Lower Risk Of Venous Thromboembolism Research Articles

Mice with Reduced PAR4 Reactivity show Decreased Venous Thrombosis and Platelet Procoagulant Activity.

Hypercoagulation and thrombin generation are major risk factors for venous thrombosis. Sustained thrombin signaling through PAR4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single-nucleotide polymorphism in PAR4 (rs2227376) changes proline to leucine extracellular loop 3 (P310L), which decreases PAR4 reactivity and is associated with a lower risk for venous thromboembolism (VTE) in a GWAS meta-analysis. The goal of this study is to determine the mechanism for the association of rs2227376 with reduced risk for VTE in using mice with a homologous mutation (PAR4-P322L). Venous thrombosis was examined using our recently generated PAR4-P322L mice in the inferior vena cava stasis and stenosis models. Coagulation and clot stability was measured using rotational thromboelastometry (ROTEM). Thrombin generating potential was measured in platelet-rich plasma. Phosphatidylserine surface expression and platelet-neutrophil aggregates were analyzed using flow cytometry. PAR4P/L and PAR4L/L had reduced size of venous clots at 48 hours. PAR4P/L and PAR4L/L platelets had progressively decreased phosphatidylserine in response to thrombin and convulxin, in addition to decreased thrombin generation and decreased PAR4-mediated platelet-neutrophil aggregation. The leucine allele in extracellular loop 3, PAR4-322L leads to fewer procoagulant platelets, decreased endogenous thrombin potential and reduced platelet-neutrophil aggregation. This decreased ability to generate thrombin and bind to neutrophils offers a mechanism for PAR4's role in VTE highlighting a key role for PAR4 signaling.

The (T) thrombosis (I) in patients with (L) lower (L) limb (I) injuries (R) requiring (I) immobilisation (TILLIRI) Study

BackgroundPatients requiring lower limb immobilisation after injury have an increased venous thromboembolism (VTE) risk. The extent of this risk in published studies varies. The TRiP(cast) model quantifies VTE risk using clinical parameters. Delineating low from high-risk patients remains challenging. AimsDetermine the 90-day incidence of symptomatic VTE following temporary lower limb immobilisation after injury in an unselected cohort. Prospectively collect data on risk factors, including those incorporated in TRiP(cast) model, to calculate TRiP(cast) scores. MethodsTILLIRI is a multi-centre, pragmatic observational cohort study including 10 sites within the Irish Network for VTE Research. Patients≥18 years with an immobilised injured lower limb were included. Twenty-one clinical variables were collected at presentation. Thromboprophylaxis was prescribed according to clinical gestalt. Patients were followed up at 90-days to determine if VTE occurred. ResultsBetween November 2018 and February 2023, 1242 patients were recruited. Follow-up was complete for 1199 patients(96.5%).43 patients(3.5%) were lost to follow-up.44(3.6%) patients and 125(10%) patients were prescribed anticoagulation and aspirin respectively. 21 patients receiving regular anticoagulation removed from final analysis. VTE incidence at 90-day follow-up was 6/1179(0.51%; CI 0.1%-0.92%). TRiP(cast) scores were calculated for 1176/1221 patients. 846 patients(71.9%) had TRiP(cast) Score< 7, received no prophylaxis and had no VTE. ConclusionTILLIRI indicates a low VTE incidence in an unselected cohort following lower limb immobilization with low rates of prophylaxis use. The proportion of patients with low TRiP(cast) scores and no symptomatic VTE suggests that thromboprophylaxis may be avoided in patients with TRiP(cast)scores< 7, with a low 90-day VTE risk.

Venous Thromboembolism Prophylaxis in Maxillofacial Surgery.

The aim of this article is to conduct a literature review concerning the need for venous thromboembolism (VTE) prophylaxis among patients undergoing maxillofacial surgery. This article addresses the diagnosis of VTE, patient risk stratification, and prophylactic measures suitable for the various groups of interest in maxillofacial surgery. From a pool of 44 articles identified, nine were chosen as the most pertinent to the aims of this review.Despite limited data on this topic, individuals undergoing oral and maxillofacial surgery generally exhibit a low risk of VTE. This review emphasizes the importance of implementing prophylactic measures tailored to individual risk factors. Pharmacological prophylaxis merits consideration, particularly when the Caprini score is ≥7. However, further research is needed to optimize prophylactic strategies in maxillofacial surgery.

