VTE In Patients Research Articles

Factors and Outcomes Associated With Venous Thromboembolism Following Bariatric Surgery.

The present national study characterized the incidence and factors associated with VTE following bariatric operations and its association with postoperative outcomes and resource use. Adults (≥18years) undergoing elective sleeve gastrectomy or gastric bypass (laparoscopic and open) were identified in the 2016-2018 Nationwide Readmissions Database. International Classification of Diseases 10th Revision codes for deep venous thrombosis and/or pulmonary embolism were used to ascertain the presence of VTE. Multivariable linear and logistic models were developed to evaluate the independent association of VTE with outcomes of interest. Of an estimated 537,522 patients meeting inclusion criteria, .55% developed VTE during index hospitalization (.14%) or within 90 days of index discharge (.41%). Compared to others, VTE patients were older (51.8 vs 44.9 years, P<.001), more commonly male (20.0% vs 31.5%, P<.001), and had gastric bypass (56.3% vs 31.9%, P<.001) or an open procedure (21.9% vs 2.6%, P<.001). After risk adjustment, several factors including increasing age, male gender, gastric bypass and open approach remained associated with increased odds of VTE. Patients with VTE during index hospitalization had greater odds of mortality (AOR 11.6, 95% CI: 6.12-22.19) and increased index LOS (β:+14.1 days, 95% CI: 11.7-16.5) and hospitalization costs (β: +$53,100, 95% CI: 43,100-63,500). Additionally, VTE patients had greater odds of readmission within 90 days (AOR 1.86, 95% CI: 1.40-2.47). Although VTE is uncommon following bariatric operations, it is significantly associated with increased mortality, readmission, and resource use. Further research is necessary to ascertain optimal management of VTE for bariatric surgery patients.

High Prevalence of Plasminogen Activator Inhibitor-1 4G/5G Polymorphism among Patients with Venous Thromboembolism in Kerala, India.

Venous thromboembolism (VTE) is a multifactorial clotting disorder in which inherited and environmental factors synergistically contribute to its pathogenesis. The aim of this case-control study was to analyze the prevalence of hereditary thrombophilic risk factors, provoking and non-provoking environmental risk factors in patients with VTE from Kerala, India. We have observed a low prevalence of factor V Leiden (7%), prothrombin G20210A (2%), and prothrombin G20030A (2%) mutations and a high prevalence of plasminogen activator inhibitor-1 (PAI-1) 4G/5G (52%), PAI-1 4G/4G (24%) genotypes in the VTE patients (n = 147). Deficiency of anticoagulants, antithrombin (3.4%), and protein C (4.1%) was relatively low. None of the risk factors were observed in 17% of the patients. Majority of VTE patients were younger than 50 years with a median age of 43 years. In conclusion, our results indicate a high prevalence of PAI-1 4G/5G polymorphism among the VTE patients which is in concordance with previous studies in the Asian population. The PAI-1 4G/5G polymorphism could be a potential biomarker for assessing VTE risk, particularly among the Indian population.

Clinical Characteristics Associated with Venous Thromboembolism in Patients with Non-APL Acute Myeloid Leukemia

INTRODUCTIONVenous thromboembolism (VTE) is an important complication of many cancers. Although more widely recognized in solid tumors, VTE is still an appreciable cause of morbidity and mortality among patients with hematologic malignancies. For example, acute promyelocytic leukemia (APL) is a well-recognized risk factor for disseminated intravascular coagulation (DIC), which can lead to thrombosis. Patients with non-APL AML are also at increased risk for VTE, though the exact mechanisms are currently unclear. Thus, we sought to explore how patient demographics, comorbidities, hematologic factors, coagulation parameters, and cytogenetic and molecular profiles impact the incidence of VTE in patients with non-APL AML. METHODSThis was a retrospective observational case-control study of 120 non-APL AML patients treated at the University of Wisconsin-Madison. The electronic health record was manually reviewed for extraction of the relevant clinical information. Coagulation parameters assessed included INR, PTT, fibrinogen, D-dimer, and fibrin monomer. Coagulation data were collected both at diagnosis and during the first 7 days of induction, if applicable. Cytogenetics was categorized based on the presence of a normal karyotype or not. Genomic data were subdivided into eight different functional categories of genes that are commonly mutated in AML. Other factors that could potentially increase the risk of thrombosis were also analyzed, including age, sex, BMI, baseline blood counts, baseline bone marrow blast percentage, previous history of VTE, use of antifibrinolytic agents, and whether blood products were transfused during the early treatment period. The variables of interest between VTE cases and non-VTE cases were compared using the nonparametric Wilcoxon rank sum test. RESULTSAcross the entire cohort (n=120), VTE developed in 25 patients (20.8%) and did not develop in 95 patients (79.2%). Table 1 and Table 2 show comparisons between VTE cases and patients without VTE for both quantitative and categorical variables. Median INR values at diagnosis and across the first 7 days of induction tended to be lower in patients with VTE and reached significance on days 3-5 (p=0.032 for INR-Day 3, p=0.046 for INR-Day 4, p=0.014 for INR-Day 5). Patients with VTE had a median BMI of 30, while patients without VTE had a median BMI of 28, which approached statistical significance (p=0.055). 8% of patients with VTE (2/25) had a history of VTE prior to the diagnosis of AML, while 3% without VTE (3/95) had a history of previous VTE (OR 2.7, p=0.281). Mutation in genes involved in DNA methylation also conferred an increased risk of VTE, with the association approaching statistical significance (p=0.083). There were no other variables that were significantly different between the two groups. CONCLUSIONSIn this cohort of patients with non-APL AML, there was a trend towards lower INR correlating with an increased incidence of VTE. Additionally, higher BMI, previous history of VTE, and mutation in DNA methylation genes were associated with increased incidence of VTE, though these trends did not reach statistical significance. The pathophysiology of VTE in this setting is likely complex and multifactorial. The shorter INR in those who developed VTE suggests a mechanism independent of the development of DIC, which is distinct from APL. The finding that obesity and personal history of VTE, both known risk factors for thrombosis, were associated with an increased incidence of VTE is also consistent with a non-DIC mechanism. Mutations in DNA methylation genes may have contributed to increased risk of VTE in this cohort; while this association is compelling, further studies with larger sample sizes are needed to confirm this finding. This study was limited by small sample size and missing data, especially regarding available data on coagulation tests. However, this analysis uncovers interesting associations that shed light on the pathophysiology of VTE in AML. More research is needed to further elucidate risk factors for VTE in order to provide optimal supportive care for this patient population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Validating Direct Oral Anticoagulants (DOAC) for Use in Children By the Throm-PED Doac Registry of the International Pediatric Thrombosis Network

