VTE In Patients Research Articles

Gene expression profiling in Venous thromboembolism: Insights from publicly available datasets

BackgroundVenous thromboembolism (VTE) is the third most common cardiovascular disease and is a major cause of mobility and mortality worldwide. VTE is a complex multifactorial disease and genetic mechanisms underlying its pathogenesis is yet to be completely elucidated. The aim of the present study was to identify hub genes and pathways involved in development and progression of blood clot during VTE using gene expression data from public repositories. MethodologyDifferential gene expression (DEG) data from two datasets, GSE48000 and GSE19151 were analysed using GEO2R tool. Gene expression data of VTE patients were compared to that of healthy controls using various bioinformatics tools. ResultsWhen the differentially expressed genes of the two datasets were compared, it was found that 19 genes were up-regulated while 134 genes were down-regulated. Gene ontology (GO) and pathway analysis revealed that pathways such as complement and coagulation cascade and B-cell receptor signalling along with DNA methylation, DNA alkylation and inflammatory genes were significantly up-regulated in VTE patients. On the other hand, differentially down-regulated genes included mitochondrial translation elongation, termination and biosysthesis along with heme biosynthesis, erythrocyte differentiation and homeostasis. The top 5 up-regulated hub genes obtained by protein-protein interaction (PPI) network analysis included MYC, FOS, SGK1, CR2 and CXCR4, whereas the top 5 down-regulated hub genes included MRPL13, MRPL3, MRPL11, RPS29 and RPL9. The up-regulated hub genes are functionally involved in maintain vascular integrity and complementation cascade while the down-regulated hub genes were mostly mitochondrial ribosomal proteins. ConclusionPresent study highlights significantly enriched pathways and genes associated with VTE development and prognosis. The data hereby obtained could be used for designing newer diagnostic and therapeutic tools for VTE management.

Oxidative Status, Iron Plasma Levels in Venous Thrombosis Patients.

Exaggerated clot induces venous thrombosis (VTE); oxidative stress (OxS) can to be postulated as additional risk factor. This study evaluates firstly OxS by measuring surrogate biomarkers (malondialdehyde-MDA, 4-hydroxinonenal-4-HNE, superoxide desmutase enzyme (SOD)), secondly the iron (Fe) plasma level and thirdly the hepcidin protein (Hep) level in patients with VTE. A case control study was performed enrolling twenty hospitalized patients and an equal number of healthy individuals. In VTE patients, the following results were found. The MDA was 8.38 ± 0.5 µM/L, the 4-HNE measured 2.75 ± 0.03 µM/L and the SOD was 0.025 ± 0.01 U/mL. The I was 73.10 ± 10 µg/dL and the He was 4.77 ± 0.52 ng/mL. In the control group, the MDA measured 5.5 ± 0.6 µM/L, the 4-HNE 2.24 ± 0.021 µM/L and the SOD 0.08 ± 0.12 U/mL. The Hep was 2.1 ± 0.55 ng/mL and the Fe was 88.2 ± 9.19 µg/dL. Differences were statistically significant. Results suggest that in VTE there is activated OxS, Fe deregulation and over-production of Hep. Fe deregulation induces OxS, leading both to inflammation in the clot activator and stimulation of the pro-thrombotic status. The study highlights OxS and Fe and their regulation as intriguing indicators for risk of VTE.

Functional limitations 3 and 12 months after venous thromboembolism: a cohort study

BackgroundVenous thromboembolism (VTE) is associated with various long-term complications. ObjectivesWe aimed to investigate the association of clinical characteristics at VTE diagnosis with functional limitations 3 and 12 months afterward. MethodsWe 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). ResultsWe 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/m2 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. ConclusionFunctional 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.

Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study

BackgroundVenous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE.MethodsThis observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was d-glutamine and d-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3′,5′-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68).ConclusionsOur findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.

A ten-year comparison of treatment and outcomes of cancer-associated thrombosis to non-cancer venous thromboembolism: from traditional anticoagulants to direct oral anticoagulants.