Implementation of a transition of care pathway for low-risk patients presenting to the emergency department with venous thromboembolism

Inpatient management of low-risk patients with venous thromboembolism (VTE) places a large resource burden on the healthcare system. Adult patients diagnosed with deep vein thrombosis (DVT) or pulmonary embolism (PE) in the emergency department (ED) have historically been hospitalized and treated with therapeutic anticoagulation. However, over the last two decades, outpatient treatment of patients with acute DVT and low risk PE has become increasingly accepted as an effective and safe option for patients given the low risk of short-term clinical deterioration. The purpose of this project was to establish a transition of care (TCM) program for patients with acute VTE presenting to the ED. The primary goals for the project included better quality patient follow-up in the Vascular Medicine Nurse Practitioner (NP) within one week and medication adherence. The second goal was increasing appropriate ED discharges for patients with low-risk VTE. Outcome metrics include the rate of early discharge of low-risk patients with VTE, follow-up in the Vascular Medicine NP clinic, and anticoagulant adherence.

Factor XIa inhibition as a therapeutic strategy for atherothrombosis.

When selecting an anticoagulant, clinicians consider individual patient characteristic, the treatment indication, drug pharmacology, and safety and efficacy as demonstrated in randomized trials. An ideal anticoagulant prevents thrombosis with little or no increase in bleeding. Direct oral anticoagulants represent a major advance over traditional anticoagulants (e.g., unfractionated heparin, warfarin) but still cause bleeding, particularly from the gastrointestinal tract which can limit their use. Epidemiological studies indicate that patients with congenital factor XI (FXI) deficiency have a lower risk of venous thromboembolism (VTE) and ischemic stroke (IS) than non-deficient individuals, and do not have an increased risk of spontaneous bleeding, even with severe deficiency. These observations provide the rationale for targeting FXI as a new class of anticoagulant. Multiple FXI inhibitors have been introduced and several are being evaluated in Phase III trials. In this review, we explain why drugs that target FXI may be associated with a lower risk of bleeding than currently available anticoagulants and summarize the completed and ongoing trials.

Venous thromboembolism in patients undergoing surgery for lung cancer: a post hoc analysis of the Cancer-VTE Registry.

The relationship between lung cancer surgery and venous thromboembolism (VTE) in Japan has not been elucidated. This was a post hoc analysis of the Cancer-VTE Registry. The 1057 patients who underwent surgery for lung cancer were divided into the surgery alone (SA) group (n=598) and the surgery plus chemotherapy (SC) group (n=459), and the 1-year incidences of VTE and cerebral ischemia were analyzed. In the SA and SC groups, composite VTE was observed in one (0.2%) and 15 (3.3%) patients, respectively, and cerebral ischemia was observed in eight (1.3%) and four (0.9%) patients, respectively. Lymph node metastasis was more common in patients with D-dimer >1.2μg/ml (odds ratio: 1.781, P=.004). SA had a low risk of VTE but a high risk of cerebral ischemia. Chemotherapy increases the risk of VTE. The D-dimer level was related to VTE and advanced cancer.

Tea Consumption, Milk or Sweeteners Addition, Genetic Variation in Caffeine Metabolism, and Incident Venous Thromboembolism.

The association between tea consumption and venous thromboembolism (VTE) remains unknown. We aimed to evaluate the association between tea consumption with different additives (milk and/or sweeteners) and incident VTE, and the modifying effects of genetic variation in caffeine metabolism on the association. A total of 190,189 participants with complete dietary information and free of VTE at baseline in the UK Biobank were included. The primary outcome was incident VTE, including incident deep vein thrombosis and pulmonary embolism. During a median follow-up of 12.1 years, 4,485 (2.4%) participants developed incident VTE. Compared with non-tea drinkers, tea drinkers who added neither milk nor sweeteners (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.76-0.94), only milk (HR: 0.86; 95% CI: 0.80-0.93), and both milk and sweeteners to their tea (HR: 0.90; 95% CI: 0.81-0.99) had a lower risk of VTE, while those who added only sweeteners to their tea did not (HR: 0.94; 95% CI: 0.75-1.17). Moreover, there was an L-shaped relationship between tea consumption and incident VTE among tea drinkers who added neither milk nor sweeteners, only milk, and both milk and sweeteners to their tea, respectively. However, a nonsignificant association was found among tea drinkers who added only sweeteners to their tea. Genetic variation in caffeine metabolism did not significantly modify the association (p-interaction = 0.659). Drinking unsweetened tea, with or without added milk, was associated with a lower risk of VTE. However, there was no significant association between drinking tea with sweeteners and incident VTE.