Background: A growing number of randomized clinical trials (RCTs) provide promising data on pharmacokinetics/ pharmacodynamics, efficacy and safety of DOAC in children and the first DOACs have recently been approved for treatment of thromboembolism in children. Based on the risk benefit profiles published so far, we expect DOACs to be widely used for treatment and prophylaxis of thrombosis in children. The strict inclusion criteria for participation in the RCTs limit their generalizability, particularly to those with more serious acute and chronic medical conditions that account for a significant proportion of pediatric VTE patients in clinical practice. Real world data complements evidence from randomized clinical trials, and is urgently needed to improve patient care.Aim: To obtain efficacy and safety data of DOACs in a large and heterogeneous pediatric patient collectives. To expand the knowledge on treatment strategies and outcomes across different risk profiles and comorbidities including cancer and renal disease.Study Design: An international, multicentre, prospective observational cohort study imbedded in the Throm-PED Registry of the International Pediatric Thrombosis Network (IPTN). Parameters included at baseline are age, gender, height, weight, thrombosis type, thrombosis location, risk factors, underlying medical conditions and comedication. Primary outcomes include 1) thrombus progression or recurrence and 2) bleeding (major, clinically relevant non major including menorrhagia) and 3) mortality. Outcomes are assessed every 3 months for a total of 12 months. Additional variables include self-reported adherence, comedication, chemotherapy, DOAC drug levels, measures of renal function and dose adjustments on children with chronic medical conditions including renal disease and cancer.Study population: Patients from 0-21 years with thromboembolic disease treated with DOACs who are enrolled in the IPTN Throm-PED Registry.Results: As of June 30, 2021 82 patients from 10 centers have been enrolled. The majority of patients were at least 12 years old (Figure 1). 66% suffered from venous thrombosis. With about 30% each, pulmonary embolism or thrombosis of the lower extremities were reported most commonly. In this cohort the majority of patients received Rivaroxaban (80%), followed by Apixaban and Edoxaban. Risk factors were manifold, including patients with cancer (13%) and renal disease (4%). Of the 33 patients with follow-up reported at 3 months, bleeding was reported in 3 (9%) of patients during treatment with a DOAC, and thrombosis progression was reported in 2 (6%) (Table 1).Summary: This initial real world data, as expected, demonstrates reduced efficacy and more bleeding than noted in published trials, however numbers are small. Further real world data collection is essential to identify specific patient groups at risk of worse outcome with DOACs and to understand drug interactions and dose adjustments. Data on younger age groups are required. IPTN registry is an important framework to collect real world data that can then be explored in clinical trials. [Display omitted] DisclosuresRaffini: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Bayer: Consultancy; XaTek: Consultancy.

Rate of Clonal Hematopoiesis in Patients with Venous Thromboembolism

BackgroundVenous thromboembolism (VTE) is the third most common cardiovascular disease with an incidence over 1% in the elderly. About 50% of VTE is unprovoked, which is associated with higher rates of recurrent VTE and complications such as post-thrombotic syndrome. Clonal hematopoiesis (CH) refers to recurrent somatic mutations associated with hematologic malignancies that are present in otherwise healthy individuals. CH is more common with increased age, occurring in more than 10% of people over the age of 70 and has been associated with an increased risk of coronary artery disease. The rates of CH in patients with VTE or complications arising from this is not known.MethodsAdult patients (age ≥ 18) with VTE were enrolled at the Ohio State University Thrombosis Clinic between 2017 and 2020. Clinical data was obtained at the time of routine clinic follow-up or ad hoc, and a research blood sample was collected with routine blood work. DNA extracted from peripheral blood mononuclear cells were analyzed for the presence of CH via error corrected next generation sequencing (NGS) using the Ion Gene Studio S5 System. A custom AmpliSeq panel IAH150087 was designed to detect CH, which included whole gene sequencing and hotspots in 25 common genes associated with myeloid malignancies, including DNMT3A, TET2, ASXL1, among others, with a sequencing depth of up to 50,000X. Data was collected and analyzed using Ion Torrent S5/GS-S5 Instrument with Torrent Suite 5.12.0 version. Final analysis of sequence data was performed using combination of software: Variant Caller v.5.12.10-1, IGV5.01 (0) and Ion Reporter v.5.12.3.0. The hg19 reference sequence was used to assess for deviation. CH was defined as a variable allele frequency ≥ 2%. Two sample t-test and chi-square test were used to compare patients with and without CH for continuous and categorical variables, respectively.ResultsA total of 167 patients are included the study. Median age is 60.3 years and 55% of patients are female. 80% of patients are white. The majority of patients have unprovoked VTE (81%); 23 patients (13.8%) have VTE associated with cancer. 84% of patients were treated with a direct oral anticoagulant. Over the median follow-up duration of 400 days, 7 patients had recurrent VTE and 19 patients had a total of 21 bleeding events (7 major bleeding and 14 clinically relevant non-major bleeding [CRNMB] by ISTH criteria).Overall, 22 patients (13.2%) have detectable CH. Patients with CH are significantly older than those without CH (mean age 70 vs 59, p <0.0001). There is a trend towards increased CH rate in male patients (17% of male patients vs 10% of female patients with CH). There are no other differences in baseline characteristics among patients with and without CH, including type or location of VTE or cancer status. Among the 144 VTE patients without cancer, the median age is 60 years old and the CH rate is also 13.2%. In this group, the mean age of patients with CH is 12 years older than those without CH (70.5 years vs 58.4 years, p <0.0001). No other significant baseline characteristics are noted.30 distinct CH mutations are noted in these 22 patients. Most patients have a single gene mutation (77%). Gene mutations in DNMT3A are the most common (46%), followed by TET2 (13%), and PPM1D (10%) (see figure). Most mutations are missense (57%), followed by nonsense (30%) and insertion/deletion mutations (13%). One patient has a JAK2 V617F mutation without known history of myeloproliferative disease. 8 CH patients with serial samples collected over a median duration of 136 days (range 91 - 490 days) showed no significant change in CH clone size over time.Patients with CH have no differences in rates of recurrent VTE or arterial thrombosis compared to those without CH. Patients with CH have a trend towards increased rate of combined major bleeding and CRNMB events (23% vs 10%, p=0.14). Patients with CH also had a trend towards increased mean corpuscular volume (MCV) (mean 93.5 vs 90.7, p=0.13), although no other cytopenias or differences in complete blood count parameters were noted.ConclusionThe CH rate in patients with VTE was not found to be much higher than what might be expected by age alone. We found no change in the CH rate after excluding cancer patients. A larger VTE population with age-matched controls will better determine the CH rate in patients with VTE. CH can be a consideration in designing future clinical VTE studies that assess bleeding risk. [Display omitted] DisclosuresByrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Newave: Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria. Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding.

