Reduction In Venous Thromboembolism Events Research Articles

675 Chemoprophylactic Anticoagulation Causes a Marked Decrease in Thromboembolic Events Following Lumbar Fusion: Causal Inferences from a Propensity-Matched Analysis of 1302 patients

INTRODUCTION: Chemoprophylactic anticoagulation is commonly used to prevent venous thromboembolic events (VTE) after lumbar fusion. However, the magnitude of the associated risk reduction is not well described, and conventional retrospective statistical methods preclude causal inferences from this association. METHODS: 1302 consecutive lumbar fusions performed at our institution over a six-year period were identified, and relevant clinical and demographic data were collected. VTE events within 30 days postoperatively were identified. Patients who were given chemoprophylaxis and controls were matched according to age, body mass index, sex, Charlson Comorbidity Index, history of VTE, estimated blood loss, length of surgery, transfusion, whether surgery was staged, and whether surgery used an anterior approach. K-nearest neighbor propensity score matching was performed, and covariate adjustments were made to draw causal inferences regarding VTE rate. RESULTS: Unadjusted, there was no difference in the rate of VTE between patients who did (3.8%) and did notreceive chemoprophylaxis (4.4%, OR = 0.86 [0.47, 1.58], p = 0.667). On multivariable regression, and chemoprophylaxis was negatively associated with VTEs (OR = 0.38 [0.15, 0.95], p = 0.039). 589 lumbar fusion patients with and without chemoprophylaxis were successfully matched. After matching, median bias was 1.9%, and overall known bias was reduced by a median of 91.4%. After matching, covariates were well balanced (Rubin's B = 21.8). A covariate adjusted logistic regression model confirmed that chemoprophylaxis was associated with reduced odds of VTE (OR = 0.40 [0.16, 0.98], p = 0.044). The average treatment effect of chemoprophylaxis was a reduction in VTE of 3.7%. The only instance of epidural hematoma occurred in the control group. CONCLUSIONS: Among patients undergoing lumbar fusions, chemoprophylactic anticoagulation causes a marked decrease in VTE.

Venous Thromboembolism Prophylaxis in Inflammatory Bowel Disease Inpatients: Systematic Review and Meta-Analysis

Background: Inflammatory bowel disease (IBD) patients are three times more likely to develop venous thromboembolism (VTE) compared to the general population, especially during disease flares and while hospitalized. Current guidelines recommend prophylaxis during all hospitalizations, though data are sparse. In this systematic review and meta-analysis, we sought to pool all existing data on the efficacy and safety of VTE prophylaxis in hospitalized IBD patients. Methods: We performed a systematic review and meta-analysis. We searched MEDLINE and other databases up to 2/2022, for studies reporting on hospitalized IBD patients (both adult and pediatric, in medical or surgical wards), who were treated with non-therapeutic dose anti-coagulation during hospitalization, compared to no prophylaxis. Our primary efficacy outcome was any VTE (deep vein thrombosis, portomesenteric vein thrombosis, catheter-related thrombosis, and pulmonary emboli), and the primary safety outcome used was major bleeding. Results were pooled using a random-effects model meta-analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Risk of bias was assessed with the ROBINS-I tool and the Cochrane Collaboration's tool for randomization method. Results: We were able to extract data from 18 observational studies, and 2 subgroups from randomized trials, published between 2003 and 2021. The studies were highly variable regarding the study populations, interventions, and outcome definitions, as well as methodological quality. Meta-analysis of all studies did not show a significant effect of prophylaxis on VTE events (OR 0.97 [95% CI 0.49-1.95]). A sensitivity analysis of 8 studies with moderate or lower risk of bias showed a statistically significant reduction in VTE events (OR 0.27 [95% CI 0.13-0.55), with a number needed to treat (NNT) of 35 (95% CI 26.8-49.8). Among studies with lower risk of bias, a significant protective effect of VTE prophylaxis persisted in subgroup analyses of long-term follow up VTEs (OR 0.24 [95% CI 0.08-0.69]), of adult patients only (OR 0.27 [95% CI 0.12-0.61]), and of a mixed population of surgical and medical patients (OR 0.37 [95% CI 0.19-0.74]). Major bleeding was reported in three studies classified with moderate or lower risk of bias, and meta-analysis showed a significantly increased risk in the prophylaxis group (OR 2.02 [95% CI 1.11-3.67], number needed to harm (NNH) of 114 (95% CI 40.7-very large number). Discussion: The main analysis did not show a reduction in VTE events in hospitalized IBD patients treated with prophylaxis. However, in studies with lower risk of bias, a protective benefit of prophylaxis consistent across several subgroups was shown (NNT=35), which should be carefully considered against an increased risk of major bleeding (NNH=114). Currently available data is limited, and mostly retrospective, and randomized controlled trials dedicated to hospitalized IBD patients are needed before universal VTE prophylaxis can be recommended. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Chemoprophylactic Anticoagulation Following Lumbar Surgery Significantly Reduces Thromboembolic Events After Instrumented Fusions, Not Decompressions.