Risk Assessment Models for Venous Thromboembolism in Medical Inpatients

Thromboprophylaxis is recommended for medical inpatients at risk of venous thromboembolism (VTE). Risk assessment models (RAMs) have been developed to stratify VTE risk, but a prospective head-to-head comparison of validated RAMs is lacking. To prospectively validate an easy-to-use RAM, the simplified Geneva score, and compare its prognostic performance with previously validated RAMs. This prospective cohort study was conducted from June 18, 2020, to January 4, 2022, with a 90-day follow-up. A total of 4205 consecutive adults admitted to the general internal medicine departments of 3 Swiss university hospitals for hospitalization for more than 24 hours due to acute illness were screened for eligibility; 1352 without therapeutic anticoagulation were included. At admission, items of 4 RAMs (ie, the simplified and original Geneva score, the Padua score, and the IMPROVE [International Medical Prevention Registry on Venous Thromboembolism] score) were collected. Patients were stratified into high and low VTE risk groups according to each RAM. Symptomatic VTE within 90 days. Of 1352 medical inpatients (median age, 67 years [IQR, 54-77 years]; 762 men [55.4%]), 28 (2.1%) experienced VTE. Based on the simplified Geneva score, 854 patients (63.2%) were classified as high risk, with a 90-day VTE risk of 2.6% (n = 22; 95% CI, 1.7%-3.9%), and 498 patients (36.8%) were classified as low risk, with a 90-day VTE risk of 1.2% (n = 6; 95% CI, 0.6%-2.6%). Sensitivity of the simplified Geneva score was 78.6% (95% CI, 60.5%-89.8%) and specificity was 37.2% (95% CI, 34.6%-39.8%); the positive likelihood ratio of the simplified Geneva score was 1.25 (95% CI, 1.03-1.52) and the negative likelihood ratio was 0.58 (95% CI, 0.28-1.18). In head-to-head comparisons, sensitivity was highest for the original Geneva score (82.1%; 95% CI, 64.4%-92.1%), while specificity was highest for the IMPROVE score (70.4%; 95% CI, 67.9%-72.8%). After adjusting the VTE risk for thromboprophylaxis use and site, there was no significant difference between the high-risk and low-risk groups based on the simplified Geneva score (subhazard ratio, 2.04 [95% CI, 0.83-5.05]; P = .12) and other RAMs. Discriminative performance was poor for all RAMs, with an area under the receiver operating characteristic curve ranging from 53.8% (95% CI, 51.1%-56.5%) for the original Geneva score to 58.1% (95% CI, 55.4%-60.7%) for the simplified Geneva score. This head-to-head comparison of validated RAMs found suboptimal accuracy and prognostic performance of the simplified Geneva score and other RAMs to predict hospital-acquired VTE in medical inpatients. Clinical usefulness of existing RAMs is questionable, highlighting the need for more accurate VTE prediction strategies.

Association of Cardiovascular Health with the Incidence of Venous Thromboembolism: A Prospective Study of 275,149 Participants from the UK Biobank.

The Life's Essential 8 (LE8) score, recently proposed by the American Heart Association, represents a new paradigm for evaluating cardiovascular health (CVH). We aimed to explore the association between CVH, estimated using LE8, and venous thromboembolism (VTE) incidence. A total of 275,149 participants were recruited from the UK Biobank and divided into high (LE8 score ≥ 80), moderate (LE8 score < 80 but ≥ 50), and low (LE8 score < 50) CVH groups. Restricted cubic spline analysis, the Kaplan-Meier method, and the Cox proportional hazards model were used to explore the association between CVH and VTE. The genetic predisposition to VTE was assessed with a polygenic risk score. Sensitivity analyses were performed to validate the results. During a median follow-up of 12.56 years, VTE developed in 506 (4.09%), 6,069 (2.78%), and 720 (1.66%) participants with low, moderate, and high CVH levels, respectively. Compared with the low CVH group, participants in the moderate and high CVH groups had a 23% (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.71-0.85) and 41% (HR: 0.59; 95% CI: 0.52-0.66) lower risk of VTE, respectively, after adjusting for demographic characteristics, medical history, socioeconomic status, and genetic predisposition. This association remained robust in multiple sensitivity analyses. Higher CVH levels led to a more pronounced reduction in the risk of VTE in females and could appreciably offset the genetic risk of VTE. Higher CVH levels were significantly associated with a lower incidence of VTE, encouraging efforts to increase LE8 scores in individuals.