Effectiveness and safety of apixaban vs warfarin among venous thromboembolism patients using five US databases: a subgroup analysis of chronic liver disease

Abstract Background Venous thromboembolism (VTE) is a serious disease in the United States affecting approximately 1 in 1000 patients each year. Patients with chronic liver disease (CLD) are at an increased risk of VTE and major bleeding (MB). Currently, insufficient clinical and real-world evidence exists on the efficacy/effectiveness and safety of apixaban or warfarin in VTE patients with CLD. Purpose To evaluate the risk of recurrent VTE, MB, and clinically relevant non-major (CRNM) bleeding among VTE patients initiating apixaban or warfarin stratified by CLD status. Methods VTE patients ≥18 years of age (≥65 years for Medicare) initiating apixaban or warfarin were identified from CMS Medicare and four commercial claims databases. To balance the characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting (IPTW) was conducted. Post-IPTW, subgroup interaction analysis was conducted to evaluate whether treatment effects of apixaban vs. warfarin were consistent across patients with and without a diagnosis of CLD. Cox proportional hazard models were used to evaluate the interaction of the treatment (apixaban vs. warfarin) and CLD on recurrent VTE, MB, and CRNM bleeding. The statistical significance of the interaction was set to p-value &amp;lt;0.10. Results A total of 60,786 apixaban and 94,333 warfarin patients with VTE were eligible for analysis. Post-IPTW, all patient characteristics were balanced between the apixaban and warfarin treatment cohorts. Apixaban treated patients had significantly lower risk of recurrent VTE, MB, and CRNM bleeding compared to warfarin patients (Figure). In the IPTW weighted population, 4,766 (7.8%) apixaban patients and 6,320 (6.7%) warfarin patients had a diagnosis of CLD. For the apixaban or warfarin patients, those with a diagnosis of CLD were generally younger (mean 64.0–65.2 vs 66.9 years), had higher Charlson comorbidity index scores (mean 3.8–3.9 vs 2.1) and were more likely to have an inpatient VTE event (67.8–69.5% vs 53.0–53.2%) or provoked VTE events (66.2–67.8% vs 55.4–55.5%) compared to patients without a diagnosis of CLD. The incidence rate of recurrent VTE, MB, and CRNM bleeding was higher among VTE patients with CLD than without CLD and was also higher for patients treated with warfarin compared to those treated with apixaban regardless of CLD status (Figure). There were no significant interactions observed between treatment and CLD status for recurrent VTE, MB or CRNM (Figure). Conclusion Treatment with apixaban had a lower risk of recurrent VTE, MB, and CRNM bleeding compared to treatment with warfarin. The benefits of apixaban were consistently observed among subgroups of VTE patients with and without CLD. Additional studies are needed to evaluate VTE patients with CLD. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer, Inc.

Effectiveness and safety of apixaban vs warfarin among older venous thromboembolism patients: a subgroup analysis of age

Abstract Background Venous thromboembolism (VTE) is the third most common cardiovascular condition in adult patients. Older patients are at an increased risk of VTE. However, they have been underrepresented in clinical trials and evidence on the safety and effectiveness of anticoagulants in older VTE patients, especially very elderly patients (≥80 years), is sparse. Purpose To evaluate the risk of recurrent VTE, major bleeding (MB), and clinically relevant non-major (CRNM) bleeding among older VTE patients initiating apixaban or warfarin according to two age sub-groups: 65–79 and ≥80 years. Methods Older VTE patients (aged ≥65 years) who initiated apixaban or warfarin were identified from the CMS Medicare database (September 2014–December 2017). To balance the characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting (IPTW) was conducted. Post IPTW, a subgroup interaction analysis was conducted to evaluate if there was any difference in treatment effects between the two age subgroups (65–79 vs. ≥80) on recurrent VTE, MB, and CRNM bleeding. Cox proportional hazard models were used to conduct the interaction analysis, and the statistical significance of the interaction was set to p-value &amp;lt;0.10. Results A total of 22,135 apixaban and 45,840 warfarin patients with VTE aged ≥65 years were eligible for analysis. Post IPTW, patient characteristics were balanced between the apixaban and warfarin treatment cohorts. Apixaban patients had significantly lower risk of recurrent VTE, MB, and CRNM bleeding compared to warfarin patients (Figure). 42,551 (62.6%) were aged 65–79 years and 25,424 (37.4%) were aged ≥80 years. Among apixaban or warfarin patients, those aged 65–79 years had lower Charlson comorbidity index scores (mean 2.7 vs 3.2) and were less likely to have a diagnosis of anemia (34.7–34.9% vs 42.3–42.5%), cerebrovascular disease (14.7–15.7% vs 20.3–20.5%), or dementia (5.0–6.9% vs 20.4–24.6%) compared to patients aged ≥80 years. Across both age subgroups, incidence rates of recurrent VTE, MB and CRNM bleeding were lower for apixaban vs. warfarin. No significant interaction was observed between the treatment and age on recurrent VTE and MB (Figure). There was a significant interaction between treatment and age on CRNM bleeding. Apixaban trended towards a lower risk of CRNM bleeding across both age groups but the treatment effect on CRNM bleeding was larger for patients aged 65–79 years. Conclusion The treatment effects of apixaban vs. warfarin on recurrent VTE and MB were consistently observed across both older age groups in this analysis. More studies are needed to evaluate management of VTE in an older and especially the very elderly population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.