Retrospective cohort. To quantify any reduction in venous thromboembolic events (VTEs) caused by chemoprophylaxis among lumbar surgery patients. Chemoprophylactic anticoagulation (chemoprophylaxis) is used to prevent VTE after lumbar surgery. However, the treatment effect of chemoprophylaxis has not been reported among spine surgery patients, as conventional statistical methods preclude such inferences. A total of 1243 consecutive lumbar fusions and 1433 noninstrumented lumbar decompressions performed at our institution over a six-year period were identified, and clinical and demographic data were collected, including on VTE events within 30 days postoperatively. Instrumented lumbar fusions and noninstrumented lumbar surgeries were analyzed separately. Patients who were given chemoprophylaxis (treatment) and controls were matched according to known VTE risk factors, including age, body mass index, sex, diabetes, chronic kidney disease, history of VTE, estimated blood loss, length of surgery, transfusion, whether surgery was staged, and whether surgery used an anterior approach. K-nearest neighbor propensity score matching was performed, and the treatment effect of chemoprophylaxis was calculated. Unadjusted, there was no difference in the rate of VTE between treatment and controls in either population. Baseline clinical and demographic characteristics differed significantly between treatment and control groups. In all, 575 lumbar fusion patients and 435 noninstrumented lumbar decompression patients were successfully propensity score matched, yielding balanced models (Rubin B <25, 0.5<Rubin R <2.0) and >60% reduction in known bias for both populations. The treatment effect of chemoprophylaxis after lumbar fusion in our patient population was a reduction in VTE incidence from 9.4% to 4.2% ( P <0.05), and propensity score adjusted regression confirmed a reduced odds of VTE with chemoprophylaxis (odds ratio=0.37, P =0.035). The treatment effect was not significant for noninstrumented lumbar decompression patients. Among patients undergoing instrumented lumbar fusions, chemoprophylactic anticoagulation causes a significant reduction in VTE, but causes no significant reduction among patients undergoing noninstrumented lumbar decompression.

Electronic health record risk-stratification tool reduces venous thromboembolism events in surgical patients

BackgroundVenous thromboembolism is a preventable cause of morbidity and mortality after surgery. To ensure that patients receive appropriate venous thromboembolism chemoprophylaxis, a nonmandatory risk-stratification tool based on patient clinical condition was implemented through the electronic health record to stratify patient risk and recommend chemoprophylaxis. We hypothesized that implementing this tool would reduce postoperative venous thromboembolism events in general surgery as well as across all surgical services. MethodsAll adult patients undergoing inpatient surgical operations (January 2012–December 2019) at a single quaternary care center and Level 1 trauma center were abstracted from institutional electronic health record database and stratified into patients admitted before and after venous thromboembolism risk-stratification tool implementation. Bivariable analyses compared venous thromboembolism chemoprophylaxis prescription and venous thromboembolism events with implementation and screening among all surgical patients as well as in general surgery patient subset. ResultsA total of 64,377 adults underwent operations: 27,819 preimplementation and 36,558 postimplementation. A significant reduction in venous thromboembolism events occurred from pre- to post-tool implementation for all cases (0.77% vs 0.47%, P < .001). General surgery patients (n = 15,723) had a significant increase in chemoprophylaxis prescription (81.9% vs 86.0%, P < .001) and a significant reduction in venous thromboembolism events (1.41% vs 0.59%, P < .001). After tool implementation, use of extended postdischarge chemoprophylaxis was greater among general surgery patient subset than the entire patient cohort (46.7% vs 29.6%, P < .001). ConclusionThe integration of a nonmandatory electronic health record risk-stratification tool was associated with a significant reduction in venous thromboembolism events. Extended chemoprophylaxis was prescribed in nearly half of general surgery patients at very high risk for postdischarge events.