Genetic assessment of efficacy and safety profiles of coagulation cascade proteins identifies Factors II and XI as actionable anticoagulant targets.

Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed. To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38-0.51, P = 2.6e-28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39-0.76, P = 4.2e-04) but not with bleeding (OR = 1.13, 95% CI = 0.93-1.36, P = 2.2e-01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58-0.64, P = 4.1e-85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69-0.86, P = 4.1e-06) but not with bleeding (OR = 1.01, 95% CI = 0.95-1.08, P = 7.5e-01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses. These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.

Bariatric Surgery and the Long-Term Risk of Venous Thromboembolism: A Population-Based Cohort Study.

Bariatric surgery is associated with a greater venous thromboembolism (VTE) risk in the weeks following surgery, but the long-term risk of VTE is incompletely characterized. We evaluated bariatric surgery in relation to long-term VTE risk. This population-based retrospective matched cohort study within three United States-based integrated health care systems included adults with body mass index (BMI) ≥ 35kg/m2 who underwent bariatric surgery between January 2005 and September 2015 (n = 30,171), matched to nonsurgical patients on site, age, sex, BMI, diabetes, insulin use, race/ethnicity, comorbidity score, and health care utilization (n = 218,961). Follow-up for incident VTE ended September 2015 (median 9.3, max 10.7years). Our population included 30,171 bariatric surgery patients and 218,961 controls; we identified 4068 VTE events. At 30days post-index date, bariatric surgery was associated with a fivefold greater VTE risk (HRadj = 5.01; 95% CI = 4.14, 6.05) and a nearly fourfold greater PE risk (HRadj = 3.93; 95% CI = 2.87, 5.38) than no bariatric surgery. At 1year post-index date, bariatric surgery was associated with a 48% lower VTE risk and a 70% lower PE risk (HRadj = 0.52; 95% CI = 0.41, 0.66 and HRadj = 0.30; 95% CI = 0.21, 0.44, respectively). At 5years post-index date, lower VTE risks persisted, with bariatric surgery associated with a 41% lower VTE risk and a 55% lower PE risk (HRadj = 0.59; 95% CI = 0.48, 0.73 and HRadj = 0.45; 95% CI = 0.32, 0.64, respectively). Although in the short-term bariatric surgery is associated with a greater VTE risk, in the long-term, it is associated with a substantially lower risk.

Thromboembolic Events After Robotic Radical Cystectomy: A Comparative Analysis of Extended and Limited Prophylaxis

ObjectiveTo compare limited (only inpatient) venous thromboembolism (VTE) prophylaxis after robot-assisted radical cystectomy (RARC) to limited plus extended prophylaxis. There is little consensus on postoperative VTE prophylaxis regimens after RARC with data mostly extrapolated from other cancers. MethodsRetrospective review of all RARC patients at our center between 2014-2022, identifying two groups: patients after a prospectively implemented protocol (January 2018 to present) utilizing a prolonged 21-day postoperative course of either enoxaparin 40mg daily or apixaban 2.5mg twice daily after discharge, or patients prior to January 2018 receiving only limited VTE prophylaxis during their immediate postoperative inpatient stay. Primary outcome: incidence of symptomatic VTE confirmed with imaging within 90-days postoperatively. Secondary outcomes: major hemorrhage, complications, readmission, and mortality within 30-days postoperatively. Descriptive statistics depicted baseline patient characteristics, operative information, and complications. Differences were compared between groups. Logistic regression was used to determine associations between variables and primary outcome. ResultsEighty-six patients received limited prophylaxis and 364 received extended prophylaxis. Twelve (2.7%) patients experienced VTE within 90-days postoperatively: (10 [2.7%] extended vs. 2 [2.3%] limited, p = 0.9). Upon stratification into EAU “low-risk” or “high +intermediate-risk” groups, no statistically significant difference in VTE rates was seen between the extended or limited groups. When controlling for prophylaxis regimen, intracorporeal approach was found to be predictive of a lower with a lower risk of VTE (p = 0.019). ConclusionsLimited and extended prophylaxis showed no significant differences in VTE rates among RARC patients. Further studies are necessary for RARC patients to improve guidelines.

