Venous Thromboembolism Prophylaxis Strategies Research Articles

Advancements in venous thromboembolism prophylaxis strategies for total hip arthroplasty: a comprehensive narrative review

Advancements in venous thromboembolism prophylaxis strategies for total hip arthroplasty: a comprehensive narrative review

Development of a Combined Risk Assessment Model for Venous Thromboembolism and Bleeding in Hematopoietic Stem Cell Transplantation Patients

Background: Venous thromboembolism (VTE) and bleeding are common complications amongst allogeneic and autologous hematopoietic stem cell transplant (HSCT) patients. Balancing risk of bleeding and thrombosis in this population is particularly challenging as HSCT patients are concurrently pancytopenic and coagulopathic. However, risk factors for bleeding and thrombosis in HSCT patients are understudied. We aimed to derive a combined bleeding and VTE risk assessment tool to be used in the immediate post-transplant period (90 days). Methods: We conducted a retrospective cohort study of adult patients who underwent allogeneic or autologous HSCT between January 1, 2011 and December 31, 2021 at a tertiary care centre in Canada. The risk models patients were followed from transplant until occurrence of the event of interest with last follow up at Day 90 post-transplant, or death. Primary outcome for VTE was the occurrence of a confirmed thrombosis including proximal upper and lower extremity deep vein thrombosis, pulmonary embolism, or thrombosis of unusual sites, including cerebral and splanchnic. Primary outcome for bleeding was the occurrence of a major or clinically significant non-major bleeding event, not related to anticoagulation, as per the definition of the International Society of Thrombosis and Hemostasis. Group characteristics were compared using chi-square, Fisher's exact, or Student's T-tests as appropriate. Potential predictors for VTE and bleed amongst our patients were evaluated using single variable logistic regression and confirmed with multiple variable logistic regression with forward selection. For continuous variables, optimal cut-off points were estimated using ROC curves. Final VTE and bleed risk scores were derived based on weighted variables and compared using Cox regression with non-parametric bootstrapping used for internal validation. Results: A total of 476 patients (317 autologous, 159 allogeneic) were included. 47 patients (9.8%) suffered from VTE, and 32 patients (6.7%) suffered from bleed unrelated to anticoagulation within 90 days post-HSCT. A VTE risk assessment tool was derived, and internally validated, and it included: second central venous catheter insertion (due to complications from first central line) (2 points), and previous cancer treatment with steroids (1 point). The overall cumulative incidence of VTE was 31.8% in the high-risk group (>2 points) versus 7.6% in the low-risk group (0-1 points). The high-risk group was associated with higher mortality at 90 days (15.9% versus 3.2%, p <0.001; Figure 1). A bleeding risk assessment tool was also derived, and internally validated, and it included: baseline (day 0 of transplant) platelet count of <90 (1 point), and baseline hemoglobin of <96 (1 point). The overall cumulative incidence of bleed was 17.2% in the high-risk group (2 points), versus 4.3% in the low-risk group (0-1 points). The high-risk group was associated with higher mortality at 90 days (12.6% versus 2.6%, p<0.001). Amongst the low-risk bleed group, overall cumulative incidence of VTE was 10.03%, with 31.03% in the high-risk VTE group versus 8.33% in the low-risk VTE group (p<0.001). The positive VTE group was associated with higher mortality at 90 days (10.26% versus 1.72%, p=0.001; Figure 2). Amongst the high-risk bleed group, overall cumulative incidence of VTE was 9.19%, with 33.33% in the high-risk VTE group, versus 4.17% in the low-risk VTE group (p<0.001). The positive VTE group was associated with higher mortality at 90 days (37.5% versus 10.13%, p=0.026). Conclusion: We derived a predictive score, VTE and Bleeding in Marrow Transplant (VBMT) - risk score, for both VTE and bleeding in the immediate post-transplant period (90 days), to be used in conjunction with other criteria for bleeding and thrombosis. Amongst the low-risk bleed patients, we recommend strong consideration of chemical VTE prophylaxis, especially amongst the high-risk VTE group. These risk assessment models will help stratify patients based on bleed and thrombosis risk, and ultimately help guide VTE prophylaxis and surveillance strategies amongst HSCT patients.

Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma

BackgroundIndividuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients.MethodsWe retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis.ResultsThe overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively.ConclusionsThe new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

707 Comparing VTE Prophylaxis Strategies in Thermal Injuries: Don't Get Burned by Heparin!

Abstract Introduction Burn patients are at high risk of venous thromboembolism (VTE) as well as bleeding complications, thus choosing the best option for thromboprophylaxis can be challenging. Previous studies have analyzed the preferred antithrombotic agent in trauma patients, but this has not been established in burns. We hypothesize that low molecular weight heparin (LMWH) is associated with better outcomes than unfractionated heparin. Methods The Trauma Quality Improvement Project (TQIP) dataset was used to identify all patients with second- or third-degree burns that were administered VTE prophylaxis. Cases with missing data, &amp;lt; 24-hour hospital length of stay, other serious traumatic injuries (any AIS &amp;gt;3), interhospital transfer, history of kidney disease, or pre-hospital history of anticoagulant use were excluded. Bleeding complications were defined as hemorrhage control surgery, embolization procedures, or blood transfusion occurring after the initiation of thromboprophylaxis, consistent with other studies analyzing bleeding complications in TQIP. Rates of VTE and bleeding complications were compared between those who received heparin versus LMWH. Propensity score matching was performed to control for age, total body surface area percent (TBSA%) burned, and ICU admission (Table 1). Results The analysis included 9,857 patients (69% male). Median age was 50 (34-62) years. LWMH was associated with fewer complications including pulmonary embolism, any VTE, and bleeding (Table 2). Initiation of thromboprophylaxis within 24 hours of arrival was associated with a lower risk of VTE (1.0% vs 2.1%, p&amp;lt; 0.001) without showing a significant difference in bleeding complications (6.4% vs 7.2%, p=0.206). Conclusions This propensity score matched analysis of nearly ten thousand burn patients has demonstrated that low molecular weight heparin is associated with reduced risk of VTE and bleeding compared to heparin. Initiation of thromboprophylaxis within 24 hours is linked to lower rates of VTE. In burn patients without contraindications, thromboprophylaxis with LMWH should be started within 24 hours. Applicability of Research to Practice Venous thromboembolism is an important complication in burn patients, which may negatively impact patient outcomes. These patients regularly receive DVT prophylaxis and it is important for their care team to be able to select the proper agents.

Prophylactic Anticoagulation in Patients with Cancer: When and How?

Cancer-associated thrombosis is a leading cause of death among patients with cancer. Historically, thromboprophylaxis efforts have focused on the highest risk patients with cancer, including post-operative patients and hospitalized patients. This review covers not only thromboprophylaxis for these groups but also emerging data supporting prophylaxis in ambulatory medical oncology patients. Several leading guidelines, backed by clinical trial data, now support the use of direct oral anticoagulants for select high-risk outpatients for primary thromboprophylaxis. However, uptake of these findings remains low. Pharmacologic venous thromboembolism prophylaxis strategies continue to improve. However, it remains challenging to balance competing risks of bleeding and thrombosis. The morbidity and mortality associated with cancer associated thrombosis may be preventable. Understanding advancements in risk prediction, anticoagulant options, and implementation of existing data, is critical to provide optimal patient care.

Chemical versus Mechanical and Chemical Venous Thromboembolism Prophylaxis in Neurocritically Ill Patients: A Cohort Study.

Patients admitted with neurocritical illness are presumed to be at high risk for venous thromboembolism (VTE). The administration of chemical and/or mechanical VTE prophylaxis is a common practice in critically ill patients. Recent data did not show a significant difference in the incidence of VTE between chemical compared to a combined chemical and mechanical VTE prophylaxis in critically ill patients with limited data in neurocritically ill population. The objective of this study is to investigate the incidence of VTE between chemical alone compared to chemical and mechanical VTE prophylaxis in neurocritically ill patients. This was a retrospective cohort study at a tertiary teaching hospital. Data were obtained from electronic medical records for all patients admitted with neurocritical illness from January 1, 2016, to December 31, 2020. Patients were excluded if they did not receive VTE prophylaxis during admission or were younger than 18 YO. Major outcomes were symptomatic VTE based on clinical and radiological findings, intensive care unit (ICU) length of stay (LOS), and hospital LOS. Minor outcomes included severe or life-threatening bleeding based on GUSTO criteria, and mortality at 28-days. Two hundred and twelve patients were included in this study. Patients did not have any significant differences in their baseline characteristics. The incidence of VTE was similar in the chemical only group compared to the combined VTE prophylaxis group (19/166 (11.3%) vs 7/46 (15.2%)); P = 0.49. No difference between groups in their ICU LOS 6 [3-16.2] vs 6.5 [3-19]; P = 0.52, nor their mortality (18/166 (10.7%) vs 3/46 (6.5%)); P = 0.38, respectively. Less bleeding events were seen in the chemical prophylaxis group compared to the combined VTE prophylaxis group (19/166 (11.3%) vs 12/46 (26.1%); P = 0.01). Our findings observed no difference between the administration of chemical VTE prophylaxis alone compared to the combined VTE prophylaxis strategy. More data are needed to confirm this finding with more robust methodology.