Oral anticoagulation in people with cancer who have no therapeutic or prophylactic indication for anticoagulation.

Oral anticoagulants may improve the survival of people with cancer through an antithrombotic effect, yet increase the risk of bleeding. To evaluate the efficacy and safety of oral anticoagulants in ambulatory people with cancer undergoing chemotherapy, targeted therapy, immunotherapy, or radiotherapy (either alone or in combination), with no standard therapeutic or prophylactic indication for anticoagulation. We conducted comprehensive searches on 14 June 2021, following the original electronic searches performed in February 2016 (last major search). We electronically searched the following databases: CENTRAL, MEDLINE, Embase. In addition, we handsearched conference proceedings, checked references of included studies, and searched for ongoing studies. As part of the living systematic review approach, we are running continual searches and will incorporate new evidence rapidly after it is identified. We included randomised controlled trials (RCTs) assessing the benefits and harms of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) in ambulatory people with cancer (i.e., not hospital inpatients during the time of their participation in trials) These people are typically undergoing systemic anticancer therapy, possibly including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, but otherwise have no standard therapeutic or prophylactic indication for anticoagulation. Using a standardised form, two review authors independently extracted data on study design, participants, intervention outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, pulmonary embolism, symptomatic deep vein thrombosis (DVT), major bleeding, minor bleeding and health-related quality of life. We assessed the certainty of evidence for each outcome using the GRADE approach. Of 12,620 identified citations, 10 RCTs fulfilled the inclusion criteria. The oral anticoagulant was a vitamin K antagonist (VKA) in six of these RCTs, and a direct oral anticoagulant (DOAC) in the remaining four RCTs (three studies used apixaban; one used rivaroxaban). The comparator was either placebo or no prophylaxis. Compared to no prophylaxis, vitamin K antagonists (VKAs) probably reduce mortality at six months slightly (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.77 to 1.13; risk difference (RD) 22 fewer per 1000, 95% CI 72 fewer to 41 more; moderate-certainty evidence), and probably reduce mortality at 12 months slightly (RR 0.95, 95% CI 0.87 to 1.03; RD 29 fewer per 1000, 95% CI 75 fewer to 17 more; moderate-certainty evidence). One study assessed the effect of a VKA compared to no prophylaxis on thrombosis; the evidence was very uncertain about the effect of VKA compared to no VKA on pulmonary embolism and symptomatic DVT (RR 1.05, 95% CI 0.07 to 16.58; RD 0 fewer per 1000, 95% CI 6 fewer to 98 more; very low-certainty evidence; RR 0.08, 95% CI 0.01 to 1.42; RD 35 fewer per 1000, 95% CI 37 fewer to 16 more; very low-certainty evidence, respectively). Also, VKAs probably increase major and minor bleeding at 12 months (RR 2.93, 95% CI 1.86 to 4.62; RD 107 more per 1000, 95% CI 48 more to 201 more; moderate-certainty evidence for major bleeding, and RR 3.14, 95% CI 1.85 to 5.32; RD 167 more per 1000, 95% CI 66 more to 337 more; moderate-certainty evidence for minor bleeding). Compared to no prophylaxis, at three to six months, direct oral anticoagulants (DOACs) probably reduce mortality slightly (RR 0.94, 95% CI 0.64 to 1.38, RD 11 fewer per 1000, 95% CI 67 fewer to 70 more; moderate-certainty evidence), probably reduce the risk of pulmonary embolism slightly compared to no prophylaxis (RR 0.48, 95% CI 0.24 to 0.98; RD 24 fewer per 1000, 95% CI 35 fewer to 1 fewer; moderate-certainty evidence), probably reduce symptomatic DVT slightly (RR 0.58, 95% CI 0.30 to 1.15; RD 21 fewer per 1000, 95% CI 35 fewer to 8 more; moderate-certainty evidence), probably do not increase major bleeding (RR 1.65, 95% CI 0.72 to 3.80; RD 9 more per 1000, 95% CI 4 fewer to 40 more; moderate-certainty evidence), and may increase minor bleeding (RR 3.58, 95% CI 0.55 to 23.44; RD 55 more per 1000, 95% CI 10 fewer to 482 more; low-certainty evidence). In ambulatory people with cancer undergoing chemotherapy, targeted therapy, immunotherapy, or radiotherapy (either alone or in combination), the current evidence on VKA thromboprophylaxis suggests that the harm of major bleeding might outweigh the benefit of reduction in venous thromboembolism. With DOACs, the benefit of reduction in venous thromboembolic events outweighs the risk of major bleeding. Editorial note: this is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence, as it becomes available. Please refer to the 'What's new' section in the Cochrane Database of Systematic Reviews for the current status of this review.

