Difference In Venous Thromboembolism Research Articles

Effectiveness and Safety of Tranexamic Acid Use in Acute Traumatic Injury in the Prehospital and In-hospital Settings: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess efficacy and safety of tranexamic acid (TXA) use in acute traumatic injuries. PubMed and Cochrane libraries were searched for relevant RCTs published between January 2011 and January 3, 2021. Cohen's Q Test for heterogeneous effects was used to determine the appropriateness of fixed versus random effects models. Twenty-two studies met inclusion criteria. Meta-analysis of relative risk of mortality between treatment and placebo groups in the in-hospital, and perioperative settings was not significant. However, the risk of mortality is significantly lower in the treatment versus placebo group when TXA was given as loading dose only. Ten of the 11 studies evaluating perioperative use of TXA included in systematic review found significantly lower blood loss in the treatment compared with placebo groups, but results of meta-analysis showed no significant difference. Results of meta-analysis indicate that the risk of venous thromboembolism (VTE) in the in-hospital treatment group is greater than that of the placebo. In subset analysis of studies using only a single loading dose, there were no significant differences in VTE. Systematic review supports TXA benefits are most evident when given shortly after injury and meta-analysis supports TXA reduces mortality as a single loading dose. Systematic review supports perioperative use of TXA when large volume blood loss is anticipated. Meta-results showed no significant difference in risk of thromboembolism in single-dose TXA treatment compared with placebo. These findings suggest that TXA is safe and effective for control of traumatic bleeding.

Risk of Venous Thromboembolism and Survival Outcomes in Patients with Lymphoma

Background: The relationship between venous thromboembolism (VTE) and lymphoma is well established. In recent years, direct oral anticoagulants (DOACs) have been adopted as a treatment option for cancer associated thrombosis, however the majority of data using DOACs is in solid tumor patients. Here, we report the risk of recurrent VTE, bleeding outcomes, and effect of VTE on survival among lymphoma patients treated in a large centralized cancer associated thrombosis clinic.Methods: We prospectively followed lymphoma patients referred to our clinic from 8/2014-01/2021. VTE events including deep venous thrombosis (DVT), pulmonary embolism (PE), and visceral vein thrombosis (VVT), were noted. Overall survival (OS) was estimated by Kaplan-Meier and compared using log rank test. Cumulative incidence rate of VTE was estimated and compared using Gray's method.Results: A total of 103 patients were referred to our clinic due to clinical suspicion of VTE, of whom 40 (38.8%) were diagnosed with an acute VTE. The median age of the study population was66 (range 19-88), 61.2% were male and 16.5% had prior VTE. Non-Hodgkin Lymphoma (NHL) compromised 87.4%, with diffuse large b-cell lymphoma (DLBCL) being the most common subtype. Most patients had stage 4 disease (55.34%), had high grade lymphoma (defined as grade 3-4) (51.46%), and were on antineoplastic treatment (71.67%) at the time of VTE diagnosis. Site of VTE was DVT in 35.9%, PE in 5.8%, both DVT and PE in 2.9% and VVT in 0.97% of patients. Of these, 21 (20.39%) received a (DOAC), 14(13.59%) received enoxaparin, and 2(1.94) had IVC filter placed due to contraindication to anticoagulation. VTE recurrence occurred in 10% patients (total n=4; 2 were on enoxaparin and 2 were on rivaroxaban). Cumulative incidence of VTE in all patients at 6 months was 1% (95% CI: 0-2.9%), at 1 year was 3% (95% CI: 0-6.4%) with no significant difference in VTE or bleeding rates between lymphoma types or grade groups (P >0.05) (Table 1). Of 37 patients on anticoagulation, 10.8% experienced bleeding events (n=4) , of which 1 (2.7%) had major bleeding on IVC filter and 3 (8.1%) had CRNMB (2 on enoxaparin and 1 on rivaroxaban) at 6 month follow-up. Median follow-up was 35.9 months (range: 0.4-77.7 months) and median 2 year OS was 76%, 95% CI (68-85%). Overall survival was negatively impacted by age (patients over age 65 had a 2 year OS rate of 67%95% CI (0.56-0.81), p=0.01). Lymphoma grade had no impact on OS (2-year OS rate= 0.69, 95% CI (0.57-0.84), P=0.1132)Conclusion: High grade and low grade lymphoma patients treated in our centralized cancer thrombosis clinic had a 10% chance of VTE recurrence when treated with DOAC or enoxaparin. Bleeding rates were low in both groups; however, we saw decreased overall survival in those treated with DOACs. This data adds to the growing knowledge of treating hematologic malignancies with direct oral anticoagulants, but larger studies are needed to study the safety and efficacy of these agents in lymphoma patients. [Display omitted] DisclosuresKhorana: Halozyme: Consultancy, Honoraria; Anthos: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Bayer: Consultancy, Honoraria. Angelini: Sanofi: Membership on an entity's Board of Directors or advisory committees.

Risk of 30-day Readmission After Knee or Hip Replacement in Rheumatoid Arthritis and Osteoarthritis by Non-Medicare and Medicare Payer Status.