DOACs have emerged as first-line treatment in most cancer-associated thrombosis (CAT), representing a paradigm shift in its management. However, CAT management remains challenging and requires careful risk-benefit considerations. A retrospective analysis of CAT presentations to a tertiary referral centre from January 2011 to December 2020. Outcomes in CAT patients were compared to VTE patients without malignancy. Subgroup analysis was also conducted for CAT according to anticoagulation type. 514 CAT cases from 491 patients were identified from 3230 total VTE cases. CAT patients had higher rates of major VTE (PE and/or proximal DVT) compared to patients without malignancy (78.4% vs. 66.8%, p < 0.001). CAT patients also had higher rates of VTE recurrence (HR 1.66, 95%CI 1.23-2.26), major bleeding (HR 3.41, 95%CI 2.36-4.93), VTE-related mortality (HR 2.59, 95%CI 1.46-4.62) and bleeding-related mortality (HR 2.66, 95%CI 1.05-6.73). There were no significant differences in rates of VTE recurrence, major bleeding, VTE-related mortality or fatal bleeding between CAT patients treated with DOACs, enoxaparin or warfarin. In the subgroup of CAT treated with DOACs, there was no significant difference in rates of GI bleeding compared to the enoxaparin subgroup (HR 0.17, 95%CI 0.02-1.26). CAT was associated with a larger clot burden and higher rates of VTE recurrence, major bleeding and mortality compared to VTE patients without malignancy in this large real-world study. This study demonstrated no significant differences in complication rates for CAT patients treated with DOACs over enoxaparin, suggesting that DOACs can be safely used in most cases of CAT.

Altered Mitochondrial DNA Methylation Patterns in Thrombosis

DNA methylation being one of the chief controllers of gene expression has not only been the reason behind the initiation of a plethora of diseases like Cancer, Alzheimer’s disease, Parkinson’s disease, etc. Still, it is an active contributor to the pathophysiology of several cardiovascular diseases like coronary artery disease (CAD), Atherosclerosis, Stroke, Cardiomyopathy, etc. The role of nuclear DNA methylation in VTE has been studied earlier, but the comparison of methylation in both nuclear genes and mitochondrial genes in high altitude VTE (HA-VTE) and sea level VTE (SL-VTE) patients has not been studied in depth. Through this present study, DNA methylation patterns of mitochondrial encoded as well as nuclear-encoded mitochondrial genes of five high-altitude VTE patients and five sea-level VTE patients have been obtained. On comparing HA-VTE vs. SL-VTE methylation, one hundred and twenty hypermethylated genes and one hundred and thirty-eight hypomethylated genes were observed. Post gene enrichment and ontology study, the TCA cycle and NADH dehydrogenase were found to be the highly enriched pathways in both the study groups. Protein-protein interaction network using STRING pointed out the enriched pathway of L-2-hydroxyglutaric acid when both the gene sets were enriched. These results show the crucial role of mitochondrial DNA methylation in the pathophysiology of thrombosis and show great potential to study the role of mitochondria in thrombosis.

Coagulation parameters correlate to venous thromboembolism occurrence during the perioperative period in patients with spinal fractures

BackgroundVenous thromboembolism (VTE) is one of the leading causes of mortality in hospitalized patients. However, whether the coagulation-related parameters of the hospitalized patients could be used to predict the occurrence of VTE in patients with spinal injury surgery remained unclear.MethodThe patients with spinal fractures who met the inclusion and exclusion criteria were enrolled to be analyzed using a retrospective analysis approach. The association of risk factors of enrolled patients and operations to VTE occurrence were analyzed. The activated partial thromboplastin time, prothrombin time, thrombin time, D-dimer (D-D), fibrinogen (FIB) and fibrinogen degradation products (FDP) were detected. ROC and HR analysis were applied to evaluate the correlation of coagulation-related parameters and other parameters to VTE occurrence.ResultThe indicators of D-D, FIB and FDP were significantly elevated in VTE patients compared to non-VTE patients. The multivariate analysis of OR showed that six risk factors, including age ≥ 60, spinal cord injury, postoperative bedtime over 5 days, plasma D-dimer ≥ 0.54 mg/L, plasma fibrinogen ≥ 3.75 g/L and plasma FDP ≥ 5.19 mg/L, were positively correlated to VTE.ConclusionThe six risk factors, including D-D, FIB, FDP, age ≥ 60, spinal cord injury, and postoperative bedtime over 5 days, could be used to predict the occurrence of VTE.

