initial choice of anticoagulant to treat DVT may have an impact on the development of PTS.

Abstract Introduction Venous thromboembolism (VTE) has a long‐term risk of recurrence, dependent on the presence or absence of provoking risk factors at the time of the event. Objective To compare clinical characteristics, anticoagulant patterns, and 12‐month outcomes in patients with transient provoking factors, active cancer, and unprovoked VTE. Methods The Global Anticoagulant Registry in the FIELD (GARFIELD)‐VTE is a prospective, observational study that enrolled 10 207 patients with objectively diagnosed VTE from 415 sites in 28 countries. Results Patients with transient provoking factors were younger (53.0 years) and more frequently women (61.2%) than patients with unprovoked VTE (60.3 years; 43.0% women) or active cancer (63.6 years; 51.7% women). After 6 months, 59.1% of patients with transient provoking factors remained on anticoagulation, compared to 71.3% with unprovoked VTE and 47.3% with active cancer. At 12 months, this decreased to 36.7%, 51.5%, and 25.4%, respectively. The risk of mortality (hazard ratio [HR], 1.21; 95% confidence interval [CI], 0.90‐1.62), recurrent VTE (HR, 0.84; 95% CI, 0.62‐1.14), and major bleeding (HR, 1.26; 95% CI, 0.86‐1.85) was comparable in patients with transient provoking factors and unprovoked VTE. Patients with minor and major transient provoking factors had a similar risk of recurrent VTE (HR, 0.99; 95% CI, 0.59‐1.66), but those with major transient risk factors had a lower risk of death (HR, 0.61; 95% CI, 0.38‐0.98). Conclusion At 1 year, nearly 40% of patients with transient provoking factors and slightly over half of patients with unprovoked VTE were on anticoagulant treatment. Event rates were comparable between the two groups. Risk of death was higher in patients with minor transient factors than in those with major transient factors.

Abstract Purpose The incidence of venous thromboembolism (VTE) is expected to increase over the next decades, further increasing its substantial impact on patients and health care resources. Registries have the benefit of reporting real‐world data without excluding clinically important subgroups. Our aim was to describe a Norwegian VTE registry and to provide descriptive data on the population and management. Registry Population The Venous Thrombosis Registry in Østfold Hospital (TROLL) is an ongoing registry of consecutive patients diagnosed with, treated, and/or followed up for VTE at Østfold Hospital, Norway, since 2005. Baseline and follow‐up data, including demographics, clinical features, risk factors, diagnostic procedures, classification of VTE, and treatment were collected during hospitalization, and at scheduled outpatient visits. Findings to Date From January 2005 to June 2021, 5037 patients were eligible for research in TROLL. Median age was 67 years (interquartile range, 55–77), and 2622 (52.1%) were male. Of these, 2736 (54.3%) had pulmonary embolism (PE), 2034 (40.4%) had deep vein thrombosis (DVT), and 265 (5.3%) had upper‐extremity DVT or splanchnic or cerebral sinus vein thrombosis. In total, 2330 (46.3%) were classified as unprovoked VTE, and 1131 (22.5%) had cancer. Direct oral anticoagulants were the most frequent therapeutic agents (39.3%) followed by low‐molecular‐weight heparins (30.4%) and vitamin K antagonists (30.3%). Outpatient treatment for PE increased from 4% in 2005 to 23% in 2019. Future Plans TROLL is a population‐based ongoing registry that represents a valuable source of real‐world data that will be used for future research on the management and outcomes of VTE.