The Birmingham Black Country Venous Thromboembolism (BBC-VTE) registry of outcomes of venous thromboembolism patients admitted to hospital

Abstract Background Venous thromboembolism (VTE) is a condition which causes significant morbidity and mortality in hospitalised patients as well as in the community. These are related to adverse outcomes associated with the first incidence of VTE, such as recurrence, major haemorrhage and mortality. These outcomes are difficult to measure and compare among the different regions of the world not least because of varying prevalence of risk factors, paucity of comparable studies and a differing approach to treatment of VTE (1–3). Purpose Our VTE registry aims to estimate the above mentioned outcomes as applicable to a developed world population with a multi-ethnic background. Furthermore, our registry has provided a data set to develop and validate a machine learning algorithm in order to predict outcomes in patients admitted to hospital with VTE. This will have profound implications for clinicians who will be able to make evidence-based decisions about which patients are low risk and so can be discharged early as well as those who are high risk and may need more intensive follow up. Methods BBC-VTE registry is a retrospective, multi-centre, observational registry. We identified all patients (N=1554) who were admitted with a final radiologically confirmed diagnosis of pulmonary embolism and/or lower limb deep vein thrombosis at three regional hospitals in the UK during the years 2012–2014. Each patient's electronic record was accessed by clinicians to confirm radiological diagnosis of VTE and also collect data on demographics, physical examination findings and laboratory analysis on admission, past medical history, and treatment plan. Outcomes were also recorded including recurrence of VTE, subsequent major bleeding and all-cause mortality. A simple multivariate analysis (logistic regression) was used to determine risk factors associated with all-cause mortality. Odds ratios (OR) and 95% CI are reported. Results The main factors determining higher all-cause mortality were age, a history of diabetes, admission laboratory analysis (c-reactive protein and neutrophil count), and previous malignancy (OR &amp;gt;1) (see Fig. 1). Conversely, hypercholesterolaemia, discharge oral anticoagulation, immobilization, and post-PE syndrome were all significantly correlated with a reduced risk of mortality (OR &amp;lt;1). Conclusions BBC-VTE provides unique data on VTE mortality risks in a multi-ethnic cohort. The strengths of our registry are that we are only including radiologically verified VTE patients unlike many of the epidemiological studies to date which rely on clinical coding. We have also shown that it is possible to risk-stratify patients admitted with VTE using simple clinical variables which has implications for their discharge decisions. Funding Acknowledgement Type of funding sources: None. Figure 1

MiRNA 126 as a New Predictor Biomarker in Venous Thromboembolism of Persistent Residual Vein Obstruction: A Review of the Literature Plus a Pilot Study.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Interleukins (ILs) and micro-ribonucleic acids (miRNAs) have been proposed as molecules able to modulate endothelial inflammation and platelet hyperactivity. At present, no early biomarkers are available to predict the outcome of VTE. We investigated in a pilot study a selected number of miRNAs and ILs as prognostic VTE biomarkers and reviewed literature in this setting. Twenty-three patients (aged 18-65) with a new diagnosis of non-oncological VTE and free from chronic inflammatory diseases were enrolled. Twenty-three age- and sex-matched healthy blood donors were evaluated as control subjects. Serum miRNAs (MiRNA 126, 155, 17.92, 195), inflammatory cytokines (IL-6, tumor necrosis factor-α, IL-8), and lymphocyte subsets were evaluated in patients at enrolment (T0) and in controls. In VTE patients, clinical and instrumental follow-up were performed assessing residual vein obstruction, miRNA and ILs evaluation at 3 months' follow-up (T1). At T0, IL-8, activated T lymphocytes, Treg lymphocytes, and monocytes were higher in patients compared with healthy controls, as were miRNA 126 levels. Moreover, miRNA 126 and IL-6 were significantly increased at T0 compared with T1 evaluation in VTE patients. Higher levels of MiR126 at T0 correlated with a significant overall thrombotic residual at follow-up. In recent years an increasing number of studies (case-control studies, in vivo studies in animal models, in vitro studies) have suggested the potential role of miRNAs in modulating the cellular and biohumoral responses involved in VTE. In the frame of epidemiological evidence, this pilot study with a novel observational approach supports the notion that miRNA can be diagnostic biomarkers of VTE and first identifies miRNA 126 as a predictor of outcome, being associated with poor early recanalization.