The incidence and risk factors of newly-diagnosed cancer after diagnosis of venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background/Introduction Venous thromboembolism (VTE) may be the earliest sign of cancer, although there are no established screening strategies for occult cancer. This could be partly due to lack of the real-world incidence and risk factors of occult cancer after diagnosis of VTE in the current era. Purpose The current study aimed to evaluate clinical characteristics and outcomes between patients who were newly diagnosed with cancer after diagnosis of VTE and those who were not, and investigate incidence and risk factors of newly-diagnosed cancer after diagnosis of VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The current study population was consisted of 3706 patients without known active cancer at diagnosis of VTE, who were divided into patients with newly-diagnosed cancer after diagnosis of VTE (N=250, 6.7%) and those without (N=3456, 93.3%). To explore risk factors of newly-diagnosed cancer, we constructed the multivariable Cox proportional hazard model which consisted of variables with P values &amp;lt;0.05 in univariate analysis. Results The cumulative incidences of newly-diagnosed cancer were 1.5% at 30-day, 3.7% at 1-year, 7.0% at 3-year, 11.1% at 5-year, and 16.0% at 7-year. The most common types of newly-diagnosed cancer was colon (17.2%), followed by lung (14.8%) and blood (8.0%). Patients with newly-diagnosed cancer were older (71.6 vs. 67.2 years, P&amp;lt;0.001) and had lower body mass index (22.9 vs. 23.8 kg/m2, P=0.004) than those without. Patients with newly-diagnosed cancer more frequently had several comorbidities such as history of cancer (35% vs. 11%, P&amp;lt;0.001), hypertension (51% vs. 44%, P=0.04), diabetes mellitus (21% vs. 16%, P=0.03), and autoimmune disorder (20% vs. 13%, P=0.004), whereas they less frequently had transient provoking risk factors for VTE (29% vs. 39%, P&amp;lt;0.001). The cumulative incidence of all-cause death was significantly higher in patients with newly-diagnosed cancer than those without (59.3% vs. 21.0% at 7-year). The multivariable Cox proportional hazard model revealed that old age (hazard ratio [HR]: 1.02 per 1 year [1.01-1.03], P&amp;lt;0.001), history of cancer (HR: 3.60 [2.75-4.67], P&amp;lt;0.001), autoimmune disorder (HR: 1.51 [1.09-2.05], P=0.01), and absence of transient provoking risk factors for VTE (HR: 1.36 [1.03-1.80], P=0.03) were independently associated with newly-diagnosed cancer after diagnosis of VTE. Conclusions In the current era, the incidence of newly-diagnosed cancer was 3.7% at 1-year with initial acute increase followed by continuous increase, and several independent risk factors were identified, which might be useful for consideration of optimal screening strategies for occult cancer based on individual risk.Newly-diagnosed cancer

Venous thromboembolic disease in admitted blunt trauma patients: what matters?

BackgroundVenous thromboembolic events (VTE) are a significant cause of morbidity and mortality following traumatic injury. We examined demographic characteristics, chemoprophylaxis, and outcomes of VTE patients with blunt trauma requiring hospitalization.MethodsA retrospective review of adult blunt trauma hospitalizations with and without VTE between 2012 and 2019 was conducted. Deaths in the emergency department were excluded. Univariate and multivariable analyses, including machine learning classification algorithms for VTE, were performed.ResultsOf 10,926 admitted adult blunt trauma patients, 177 had VTE events. VTE events occurred at a median of 6 [IQR 3–11] days, with 7.3% occurring within 1 day of admission. VTE patients were more often male, and more often underwent surgery. They had higher injury severity as well as longer intensive care unit and hospital lengths of stay. While VTE occurred throughout the spectrum of injury severity, 27.7% had low injury severity (ISS < = 9). In multivariable analyses, both heparin and enoxaparin had reduced adjusted odds ratios for VTE.ConclusionApproximately 7.3% of VTE events occurred within one day of admission. A substantial proportion of VTE events occurred in patients with low injury severity (ISS < = 9). Subcutaneous unfractionated heparin and enoxaparin chemoprophylaxis were both inversely associated with VTE. These findings underscore the need for vigilance for VTE identification in blunt trauma patients throughout their hospitalization and VTE prevention efforts.