Abstract Background Venous thromboembolism (VTE) affects approximately 1–2 individuals per 1000 annually and is associated with an increased risk for pulmonary hypertension, postthrombotic syndrome, and recurrent VTE. Objective To determine risk factors, incidence, treatments, and outcomes of VTE through a 2‐year surveillance program initiated in Durham County, North Carolina (population approximately 280,000 at time of study). Patients/Methods We performed a retrospective analysis of data actively collected from three hospitals in Durham County during the surveillance period. Results A total of 987 patients were diagnosed with VTE, for an annual rate of 1.76 per 1000 individuals. Hospital‐associated VTE occurred in 167 hospitalized patients (16.9%) and 271 outpatients who were hospitalized within 90 days of diagnosis (27.5%). Annual incidence was 1.98 per 1000 Black individuals compared to 1.25 per 1000 White individuals (p

Abstract Background Understanding venous thromboembolism (VTE) recurrence risk is central to determining the appropriate treatment course. Whether this risk varies after discontinuing anticoagulation or overall by type of incident event (pulmonary embolism [PE] vs deep vein thrombosis [DVT]) and by the detailed location of the DVT needs further clarification. Methods In this population‐based inception cohort of incident VTE cases with follow‐up by electronic health record review, incident DVT was categorized as distal, popliteal, or iliofemoral. We used the Fine‐Gray regression model to describe the predictive association of the thrombus location with the risk of recurrence before death. Results Among 2766 participants with an incident event from 2002 to 2010, 1713 (62%) ceased anticoagulation and were followed for recurrent events; 301 events were observed during the 4.5 years of follow‐up. Relative to participants with an incident thrombus in an iliofemoral location and no PE, those with a thrombus in a popliteal location and no PE had a similar risk of recurrence (adjusted subdistribution hazard ratio [aSHR], 0.82 [95% confidence interval (CI), 0.57–1.19]), while those with a thrombus in a distal location and no PE and those with a thrombus that included a PE had lower risk of recurrence: aSHR, 0.34 (95% CI, 0.20‐0.57); and aSHR, 0.58 (95% CI 0.45‐0.76), respectively. Conclusions The findings of this population‐based inception cohort confirm that the risk of recurrent VTE after discontinuing anticoagulants is similar after iliofemoral and popliteal DVT but is lower after distal DVT. Recurrence may be lower after PE than proximal DVT.

Abstract Background Knowledge on differences in patients who present with deep vein thrombosis (DVT) and those with pulmonary embolism (PE) is incomplete. Objective To determine comorbidities and temporary provoking factors in patients with a first‐time PE or DVT. Methods This was a nationwide Swedish registry‐based, retrospective, case‐control study including 298 172 patients with first‐time venous thromboembolism (VTE) and 1 185 079 controls matched for age, sex, and county of residence, free of VTE at the time of matching. Results Patients with PE were older than those with DVT (mean age, 69 vs 66 years) and included slightly more women (PE, 53.4% vs DVT, 52.1%). After multivariable adjustment for comorbidities (within 7 years) and temporary provoking factors (within 3 months), heart failure (PE: adjusted odds ratio [aOR], 2.64 [99% confidence interval [CI], 2.55‐2.73]; DVT: aOR, 1.66 [99% CI, 1.60‐1.72]), ischemic heart disease (PE: aOR, 1.51 [99% CI, 1.47‐1.56]; DVT: aOR, 1.01 [99% CI, 0.98‐1.04]), and chronic obstructive pulmonary disease (PE: aOR, 2.51 [99% CI, 2.40‐2.63]; DVT, 1.54 [99% CI, 1.47‐1.62]) were among diseases that showed higher odds ratios in patients with PE than in those with DVT, compared with controls. Comorbidities registered within 6 months were associated with higher aORs than those within 7 years. The highest population attributable risks for PE were for cancer (13.0%) and heart failure (11.7%). Conclusion Cardiopulmonary diseases, particularly with recent onset, imply a higher risk for PE, whereas orthopedic surgery and lower‐extremity fractures carry a higher risk of DVT.

Abstract 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.