Caprini versus Padua venous thromboembolism risk assessment scores: A comparative study in hospitalized patients at a tertiary center.

To assess and compare the Caprini and Padua risk assessment models (RAMs) for predicting venous thromboembolism (VTE) in hospitalized patients. We retrospectively reviewed 28 VTE and 450 non-VTE patients hospitalized at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, in 2019. Their baseline medical, demographic, and radiological reports were recorded. We compared Caprini scores (defined at admission) and Padua scores (calculated retrospectively) for their ability to predict VTE. A cumulative risk score was created by adding the individual scores for each risk factor. We also analyzed the sensitivity, specificity, and diagnostic accuracy of the RAM scores. Major differences in risk factors were shown between patients with and without VTE. Previous VTE was significantly associated with a higher risk of VTE (28.6%), as was reduced mobility (57.1%), acute infection (25%), high Caprini score (50%), and high Padua score (64.3%, p<0.05). The sensitivity of the Caprini score (96%) was higher than that of the Padua score (64.3%), as was the specificity (92.1% vs. 46.9%), positive predictive value (93% vs. 7%), and accuracy (94.1% vs. 47.9%). The specificity of the Caprini score was higher than that of the Padua score in Critical Care, Gynecology/Obstetrics, and Surgical departments. The Caprini RAM showed the lowest level of specificity in the medical department. The Caprini RAM demonstrated higher sensitivity, specificity, and predictive accuracy than did the Padua RAM and thus distinguished low and high VTE risk in hospitalized patients.

Risk stratification-based thromboprophylaxis does not affect mortality after fast-track hip and knee arthroplasty.

Use of thromboprophylaxis effectively prevents pulmonary embolism (PE) and deaths after total hip and knee arthroplasty (THA and TKA). The optimum length of thromboprophylaxis is not known and has traditionally been based on the type of operation. Nowadays, a more individualized approach is preferred. This study analyzed if risk stratification-based planning of thromboprophylaxis has an association with the all-cause mortality after fast-track THA and TKA. We compared fast-track THAs and TKAs operated between 2015-2016 and 2020-2021. Between 2015 and 2016, all patients received a routine length of thromboprophylaxis. From 2020 onwards, thromboprophylaxis was planned by risk stratification, and patients at low risk for venous thromboembolism received thromboprophylaxis only during hospitalization. All causes of death within 90 days of surgery were identified and the incidence of mortality was calculated. Mortality rates between the two periods were then compared. Between 2015 and 2016, 3192 arthroplasties were performed. A total of eight deaths occurred within 90 days of surgery, yielding an incidence of all-cause mortality of 0.3% (95% CI 0.1-0.5). Between 2020 and 2021, a total of 3713 arthroplasties were performed to patients who received risk stratification-based thromboprophylaxis. Thirteen of these patients died within 90 days of surgery, yielding an all-cause mortality incidence of 0.4% (95% CI 0.2-0.6). Cardiovascular diseases were the main cause of death during both study periods. None of the deaths were caused by PEs. Risk stratification-based thromboprophylaxis was not associated with increased all-cause mortality within 90 days of fast-track THA and TKA.

Aspirin is as effective as low molecular weight heparins in preventing symptomatic venous thromboembolism following arthroscopic anterior cruciate ligament reconstruction