GDF15 affects venous thrombosis by promoting EndMT through smad2/p-smad2 pathway

BackgroundEndothelial-to-mesenchymal transition (EndMT) is a pathophysiological change in the vascular endothelium commonly seen in the cardiovascular system. Elevated serum Growth differiention factor 15 (GDF15) has been reported in VTE patients, but the relationship and mechanism between GDF15, EndMT and VTE are still unclear.MethodsWe performed a retrospective clinical study, and human serum GDF15 expression levels were detected. The mouse DVT model was established through subtotal ligation of the mouse inferior vena cava, and then we detected intimal changes and thrombi in the stenotic inferior vena cava by haematoxylin-eosin (HE) staining, Masson staining, and Sirius Red staining. The expression levels of GDF15 and SM22 were detected by immunohistochemistry and RT‒qPCR. Serum samples of mice were collected, and the expression level of GDF15 in serum was detected. Human umbilical vein endothelial cells (HUVECs) were stimulated with a cytokine mixture (TGF-β1 + TNF-α + IL-1β). The role and mechanism of GDF15 in EndMT and VTE were detected in HUVECs and in a DVT mice model.ResultsWe found that serum GDF15 levels in both VTE patients and mouse DVT models were higher than those in the control group. EndMT was increased in the stenotic vascular tissue of mice. Further experiments showed that GDF15 could promote the EndMT of HUVECs and reduce their anticoagulation and antifibrinolytic ability through the smad2/p-smad2/snail pathway. Inhibition of mature GDF15 release can significantly reduce venous thrombotic fibre deposition in mice.ConclusionsGDF15 positively promotes EndMT through activation of the Smad2/psmad2/snail pathway, and inhibition of GDF15 expression can alleviate the EndMT process, further improving the coagulation and fibrinolytic function of endothelial cells and thus reducing the local fibre deposition of venous thrombi.

Comparative Efficacy of Direct Oral Anticoagulants and Low-Molecular-Weight Heparin in Cancer-Associated Thromboembolism: A Systematic Review and Meta-Analysis.

Patients diagnosed with cancer often experience an abnormal occurrence of venous thromboembolism (VTE) and its related complications. In order to evaluate the safety and effectiveness of both treatment approaches, we conducted a comprehensive systematic review and meta-analysis within the realm of cancer-associated thromboembolism. A thorough search was conducted across PubMed, the Cochrane Library, and Embase databases to find studies comparing direct oral anticoagulants (DOACs) with low molecular weight heparins (LMWHs) for the treatment of VTEin patients with malignancy. The analyses utilized the random-effects model. This meta-analysis included 11 studies. The results showed that DOACs were associated with a significantly reduced risk of VTE recurrence (RR: 0.67; 95% CI: 0.55, 0.81, p<0.0001; I2: 0%) and deep vein thrombosis (DVT) (RR: 0.63; 95% CI: 0.46, 0.86, p<0.0001; I2: 0%) compared to LMWHs. However, there was no significant difference in the risk of pulmonary embolism (PE) (RR: 0.76; 95% CI: 0.54, 1.06, p=0.11; I2: 11%) between the two groups. The use of DOACs was also associated with a non-significant increase in the risk of major bleeding events (RR: 1.23; 95% CI: 0.85, 1.78, p: 0.26; I2: 49%), while clinically relevant non-major bleeding (CRNMB) was significantly higher with DOACs (RR: 1.92; 95% CI: 1.11, 3.30, p: 0.02; I2: 81%). Secondary outcomes, such as survival rates and fatal PE, did not show significant differences between the two treatment groups. Our analysis indicates that direct oral anticoagulants exhibit a substantial decrease in the occurrence of VTE recurrence, deep vein thrombosis, and pulmonary embolism when compared to low molecular weight heparin in cancer-associated thromboembolism. However, it should be noted that DOACs carry a higher risk of CRNMB. Based on these findings, DOACs are recommended as a superior therapeutic option for managing cancer-associated thromboembolism compared to LMWH.