Abstract Background The optimal therapy of patients with acute subsegmental pulmonary embolism (PE) is controversial. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic PE recurrences during anticoagulation in patients with subsegmental, segmental, or more central PEs. Results Among 15 963 patients with a first episode of symptomatic PE, 834 (5.2%) had subsegmental PE, 3797 (24%) segmental, and 11 332 (71%) more central PE. Most patients in all subgroups received initial therapy with low‐molecular‐weight heparin, and then most switched to vitamin K antagonists. Median duration of therapy was 179, 185, and 204 days, respectively. During anticoagulation, 183 patients developed PE recurrences, 131 developed deep vein thrombosis (DVT), 543 bled, and 1718 died (fatal PE, 135). The rate of PE recurrences was twofold higher in patients with subsegmental PE than in those with segmental (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.16‐3.85) or more central PE (HR, 1.89; 95% CI, 1.12‐3.13). On multivariable analysis, patients with subsegmental PE had a higher risk for PE recurrences than those with central PE (adjusted HR, 1.75; 95% CI, 1.02‐3.03). After stratifying patients with subsegmental PE according to ultrasound imaging in the lower limbs, the rate of PE recurrences was similar in patients with DVT, in patients without DVT, and in those with no ultrasound imaging. Conclusions Our study reveals that the risk for PE recurrences in patients with segmental PE is not lower than in those with more central PE, thus suggesting that the risk of PE recurrences is not influenced by the anatomic location of PE.

Abstract Background Distal deep vein thrombosis (infrapopliteal DVT without proximal DVT or pulmonary embolism [PE]) generally shares the same triggering risks factors as proximal DVT. In women of childbearing age, a frequent triggering risk factor is the use of combined oral contraceptive (COC) pills. However, data on the epidemiology and long‐term outcomes of COC‐associated distal DVT are lacking. Objectives To assess the epidemiology and long‐term outcomes of COC‐associated distal DVT. Methods Using data from the OPTIMEV (Optimisation de l’Interrogatoire dans l’évaluation du risque thrombo‐Embolique Veineux [Optimization of Interrogation in the Assessment of Thromboembolic Venous Risk]) multicenter cohort study of patients with objectively confirmed venous thromboembolism (VTE) enrolled between 2004 and 2006, we assessed in nonpregnant or postpartum women aged ≤ 50 years without cancer or history of VTE (i) proportion of COC‐associated distal DVTs among women with distal DVTs and among women with COC‐associated VTEs (distal DVT, proximal DVT, or PE) and (ii) 3‐year incidence of death, bleeding, and VTE recurrence. Results COC‐associated distal DVTs (n = 54) represented 43.9% of all distal DVTs and 51.9% of COC‐associated VTEs. All but one woman with a COC‐associated distal DVT received therapeutic anticoagulation for a median of 3 months. At 3‐year follow‐up, all women with COC‐associated distal DVTs were alive, and none had bled during anticoagulant treatment or had experienced a DVT or PE recurrence after stopping anticoagulants. Similar results were found in patients with COC‐associated proximal DVT and PE: The VTE recurrence rate was 1.7% per patient‐year (PY) and 0% PY, respectively, and there were no deaths or major bleeds in either group. Conclusions Distal DVT was the most frequent clinical presentation of COC‐associated VTE and had similarly favorable long‐term outcomes as other COC‐associated VTE.

Abstract Background In patients with a venous outflow obstruction following iliofemoral deep vein thrombosis stenting of the venous tract to prevent or alleviate postthrombotic syndrome is applied with increasing frequency. The impact of the quality of anticoagulant therapy with vitamin K antagonists (VKAs) on the development of in‐stent thrombosis is currently unknown. Objectives To determine the association between the quality of postinterventional VKA treatment and the occurrence of in‐stent thrombosis. Methods Seventy‐nine patients with iliofemoral and/or caval venous stent placement for obstruction of the venous outflow were included in this study. All patients received postinterventional VKA. The quality of VKA anticoagulant therapy was expressed as the time within therapeutic range (TTR) calculated using the linear interpolation method and as the proportion of International Normalized Ratio (INR) values