Early chemoprophylaxis for deep venous thrombosis does not increase the risk of hematoma expansion in patients presenting with spontaneous intracerebral hemorrhage.

Background: Spontaneous intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. The development of venous thromboembolism (VTE), including deep venous thrombosis or pulmonary embolism, is correlated with negative outcomes following ICH. Due to the risk of hematoma expansion associated with the use of VTE chemoprophylaxis, there remains significant debate about the optimal timing for its initiation following ICH. We analyzed the risk of early chemoprophylaxis on hematoma expansion following ICH.Methods: We performed a retrospective analysis of patients presenting with spontaneous ICH at single institution between 2011 and 2018. The rate of hematoma expansion was compared between patients that received early chemoprophylaxis (on admission) and those that received conventional chemoprophylaxis (>24 h).Results: Data for 235 patients were available for analysis. Eleven patients (7.5%) in the early prophylaxis cohort and seven patients (8.0%) in the conventional prophylaxis cohort developed VTE (P = 0.9). Hematoma expansion also did not differ significantly (early 19%, conventional 23%, P = 0.5).Conclusion: The use of early chemoprophylaxis against venous thromboembolic events following ICH appears safe in our patient population without increasing the risk of hematoma expansion. Given the increased risk of poor outcome in the setting of VTE, early VTE chemoprophylaxis should be considered in patients who present with ICH. Larger, prospective, and randomized studies are necessary to better elucidate the risk of early chemoprophylaxis and potential reduction in venous thromboembolic events.

Quality Improvement at an Academic Cancer Center: Venous Thromboembolism Prophylaxis in Patients With Multiple Myeloma.

Patients with multiple myeloma are at elevated risk of venous thromboembolism (VTE), the second leading cause of death in patients with cancer, but physician adherence to VTE prevention guidelines is low. Several organizations partnered in designing and implementing a 2-year quality improvement (QI) program in a tertiary care/academic cancer center, to increase awareness of VTE prophylaxis for patients with multiple myeloma and thus improve adherence to prophylaxis guidelines and protocols. The QI arm included 2 chart audits, conducted 2 years apart, of unmatched cohorts of 100 patients with multiple myeloma. An Education arm included 2 grand rounds presentations, 3 web-based case discussions, and a patient education module. Twenty providers took part in the continuous QI arm. More than 1100 learners participated in the online cases; the patient education curriculum reached 112 multiple myeloma patients. The initiative proved helpful in defining barriers to guideline adherence and identifying data-driven practice improvement strategies for VTE prophylaxis. It also increased learner awareness of VTE guidelines, patient risk stratification, and optimal thromboprophylaxis strategies. There was a reduction in VTE events (primary clinical outcome) from 10% at baseline to 4% in the follow-up cohort, although this was not statistically significant. Higher rates of guideline-based prophylaxis were observed in low-risk patients, and a lower incidence of VTE was observed in multiple myeloma patients with a prior history of VTE. Additional research is needed to refine prophylaxis guidelines. With appropriate institutional support, this type of QI program can be readily adopted by other organizations to address practice improvement needs.

A Systematic Review and Meta- Analysis of Randomized Controlled Trials on Primary Ambulatory Thromboprophylaxis (PATP) in Patients with Gastrointestinal Cancers Receiving Chemotherapy