ObjectiveThe optimal agent for thromboprophylaxis following arthroscopic anterior cruciate ligament reconstruction (ACLR) remains unclear, particularly in patients with a low baseline risk for venous thromboembolism (VTE). This retrospective cohort study aims to compare the effectiveness and safety of aspirin versus low molecular weight heparins (LMWHs) in this specific patient population.MethodsWe analyzed data from patients who underwent ACLR between March 2016 and March 2021, focusing on those with a low risk for VTE. High-risk individuals, identified by factors such as cardiac disease, pulmonary disease, diabetes mellitus, previous VTE, inflammatory bowel disease, active cancer, and a BMI > 40, were excluded (n = 33). Our approach included a thorough review of medical charts, surgical reports, and pre-operative assessments, complemented by telephone follow-up conducted over a 3-month period by a single investigator. We assessed the incidence of symptomatic VTE, including deep vein thrombosis and pulmonary thromboembolism, as the primary outcome. The secondary outcomes included to complications related to the surgery and thromboprophylaxis. Statistical analysis included descriptive statistics, univariate logistic regression models, and calculations of incidence rates.ResultIn our study, 761 patients (761 knees) were included, with 458 (60.18%) receiving aspirin and 303 (39.82%) receiving LMWH. The two groups showed no significant differences in demographic factors except for age. The incidence of VTE was reported at 1.31% (10 individuals). Specifically, five patients in the aspirin group (1.09%) and five patients in the LMWH group (1.65%) developed a symptomatic VTE event (p = 0.53). Additionally, the two groups did not significantly differ in terms of other complications, such as hemarthrosis or surgical site infection (p > 0.05). Logistic regression analysis revealed no statistically significant difference in VTE risk between the two groups.ConclusionThis study, focusing on isolated ACLR in patients with a low baseline risk for venous thromboembolism, demonstrated that aspirin is equally effective as low molecular weight heparins for VTE prophylaxis following this surgery.Level of EvidenceIII

Targeted prophylactic anticoagulation based on the TRiP(cast) score in patients with lower limb immobilisation: a multicentre, stepped wedge, randomised implementation trial

Prophylactic anticoagulation in emergency department patients with lower limb trauma requiring immobilisation is controversial. The Thrombosis Risk Prediction for Patients with Cast Immobilisation-TRiP(cast)-score could identify a large subgroup of patients at low risk of venous thromboembolism for whom prophylactic anticoagulation can be safely withheld. We aimed to prospectively assess the safety of withholding anticoagulation for patients with lower limb trauma at low risk of venous thromboembolism, defined by a TRiP(cast) score of less than 7. CASTING was a stepped-wedge, multicentre, cluster-randomised trial with blinded outcome assessment. 15 emergency departments in France and Belgium were selected and randomly assigned staggered start dates for switching from the control phase (ie, anticoagulation prescription according to the physician's usual practice) to the intervention phase (ie, targeted anticoagulation according to TRiP(cast) score: no prescription if score <7 and anticoagulation if score was ≥7). Patients were included if they presented to a participating emergency department with lower limb trauma requiring immobilisation for at least 7 days and were aged 18 years or older. The primary outcome was the 3-month cumulative rate of symptomatic venous thromboembolism during the intervention phase in patients with a TRiP(cast) score of less than 7. The targeted strategy was considered safe if this rate was less than 1% with an upper 95% CI of less than 2%. The primary analysis was performed in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT04064489). Between June 16, 2020, and Sept 15, 2021, 15 clusters and 2120 patients were included. Of the 1505 patients analysed in the intervention phase, 1159 (77·0%) had a TRiP(cast) score of less than 7 and did not receive anticoagulant treatment. The symptomatic venous thromboembolism rate was 0·7% (95% CI 0·3-1·4, n=8/1159). There was no difference between the control and the intervention phases in the cumulative rate of symptomatic venous thromboembolism or in bleeding rates. Patients with a TRiP(cast) score of less than 7 who are not receiving anticoagulation have a very low risk of venous thromboembolism. A large proportion of patients with lower limb trauma and immobilisation could safely avoid thromboprophylaxis. French Ministry of Health.

High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism: the HUNT study

AbstractMicroRNA-145 (miR-145) has been reported to downregulate the expression of tissue factor and factor XI in vitro and decrease venous thrombus formation in animal models. However, the association between miR-145 and risk of future venous thromboembolism (VTE) in the general population remains unknown. We investigated the association between plasma levels of miR-145 and risk of future VTE in a case-cohort study. Incident VTE cases (n = 510) and a subcohort (n = 1890) were derived from the third survey of the Trøndelag Health Study (HUNT3), a population-based cohort. The expression levels of miR-145 were measured in plasma samples obtained at baseline. The study population was divided into quartiles based on miR-145 levels in participants in the subcohort, and weighted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma levels of miR-145 were inversely associated with VTE risk. Participants with miR-145 levels in the highest quartile had a 49% lower risk of VTE (HR, 0.51; 95% CI, 0.38-0.68) than those with miR-145 in the lowest quartile in age- and sex-adjusted analysis, and the inverse association was most pronounced for unprovoked VTE (HR, 0.39; 95% CI, 0.25-0.61). Risk estimates remained virtually the same after further adjustment for body mass index, and cancer and arterial cardiovascular disease at baseline. In conclusion, elevated expression levels of miR-145 in plasma were associated with decreased risk of future incident VTE. The protective role of miR-145 against VTE is consistent with previous experimental data and suggests that miR-145 has the potential to be a target for VTE prevention.