Abstract Background There is an unmet need for antithrombotic treatments for venous thromboembolic disease that do not increase bleeding risk. Selectins are cell adhesion molecules that augment thrombosis by activating immune cells to initiate the coagulation cascade. GMI‐1271, a potent small‐molecule E‐selectin antagonist, has been shown in mouse models to decrease thrombus burden with a low risk of bleeding. Methods A first‐in‐human study of GMI‐1271 was conducted to assess its safety, tolerability, and pharmacokinetic (PK) profile. As a secondary end point, biomarkers of coagulation, cell adhesion, and leukocyte/platelet activation were evaluated. Aims 1 and 2 were performed in healthy volunteers and evaluated single and multiple doses of the study drug, respectively. Aim 3 included 2 patients with isolated calf‐level deep vein thrombosis (DVT). Results GMI‐1271 showed consistent PK parameters for doses ranging from 2 to 40 mg/kg. Plasma levels increased in a linear manner with respect to dose, while clearance, volume of distribution, and half‐life were not dose dependent. No accumulation was seen with multiple consecutive doses. No serious adverse events (grade 3 or 4) were reported. Biomarker analysis demonstrated a trend in reduction of soluble E‐selectin (sEsel) levels with GMI‐1271 exposure, while exposure did not impact laboratory testing of coagulation. Two patients with calf vein DVT were treated with GMI‐1271 and demonstrated rapid improvement of symptoms after 48 hours, with repeat ultrasound showing signs of clot resolution. Conclusions We demonstrate that GMI‐1271 is safe in healthy volunteers and provide proof of concept that an E‐selectin antagonist is a potential therapeutic approach to treat venous thrombosis.

Abstract Introduction Elastic compression stockings (ECSs) are used to treat symptoms of venous insufficiency. However, lack of patient compliance can limit their effectiveness. In a secondary analysis of the SOX Trial, a randomized trial of active vs. placebo ECSs worn for 2 years to prevent postthrombotic syndrome after deep vein thrombosis, we aimed to describe patient‐reported reasons for nondaily use of ECS and to identify predictors of noncompliance during follow‐up. Methods At each follow‐up visit of the SOX Trial, patients were asked how many days per week they wore study stockings, and if not worn daily, to specify the reason(s). Reasons for nondaily use of ECSs were tabulated. Multiple logistic regression modeling was used to identify predictors of stocking noncompliance during follow‐up (defined as use

Abstract Essentials A few studies suggested that migraine increases venous thromboembolism (VTE) risk. We conducted a prospective US population‐based study. Migraine history did not appear to increase risk of VTE. Older patients with migraine should require only standard VTE prophylaxis. Background Limited evidence suggests that migraine might be a risk factor for venous thromboembolism (VTE). We conducted an epidemiologic study to assess whether migraine history is associated prospectively with VTE or cross sectionally with hemostatic risk markers for VTE. Methods In a population‐based US cohort, 11 985 participants free of VTE reported headache symptoms in 1993‐1995. We classified participants as having either migraines with or without aura, severe nonmigraine headaches, or no severe headaches. We followed them through 2015 for incident VTE verified by medical records. Results Participants’ mean age at baseline was 60 years (SD: 6). Eleven percent were classified as having a migraine history (932 without aura and 396 with aura). Over a mean of 18 years and 211 913 person‐years at risk, 688 participants developed VTE. Participants with a migraine history had no greater risk of VTE compared with those free of severe headache (adjusted hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 0.82‐1.36). Those with migraine history with aura had an HR of 1.25 (95% CI: 0.85‐1.85). Self‐reported physician diagnosis of migraine carried an HR of 1.22 (0.96‐1.55). At baseline, those with a history of migraine, furthermore, did not have a higher frequency of elevated hemostatic risk factors or a higher genetic risk score for VTE. Conclusion This study does not support the hypothesis that migraine history is an important risk factor for VTE in older adults.