#2827 RISK FACTORS FOR VENOUS AND ARTERIAL THROMBOEMBOLIC COMPLICATIONS IN NEPHROTIC SYNDROME: A COHORT STUDY

Abstract Background and Aims Venous thromboembolic events (VTE) and arterial thromboembolic events (ATE) are serious complications of nephrotic syndrome (NS). Studies are needed to identify patients at high risk for VTE and ATE. We aimed to describe patient-related risk factors for VTE and ATE in a mixed population of nephrotic patients. Method This multicentre cohort study included adult NS patients with plasma albumin &amp;lt;30 g/l and urine albumin-creatinine ratio (uACR) &amp;gt;2,200 mg/g, who were hospitalized or followed at an outpatient clinic in the Central Denmark Region between 2014-2018. Using computerized data extraction from medical files, patients were identified and followed until dialysis, transplantation, or end of study. We recorded comorbidities, family history, renal parameters and, histological diagnosis at index time as well as, renal parameters and medication at the time of VTE/ATE event. Categorical and continues data were compared using a risk difference and mean difference respectively. The incidence of event is presented as incidence rate. Results Among 531 included patients, 22 patients had their first VTE and 46 their first ATE within the first observation year (median time to event VTE 0.8 vs. ATE 0.9 years). Incidence rates were 11 per 1000 person-years (95% CI: 7-17) for VTE and 24 (95% CI: 18-32) for ATE. Plasma-albumin levels (27 g/l) were identical in the VTE and ATE group at event time, but eGFR was lower (Table 1), and uACR was higher in the ATE group (median uACR; VTE 1055 mg/g vs. ATE 2752 mg/g). Hypercholesterolemia was more prevalent among patients with VTE, and they were more often on corticosteroids than patients with ATE. Diabetes, hypertension, and heart failure was more prevalent at baseline in patients with ATE resulting in an increased CHADS-VASC score. Mortality was higher among patients with ATE (83%) than VTE patients (32%). Conclusion Patients with NS have a high risk of VTE and ATE. Corticosteroid use was more common among patients with VTE than ATE. ATE was associated with a higher uACR, higher CHADS2-VASC score, and increased mortality compared to patients with VTE.

Understanding etiopathology of high altitude induced venous thrombo-embolism (HA-VTE) by variant analysis using whole exome sequencing (WES) data

BackgroundVenous thrombo-embolsim(VTE) is a complex disease and a significant cause of morbidity and mortality worldwide. Its manifestation attributes to various acquired and genetic risk factors. Environmental condition at high altitude (HA) such as hypoxia (oxygen deprivation) has been regarded as independent risk factor for VTE. Individual variations in coagulation genes play a major role in predisposing a person towards VTE. MethodologyPresent study evaluates genetic variants in VTE patients from HA (n = 6) and from sea level(SL) (n = 15) in comparison to healthy controls (n = 19). To unfold a unique thrombophilia panel in Indian population, whole exome sequencing (WES) was performed on IlluminaHiSeq platform. Presence or absence of known variants was studied across the three study groups. Statistically significantly variants were enlisted for each study group. ResultsOur findings suggest that VTE pathology is associated with total 38 variants in pro-coagulant and anti-coagulant genes. These variants were distinct for HA-VTE and SL-VTE patients. Eighteen significant variants in HA-VTE group primarily included coagulation factors, rs6035 and rs6030 in F5 gene; rs3136434, rs216311, rs216902 and rs2192205 in F2 gene and anti-coagulants, rs2759328 in SERPINC1 and rs758232970 in PROS1 gene. Amongst 7 significant variants in SL-VTE, rs6035 was common with HA-VTE. Besides, 13 variants significantly appeared when the two patient groups, HA-VTE and SL-VTE were compared with each other. ConclusionWES study delineated variants in VTE patients, from HA and SL. Our findings have generated a unique thrombophilia panel which could be helpful in predicting individual's susceptibility towards VTE at HA and even at SL.