To determine the indication and risk of 30-day rehospitalization after hip or knee replacement among patients with rheumatoid arthritis (RA) and osteoarthritis (OA) by Medicare and non-Medicare status. Using the Nationwide Readmission Database (2010-2014), we defined an index hospitalization as an elective hospitalization with a principal procedure of total hip (THR) or knee replacement (TKR) among adults aged ≥ 18 years. Primary payer was categorized as Medicare or non-Medicare. Survey logistic regression provided the odds of 30-day rehospitalization in RA relative to OA. We calculated the rates for principal diagnoses leading to rehospitalization. Overall, 3.53% of 2,190,745 index hospitalization had a 30-day rehospitalization. Patients with RA had a higher adjusted risk of rehospitalization after TKR (OR 1.11, 95% CI 1.02-1.21) and THR (OR 1.39, 95% CI 1.19-1.62). Persons with RA and OA did not differ with respect to rates of infections, cardiac events, or postoperative complications leading to the rehospitalization. After TKR, RA patients with Medicare had a lower venous thromboembolism (VTE) risk (OR 0.58, 95% CI 0.58-0.88), whereas those with RA had a greater VTE risk (OR 2.41, 95% CI 1.04-5.57) after THR. Patients with RA had a higher 30-day rehospitalization risk than OA after TKR and THR regardless of payer type. While infections, postoperative complications, and cardiac events did not differ, there was a significant difference in VTE as the principal diagnosis of rehospitalization.

Risk of venous thromboembolism in a Swedish healthcare system during the COVID-19 pandemic: A retrospective cross-sectional study.

ObjectiveThe objective of this study was to investigate the risk and prevalence of venous thromboembolism (VTE) for patients undergoing a diagnostic test for VTE with confirmed COVID‐19 infection compared with patients with no COVID‐19 infection.MethodsThis was a retrospective cross‐sectional study of patients in an integrated healthcare system in Sweden, covering a population of 465,000, with a diagnostic test for VTE between March 1 and May 31 in the years 2015 to 2020. Risk for VTE with COVID‐19 was assessed by logistic regression, adjusting for baseline risk factors.ResultsA total of 8702 patients were included, and 88 of those patients tested positive on the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) polymerase chain reaction test. A positive SARS‐CoV‐2 test did not increase the odds for VTE (odds ratio, 0.97; 95% confidence interval [CI], 0.55–1.74) and did not change when adjusting for sex, previous VTE, previous malignancy, Charlson score, hospital admission, intensive care, or ongoing treatment with anticoagulation (odds ratio, 0.72; 95% CI, 0.16–3.3). The prevalence of VTE was unchanged in 2020 compared with 2015 to 2019 (16.5% vs 16.1%, respectively), and there was no difference in VTE between the SARS‐CoV‐2 positive, negative, or untested groups in 2020 (15.9%, 17.6%, and 15.7%, respectively; P = 0.85).ConclusionsWe found no increased prevalence of VTE in the general population compared with previous years and no increased risk of VTE in patients who were SARS‐CoV‐2 positive, suggesting that SARS‐CoV‐2 status should not influence VTE workup in the emergency department. The prevalence of VTE was high in patients with SARS‐CoV‐2 treated in the intensive care unit (ICU), where the suspicion for VTE should remain high.

Anticoagulation strategies and risk of bleeding events in critically ill COVID-19 patients.

ObjectiveTo evaluate the rate of thrombosis, bleeding and mortality comparing anticoagulant doses in critically ill COVID-19 patients.DesignRetrospective observational and analytical cohort study.SettingCOVID-19 patients admitted to the intensive care unit of a tertiary hospital between March and April 2020.Patients201 critically ill COVID-19 patients were included. Patients were categorized into three groups according to the highest anticoagulant dose received during hospitalization: prophylactic, intermediate and therapeutic.InterventionsThe incidence of venous thromboembolism (VTE), bleeding and mortality was compared between groups. We performed two logistic multivariable regressions to test the association between VTE and bleeding and the anticoagulant regimen.Main variables of interestVTE, bleeding and mortality.Results78 patients received prophylactic, 94 intermediate and 29 therapeutic doses. No differences in VTE and mortality were found, while bleeding events were more frequent in the therapeutic (31%) and intermediate (15%) dose group than in the prophylactic group (5%) (p < 0.001 and p < 0.05 respectively). The anticoagulant dose was the strongest determinant for bleeding (odds ratio 2.4, 95% confidence interval 1.26–4.58, p = 0.008) but had no impact on VTE.ConclusionsIntermediate and therapeutic doses appear to have a higher risk of bleeding without a decrease of VTE events and mortality in critically ill COVID-19 patients.

Should Exogenous Estrogens Be Stopped for Surgery in Transgender Women?

Should Exogenous Estrogens Be Stopped for Surgery in Transgender Women?

Venous thromboembolism in COVID-19 compared to non-COVID-19 cohorts: A systematic review with meta-analysis

BackgroundMany studies confirmed an association between COVID-19 and venous thromboembolism (VTE). Whether the risk of VTE significantly differed between COVID-19 cohorts and non-COVID-19 cohorts with similar disease severity remains unknown. ObjectivesThe aim of this systematic review with meta-analysis was to compare the rate of VTE between COVID-19 and non-COVID-19 cohorts with similar disease severity. MethodsA systematic literature search (MEDLINE, Embase and Google Scholar) was conducted from January 1, 2020 to March 31, 2021 to identify studies reporting VTE in COVID-19. Relative risks (RR) were estimated for the effect measure with 95% confidence intervals. ResultsSeven studies (41,768 patients) evaluated VTE in COVID-19 cohorts compared to non-COVID-19 cohorts. The overall risk of VTE (RR 1.18; 95%CI 0.79–1.77; p = 0.42; I2 = 54%), pulmonary embolism (RR 1.25; 95%CI 0.77–2.03; p = 0.36; I2 = 52%) and deep venous thrombosis (RR 0.92; 95%CI 0.52–1.65; p = 0.78; I2 = 0%) did not significantly differ between COVID-19 and non-COVID-19 cohorts. However, subgroup analyses suggested an increased risk of VTE amongst CODID-19 versus non COVID-19 cohorts when only patients hospitalized within the intensive care unit (ICU) were considered (RR 3.10; 95%CI 1.54–6.23), which was not observed in cohorts of predominantly non-ICU patients (RR 0.95; 95%CI 0.81–1.11) (Pinteraction = 0.001). ConclusionThere was no signal for a difference in VTE in COVID-19 cohorts compared to non-COVID-19 cohorts, except for the subgroup of patients hospitalized in the ICU. These results should be viewed as exploratory and further studies are needed to confirm these results.