Risk factors for venous thromboembolism in patients with diabetes undergoing joint arthroplasty

BackgroundVenous thromboembolism (VTE) is a significant complication after joint arthroplasty. Diabetes is related to a few changes in coagulation and fibrinolysis that may lead to thrombophilia. We aimed to investigate the incidence of postoperative VTE and associated risk factors among patients with diabetes undergoing total hip (THA) or total knee anthroplasty (TKA) in a single centre in China.MethodsPatients with diabetes who underwent THA or TKA from January 2016 to December 2018 (n = 400) at Beijing Jishuitan Hospital were recruited in this study. Lower limb venous Doppler ultrasound was performed before and after surgery to confirm deep venous thrombosis (DVT). Computer tomography pulmonary angiography was done to confirm pulmonary embolism (PE) for those with new postoperative DVT and typical symptoms of PE. A multivariate logistic regression model was conducted to examine factors associated with the development of postoperative VTE.ResultsThe overall incidence of postoperative VTE in patients with diabetes after THA or TKA was 46.8 % (187 out of 400). Among the 187 VTE patients, 7.5 % (14 out of 187) had proximal vein thrombosis and 92.5 % (173 out of 187) had distal vein thrombosis. No PE occurred. Female patients and patients undergoing TKA had higher incidence of postoperative VTE. Patients who developed postoperative VTE were older, and had higher levels of preoperative D-Dimer and Caprini score. A high level of preoperative D-dimer (OR = 2.11, 95 %CI = 1.35–3.30) and the surgery of TKA (OR = 2.29, 95 %CI = 1.29–4.01) significantly increased the risk of developing postoperative VTE. Postoperative initiation of concomitant mechanical prophylaxis and low molecular weight heparin (LMWH) was protective for postoperative VTE (OR = 0.56, 95 %CI = 0.37–0.86).ConclusionsVTE is common in patients with diabetes undergoing joint arthroplasty. Patients undergoing TKA or with a high level of preoperative D-dimer are at a considerable risk of developing postoperative VTE. There may be a protective role of postoperative initiation of concomitant mechanical prophylaxis and LMWH for VTE.

Rebound Hypercoagulability Following a Conventional Course of Anticoagulation and the Risk of Recurrent Venous Thromboembolism in Young Patients: First Analysis of the Kids-DOTT Multicenter Trial-Derived Biobank

Background:Knowledge of prognostic factors for recurrence in adult and pediatric VTE is limited. Elevated plasma levels of D-dimer (a marker of coagulation activation) following a 6-month course of anticoagulation in adults with unprovoked VTE are associated with a heightened risk of VTE recurrence, warranting prolonged therapy. In patients with provoked VTE, and in young VTE patients more generally, prognostic factors remain largely undefined. Recently, using a global assay of clot formation and lysis on plasma samples collected serially over time, we observed a phenomenon of rebound hypercoagulability at 3 months post-diagnosis, relative to 4-6 weeks post-diagnosis, in a group of children with provoked VTE who were enrolled in a single-institution prospective inception cohort study.Objectives:The objectives of this work were:(1) toevaluate the prevalence of relative rebound hypercoagulability at 3 months status-post acute VTE in patients <21 years old; and (2) to investigate an association of relative rebound hypercoagulability with recurrent VTE.Methods:We combined clinical data and banked plasma biospecimens from an ongoing NHLBI-sponsored multinational multicenter trial of VTE treatment in patients <21 years old (the Kids-DOTT trial) with those from a single-institutional prospective cohort study of pediatric VTE at Johns Hopkins All Children's Hospital (St. Petersburg, FL, USA). The clot formation and lysis (CloFAL) spectrophotometric assay was performed as previously described, on banked plasma samples from 4-6 weeks and 3 months post-diagnosis of acute VTE, with heparinase pre-treatment of samples prior to assay. Those few patients (n=3) who received agents other than low molecular weight heparin at these time points were excluded. Assay measurements included maximal amplitude of the CloFAL waveform (MA), time to maximal amplitude (T1), and area under the curve at 60 minutes, indexed to that of the pooled normal plasma standard (AUC60). For each patient, the change in each CloFAL parameter between the 3 months and the 4-6 week post-VTE time points was then calculated. We used descriptive statistics to summarize data on patient characteristics VTE presentation, treatment, and outcomes. To explore prognostic cutoffs for percent change in each parameter receiver operating characteristics curves were generated, and inter-assay coefficients of variation of the assay were also considered. Thresholds of 50% increase in MA or AUC60, or 50% decrease in T1, were ultimately selected as candidate phenotypes of relative rebound hypercoagulability. An association between relative rebound hypercoagulability and VTE recurrence was determined via univariate logistic regression, using odds ratios (OR) and 95% confidence intervals (CI), with two-sided alpha=0.05. The blind was maintained in the Kids-DOTT trial throughout data transfer and analysis.Results: The final study population consisted of 88 patients, with a median age of 12.6 years (range, 0.01-20.8 years). VTE was classified as provoked in 98% of cases. Patient and VTE characteristics at baseline and outcomes during follow-up are shown in Table 1. Median follow up time was 52 weeks (range 9-123 weeks). Relative rebound hypercoagulability was found in 13% of the study population at 3 months post-diagnosis. Recurrent VTE developed in 10% of patients. Logistic regression analysis revealed that change in CloFAL AUC60 and T1 were not prognostic of VTE recurrence. However, relative rebound hypercoagulability as measured by change in MA was associated with a statistically significant, 4-fold increase in the risk of recurrent VTE (OR=4.47, 95%CI=1.05-19.0; P=0.04).Conclusions:Relative rebound hypercoagulability, as measured by change in MA in the CloFAL assay, developed in 13% of a multicenter study population of patients <21 years of age with predominantly-provoked VTE, and was associated with a 4-fold increased risk of recurrent VTE. Future work should seek to investigate mechanisms of relative rebound hypercoagulability following a conventional course of anticoagulation in young VTE patients, and to substantiate findings of its prognostic significance for VTE recurrence, via a future multicenter validation cohort.Acknowledgment:The Kids-DOTT trial is supported via dual U01 awards from NIH NHLBI (Clinical Coordinating Center U01, Goldenberg, PI; Data Coordinating Center U01, Hiatt, PI). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Trends of Ordering Hypercoagulability Work-Up at an Academic Medical Center.