Impact of venous thromboembolism on incidence of arterial thromboembolism - An analysis of German outpatient claims data

BackgroundVenous thromboembolism (VTE) and arterial thromboembolism (ATE) are considered as two separate disease-entities. In recent years, studies have reported clear associations between VTE and atherosclerosis. We aimed to evaluate the long-term risk of ATE in VTE patients in comparison to controls without VTE. MethodsNationwide outpatient claims data of all inhabitants with statutory health insurance in Germany were used for secondary data analysis between the years 2011 and 2020. Patients treated in 2013 were stratified by VTE event, and groups were 1:2-matched by age and sex. The hazard for an ATE event in a 5-year follow-up period between patients with and without VTE was calculated with multivariable Cox regression adjusted for age, sex, cardiovascular risk factors, and comorbidities. ResultsOf 69,699,277 individuals treated in the year 2013 by German physicians in outpatient care, in total 686,382 individuals (age 59.8 ± 17.5 years, 65.4 % females) were included comprising 228,794 patients with VTE and 457,588 controls without VTE. VTE patients more often had cardiovascular risk factors (81.6 % vs. 62.2 %) and traditional VTE risk factors. The occurrence of ATE events during follow-up was 1.8 %-points higher in VTE patients in comparison to the controls (9.7 % vs. 7.9 %). VTE events were independently associated with increased occurrence of ATE events within follow-up (HRadjusted 1.19 [99%CI 1.16–1.23], p < 0.0001). ConclusionsPatients with a VTE event have an increased long-term risk for subsequent arterial cardiovascular events. Large prospective cohorts are needed to identify patient subgroups with a very high ATE risk after VTE.

The Risk Assessment Profile is suboptimal for guiding duplex ultrasound surveillance in trauma patients

The utility of the Risk Assessment Profile (RAP) score in predicting VTE was assessed, and VTE risk factors identified to guide a duplex ultrasound (DUS) protocol in injured patients. Secondary analysis of prospective data on trauma inpatients (March 2017 - September 2019), with admission RAP ≥5. Inhospital VTE patients compared to those without. Regression analyses in DVT, PE and proximal DVT, and ROC analysis evaluating RAP's VTE predictability were performed. 1,989 patients were analyzed. VTE was identified in 163(8.2%), DVT 159(8.0%), and PE 10(0.5%) patients. Strongest VTE predictors were massive transfusion (OR 5.97, p=0.005) and spinal cord injury (OR 2.43, p=0.03). AUC 0.61 (p<0.001) on ROC analysis evaluating RAP on VTE. Abdominal injury and major surgery were unique risk factors to non-screened patients. Performance of RAP to predict VTE was moderate. VTE predictor variables could serve as the foundation for a novel approach guiding DUS surveillance. Derivation and validation are warranted.

Abstract 11900: Should Venous Thromboembolism Patients Treated With DOACs Be Dose Adjusted Like Patients With Atrial Fibrillation: Lessons From Apixaban