Clinical Benefits of Oral Anticoagulant Use in Cancer Patients at Increased Risk for Venous Thromboembolism per Khorana Index

BackgroundCancer patients are at increased risk for venous thromboembolism (VTE) due to cancer-induced hypercoagulability. However, current guidelines do not routinely recommend prophylactic use of oral anticoagulants to prevent VTE in cancer patients.ObjectiveTo evaluate the efficacy and safety of novel oral anticoagulants (NOACs) versus no anticoagulant use (no-use) and, additionally, differential effects between NOACs and warfarin, in VTE and adverse bleeding prevention among cancer patients, in consideration of risk stratification by gender, high-risk chemotherapy exposure, and Khorana index.MethodsThis national health insurance data-based study with a 180-day follow-up enrolled cancer patients with or without oral anticoagulant use in 2017. The primary outcome was VTE risk in oral anticoagulant users vs non-users. Four propensity score-matched comparison pairs were designed: use vs no-use, NOAC vs no-use, warfarin vs no-use, and NOAC vs warfarin. A logistic regression model was used to investigate between-group differences in VTE and bleeding risk.ResultsWhen compared to no-use, NOACs showed substantial effects in preventing VTE complications (OR=0.40, p<0.001), primarily deep vein thrombosis (DVT) events (OR=0.38, p<0.001), in both male and female cancer patients as well as those with a Khorana score ≥1. Adverse bleeding risk was comparable or lower in NOAC-receiving female patients (p=0.13) and male patients (p=0.04), respectively. In contrast, no protective effects were found with warfarin compared to no-use in controlling thrombosis and adverse bleeding risk. In a head-to-head comparison of NOACs versus warfarin, DVT risk in those patients exposed to high-risk chemotherapy was significantly decreased with NOAC use (OR=0.19, p=0.03).ConclusionNOACs can be a promising thromboprophylactic option in both male and female cancer patients with VTE risk.

Impact of Weight on Anti-Xa Attainment in High-Risk Trauma Patients on Enoxaparin Chemoprophylaxis

BackgroundSerum anti-factor Xa (anti-Xa) concentration may guide low molecular weight heparin chemoprophylaxis in trauma patients. Higher total body weight (TBW) is a risk factor for subprophylactic anti-Xa and venous thromboembolism (VTE). The purpose of this study was to evaluate TBW differences in patients with subprophylactic versus prophylactic trough anti-Xa. MethodsThis retrospective study included adults admitted to the trauma service who received enoxaparin chemoprophylaxis, trough anti-Xa assessment, and screening duplex ultrasound. Initial enoxaparin dose was determined per trauma team weight-tiered protocol with subsequent 10 mg increase if anti-Xa was subprophylactic. Patients were stratified into subprophylactic (anti-Xa <0.1 IU/ml) and prophylactic (anti-Xa ≥0.1 IU/mL) groups. The primary outcome was difference in TBW. Secondary outcomes were weight-adjusted enoxaparin dose (mg/kg), VTE, red blood cell (pRBC) transfusions. ResultsA total of 887 patients were included with 681 (76.8%) having subprophylactic anti-Xa. The subprophylactic group had significantly younger age, higher proportion male sex, higher Injury Severity Score (ISS), higher BMI, and longer length of hospital stay. The subprophylactic group had higher TBW (median [IQR], 87.8 [74-102] kg vs. 78.9 [68-91.8] kg; P < 0.001) which equated to a lower weight-adjusted dose (0.34 [0.3-0.41] mg/kg vs. 0.38 (0.33-0.44) mg/kg; P < 0.001). There were no differences in VTE (10.4% vs. 9.2%; P = 0.71) or pRBC administration (17.0% vs. 16.0%; P = 0.81). ConclusionsTBW is higher and weight-adjusted enoxaparin dose is lower in high-risk trauma patients with subprophylactic anti-Xa concentrations. These data suggest TBW should be considered when determining the optimal prophylactic enoxaparin dose in high-risk trauma patients.

Tranexamic Acid Is Safe in Patients with a History of Coronary Artery Disease Undergoing Total Joint Arthroplasty.