Introduction: PATP in solid cancer patients remains uncertain and is not routinely recommended although thrombosis is shown to be the second leading cause of death in cancer patients. Many studies failed to demonstrate in solid cancer outpatients improvement in overall survival despite decreasing venous thromboembolism (VTE) rates by PATP. We conducted a systematic review and meta-analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) in patients with gastrointestinal cancers receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. The primary meta- analytic approach was a fixed effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Results: A total of 1,932 patients with gastric, gastroesophageal junctional (GEJ) and colorectal cancers from a subgroup of three RCTs were included in our meta-analysis. The prophylactic doses of LMWHs and DOAC (rivaroxaban) were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2 statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The VTE incidence was 13 (1.26%) in PATP group and 23 (2.55%) in control group with a RR of 0.49 (95% CI: 0.25 to 0.96, P = 0.04). The absolute RD in VTE was -0.01 (95% CI: -0.03 to -0.00, P 0.04) with an estimate of the number needed to treat (NNT) of 78 to prevent one VTE event. In a subset of patients with gastric and GEJ cancers (n=587), the VTE incidence was 4 (1.37%) in PATP group and 10 (3.40%) in control group with a RR of 0.40 (95% CI: 0.13 to 1.24, P = 0.11). Conclusions: In our study, the relative risk reduction is 48% with a NNT of 78 to prevent one VTE in ambulatory patients with gastrointestinal cancers. Nevertheless, there is no statistically significant reduction in VTE events in a subset of gastric and GEJ cancers which are considered high risk in Khorana score. Based on the findings, PATP is not recommended in patients with gastrointestinal cancers on chemotherapy at this time. Further studies are necessary to define high risk subsets of gastrointestinal cancer patients receiving chemotherapy who may benefit from PATP. Disclosures Oo: Medical Education Speakers Network: Honoraria; Janssen and Janssen: Other: site co-investigator.

Thromboprophylaxis Strategies in Acute Medically Ill Patients

We review pivotal clinical trials of extended-duration venous thromboembolism (VTE) prophylaxis strategies in acute medically ill patients. For VTE prophylaxis in medically ill patients, current guidelines recommend the use of parenteral anticoagulants during hospitalization but not for extended duration prophylaxis. In 2017, betrixaban was approved for VTE prophylaxis in acute medically ill patients based on the results of the APEX trial. The MARINER trial missed its primary endpoint of reducing the composite of symptomatic VTE and VTE-related mortality with rivaroxaban compared with placebo. It did show that rivaroxaban halved the symptomatic VTE rate compared with placebo and did achieve its secondary endpoint. The EXCLAIM, ADOPT, and MAGELLAN trials did not demonstrate a net clinical benefit in reduction of VTE events due to an increase in bleeding events. The risk of VTE remains high in acute medically ill patients after hospital discharge. Based on the results of the APEX trial which showed a reduction in VTE, the FDA approved betrixaban for use in acute medically ill patients for extended duration VTE prophylaxis. Next steps are to implement the findings from APEX and MARINER into clinical practice to reduce recurrent VTE, lower healthcare cost, and reduce rehospitalization.

Potent Anticoagulation Does Not Reduce Venous Thromboembolism in High-Risk Patients.

Based on current guidelines from the American Academy of Orthopaedic Surgeons (AAOS), a number of prophylactic modalities for the prevention of venous thromboembolism in total joint arthroplasty may be used. It is common practice that more potent prophylactic agents are used for patients at higher risk of venous thromboembolism. However, we are aware of no studies that have investigated the efficacy of potent anticoagulation in higher-risk individuals. Therefore, the purpose of our study was to test the hypothesis that low-molecular-weight heparin and warfarin result in a reduction in venous thromboembolism events in high-risk patients. A retrospective, multi-institutional study of 60,467 primary and revision total joint arthroplasties from 2000 to 2015 was performed. Identified medications were classified as aspirin, low-molecular-weight heparin, or warfarin. Patients with unavailable venous thromboembolism prophylaxis information or those not receiving the aforementioned prophylaxis were excluded. Information pertinent to the objective of this study was collected and a venous thromboembolism risk score was calculated based on 26 variables. Treatment outcomes assessed included 90-day rate of symptomatic venous thromboembolism and periprosthetic joint infection. Propensity score matching was performed (1:1), as well as logistic regression analysis on the total sample. Aspirin prophylaxis demonstrated a lower rate of deep vein thrombosis, pulmonary embolism, and venous thromboembolism than warfarin and low-molecular-weight heparin alone throughout all risk scores. In the matched propensity score analysis, low-molecular-weight heparin and warfarin demonstrated increased odds of venous thromboembolism for both standard-risk and high-risk patients undergoing total knee arthroplasties compared with aspirin. For primary total hip arthroplasty, warfarin demonstrated an increased risk for high-risk patients and low-molecular-weight heparin demonstrated an increased risk for standard-risk patients. The prevalence of periprosthetic joint infection was higher in patients receiving warfarin (p < 0.001 for both comparisons of warfarin with aspirin and low-molecular-weight heparin). The results of this multi-institutional study demonstrate that the use of warfarin and low-molecular-weight heparin in higher-risk patients does not necessarily result in a reduction in symptomatic venous thromboembolism. Aspirin administered to higher-risk patients seems to be as effective as potent anticoagulation and more effective than warfarin. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Reducing the burden of venous thromboembolism in the acute medically ill population with extended-duration thromboprophylaxis.