Abstract Background Upper extremity deep vein thrombosis (UEDVT) constitutes approximately 10% of all deep vein thromboses (DVTs). The incidence of UEDVT is increasing in association with use of peripherally inserted central venous catheters. Treatment for UEDVT is derived largely from evidence for treatment of lower extremity DVT. Limited evidence exists for the use of a direct oral anticoagulant for the treatment of UEDVT. Population Sequential patients identified within the Intermountain Healthcare System and University of Utah Healthcare system with symptomatic UEDVT defined as the formation of thrombus within the internal jugular, subclavian, axillary, brachial, ulnar, or radial veins of the arm. Intervention Apixaban 10 mg PO twice daily for 7 days followed by apixaban 5 mg twice daily for 11 weeks. Comparison The historical literature review rate of venous thrombosis reported for recurrent clinically overt objective venous thromboembolism (VTE) and VTE‐related death. If the confidence interval for the observed rate excludes the threshold event rate of 4%, we will conclude that treatment with apixaban is noninferior and therefore a clinically valid approach to treat UEDVT. Sample Size We elected a sample size of 375 patients so that an exact 95% confidence interval would exclude an event rate of VTE in the observation cohort of 4%. Outcome Ninety‐day rate of new or recurrent objectively confirmed symptomatic venous thrombosis and VTE‐related death. The primary safety outcome is the composite of major and clinically relevant nonmajor bleeding.

Background: Venous thromboembolism (VTE) is associated with various long-term complications., Objectives: We aimed to investigate the association of clinical characteristics at VTE diagnosis with functional limitations 3 and 12 months afterward., Methods: We conducted a prospective cohort study of VTE patients, excluding patients with cancer, pregnancy, and postpartum period. Functional limitations were assessed with the post-VTE functional status (PVFS) scale (range, 0-4) within 21 days of diagnosis, after 3 and 12 months (prospectively), and 1 month before diagnosis (retrospectively). Twelve-month follow-up was only performed in patients on anticoagulation. We fitted 2 proportional odds logistic regression models for the 3- and 12-month follow-ups and computed odds ratios (ORs) with 95% bootstrap percentile confidence intervals (CIs)., Results: We included 307 patients (42% female, median age 55.6 years) with a median (IQR) PVFS scale grade of 2 (2-3) at study inclusion and 0 (0-0) before diagnosis. After 3 months, PVFS scale grade in 269 patients was 1 (0-2). Female sex (OR, 2.15; 95% CI, 1.26-4.14), body mass index (OR per 1 kg/m 2 increase, 1.05; 95% CI, 1.00-1.10), functional limitations at baseline, and older age were associated with functional limitations. After 12 months, PVFS scale grade in 124 patients was 1 (0-2). Female sex (OR, 4.47; 95% CI, 2.11-16.00), history of cardiovascular/pulmonary disease (OR, 2.36; 95% CI, 1.01-6.89), and functional limitations at baseline were associated with functional limitations., Conclusion: Functional limitations in VTE patients improved 3 and 12 months after diagnosis but did not return to pre-VTE values. We identified clinical characteristics that could help identify patients at risk of persisting functional limitations after VTE., (© 2024 The Author(s).)

Background: Data on walking impairment during the acute phase of deep vein thrombosis (DVT) are limited., Objectives: This study aimed to assess the degree of walking impairment in patients with acute DVT, with a particular focus on the relation to the DVT's anatomical location., Methods: Patients with sonographically confirmed DVT were eligible for inclusion in this cohort study. Pain-free walking distance (PWD) and maximum walking distance (MWD) were determined using standardized treadmill ergometer tests and analyzed in relation to DVT location. The impact of previous DVT on walking capacity was evaluated in an exploratory analysis., Results: The study included 64 patients (31% women; median age, 55 years). The median (IQR) time from diagnosis to exercise test was 3 (1-5) days. Patients with suprainguinal DVT demonstrated significantly shorter median (IQR) MWD than those with infrainguinal DVT (130 (61-202) m vs 565 (128-750) m; P  < .01), while PWD did not significantly differ (PWD: 20 (0-30) m vs 40 (0-222) m; P  = .14). The proportion of patients who had to terminate treadmill tests prematurely was higher in patients with suprainguinal DVT (91.7% vs 57.7%; P  = .04). PWD and MWD seemed to be similar in patients with and without a history of DVT. Premature test termination and suprainguinal DVT location were associated with reduced quality of life, as measured by the EuroQoL Group 5-Dimension 5-Level questionnaire and visual analog scale., Conclusion: Suprainguinal DVT was linked to a more pronounced walking impairment compared with infrainguinal DVT. Limited walking capacity was associated with a reduced quality of life., (© 2024 The Author(s).)