Tranexamic acid (TXA) is increasingly used to minimize blood loss during total joint arthroplasty (TJA). Although TXA has been shown to be highly effective in reducing operative blood loss, many surgeons believe that it places patients with coronary artery disease (CAD) or a history of coronary stents at an increased risk for myocardial infarction. The purpose of this study was to determine if TXA is safe to use in patients with a history of CAD or coronary stents. We performed a retrospective analysis at a single, tertiary academic medical center identifying consecutive total hip and knee arthroplasty cases over an 8-year period. From this cohort who received TXA intraoperatively, we identified patients with a history of CAD or coronary stents and determined the total myocardial infarction and venous thromboembolism (VTE) rates within a 90-day postoperative period. Chi-square analyses were used to identify differences in VTE rates between cohorts. A post hoc power analysis was also performed to determine whether our results were powered to detect a difference in VTE rates. In the 26,808 identified at-risk patients, there were no postoperative myocardial infarctions. No significant differences were observed for VTE rates compared with the control cohort using either topical or intravenous TXA, with regard to CAD (0.29% compared with 0.76%; p = 0.09) or coronary stents (0% compared with 0.76%; p = 0.14). Moreover, there was no significant difference observed in VTE rates when administration was subcategorized into intravenous and topical methods with regard to CAD (0.13% compared with 0.72%; p = 0.12) or coronary stents (0% compared with 0%; p = 1.0). In our series, topical and intravenous TXA were equally safe when used in patients with a history of CAD and coronary stents in comparison with the control cohort. With equal efficacy and risk of adverse events, we recommend intravenous TXA, which may enable easier institutional implementation. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Time to surgery and complications in hip fracture patients on novel oral anticoagulants: a systematic review.

Early surgery has been consistently demonstrated to reduce complications and mortality in hip fracture patients. There remains no general consensus, however, regarding the optimal time to surgery for hip fracture patients who are on novel oral anticoagulants (NOAC) on admission and its effect on clinical outcomes after surgery. The objective of this review was to assess the effect of preoperative NOAC therapy on time to surgery and postoperative complications in hip fracture patients. We performed a systematic review of the literature using the PubMed, Embase, and Cochrane Library electronic databases. Relevant articles were identified and included if they: (i) included patients on NOAC therapy on admission who did not undergo reversal; (ii) included a control group of patients not on any anticoagulation; (iii) included time from admission to surgery; and (iv) included one of the following outcomes: blood transfusion, venous thromboembolism (VTE), stroke, readmission, and mortality. Nine studies were included with a total of 4,419 patients. There were 414 NOAC patients and 4,005 non-anticoagulated patients. Six of the nine studies found a significant increase in time to surgery for patients on NOAC therapy. Three of the seven studies that reported rates of blood transfusion found a significantly higher incidence of transfusion in patients on NOACs. None of the studies found a significant difference in VTE and stroke. One of the two studies that reported readmissions showed a higher risk of readmission for patients on NOACs. Eight of the nine included studies found no significant difference in postoperative mortality rates between the NOAC and control groups, with the remaining study finding a higher mortality rate only in patients on NOAC therapy who underwent fixation and not those who underwent arthroplasty. These mixed findings suggest that delay to surgery may not be warranted in the urgent surgical setting of patients on NOAC therapy who sustain hip fractures.

Prevention of Venous Thromboembolism in Patients with Multiple Myeloma Receiving Immunomodulatory Therapy: Real-World Examination of the Impede Study

Patients with multiple myeloma are at high risk of developing venous thromboembolism (VTE) owing to patient disease and treatment including immunomodulatory drugs (IMiDs). In early 2020, the National Comprehensive Cancer Network (NCCN) adopted the IMPEDE risk assessment for VTE prevention in multiple myeloma. The guidelines on Cancer Associated Venous Thromboembolic Disease recommend using aspirin 81-325 mg in patients with low risk for VTE and low molecular weight heparin 40 mg SQ or warfarin with goal INR 2-3 in patients with high risk. A growing body of literature supports the use of direct oral anticoagulants (DOACs) in cancer patients; however, DOACs do not have sufficient evidence in multiple myeloma patients on IMiDs yet. This study aims to describe the efficacy and safety of DOACs for VTE prophylaxis in patients with multiple myeloma in comparison to other regimens in the context of the new IMPEDE strategy versus the previous NCCN VTE risk assessment by the International Myeloma Working Group (IMWG). A single-center, retrospective, descriptive study from June 2015 to February 2019 was conducted of all multiple myeloma patients on IMiDs at the center. Primary endpoints are (1) the 6-month rate of symptomatic VTE and (2) major and clinically relevant bleeding. Secondary endpoints are (1) assessment of risk factors associated with VTE and bleeding and (2) comparison of two VTE risk assessment tools for myeloma patients: IMPEDE versus IMWG. Chi-square test was used to compare four VTE prophylaxis regimens: aspirin, low molecular weight heparin (LMWH), warfarin, and DOACs. Multivariable logistic regression models were used to assess predictors of VTE and bleeding events. Of 203 patients, 200 were included in adherence analysis. Primary analysis included a total of 334 prophylactic regimens during treatment with IMiDs: 160 aspirin, 51 LMWH, 42 warfarin, and 81 DOACs. There was no significant difference in VTE (p=.0525) or bleeding events (p=.6910) among the four groups. Subgroup analyses on high risk patients using either the IMWG scoring tool (N=193) or IMPEDE VTE scoring tool (N=197) demonstrated that DOACs have significantly less risk for VTE events (p=0.0048 and p=0.0056, respectively). In a multivariable regression model, BMI &amp;gt;25 kg/m2 and prechemotherapy WBC &amp;gt;11K have shown significant association with VTE events. A history of atrial fibrillation was protective against VTE, a result of previously initiated anticoagulation. The study was not powered for history of VTE prior to starting therapy. In a multivariable regression model for bleed events, age &amp;gt;80 and concurrent use of NSAIDS were also found to be significantly associated with bleed events. Use of DOACs as a VTE prophylaxis regimen in multiple myeloma patients taking IMiDs was found to be as safe as other recommended prophylactic regimens with a trend towards improved efficacy. The IMPEDE risk assessment, recently adopted by the NCCN, categorized nearly all of our patients on IMiDs as high risk, thus questioning its utility. In addition, we found key determinants of bleeding risk. Our data provide a novel strategy for VTE prevention in myeloma: To anticoagulate all patients on IMiDs except those at risk for bleeding. Disclosures Parnes: Geron: Current equity holder in publicly-traded company; Shire/Takeda: Consultancy, Research Funding; Sigilon: Consultancy; UniQure: Consultancy; I-Mab: Consultancy; Bayer: Consultancy; Sunovion: Consultancy; Genentech: Research Funding.