The effectiveness of pneumatic compression devices in preventing venous thromboembolism in patients undergoing elective spine surgeries

Objectives: Venous thromboembolic events are devastating complications that may arise following spine surgery with rates ranging from 0% to 14% in the literature. Orthopedic procedures increase the risk of thromboembolic events, and diagnosis is often challenging due to the varying presentations. Most research on venous thromboembolism (VTE) and international standards emphasizes that prevention such as mechanical prophylaxis is more crucial than therapy. This study aimed to assess the effectiveness of pneumatic compressive devices in preventing VTE in spinal surgery patients. Methods: This retrospective cohort study assessed the outcomes of mechanical prophylaxis in the form of pneumatic devices in 547 patients at our institution over five years from 2016 to 2021. Above-knee pneumatic compression stockings were applied before, during, and after surgery with patient outcomes being recorded. Results: Data was collected from 547 patients, who underwent elective spinal surgery at our center between January 2016 and January 2021. The mean age was 47.27 years (±20.84), and most patients were male (63.1%). Most patients were classified as having a low risk (35.6%) or mild risk (43.5%) of VTE determined by the Caprini score. Following spinal surgery, only one patient in our cohort experienced post-operative VTE (0.18%). Conclusion: Pneumatic compression effectively prevents VTE in patients undergoing elective spine surgery. Although pharmacologic prophylaxis has traditionally been used to prevent VTE, pneumatic compressive devices represent an alternative or supplementary approach to reduce the risk of VTE further.

Bleeding Risk from Anticoagulant Thromboprophylaxis in Patients with Multiple Myeloma

Introduction: Patients with multiple myeloma (MM) have a high risk of venous thromboembolism (VTE) due to unique disease-related (i.e., vascular inflammation, hyperviscosity) and treatment-related factors (i.e., immunomodulatory drugs [IMiDs], high-dose dexamethasone). Thromboprophylaxis is recommended for most patients starting MM therapy. Anticoagulants are preferred over aspirin except in patients at low risk for VTE. However, compliance with prophylaxis guidelines is low. The risk of bleeding from thromboprophylaxis is not well described in these patients so an excessive perceived risk may influence clinicians' practice. We conducted a real-world analysis of bleeding complications from VTE prophylaxis in MM. Methods: The IBM MarketScan Commercial Claims Database was used to identify MM cases between 2013 and 2021. Cases required MM diagnosis from 1 inpatient or 2 outpatient claims, based on ICD-9 or ICD-10 codes, and MM-specific therapy started between 7 days before and 90 days after index diagnosis code, based on HCPCS codes and prescription records. Those with preexisting VTE, atrial fibrillation or stroke were excluded. Thromboprophylaxis was defined as at least 1 prescription for warfarin, low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOAC) within 30 days of diagnosis. Major bleeding was defined as bleeding requiring hospitalization using inpatient ICD codes previously validated (Cunningham algorithm). Patients were followed from end of prophylaxis exposure window (index MM + 30 days) to first major bleeding event, disenrollment (due to death or other reasons) or December 31, 2021. Descriptive statistics were used to calculate rates of bleeding. Cox regression was used to assess the risk of bleeding from thromboprophylaxis and define risk factors associated with major bleeding. Results: We included 6,656 patients diagnosed and treated for MM, with mean age 62.7 years and 55.3% males. Although over 50% of the population would have had a high thrombotic risk based on consensus guidelines, concurrent anticoagulant prophylaxis was prescribed in only 6.6% (436). Prophylaxis agent of choice was warfarin in 23% (102), LMWH in 39% (169), and DOAC in 38% (165), respectively. There was a trend over time favoring DOAC over other agents (25% increase in DOAC use vs. other agents per year on average, p&amp;lt;0.01). Patients on prophylaxis had a higher rate of IMiD-based therapy (63.8% vs. 46.7%, p&amp;lt;0.01) and lower concomitant anti-platelet use (2.1% vs. 4.7%, p=0.01) than those not receiving prophylaxis. There were no differences in age/sex distribution, Charlson comorbidity index (CCI) or history of bleeding between groups. With a median 1.3 years follow-up, the incidence of major bleeding among MM patients receiving VTE prophylaxis was 1.4% or 7.8 bleeding events per 1,000 person-years. This was numerically but not statistically lower than the incident bleeding rate in patients not receiving prophylaxis: 1.8% or 10.1 events per 1,000 person-years. Table 1 shows risk factors for bleeding in this MM population, adjusting for age and sex, including higher age (per 10-year increase, HR 1.38), higher CCI (per SD increment, HR 1.18), history of bleeding (HR 1.54), hypertension (HR 1.87), and renal disease (HR 1.56). IMiD-based MM therapy was associated with decreased risk of bleeding (HR 0.69). Table 2 shows the estimated bleeding risk associated with prophylaxis across several models. No statistically significant association was identified between major bleeding and anticoagulant prophylaxis. Discussion: In a real-world analysis of commercial claims data, the risk of major bleeding associated with VTE prophylaxis in patients with MM undergoing cancer therapy is low and no significant increase in bleeding risk was identified for concurrent anticoagulant use. The rate of major bleeding events appears to be comparable between patients who receive VTE prophylaxis and those who do not. Nevertheless, underutilization of VTE prophylaxis is frequent. Higher CCI, bleeding history, hypertension, and renal disease were clinical factors associated bleeding risk, which may be included in models to help clinicians assess individual patient's risk and guide clinical decisions.