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., (© 2023 The Authors.)

Background: Guidelines suggest but cannot recommend the optimal management of superficial vein thrombosis (SVT)., Objectives: To identify the prevalence of asymptomatic deep vein thrombosis (DVT) at the time of SVT diagnosis, and to report the treatment and 3-month complications of patients with only SVT more than 3 cm from deep vein junction (or unknown distance)., Methods: We performed a single-center retrospective review of patients referred to the Ottawa Hospital thrombosis unit with ultrasound (US)-diagnosed SVT, and followed patients with only SVT for 3 months., Results: Three hundred sixteen patients with SVT were included. Of the 218 patients without DVT symptoms at presentation, 19 (8.7%; 95% CI, 5.7%-13.2%) were found to have asymptomatic concomitant DVT (11 proximal and 8 distal), and 45 (20.6%) had SVT within 3 cm of the saphenofemoral or saphenopopliteal junctions. Among the 192 patients diagnosed with SVT only, we observed 3-month thrombotic complications in 56 (29.2%; 95% CI, 23.2%-36.0%) patients, with a total of 69 events: 11 (5.7%) DVTs, 2 (1.0%) pulmonary embolisms, 37 (19.2%) SVT extensions, and 19 (9.8%) SVT recurrences. Eighty-two percent (9/11) of the 3-month DVT and pulmonary embolism events occurred in patients who initially received conservative management. Therapeutic treatment doses were most effective., Conclusion: At the time of SVT diagnosis, many patients had asymptomatic DVT and SVT near the deep venous system, supporting the systematic use of initial US in patients clinically diagnosed with SVT. The observed differences in 3-month complication rates, according to the treatment provided, highlight the need for large-scale randomized controlled trials to establish optimal management., (© 2023 The Authors.)

Patients with acute ischemic stroke are at a high risk of venous thromboembolism (VTE), such as deep vein thrombosis (DVT), estimated to affect approximately 80,000 patients with stroke each year in the United States. The prevalence of symptomatic DVT after acute stroke is approximately 10%. VTE is associated with increased rates of in-hospital death and disability, with higher prevalence of in-hospital complications and increased 1-year mortality in patients with stroke. Current guidelines recommend the use of pharmacologic VTE prophylaxis in patients with acute ischemic stroke. However, thromboprophylaxis prevents only half of expected VTE events and is associated with high risk of bleeding, suggesting the need for targeted alternative treatments to reduce VTE risk in these patients. Neutrophils are among the first cells in blood to respond after ischemic stroke. Importantly, coordinated interactions among neutrophils, platelets, and endothelial cells contribute to the development of DVT. In case of stroke and other related immune disorders, such as antiphospholipid syndrome, neutrophils potentiate thrombus propagation through the formation of neutrophil-platelet aggregates, secreting inflammatory mediators, complement activation, releasing tissue factor, and producing neutrophil extracellular traps. In this illustrated review article, we present epidemiology and management of poststroke VTE, preclinical and clinical evidence of neutrophil hyperactivation in stroke, and mechanisms for neutrophil-mediated VTE in the context of stroke. Given the hyperactivation of circulating neutrophils in patients with stroke, we propose that a better understanding of molecular mechanisms leading to neutrophil activation may result in the development of novel therapeutics to reduce the risk of VTE in this patient population., (© 2023 The Author(s).)