Hospitalized acute medically ill patients are vulnerable to venous thromboembolism (VTE), known as hospital-acquired thrombosis (HAT). The elevated risk of HAT is usually due to a combination of factors, with immobility and a prothrombotic state due to acute illness being the most frequent. The HAT risk persists well after hospital discharge, with more than half of events occurring after patient release. These HAT events may be fatal, and patients who survive the initial event may be subject to VTE recurrence, chronic discomfort from post-thrombotic syndrome and, although rare, may develop chronic thrombo-embolic pulmonary hypertension, which is often debilitating. The risk of HAT can be reduced with effective thromboprophylaxis. Current guidelines recommend thromboprophylaxis with subcutaneous heparin, low molecular weight heparin (LMWH) or fondaparinux for at-risk acute medically ill patients, but reports of real-world practice indicated that some patients do not receive protection in the short-term as outlined by the guidelines. Previous studies that have assessed extended thromboprophylaxis for 4–5 weeks with LMWH or direct oral anticoagulants in medically ill patients found they did not offer a net clinical benefit; any demonstrated efficacy was outweighed by the significantly increased risk of major haemorrhage. Therefore, there is an ongoing need for improved VTE prevention without increasing the risk of bleeding. In the APEX trial, conducted in an acute medically ill population, betrixaban provided a significant reduction in VTE events after 35 to 42 days of treatment compared with short-term enoxaparin without an increase in major bleeding.

Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients.

Prophylaxis for venous thromboembolism (VTE) in hospitalized acutely ill medical patients is a well-established practice. Despite the increased use of inpatient prophylaxis, the duration of hospitalization is typically shorter than the duration of VTE prophylaxis provided in clinical trials. In addition, VTE events after hospitalization are not unusual, with most events occurring within 30 days of hospital discharge. Therefore, the 30-day time period postdischarge has been identified as a stage in which patients are still at high risk of developing VTE. Attempts to provide extended prophylaxis with enoxaparin, rivaroxaban, or apixaban in patients with acute medical illness have been met with mixed results. Although some of these agents have reduced the incidence of VTE with extended prophylaxis, all of these agents have also demonstrated a significant increase in major bleeding that seems to offset any potential benefit. A recent trial of a new direct factor Xa inhibitor, betrixaban, demonstrated a reduction in VTE events with extended prophylaxis without significantly increasing the risk of major bleeding. Understanding appropriate patient selection, dosing, and outcomes associated with betrixaban will be important to potentially reducing the continued risk of VTE in patients with acute medical illness.

Use of Computerized Clinical Decision Support Systems to Prevent Venous Thromboembolism in Surgical Patients

ImportanceHealth care professionals do not adequately stratify risk or provide prophylaxis for venous thromboembolism (VTE) among surgical patients. Computerized clinical decision support systems (CCDSSs) have been implemented to assist clinicians and improve prophylaxis for VTE.ObjectiveTo evaluate the effect of implementing CCDSSs on the ordering of VTE prophylaxis and the rates of VTE.Data SourcesPubMed, MEDLINE via OVID, EMBASE via OVID, Scopus, Cochrane CENTRAL Register of Controlled Trials, and clinicaltrials.gov were searched in June 2016 for articles published in English from October 15, 1991, to February 16, 2016. A manual search of references from relevant articles was also performed.Study SelectionClinical trials and observational studies among surgical patients comparing CCDSSs with VTE risk stratification and assistance in ordering prophylaxis vs routine care without decision support were included. Of the 188 articles screened, 11 (5.9%) were eligible for meta-analysis.Data Extraction and SynthesisMeta-analysis of Observational Studies in Epidemiology guidelines were followed. Two reviewers extracted data and assessed quality independently. Main Outcomes and MeasuresRates of prophylaxis for VTE and VTE events. Random- and fixed-effects models were used to summarize odds ratios and risk ratios.ResultsEleven articles (9 prospective cohort trials and 2 retrospective cohort trials) comprising 156 366 individuals (104 241 in the intervention group and 52 125 in the control group) were included. The use of CCDSSs was associated with a significant increase in the rate of appropriate ordering of prophylaxis for VTE (odds ratio, 2.35; 95% CI, 1.78-3.10; P < .001) and a significant decrease in the risk of VTE events (risk ratio, 0.78; 95% CI, 0.72-0.85; P < .001).Conclusions and RelevanceUse of CCDSSs increases the proportion of surgical patients who were prescribed adequate prophylaxis for VTE and correlates with a reduction in VTE events.