Thrombosis in patients with myeloma treated in the Myeloma IX and Myeloma XI phase 3 randomized controlled trials

AbstractNewly diagnosed multiple myeloma (NDMM) patients treated with immunomodulatory drugs are at high risk of venous thromboembolism (VTE), but data are lacking from large prospective cohorts. We present thrombosis outcome data from Myeloma IX (n = 1936) and Myeloma XI (n = 4358) phase 3 randomized controlled trials for NDMM that treated transplant-eligible and transplant-ineligible patients before and after publication of thrombosis prevention guidelines. In Myeloma IX, transplant-eligible patients randomly assigned to cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) induction had higher risk of VTE compared with patients treated with cyclophosphamide, thalidomide, and dexamethasone (CTD) (22.5% [n = 121 of 538] vs 16.1% [n = 89 of 554]; adjusted hazard ratio [aHR],1.46; 95% confidence interval [95% CI], 1.11-1.93). For transplant-ineligible patients, those randomly assigned to attenuated CTD (CTDa) induction had a higher risk of VTE compared with those treated with melphalan and prednisolone (MP) (16.0% [n = 68 of 425] vs 4.1% [n = 17 of 419]; aHR, 4.25; 95% CI, 2.50-7.20). In Myeloma XI, there was no difference in risk of VTE (12.2% [n = 124 of 1014] vs 13.2% [n = 133 of 1008]; aHR, 0.92; 95% CI, 0.72-1.18) or arterial thrombosis (1.2% [n = 12 of 1014] vs 1.5% [n = 15 of 1008]; aHR, 0.80; 95% CI, 0.37-1.70) between transplant-eligible pathways for patients treated with cyclophosphamide, lenalidomide, and dexamethasone (CRD) or CTD. For transplant-ineligible patients, there was no difference in VTEs between attenuated CRD (CRDa) and CTDa (10.4% [n = 95 of 916] vs 10.7% [n = 97 of 910]; aHR, 0.97; 95% CI, 0.73-1.29). However, arterial risk was higher with CRDa than with CTDa (3.1% [n = 28 of 916] vs 1.6% [n = 15 of 910]; aHR, 1.91; 95% CI, 1.02-3.57). Thrombotic events occurred almost entirely within 6 months of treatment initiation. Thrombosis was not associated with inferior progression-free survival (PFS) or overall survival (OS), apart from inferior OS for patients with arterial events (aHR, 1.53; 95% CI, 1.12-2.08) in Myeloma XI. The Myeloma XI trial protocol incorporated International Myeloma Working Group (IMWG) thrombosis prevention recommendations and compared with Myeloma IX, more patients received thromboprophylaxis (80.5% vs 22.3%) with lower rates of VTE for identical regimens (CTD, 13.2% vs 16.1%; CTDa, 10.7% vs 16.0%). However, thrombosis remained frequent in spite of IMWG-guided thromboprophylaxis, suggesting that new approaches are needed.

Venous thromboembolism in cancer patients: report of baseline data from the multicentre, prospective Cancer-VTE Registry.

BackgroundThe Cancer-VTE Registry evaluates the occurrence and management of venous thromboembolism in Japanese participants with major solid tumors. Using Registry data, we evaluated the frequency of concurrent venous thromboembolism in cancer patients prior to treatment initiation by cancer type.MethodsThe Cancer-VTE Registry is an ongoing (March 2017–September 2020) prospective cohort study using a nationwide, multicentre clinical registry. Participants aged ≥20 years with colorectal, lung, stomach, pancreatic, breast or gynecologic cancer, confirmed staging, ≥6 months life expectancy post-registration and who had undergone venous thromboembolism screening were managed with routine clinical care. Venous thromboembolism frequency at registration was evaluated.ResultsOf 9735 participants, 571 (5.9%) had venous thromboembolism at baseline, including asymptomatic [5.5% (n = 540)] and symptomatic venous thromboembolism [0.3% (n = 31)]. Most participants with venous thromboembolism (n = 506, 5.2%) had deep vein thrombosis only; 65 (0.7%) had pulmonary embolism with/without deep vein thrombosis. The prevalence of distal and proximal deep vein thrombosis was 4.8% (n = 466) and 0.9% (n = 83), respectively. The highest prevalence of venous thromboembolism was for pancreatic cancer (8.5%) and the lowest for breast cancer (2.0%). Venous thromboembolism prevalence increased as cancer stage advanced.ConclusionsAlthough there was a marked difference in venous thromboembolism by cancer type, the data suggest that cancer stage is an important risk factor for venous thromboembolism. Thus, metastasis seems a critical risk factor for venous thromboembolism. This is the first demonstration of venous thromboembolism prevalence and risk factors in Japanese cancer patients prior to treatment.Trial registrationUMIN000024942.