Context: There are no clear pediatric guidelines on the return to physical activity following deep vein thrombosis (DVT) or pulmonary embolism (PE), particularly while being treated with anticoagulation., Objective: This scoping review aimed to examine the current literature on physical activity beyond simple ambulation for patients with DVT/PE being treated with anticoagulation., Data Sources: An electronic search for articles in MEDLINE, Epub Ahead of Print, In-Process, and Other Non-Indexed Citations, Daily (1946 to April 4, 2022), and Embase+Embase Classic (1946 to 2022, week 13) was conducted., Study Selection: (1) Patients of any age with DVT/PE, treated with anticoagulation; (2) studies of any design providing information on physical activity (ie, sport, exercise) while on anticoagulation; and (3) studies in English., Data Extraction: Data from eligible studies obtained included the study design, population, disease characteristics, and information on physical activity participation., Results: A total of 26 eligible studies were included. Only 2 studies were specific to children. Studies recommend a gradual return to participation in noncontact or low-risk activities after the first 3-4 weeks of anticoagulation, with close monitoring of symptoms. Participation in contact sports and activities is typically delayed until after anticoagulants are discontinued. However, personalized anticoagulation with intermittent dosing schedules has been proposed for athletes after the first 3 months of anticoagulation treatment., Conclusions: Physical activity participation guidelines for children with DVT/PE being treated with anticoagulation are needed, and the evidence currently available is limited. Largely based on evidence from adult patients, we present evidence-informed options to facilitate clinician recommendations for returning to activity., (© 2023 The Authors.)

Background: Clinical trials that evaluated interventions to prevent postthrombotic syndrome (PTS) used the Villalta scale (VS) to define PTS, but there is a lack of consistency in its use., Objectives: This study aimed to improve the ability to identify patients with clinically meaningful PTS after DVT in participants of the ATTRACT trial., Methods: We conducted a post hoc exploratory analysis of 691 patients from the ATTRACT study, a randomized trial evaluating the effectiveness of pharmacomechanical thrombolysis to prevent PTS in proximal deep vein thrombosis. We compared 8 VS approaches to classify patients with or without PTS in terms of their ability to discriminate between those with poorer vs better venous disease-specific quality of life (Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL]) between 6- and 24-months follow-up. The difference in the average area under the fitted curve of VEINES-QOL scores between PTS and no PTS ( Δ A U C ¯ ) were compared among approaches., Results: For any PTS (a single VS score ≥5), approaches 1 to 3 had similar Δ A U C ¯ (-21.2, -23.7, -22.0, respectively). Adjusting the VS for contralateral chronic venous insufficiency (CVI) or restricting to patients without baseline CVI (approaches 7 and 8) did not improve Δ A U C ¯ (-13.6, -19.9, respectively; P >.01). For moderate-to-severe PTS (a single VS score ≥10), approaches 5 and 6 requiring 2 positive assessments had greater but not statistically significant Δ A U C ¯ than approach 4, using one single positive assessment (-31.7, -31.0, -25.5, respectively; P >.01)., Conclusion: A single VS score of ≥ 5 reliably distinguishes patients with clinically meaningful PTS as assessed by impact on QOL and is preferred because of greater convenience (only one assessment needed). Alternative methods to define PTS (ie, adjusting for CVI) do not improve the scale's ability to identify clinically meaningful PTS., (© 2022 The Authors.)

Background: Studies on the association between long-chained n-3 polyunsaturated fatty acids (n-3 PUFAs) and risk of venous thromboembolism (VTE) are conflicting, potentially due to challenges related to assessment of n-3 PUFA intake and changes in diet during follow-up., Objectives: To investigate whether dietary intake of marine n-3 PUFAs was associated with risk of incident VTE in a population-based cohort with repeated assessments of n-3 PUFA intake., Methods: We recruited 21 970 participants (after excluding 7570 with incomplete data) from the fourth (1994-1995) and sixth (2007-2008) surveys of the Tromsø Study, and recorded incident VTEs up to 2016. Intake of n-3 PUFAs was computed from self-reported consumption of fat and lean fish, fish spread, and supplements. Cox proportional hazards regression models with n-3 PUFA intake as a time-varying variable were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE across quartiles (Q) of n-3 PUFA intake., Results: There were 541 incident VTEs during follow-up. Compared to Q1, subjects in Q2-4 had 22%-26% lower risk of VTE (HR Q2 0.74, 95% CI 0.57-0.96; HR Q3 0.77, 95% CI 0.59-0.99; HR Q4 0.78, 95% CI 0.61-1.00). The association was most pronounced for provoked VTE, particularly provoked pulmonary embolism (PE), with risk estimates of 0.42 (95% CI 0.25-0.72), 0.40 (95% CI 0.23-0.68), and 0.61 (95% CI 0.38-0.96) for Q2-4, respectively., Conclusions: Dietary intake of marine n-3 PUFAs was associated with a lower risk of VTE, particularly provoked PE. The association displayed a threshold pattern and suggested a protective effect of an n-3 PUFA intake ≥4.7 g/week.