Introduction: In contrast to atrial fibrillation (AF), dose adjustment of apixaban and other DOACs is not recommended for pts with DVT or PE (VTE). Median DOAC levels were lower in VTE trials (e.g. apixaban 5-mg BID, AF 171 and 103 ng/mL vs. DVT 132 and 63 ng/mL, peak and trough, respectively), the result of a younger, lower weight population with better kidney function. Thus, VTE patients who meet or approach the apixaban dose reduction criteria may have levels far in excess of what’s needed to prevent recurrence. Hypothesis: Apixaban over exposure occurs in VTE pts at risk for elevated apixaban levels. Methods: Patients ≥ 75 yrs of age who had clinical markers that identified them as being at high risk for over exposure, including: 1) apixaban AF dose risk reduction criteria (age ≥ 80, creatinine ≥ 1.5, and wt ≤ 60-kg) and 2) approaching but not meeting dose reduction criteria (e.g. creatine 1.4, weight 65-kg) had a DOAC level measured at their anticoagulation clinic appointment. Levels were determined using liquid chromatography-mass spectrometry. Clinical decisions were made based on the “expected” apixaban levels. Results: Apixaban levels were obtained in 15 male pts. All 10 pts who were initially treated with apixaban 5-mg (2 of whom met the AF dose reduction criteria) had supratherapeutic apixaban levels on 5-mg BID. Of the 5 pts treated initially with apixaban 2.5-mg BID, 3 had adequate apixaban levels, while the other 2 had trough levels that were on the lower side. All 3 pts who met the AF dose reduction criteria (1 treated initially with 2.5-mg) had an adequate apixaban level on 2.5-mg BID. Conclusions: Apixaban treated VTE pts who meet or approach the AF dose reduction criteria are candidates for apixaban dose reduction, especially in light of the fact that peak and trough levels for VTE pts in general are lower than pts with AF.

The High Expression of Adhering and Circulating Integrin Serves as a Diagnostic Marker in Venous Thromboembolism.

Objective To investigate the diagnostic value of circulating integrins β1, 2, and 3 in venous thrombosis (VTE). Materials and Methods A total of 474 VTE patients and 306 patients with nonhigh risk for VTE as the control group were studied. Levels of adhering integrins β1, 2, and 3 were detected by flow cytometry. Levels of circulating integrins β1, 2, and 3 in serum were measured by enzyme-linked immunosorbent assay. Results We found that integrins β1, 2, and 3 were expressed highly both in serum and on the surface of leukocytes and platelets in venous thromboembolism. The levels of circulating integrins β1, 2, and 3 are positively correlated with adhering integrins. It showed excellent clinical diagnostic performance of circulating integrins β1, 2, and 3 in venous thromboembolism. Conclusions Integrin subunit β can be used as a diagnostic marker with high sensitivity and specificity for venous thromboembolism.

Prevalence of venous thromboembolism and evaluation of a modified caprini risk assessment model: a single-centre, prospective cohort study involving patients undergoing lung resections for bronchiectasis

BackgroundVenous thromboembolism (VTE) is a common postoperative complication in general thoracic surgery, but the incidence of patients undergoing surgery for bronchiectasis was not known. The purpose of our study was to investigate the incidence of VTE in bronchiectasis patients undergoing lung resection and to evaluate the risk stratification effect of the modified caprini risk assessment model (RAM).MethodsWe prospectively enrolled patients with bronchiectasis who underwent lung resection surgery between July 2016 and July 2020.The postoperative duplex lower-extremity ultrasonography or(and) computed tomographic pulmonary angiography (CTPA) was performed to detect VTE. The clinical characteristics and caprini scores of VTE patients and non-VTE patients would be compared and analyzed. Univariate logistic regression was performed to evaluate whether higher Caprini scores were associated with postoperative VTE risk.In addition, We explored the optimal cutoff for caprini score in patients with bronchiectasis by using the receiver operating characteristic (ROC) curve.ResultsOne hundred and seventeen patients were eligible based on the prospective study criteria. The postoperative VTE incidence was 8.5% (10/117). By comparing the clinical characteristics and Caprini scores of VTE and non-VTE patients, the median preoperative hospitalization (7 vs 5 days, P = 0.028) and Caprini score (6.5 vs 3,P < 0.001) were significantly higher in VTE patients. In univariate logistic regression, a higher Caprini score was associated with higher odds ratio (OR) for VTE of 1.7, 95% confidence interval (CI) was from 1.2 to 2.5 (P = 0.001), C-statistics was 0.815 in the modified caprini RAM for predicting VTE. In a multivariable analysis adjusting for preoperative hospitalization, a higher Caprini score was associated with higher odds OR for VTE of 1.8 (95%CI: 1.2–2.6, P = 0.002), C-statistics was 0.893 in the caprini RAM for predicting VTE. When taking the Caprini score as 5 points as the diagnostic threshold, the Youden index is the largest.ConclusionsThe postoperative VTE incidence in patients undergoing lung resection for bronchiectasis was 8.5%.The modified caprini RAM effectively stratified bronchiectasis surgery patients for risk of VTE and showed excellent predictive power for VTE. The patients with postoperative caprini scores = 5, should be recommended to take positive measures to prevent postoperative VTE.Trial RegistrationChinese Clinical Trial Register: ChiCTR-EOC-17010577.