Implementation of Venous Thromboembolism Prophylaxis After Cesarean at a High Volume Military Treatment Facility [17L

INTRODUCTION: Venous thromboembolism (VTE) is a leading cause of maternal morbidity. In 2016 the National Partnership for Maternal Safety (NPMS) published a Consensus Bundle on Venous Thromboembolism recommending postcesarean dual VTE prophylaxis for a modified Caprini score of 5 or more. The purpose of our study is to determine the impact of policy change from American College of Chest Physicians 2012 guidelines to NPMS in our facility. METHODS: Following stepwise implementation of NPMS guidelines, Caprini score calculation became mandatory after cesarean delivery. We reviewed inpatient enoxaparin prescriptions rate of postcesarean patients, comparing the 12 months before implementation with 12 months post-implementation, excluding 5 months of transition period. We also compared the rate of various adverse outcomes including blood transfusion, epidural hematoma, maternal death, wound hematoma or wound separation, re-operation, heparin induced thrombocytopenia, and venous thromboembolism. Student t-test was performed to compare average rate pre and post policy change. A P&lt;.05 was considered significant. RESULTS: The analysis included 888 cesarean deliveries pre-implementation and 1,515 post-implementation with no difference in demographics or indication for cesarean. Prior to change in policy, 3.6% (+/- 1.5% SD) of patients received dual prophylaxis. After implementation, this rose to 32.7% (+/- 6.7% SD) (P=.001). The number of cesarean deliveries with adverse outcomes up to 84 days postpartum remained stable. There was no statistically significant difference in VTE in the pre-implementation and post-implementation groups. CONCLUSION: Successful implementation of a dual VTE prophylaxis policy postcesarean delivery is possible without adversely affecting complication rates.

Preoperative Heparin for Lung Cancer Resection Increases Risk of Reoperation for Bleeding

Lung cancer patients are at risk for venous thromboembolism (VTE). Preoperative heparin administration may increase the risk of bleeding requiring reoperation. The purpose of this study was to evaluate preoperative heparin's effect on reoperation for bleeding. A retrospective review compared outcomes for patients undergoing pulmonary resection for primary lung cancer from January 2006 to April 2018. Preoperative heparin was administered at the discretion of the attending surgeon. Comparisons were performed between preoperative subcutaneous heparin (5000 U) and no heparin groups. A total of 3325 lung resections were reviewed, 1.4% (n = 48) required reoperation for bleeding. VTE occurred in 1.1% (n = 38). Four hundred sixty-four patients (14.0%) did not receive preoperative heparin. The preoperative heparin group had increased rates of prior thoracic surgery (5.1% [n = 146] vs 1.7% [n = 8], P < 0.001), minimally invasive approach (40.2% [n = 1150] vs 10.6% [n = 49], P < 0.001), and sublobar resections (17.7% [n = 506] vs 10.6% [n = 49], P < 0.001). There were no differences in blood loss/transfusions. Reoperation for bleeding was significantly increased in the preoperative heparin group (1.6% [n = 47] vs 0.2% [n = 1], P = 0.017). There were no differences in VTE (1.5% [n = 7] vs 1.1% [n = 31], P = 0.424). On logistic regression, preoperative heparin was independently associated with increased reoperation for bleeding (odds ratio 8.13, P = 0.039); however, preoperative heparin was not independently associated with VTE. Preoperative heparin was associated with increased reoperation for bleeding. VTE rates are low after pulmonary resection for lung cancer and are not decreased by preoperative heparin. Preoperative heparin use should be determined by risk factor stratification for VTE and reoperation for bleeding in patients undergoing lung cancer resection.

The Role of Medical Comorbidities and Socioeconomic Factors in the Prevalence of Venous Thromboembolism Among Different Ethnic/Racial Groups in a Hospitalized Population