Background: May-Thurner Syndrome (MTS) is caused by compression of the left common iliac vein between the right common iliac artery and the pelvis. It likely predisposes an individual to lower extremity deep vein thrombosis (DVT) as well as symptoms of unilateral lower extremity swelling and discomfort in the absence of a known history of thrombosis. In the case of MTS-associated acute thrombosis, there is low-quality evidence to suggest that endovascular intervention including thrombolysis and endovascular stent placement reduces the risk of recurrent thrombosis. However, the optimal type and duration of antithrombotic therapy after stent placement for left iliofemoral vein stenosis is not known., Methods: A systematic literature search including studies that evaluated the outcome of endovascular stent occlusion and systemic anticoagulant use in patients with MTS associated DVT was performed. The primary outcome of interest was 12-month risk of endovascular stent occlusion or recurrent DVT., Results: A total of five studies encompassing 61 patients were included in our study. All studies were retrospective without a comparator group. A variety of anticoagulants and durations were prescribed. Of the 55 patients evaluable, the 12-month rate of endovascular stent occlusion or recurrent DVT ranged from 0% to 40%. The 12-month stent patency rate ranged from 60% to 100%., Conclusions: The published evidence regarding antithrombotic treatment for patients with MTS who have undergone stent placement for a DVT is limited. Further high-quality, prospective studies are needed in this setting to inform clinical decision making.

Post thrombotic syndrome (PTS) is a common chronic complication of deep vein thrombosis of the leg (DVT). Treatment options are limited therefore emphasis is placed on its prevention. Several risk factors have been recognized, but were so far not used for risk stratification or translation into prediction models. Early interventions did not yet result in more successful preventive treatment strategies; for the acute phase of DVT there is equipoise on the value of elastic compression, as well as on catheter directed thrombolysis. There are no drugs specifically targeted at PTS prevention. The use of anticoagulant medication such as direct oral anticoagulants (DOACs) might decrease PTS incidence, but this needs to be corroborated. Both research into more effective treatment options as well as future PTS management may benefit from a uniform diagnostic strategy and the use of prediction rules to better allocate treatment and thereby increase treatment efficacy.

Introduction: Whether statin use after first venous thrombosis reduces the risk of recurrence is uncertain. Therefore, we aimed to examine the risk of recurrent venous thrombosis in statin users vs non-users., Methods: Patients with a first venous thrombosis were recruited from the MEGA follow-up study. Information on statin use was obtained by linkage to the Dutch Foundation for Pharmaceutical Statistics register. Linkage was successful in 54% of all patients (n = 2,547). Cox-regression models with statin-exposure as a time-dependent co-variate were used to estimate hazard ratios (HR) with 95% confidence intervals (CI 95) for recurrence., Results: Statin therapy was continued in 153 (6.0%) patients and initiated in 233 (9.1%) patients during a median follow-up of 5.7 years. There were 367 recurrent venous thrombotic events, of which 32 occurred among statin users. Incident statin use was associated with 22% reduced risk of recurrence after multivariable adjustments (HR 0.78, CI 95: 0.46-1.31), and 13% reduced risk after propensity score adjustment (HR 0.87, CI 95: 0.52-1.47). Statin use seemed not to have an effect on recurrence in patients with an unprovoked first event (multivariable HR 1.03, CI 95: 0.54-1.98), but the statistical power was low due to few events and the results must be interpreted with caution. In general, the risk estimates were slightly attenuated when prevalent users were included in the analyses., Conclusion: Our findings suggest that statins may have a modest decreasing effect on the risk of recurrent venous thrombosis. While we took care to minimize bias and confounding, the causality of the association is still unsettled.