BackgroundVenous thromboembolism is a significant clinical event, with an annual incidence of 1–2 per 1000 population. Risk factors include recent surgery, prolonged immobility, oral contraceptive use, and active cancer. Inherited risks include protein C and S deficiencies, antithrombin deficiency, factor V Leiden mutation and prothrombin. These factors can be tested to guide therapy, but current evidence suggests that testing for inherited thrombophilia is not recommended in most inpatient settings. In the era of high value care, hypercoagulable testing for VTE creates a financial burden for the hospital and patients. We performed a retrospective chart review of hypercoagulable orders on VTE patients at our institution.MethodsInstitutional Review Board approval was obtained. A total of 287 adult patients admitted over a 3-month period with the diagnosis of VTE were included. Patients were identified via ICD-10 codes and data were collected from electronic medical records. Patient characteristics, provoked versus unprovoked VTE, and relative contraindications for hypercoagulability work-up were analyzed. Our primary outcome was to assess the appropriateness of thrombophilia testing in VTE patients based on screening guidelines. Our secondary outcome was to analyze the cost burden of ordering these tests.ResultsA total of 287 patients were included in our data analysis. Patient risk factors for VTE were malignancy, previous DVT, immobilization, surgery 3 months prior, and central line placement. Fifty-seven of 287 patients had at least one hypercoagulable test ordered during hospitalization which did not adhere to guidelines. Misuse of testing occurred during active thrombosis, active anticoagulation, presence of risk factors, first episode of VTE, and malignancy. The cost of ordering these 5 thrombophilia tests totaled over $40,000.ConclusionIn our study, numerous patients were tested without compliance to standard recommendations, which created financial and value-based burdens on our health care system. Increased awareness among clinicians is thus warranted to ensure high value care.

Diagnostic accuracy of D-Dimer testing for recurrent venous thromboembolism: A systematic review with meta-analysis.: VTE recurrence and D-dimer

ObjectiveVenous thromboembolism (VTE) recurrence is a major concern after a first symptomatic episode, potentially impacting survival and healthcare needs in community, hospital and rehabilitation settings. We evaluated the association of D-Dimer positivity after oral anticoagulant therapy (OAT) discontinuation with VTE recurrence. MethodsPubMed, Web of Science, Scopus and EMBASE databases were systematically searched. Differences were expressed as Odds Ratio (OR) with 95% confidence intervals (95%CI). Pooled sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and summary ROC (sROC) curve were calculated. ResultsTwenty-six articles on 10,725 VTE patients showed that the absolute risk of recurrence was 16.1% (95%CI: 13.2%-19.5%) among 4,049 patients with a positive D-Dimer and 7.4% (95%CI: 6.0%-9.0%) in 6,676 controls (OR: 2.1, 95%CI: 1.7-2.8, P<0.001), with an attributable risk of 54.0%. sROC curve of the association between positive D-Dimer and recurrence showed a diagnostic AUC of 63.8 (95%CI: 60.3-67.4), with a pooled sensitivity of 54.3% (95%CI: 51.3%-57.3%), specificity of 64.2% (95%CI: 63.2-65.1), PLR of 1.53 (95%CI: 1.37-1.72), and NLR of 0.71 (95%CI: 0.60-0.84). Subgroup and meta-regression analyses suggested that a positive D-Dimer may have a higher discriminatory ability for patients with provoked events, confirmed by better pooled diagnostic indexes for recurrence and a diagnostic AUC of 70.6 (95%CI: 63.8-77.4). Regression models showed that the rate of OAT resumption after the evidence of D-Dimer positivity was inversely associated with VTE recurrence (Z-score: -3.91, P<0.001). ConclusionsD-Dimer positivity after OAT may identify VTE patients at higher risk of recurrence, with a better diagnostic accuracy for provoked events.

Venous thromboembolism during systemic inflammatory and autoimmune diseases associated with myelodysplastic syndromes, chronic myelomonocytic leukaemia and myelodysplastic/myeloproliferative neoplasms: a French multicentre retrospective case-control study.

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE. This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders. During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83). VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.

Venous thromboembolism and risk of cancer in users of statins: A Danish population-based cohort study

BackgroundVenous thromboembolism (VTE) may be the first symptom of cancer. Statins are suggested to prevent VTE, but the risk of cancer in VTE patients using statins remains poorly understood. ObjectivesTo examine if VTE is a marker of cancer in users of statins. MethodsWe identified all Danish patients during 1996–2017 with a first-time diagnosis of VTE and a filled prescription for a statin within 90 days prior to the VTE diagnosis. We classified patients as prevalent users if the first filling of a statin occurred more than one year preceding the VTE diagnosis, and as new users if the first filling occurred within the preceding year. We computed cumulative incidences of cancer, with death as a competing risk, and age-, sex-, and calendar-period standardized incidence ratios (SIRs), comparing the observed cancer incidence with the expected based on national cancer statistics. ResultsAmong 9280 (85%) prevalent users of statin and 1580 (15%) new users, the one-year cumulative incidence of any cancer was 6.6 (95% CI: 6.1–7.2) for prevalent users and 6.4 (95% CI: 5.2–7.6) for new users; the corresponding SIRs were 3.1 (95% CI: 2.9–3.3) and 3.5 (95% CI: 2.9–4.3). In the second and subsequent years, the SIRs diminished and approached unity for both prevalent (1.1 [95% CI: 1.1–1.2]) and new users (1.1 [95% CI: 0.9–1.3]). ConclusionsVTE patients using statins had a 3-fold increased rate of cancer in the first year after diagnosis. A first VTE serves as an important marker of cancer, regardless of statin use.