Background: The prevalence of venous thromboembolism (VTE) varies by race/ethnicity, with African-Americans displaying a significantly higher rate compared to Caucasians, and with Asian/Pacific Islanders and Hispanics experiencing the lowest rates. Genetic polymorphisms associated with thrombosis and molecular mutations in clotting factors do not explain the differential risk. There is a paucity of data to explain the reasons that underlie disparities in VTE prevalence among race/ethnic subgroups. The MEGA study established that major illness is associated with increased risk of VTE. Socioeconomic factors such as income and healthcare access may also contribute to VTE prevalence. In this study, we examined whether medical or socioeconomic factors experienced by hospitalized patients contributed to the variation in VTE prevalence across race/ethnic subgroups. Such an analysis explores the extent to which race itself is a risk factor versus race serving as a surrogate for differential comorbidity or socioeconomic profiles that affect VTE prevalence. Methods We conducted a serial cross-sectional study using 2002-2014 data from the National Inpatient Sample, the largest all-payer inpatient database in the US, to examine the prevalence of VTE (both deep vein thrombosis (DVT) and pulmonary embolism (PE)) among non-pregnant, adult (18+ years) African Americans, Caucasians, Hispanics and non-Hispanic others (primarily Asian Americans). Patients hospitalized with a principal diagnosis of lower extremity DVT and/or PE, as determined by ICD-9-CM codes, were included in the cohort. Codes for superficial venous thrombi and upper extremity DVT were not included. We used the Elixhauser comorbidity algorithm to assess the contribution of comorbid conditions. Socioeconomic factors investigated included zip code-level household income quartile and insurance type. VTE prevalence was defined as the number of cases per 1000 hospitalized patients. Prevalence of comorbid illness is reported as a percentage of total cases affected. To compare the role of comorbid conditions contributing to VTE with other thrombotic complications, we performed the same analysis in patients admitted with principal diagnosis of acute myocardial infarction (AMI). Results VTE prevalence was higher in patients aged 40 to 79 than those in the youngest (18-39) or oldest (80+) age groups (Figure 1). The prevalence of VTE was highest among African Americans, followed by Caucasians. Hispanics exhibited the lowest prevalence of VTE. Age did not affect this race/ethnic pattern. Diagnosis of chronic anemia, hypertension, renal failure, heart failure and obesity were more frequent in the African American population (Table 1). Subjects with a diagnosis of AMI also had a majority of African Americans with these diagnoses yet the prevalence of AMI was higher in Caucasians and non-Hispanics (Figure 2), suggesting this chronic illness milieu is not the underlying driver for the increase in VTE. Neither type of insurance (private, Medicare, Medicaid or underinsured) nor community-level household income level explain the differential prevalence of VTE across race/ethnic groups, suggesting that lack of resources does not skew the prevalence of VTE among hospitalized patients with regards to race. Conclusions Our nationally-representative study of hospitalized patients in the US confirms previously reported findings that African Americans exhibit a higher prevalence of VTE. In our study cohort, Hispanics displayed lowest prevalence. Number of comorbidities and type of comorbid conditions did not shed any light on the differences in VTE observed among different ethnic groups. Hemoglobinopathy status is thought to influence VTE risk particularly in the African American population. We excluded patients who had diagnoses of sickle cell disease and did not observe any differences in the reported prevalence pattern. We were unable to explore the contribution of sickle cell trait as this condition is rarely reported as a contributing admission diagnosis. Insurance status and income level did not influence the likelihood of being admitted with VTE diagnosis. Our findings do not suggest that race is acting as a surrogate for chronic illness or socioeconomic factors; however, this study is observational and largely descriptive in nature. To fully exclude this possibility, more sophisticated, inferential analyses are needed. Disclosures No relevant conflicts of interest to declare.

Investigation of Direct-Acting Oral Anticoagulants and the Incidence of Venous Thromboembolism in Patients Weighing ≥120 kg Compared to Patients Weighing

Background: Direct oral anticoagulants (DOACs) present a favorable alternative to warfarin based on the decreased burden of monitoring and fewer drug and food interactions. Although studied in the general population, limited clinical data justifying efficacy in patients weighing ≥120 kg present concern for using DOACs in this specific population. Objective: The purpose was to identify if a difference exists in incidence of recurrent thromboembolic events in patients receiving a DOAC for the indication of venous thromboembolism (VTE) weighing ≥120 kg compared to patients weighing <120 kg. Methods: A retrospective database analysis was conducted with patients on apixaban, dabigatran, or rivaroxaban for treatment of VTE from the Veterans Integrated Service Network 8 between January 2012 and June 2017. The primary outcome was incidence of recurrent VTEs while on anticoagulation. Fisher’s exact tests were used to evaluate difference in VTEs between the groups. Results: There were 133 patients weighing ≥120 kg and 1063 patients weighing <120 kg identified within the 5-year time frame that met inclusion criteria. Although no statistically significant difference was found in incidence of recurrent VTEs between study groups (0.8% vs 1.1%; odds ratio: 0.66; 95% confidence interval: 0.09-5.14; P = .69) few events occurred limiting the power to be able to detect a difference. Conclusion: This study found no difference in VTE recurrence in patients weighing ≥120 kg compared to patients <120 kg with few events in either group. Although promising, additional studies are needed to confirm these findings.

PF638 VENOUS AND ARTERIAL THROMBOTIC EVENTS IN MYELOMA PATIENTS TREATED WITH IXAZOMIB, LENALIDOMIDE AND DEXAMETHASONE (IRD) OR LENALIDOMIDE AND DEXAMETHASONE (RD)