The use of enoxaparin as venous thromboembolism prophylaxis in bariatric surgery: A retrospective cohort study

IntroductionVenous thromboembolism (VTE) is one of the major causes of morbidity and mortality in bariatric patients. The use of low-molecular-weight heparin (LMWH), as enoxaparin, is considered one of the mainstays thromboprophylaxis regimens in postoperative bariatric patients. Despite the universal agreement on the importance of thromboprophylaxis in these patients, there are inadequate strong recommendations for its dosing and duration. The aim of our study is to explore the current practice on using enoxaparin in bariatric patients, as well as to assess both the efficacy and safety of varying dosing regimens. Material and methodsThis is a retrospective cohort study of morbidly obese patients who underwent bariatric procedure at a tertiary care hospital between 2016 and 2019. All adult patients who met the eligibility criteria for bariatric surgery and received enoxaparin with a minimum follow-up period of one month were included in our study. Participants with a history of coagulopathy, renal or hepatic insufficiency were excluded from the study. Data collected include patient demographics, VTE risk factors, and co-morbidities. The outcome of treatment failure was defined as the composite of either VTE or major bleeding. ResultsA total of 1,169 patients who underwent bariatric surgery were included in the study. The mean age was 35.54 years, with mean body mass index (BMI) of 45.78 kg/m2. The mean duration of enoxaparin use was 9 days, and the majority of patients (78%) received a prophylaxis dose of 40 mg subcutaneously (SC) once daily. The overall rate of VTE at 90 days was 1.4% while only 0.1% of patients developed major bleeding. There was no statistically significant difference in patients’ age, gender, BMI, or various enoxaparin dosing regimens between patients who developed VTE or bleeding versus patients who did not develop. Patient’s weight was the only statistically significant risk factor that directly correlated to higher risk of complications (P = 0.006). In the multivariable logistic regression model, higher BMI was significantly associated with treatment failure, either VTE or major bleeding [OR 1.05 (95% CI 1.0–1.09); P = 0.038]. ConclusionsThe rate of VTE or major bleeding did not differ in patients who received various enoxaparin regimens. Patients undergoing bariatric surgery may benefit from enoxaparin thromboprophylaxis dose of 40 mg SC daily for a total duration of 14 days, with higher doses may be needed for extremely obese patients. We recommend standardizing the current practice of VTE prophylaxis post bariatric surgery and unifying the optimal dose and duration.

Characteristics and Prognostic Factors of Venous Thromboembolism in Cancer Patients.

Background: Improving the prognosis of patients with malignant tumors is increasing the number of patients who develop venous thromboembolism. We examined the characteristics and prognostic factors of VTE patients with cancer.Methods: We diagnosed 725 VTE patients from April 2005 to March 2018. There were 322 cancer associated patients (CAT) and 403 non-cancer associated patients (nonCAT). We examined characteristics and prognostic factors of VTE in CAT patients.Results: There were 156 women and 166 men in CAT, and 132 women and 271 men in nonCAT. There was no significant difference in the location of proximal portion of thrombus. When locations were divided into left leg, right leg, and bilateral legs, bilateral cases were more common in CAT group. Comparing the overall survival after VTE diagnosis in the CAT group, the prognosis was poor in patients with high D-dimer level (≧6 µg/mL) along with cancer metastasis and recurrence.Conclusions: Various VTE factors predict prognosis in CAT patients, and CAT is important in the treatment of cancer patients. (This is secondary publication from Jpn J Phlebol 2020; 31(3): 153–159.)