Predictive value of the Kuijer score for bleeding and other adverse in-hospital events in patients with venous thromboembolism

BackgroundVenous thromboembolism (VTE) constitute a major global burden of disease. Current international guidelines recommend treatment with anticoagulant therapy after VTE for a duration of at least 3 months. Since anticoagulation also imposes an increased risk for bleeding events, the individual risk has to be evaluated to determine adequate treatment plans. MethodsThe nationwide German inpatient sample of the years 2005–2017 was used for this analysis. Hospitalized VTE patients were stratified according to Kuijer risk class and the performance of the Kuijer score was evaluated to predict adverse in-hospital events. ResultsOverall, 1,204,895 VTE patients were treated between 2005 and 2017 in Germany and were included in the present study (839,143 patients had deep venous thrombosis and/or thrombophlebitis and 669,881 patients pulmonary embolism). According to Kuijer risk class stratification, in total, 176,723 (14.7%) of the hospitalized VTE patients were classified as low risk, 914,964 (75.9%) as intermediate risk and 113,208 (9.4%) as high risk.A higher Kuijer risk class was predictive for in-hospital death (odds ratio [OR] 1.99 [95% confidence interval (CI) 1.96–2.02], P < 0.001), major adverse cardiovascular and cerebrovascular events (MACCE, OR 1.90 [95%CI 1.87–1.93], P < 0.001), intracerebral bleeding (OR 1.28 [95%CI 1.14–1.44], P < 0.001), gastrointestinal bleeding (OR 1.56 [95%CI 1.48–1.64], P < 0.001) as well as necessity of transfusion of blood constituents (OR 2.94 [95%CI 2.88–3.00], P < 0.001) independently of important comorbidities. ConclusionsThe Kuijer score is an important risk stratification tool to predict individual risk regarding in-hospital outcomes comprising major bleeding events such as intracerebral bleeding and necessity of transfusion of blood constituents, but also in-hospital mortality and MACCE in VTE patients.

Effectiveness and Safety of Apixaban Vs Warfarin Among Venous Thromboembolism Patients Using Five US Databases: A Subgroup Analysis of Obesity

Background: Obesity is associated with an increased risk of VTE. Although four direct oral anticoagulants (DOACs) have been approved for the treatment of VTE, limited real-world evidence is available on their effectiveness and safety in obese patients. This study pooled 5 US healthcare claims databases to evaluate the risk of recurrent VTE, major bleeding (MB), and clinically relevant non-major (CRNM) bleeding among VTE patients initiating apixaban or warfarin stratified by obesity. Methods: A pooled retrospective study of adult VTE patients who initiated apixaban or warfarin from 01MAR2014-31DEC2018 was conducted using CMS Medicare and four other claims databases. Patients were followed to the earliest of: index therapy discontinuation, switch to another oral anticoagulant, initiation of a new parenteral anticoagulant, health plan disenrollment, death, study end, or a maximum of 6 months. Stabilized inverse probability treatment weighting (IPTW) was conducted to balance patient characteristics between the treatment cohorts within each database. After pooling post-IPTW cohorts from the five databases, subgroup interaction analysis was conducted to evaluate whether treatment effects were consistent across patients with and without obesity. Obesity was identified based on diagnosis codes that indicated obesity or codes that indicated a body mass index of at least 30. Cox proportional hazard models were used to evaluate the risk of recurrent VTE, MB, and CRNM bleeding. The statistical significance (P&amp;lt;0.10) of the interaction between treatment and obesity was evaluated. Results: After applying eligibility criteria, 60,786 VTE patients were selected into the apixaban treatment cohort, and 94,333 were selected into the warfarin treatment cohort. Apixaban patients were younger (65 vs 67 years) and had a lower mean CCI (2.1 vs. 2.3) compared to warfarin patients. After IPTW, all patient characteristics were balanced. In the post-IPTW population, apixaban was associated with a significantly lower risk of recurrent VTE, MB, and CRNM bleeding compared to warfarin during the follow-up (p&amp;lt;0.001 [Figure]). When stratified by obesity, for each treatment cohort, obese patients were younger (64-65 vs. 68 years), more likely to be diagnosed with PE (51.2%-53.0% vs. 39.9%-40.5%), experienced a higher proportion of provoked VTE events (63.3-63.9% vs. 53.3-53.7%), had higher mean CCI (2.6-2.7 vs. 2.0) and were more likely to have comorbidities such as hypertension (80.2%-80.3% vs. 64.7%-64.8%), hyperlipidemia (57.1%-57.8% vs. 44.6%-44.7%), and diabetes (41.9%-43.9% vs. 24.4-26.7%) compared to non-obese patients. Comparison of apixaban with warfarin when stratifying by obesity showed consistently lower risk of recurrent VTE, MB, and CRNM bleeding associated with apixaban across obese and non-obese patients and these subgroup findings were consistent with those of the overall population. No significant interactions were observed for treatment and obesity on recurrent VTE, MB, or CRNM bleeding (Figure). Conclusion: In the VTE patients initiating apixaban or warfarin, obese patients showed differences in patient characteristics as compared to non-obese patients. Across subgroups of patients with and without obesity, apixaban patients had a lower risk of recurrent VTE, MB, and CRNM bleeding compared to warfarin patients, which was consistent with the overall population results. These findings may be useful in informing treatment decisions for this high-risk subgroup of VTE patients. Disclosures Cohen: Pfizer, Inc.: Research Funding; Bristol-Myers Squibb Company: Research Funding. Sah:Bristol-Myers Squibb Company: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company; Pfizer, Inc.: Other: I am a paid employee of STATinMED Research which is a paid consultant to Pfizer, Inc.. Lee:Pfizer, Inc.: Current Employment. Wygant:Bristol-Myers Squibb Company: Current Employment. Rosenblatt:Bristol-Myers Squibb Company: Current Employment. Hlavacek:Pfizer, Inc.: Current Employment. Emir:Pfizer, Inc.: Current Employment. Keshishian:Pfizer, Inc.: Other: I am a paid employee of STATinMED Research which is a paid consultant to Pfizer, Inc.; Bristol-Myers Squibb Company: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company.. Delinger:Bristol-Myers Squibb Company: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company.; Pfizer, Inc.: Other: I am a paid employee of STATinMED Research which is a paid consultant to Pfizer, Inc.. Luo:Pfizer, Inc.: Current Employment.