Background: Patients with multiple myeloma (MM) are at increased risk of venous thromboembolism (VTE). Immunomodulatory agents (IMiDs) are known to contribute to this increased VTE risk. Less is known about the risk of arterial thrombosis. Combining proteasome inhibitors (PI) or monoclonal antibodies to IMiDs improves clinical outcomes and is now a standard of care. Addition of the oral PI (Ixazomib) to Lenalidomide Dexamethasone (RD) significantly improves progression-free survival in patients with relapsed / refractory MM (RRMM), with no significant difference in VTE and arterial events with addition of Ixazomib to RD. Aims: To compare the incidence of VTE and arterial events in patients with RRMM treated with RD and IRD, with reference to previous VTE history, cardiovascular (CV) risk factors and use of thromboprophylaxis (TP). Methods: A retrospective review of patient records noting prior venous thrombosis and arterial risk factors in patients treated with RD or IRD. To avoid bias in patient selection, we reviewed RRMM patients treated with RD alone (July 2014 to February 2016) or after we routinely used Ixazomib with RD (IRD, February 2016 to July 2018). VTE and arterial events whilst receiving RD or IRD were noted. Results: Each group consisted of 88 patients (176 in total). Baseline patient characteristics were: median age 65 years in both groups (Range: 32–85 for IRD, 30–88 for RD); 54% male in both groups; median number of prior lines of therapy was 3 (range 1–5); median number cycles delivered 7 (range 1–32, IRD) and 7.5 (range 1–48, RD); 8 (9%) patients were still on treatment in the RD and 35 (40%) in IRD patients at the time of data collection. Prior VTEs were higher in the IRD group; 13 (15%) patients, compared to the RD group 8 (9%) patients. Potential arterial risk factors were higher in the RD group; 31 (35%) patients, compared to the IRD group, 20 (23%) patients. The commonest arterial risk factor was hypertension; 16 (52% of those with CV risk factors) on RD and 11 (55% of those with CV risk factors) on IRD patients. Four (5%) patients in each cohort had a prior CVA/TIA. Obesity (Body Mass Index ≥ 30) was higher in the RD group: 26 (30%) patients compared to the IRD group 18 (21%) patients. Aspirin VTE TP was given in 60 (62%) and 68 (77%) IRD and RD patients respectively. More DOAC prescriptions were noted in the IRD group (12 patients, 13%), vs RD (2 patients, 2%). In those patients receiving IRD; 5 (5.7%) VTEs (3 PE, 1 venous sinus thrombosis, 1 DVT). Four VTEs occurred on aspirin, the other on rivaroxaban TP. For RD there were 3 (3.4%) VTEs (1 PE and 2 DVT), all on aspirin TP. Two patients (2.3%) had arterial events whilst receiving IRD (TIA after 6 months with no risk factors; stroke after 3 months, hypertension only risk factor), 1 RD patient (1.1%) developed a stroke 11 months after starting RD (known hypertensive and diabetic). Summary/Conclusion: VTEs occur at a lower rate than reported; between 3 and 6%, compared to 8–11% in the Touramaline MM1 trial, however we note VTEs of potential clinical concern (PE or venous sinus thrombosis), 4 events in the IRD and 1 in the RD group. VTEs still occurred despite thromboprophylaxis. The IRD group had more previous VTEs, but a lower obesity rate. This requires further exploration. Arterial events occur at a similar rate to that reported (1–2%), and occur early in treatment, despite aspirin TP and in the absence of other risk factors. Strategies to prevent this are urgently needed.

Efficacy and Safety of Direct Oral Factor Xa Inhibitors in 795 Morbidly Obese Patients

Background: Studies of acute venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF) have shown comparable therapeutic efficacy and similar or lower bleeding risk for direct oral anticoagulants (DOACs) compared to warfarin. Because the representation of morbidly obese patients (BMI ≥40 kg/m2) in pivotal clinical trials has been minimal, efficacy and safety of DOACs in this population are unclear. Our goal was to investigate whether direct oral factor Xa inhibitors, apixaban and rivaroxaban, are as effective and safe as warfarin in morbidly obese (BMI ≥40) patients.Methods: Using our institutional database, we identified all adult patients at Montefiore Medical Center with BMI ≥40 who were started on anticoagulation with apixaban, rivaroxaban or warfarin, for either AF or VTE, between March 1, 2013 and March 1, 2017. We reviewed charts to obtain detailed information on patient demographics and to document clinical outcomes of recurrent VTE, ischemic stroke (CVA) and bleeding from the first prescription date to the earliest of a thrombotic event, discontinuation of medication, death, or June 30, 2017. VTE and CVA episodes were confirmed by imaging (compression sonography, CT scans, ventilation/perfusion scans, MRIs). Bleeding events were classified according to criteria from the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Analyses were stratified by anticoagulation indication. Chi-squared tests or Fisher's exact tests were used to assess statistical significance of the differences in VTE, CVA and bleeding rates between anticoagulant cohorts. Differences in times from first prescription date to VTE, CVA and bleeding were analyzed with Kaplan-Meier curves, Log-rank tests, and Cox proportional hazards models. Data were adjusted for age, CHA2DS2-VASc, and Charlson scores. Subgroup analyses were performed for patients with BMI ≥50 kg/m2.Results: Data on 795 patients were collected. In 366 patients with a history of VTE, the rates of recurrent VTE were low and comparable among the apixaban, rivaroxaban and warfarin cohorts [1/47 (2.1%), 3/152 (2%), and 2/167 (1.2%), respectively, p=0.74]. In the subgroup of individuals with BMI ≥50 kg/m2 (n=92), none of the 40 DOAC patients had recurrent VTE. The rates of clinically relevant bleeding, including major bleeding, among VTE patients, were comparable between the three cohorts.Among the 429 patients with AF, stroke rates were also low and similar among anticoagulant cohorts [1/103 (1%) for apixaban, 4/174 (2.3%) for rivaroxaban, and 2/152 (1.3%) for warfarin, p=0.71]. CVAs were similarly rare in patients with BMI ≥50 (1/19 patients on apixaban, 0/37 on rivaroxaban and 1/44 patients on warfarin). In the AF sample, there was no statistically significant difference in the rate of bleeding, including major bleeding, among the 3 cohorts. In an analysis with combined DOAC cohort (apixaban + rivaroxaban vs. warfarin), the recurrent VTE and stroke rates were still low and comparable. There were more major bleeding events in AF patients on warfarin than the combined DOAC cohort (7.9% vs. 2.9%, p=0.02), a finding that became non-significant when adjusted for age, CHA2DS2-VASc, and Charlson scores (p=0.06). The rates of bleeding, including major bleeding, were comparable among the three anticoagulants in both VTE and AF patients with BMI ≥50.Conclusions: Our study is the largest study examining morbidly obese patients on DOACS and provides further evidence of comparable efficacy and safety of the direct oral anti-Xa inhibitors, compared to warfarin, in morbidly obese patients with AF and VTE. [Display omitted] DisclosuresKushnir:Janssen: Research Funding. Billett:Bayer: Consultancy; Janssen: Research Funding.