The Efficacy and Safety of Edoxaban for VTE Prophylaxis Post-Orthopedic Surgery: A Systematic Review.

Venous thromboembolism (VTE) is a common complication that manifests during and/or after hospitalization, as well as postsurgeries including orthopedic surgeries. Edoxaban is a new oral direct factor Xa inhibitor that has been recently approved for treating VTE in patients who have already been treated with a parenteral anticoagulant and for the prevention of stroke and non-central nervous system systemic embolism in patients with nonvalvular atrial fibrillation. The purpose of this systematic review was to evaluate the safety and efficacy of edoxaban for VTE prophylaxis after lower limb orthopedic surgery. A comprehensive search was conducted in Google Scholar, PubMed, MEDLINE, and ScienceDirect to identify potential records, then titles, abstracts, and full texts were screened using the inclusion criteria to filter out irrelevant studies. Moreover, the data extraction and quality assessment were undertaken using standardized tools, and the results were narratively synthesized and presented in tables. Six studies were included in this systematic review after screening 2989 records. The majority of studies demonstrated a statistically significant reduction in VTE events in the edoxaban group(s) compared to the dalteparin, placebo, or enoxaparin groups (P < .05). The differences in VTE cases in some studies reached to approximately 50% favoring edoxaban 30 mg over the comparator (P < .05). However, other studies uncovered a statistically insignificant difference between edoxaban and the comparator "enoxaparin" when used for VTE prophylaxis (P > .05). On the other hand, although edoxaban found to cause more bleeding, the differences between edoxaban and the comparator are statistically insignificant (P > .05). This study helped to amalgamate evidence with regard to the use of edoxaban for VTE prophylaxis post-lower limb orthopedic surgery. In line with the results of the reviewed studies, edoxaban seems to be highly effective in reducing VTE post-lower limb orthopedic surgery.

Reduction in Venous Thromboembolism Events: Trauma Performance Improvement and Loop Closure Through Participation in a State-Wide Quality Collaborative

The Michigan Trauma Quality Improvement Program (MTQIP) is a collaborative quality initiative sponsored by Blue Cross Blue Shield of Michigan and Blue Care Network (BCBSM/BCN). The MTQIP benchmark reports identified our trauma center as a high outlier for venous thromboembolism (VTE) episodes. This study outlines the performance improvement (PI) process used to reduce the rate of VTE using MTQIP infrastructure. Trauma patients admitted for > 24 hours, with an Injury Severity Score (ISS) ≥ 5, were included in this study. We performed a preliminary analysis examining prophylaxis drug type to VTE, adjusted by patient confounders and timing of first dose, using MTQIP data abstracted for our hospital. It showed that patients receiving enoxaparin had a VTE rate that was half that of those receiving unfractionated heparin (odds ratio 0.46, 95% CI 0.25 to 0.85). Guided by these results, we produced the following plan: consolidation to single VTE prophylaxis agent and dose, focused education of providers, initiation of VTE prophylaxis for all patients-with clear exception rules-and dose withholding minimization. Results were monitored using the MTQIP platform. After implementation of our focused PI plan, the VTE rate decreased from 6.2% (n = 36/year) to 2.6% (n = 14/year). Our trauma center returned to average performance status within MTQIP. Participation in MTQIP provided identification of trauma center outlier status for the outcome of VTE. Analysis of MTQIP data allowed creation of a local action plan. The MTQIP infrastructure supported execution and monitoring of the action plan consistent with loop-closure practices, as advocated by the American College of Surgeons Committee on Trauma, and a positive performance improvement result was achieved with VTE reduction.