PMU6 Evaluation of the Application of the Hospital Management Program for Prevention and Treatment of Venous Thrombosis Based on Information Technology

To evaluate the clinical effect and cost-effectiveness of the hospital management programfor prevention and treatment of venous thrombosis based on information technology. Inpatients with deep venous thrombosis were included in the study. Relevant data from January to May 2016 were selected as the control group and those from June to December 2016 as the trial group. T test was used for comparison among groups, and X2test was used for inter-group comparison of count data. This study uses incremental cost effectiveness ratio to analyze the effectiveness of the program. A total of 75 VTE patients were diagnosed in the control group and 117 patients in the trial group. There was no significant difference in age and sex between two groups. After the implementation of VTE prevention management program, the rate of treatment increased (81.9% vs 63.2%, p=0.017), VTE caused deaths decreased (0case vs 2cases). The average length of Stay (14.7d vs 17.9d, p>0.05) in the trial group was reduced by 3.2 days compared with the control group, and the difference was not statistically significant. The average hospitalization cost of the patients during the trial group was 45330.5 RMB, and the control group was 47037.2 RMB, but the difference was not statistically significant (P>0.05). This management program is to embed risk assessment tools into HIS system, HIS system can realize automatic calculation of risk level and early warning management for high-risk patients who need intervention. Therefore, the improvement of this management program has no cost increase and has increased clinical implementation effect, so this management program is cost-effective. Establishing an information-based hospital management system for prevention and treatment of venous thromboembolism can effectively improve the early diagnosis and intervention rate of VTE patients in our hospital, effectively reduce the risk of VTE without increasing the cost of medical treatment.

Therapeutic anticoagulation for venous thromboembolism after recent brain surgery: Evaluating the risk of intracranial hemorrhage

ObjectiveVenous thromboembolism (VTE) is particularly prevalent in neurosurgical patients. A major dilemma arises when a patient needs to be treated with therapeutic anticoagulation during the early days after brain surgery due to the concern of intracranial hemorrhage (ICH). There is still a lack of studies regarding the optimal time to start therapeutic anticoagulation and risk assessment of ICH in this setting. This study aims to assess the risk of ICH for patients with venous thromboembolism treated with therapeutic anticoagulation started within the first 30 days after intracranial neurosurgical procedure. Patients and methodsThis study was an analytical observational research based on a retrospective record review of VTE patients submitted to therapeutic anticoagulation started within the first 30 days after intracranial neurosurgical procedure at Paulo Niemeyer State Brain Institute, from September 2013 to February 2020. Patients’ clinical and surgical data, anticoagulation drug therapy, time interval between surgery and start of therapeutic anticoagulation, bleeding complications and hemorrhage-related deaths were some of variables evaluated. A p value < 0.05 was considered statistically significant. ResultsA series of 53 consecutive patients and 54 intracranial neurosurgical procedures met the criteria. Twenty-nine (53.7 %) patients were treated with warfarin, 21 (38.9 %) with new oral anticoagulant (NOAC) and 4 (7.4 %) only with enoxaparin. VTE diagnosis between the postoperative days 0 and 4 was statistically associated with a delay in starting therapeutic anticoagulation of more than two days (p < 0.001). The frequency of bleeding complication was statistically significant higher in patients treated with warfarin (p = 0.03). Although with no statistical significance, there were a higher rate of ICH in patients receiving warfarin (13.8 % vs. 0% in NOAC group, p = 0.13). There was no statistical difference about ICH incidence between the postoperative intervals from 2nd to 7th, 8th to 14th, 15th to 21 st and 22th to 29th days (p = 0.35). Hemorrhage-related mortality rate was 3.7 %. ConclusionICH was not statistically associated with the timing of therapeutic anticoagulation after brain surgery between the 2nd and 29th postoperative days, which may encourage the strategy of early treatment considering the life-threatening potential of VTE. However, the risk of ICH should not be ignored in the setting of warfarin use, which had a remarkable incidence of 13.8 %. Warfarin must be used cautiously, especially in high-grade gliomas.

Efficacy and safety of non-vitamin K antagonist versus vitamin K antagonist oral anticoagulants in the prevention and treatment of thrombotic disease in active cancer patients: a systematic review and meta-analysis of randomized controlled trials

Object We aimed to compare the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonist (VKA) in the prevention and treatment of thrombotic diseases in patients with active cancer. Methods: To find randomized controlled trials (RCT) in which NOACs were compared VKAs in active cancer, we searched the electronic databases (PubMed, Web of Science and Clinical Trials) up to May 2019 and and languages restricted to Chinese and English. According to the screening strategy, two researchers independently screened and extracted literature, evaluated the quality of literature, the suitability of collected cross study data for analysis, and tested the heterogeneity. The relative risk (RR) and 95% confidence interval (95%CI) of major bleeding, clinically related non-major bleeding, VTE, stroke and all-cause mortality in active cancer patients with VTE, active cancer patients with non-valvular atrial fibrillation (NVAF) was calculated and the results were compared between NOAC with VKA. Results: A total of 9 RCTs were included, including 5 cancers with VTE (5/9) and 4 cancers with NVAF (4/9). A total of 5 867 patients were included. After excluding 1 818 (30.99%) patients with cancer history, 4 049 (68.86%) patients with active cancer were statistically analyzed. Among them, 2 278 (56.26%) received NOAC treatment, 1 771 patients (43.74%) received VKA treatment. The quality of the included documents was high (all scores were>5 points), and the data of each included document could be summarized and analyzed (P>0.05). The heterogeneity of main outcome events was very low (I2 = 0). In VTE patients with active cancer, NOACs were more effective in reducing recurrence of VTE （RR=0.55, 95%CI 0.36 -0.84; P = 0.005) and clinically related non-major bleeding (RR=0.77, 95%CI 0.60 -0.98; P = 0.03) than VKAs. In NVAF patients with active cancer, efficacy of NOACs and VKAs was similar in terms of reducing VTE, stroke, clinically related non-major bleeding, major bleeding and all-cause mortality events (P>0.05). Conclusions: For patients with active cancer accompanied by VTE, NOAC may has more advantages in efficacy and safety compared to VKA in the prevention and treatment of thrombotic diseases.