A Mouse Model of the PAR4 Sequence Variant P310L Shows Decreased Platelet Reactivity and Thrombosis

Protease activated receptors 1 and 4 (PAR1, PAR4) on platelets mediate thrombin signaling and are vital for thrombus development. Hypercoagulation and thrombin generation are major risk factors for thrombosis. Sustained thrombin signaling through PAR4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single-nucleotide polymorphism (SNP, rs2227376) leads to an amino acid change in extracellular loop 3 (ECL3) of PAR4, which decreases PAR4 activation (PAR4-P310L). This SNP is also associated with a significantly lower risk for venous thromboembolism (VTE) in a GWAS meta-analysis. We aim to determine the mechanism by which PAR4-P310L (rs2227376) impacts platelet function and reduces the risk of VTE using mice with a homologous mutation (PAR4-P322L). Ex vivo platelet function was determined using flow cytometry and aggregometry. Arterial and venous thrombosis was examined using the ferric-chloride induced carotid artery injury and inferior vena cava (IVC) stasis models, respectively. Platelets from heterozygous (PAR4-322P/L) and homozygous (PAR4-322L/L) mice had decreased thrombin-mediated aggregation and decreased PAR4 reactivity compared to wild types. These mice also had a prolonged time to occlusion in arterial thrombosis, with 55% of PAR4-322P/L mice unable to develop stable thrombi within 30 minutes. In venous thrombosis, wild-type mice developed clotted IVCs that averaged 31 mg after 48 hours, while global PAR4-knockout mice averaged 21 mg (p&amp;lt;0.01), PAR4-322P/L 23 mg (p&amp;lt;0.01), and PAR4-322L/L 28 mg. Since platelet procoagulant activity is known to drive venous thrombosis, we used lactadherin to show that PAR4-P322L platelets express less phosphatidylserine in response to thrombin (5 nM) and convulxin (1 nM). Platelet-rich plasma from PAR4-P322L mice also generated less thrombin compared to wild-types, and whole blood from mice lacking PAR4 showed delayed clot formation in rotational thromboelastometry. Altogether, this suggests a direct impact of PAR4 signaling on platelet-mediated thrombin generation. Our new mouse model shows that the polymorphism in ECL3, PAR4-322L, decreases platelet reactivity and thrombosis. We also show PAR4-322L leads to less procoagulant platelets and decreases the endogenous thrombin potential. This decreased ability to generate thrombin offers a mechanism for PAR4's role in VTE. Our findings highlight a key role of PAR4 signaling in platelet activation and procoagulant activity in thrombosis.