Thromboprophylaxie en médecine : quelles modifications avec les nouveaux anticoagulants oraux ?

Thromboprophylaxis with low molecular weight heparin or fondaparinux is associated with a 50% reduction in the risk of venous thrombo-embolism (VTE) in medical patients. Thromboprophylaxis is indicated in the prevention of VTE in medical patients at risk of VTE. Extended thromboprophylaxis with apixaban is associated with a greater reduction in VTE events but also with an increase in bleeding events when compared to standard therapy with enoxaparine. Extended thromboprophylaxis with rivaroxaban is associated with a greater reduction in VTE events but also with an increase in bleeding events, when compared to standard therapy with enoxaparine. Rivaroxaban and apixaban are currently not indicated in medical prophylaxis.

Metabolic, electrolytes disorders and tromboembolic risk in malignant glioma patients

In malignant gliomas, the management of symptoms and minimization of side effects assume major importance. Corticosteroids provide transient relief from neurological symptoms. However, treatment with steroids is also commonly associated with considerable side-effects including: hyperglycemia, osteoporosis, myopathy, lymphopenia and others. Sometimes, antiepileptic drugs may contribute to clinical decline of neuro-oncological patients in stable disease not only by neuropsychological impairment but also by metabolic interations. Several studies have demonstrated a high frequency of hyponatremia among patients treated with carbamazepine and particularly with oxacarbamazepine. Venous thromboembolism is a common complication in patients with cancer and it is particularly high in malignant gliomas, occurring in approximately 20-30% of such patients. Prophylactic treatment in patients with glioblastoma is a key topic. The role of prophylaxis has not yet been established with certainty. Overall the data show a clear reduction of venous thromboembolic events in patients treated with intermittent pneumatic compression (IPC). The addition of enoxaparin dose of 6.000UI, starting in the perioperative period, induces an increase of major bleeding events. In the absence of availability of IPC, the use of enoxaparin 4.000UI in addition to graduated compression stockings, reduces thromboembolic events without major bleeding events.

Biologic Use Is Associated with a Major Reduction in Venous Thromboembolic Events Compared With Steroid Use in the Treatment of Inflammatory Bowel Disease

Biologic Use Is Associated with a Major Reduction in Venous Thromboembolic Events Compared With Steroid Use in the Treatment of Inflammatory Bowel Disease

Edoxaban for the prevention of thromboembolic events after surgery

Without thromboprophylaxis, hospital-acquired deep vein thrombosis following major orthopedic surgery occurs with an incidence of approximately 40-60%, which is why thromboprophylaxis has been standard of care in these cases for more than 20 years. Edoxaban (DU-176b; Lixiana) is a novel, once-daily, orally active antithrombotic agent that directly inhibits factor Xa activity in a potent and selective way. It was recently approved in Japan for the prevention of venous thromboembolism after total knee replacement, total hip replacement and hip fracture surgery. In phase III trials performed in patients eligible for total knee replacement or total hip replacement, edoxaban 30 mg demonstrated a statistically significant reduction in venous thromboembolic events compared with enoxaparin, with no difference between both treatments in the incidence of major bleeding events. Edoxaban is safe and well tolerated, with predictable pharmacokinetics (low intersubject variability and low protein binding), suggesting that coagulation monitoring may not be required.

Low-molecular-weight heparin for thromboprophylaxis

Venous thromboembolism represents a potentially threatening complication in surgical and medical patients. Thromboprophylaxis showed a significant reduction of venous thromboembolic events, and low-molecular-weight heparins have been considered the standardized prophylactic regimen for a long time. The purpose of this review is to provide updated evidence on the use of low-molecular-weight heparins for prevention of venous thromboembolism after the publication of the latest American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on antithrombotic and thrombolytic therapy. Low-molecular-weight heparins, used as comparator or investigational drug, have been investigated in several studies not included in the analysis of the latest American College of Chest Physicians Guidelines on Antithrombotic and Thrombolytic Therapy. Data gathered from studies published from December 2007 up to May 2009 dealing with surgical and medical patients have been collected and discussed. Low-molecular-weight heparins are expanding their application, but progressively they will be replaced by other new antithrombotics for the prophylaxis of venous thromboembolism. Surgical patients undergo a more concerted approach to thromboprophylaxis than medical patients. Future research should aim at improving prophylaxis in the latter setting in order to significantly reduce the rate of venous thromboembolic events.