958 Enoxaparin Venous Thromboembolism Prophylaxis in Bariatric Surgery: A Best Evidence Topic Update

Abstract Aim To examine the literature and identify the best dosing regimen of enoxaparin for perioperative venous thromboembolism (VTE) prophylaxis in patients undergoing bariatric surgery. This presentation reviewed publications from 2015 to 2021 to determine whether previous recommendations based on a similar examination of evidence conducted in 2015 needed to be updated, considering new evidence. Method A literature search was conducted in accordance with a structured format. One hundred and one papers were identified using a standardised literature search from 2015 to 2021 on Medline and EMBASE using the same search terms “bariatric surgery” AND “venous thromboembolism” AND “enoxaparin”. The author, date and country of publication, patient groups and VTE prophylaxis strategy, level of evidence, outcomes, key results, and study weaknesses were tabulated. Results Three studies were selected as the best available evidence to answer the question. All three articles were non-randomised cohort studies analysing VTE and major bleeding rates following different bariatric thromboprophylaxis regimens. There was still no level 1 evidence available to answer this question. Conclusion Enoxaparin 40mg/day starting 12 hours after the operation, continuing for at least one-week post-discharge may be the best enoxaparin dosing regimen for VTE prophylaxis in bariatric surgery patients based on the best evidence available to 2021. New evidence suggests that the previously recommended 40mg enoxaparin twice daily for in-hospital patients may increase major bleeding risk. A Randomised Controlled Trial would probably require 3500 patients in each arm to identify the best enoxaparin dosing regimen.

Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19

The risk of venous thromboembolism (VTE) in ambulatory COVID-19 is controversial. In addition, the association of vaccination with COVID-19-related VTE and relevant clinical and genetic risk factors remain to be elucidated. To quantify the association between ambulatory COVID-19 and short-term risk of VTE, study the potential protective role of vaccination, and investigate clinical and genetic risk factors for post-COVID-19 VTE. This population-based cohort study of patients with COVID-19 from UK Biobank included participants with SARS-CoV-2 infection that was confirmed by a positive polymerase chain test reaction result between March 1, 2020, and September 3, 2021, who were then propensity score matched to COVID-19-naive people during the same period. Participants with a history of VTE who used antithrombotic drugs (1 year before index dates) or tested positive in hospital were excluded. First infection with SARS-CoV-2, age, sex, ethnicity, socioeconomic status, obesity, vaccination status, and inherited thrombophilia. The primary outcome was a composite VTE, including deep vein thrombosis or pulmonary embolism, which occurred 30 days after the infection. Hazard ratios (HRs) with 95% CIs were calculated using cause-specific Cox models. In 18 818 outpatients with COVID-19 (10 580 women [56.2%]; mean [SD] age, 64.3 [8.0] years) and 93 179 matched uninfected participants (52 177 women [56.0%]; mean [SD] age, 64.3 [7.9] years), the infection was associated with an increased risk of VTE in 30 days (incidence rate of 50.99 and 2.37 per 1000 person-years for infected and uninfected people, respectively; HR, 21.42; 95% CI, 12.63-36.31). However, risk was substantially attenuated among the fully vaccinated (HR, 5.95; 95% CI, 1.82-19.5; interaction P = .02). In patients with COVID-19, older age, male sex, and obesity were independently associated with higher risk, with adjusted HRs of 1.87 (95% CI, 1.50-2.33) per 10 years, 1.69 (95% CI, 1.30-2.19), and 1.83 (95% CI, 1.28-2.61), respectively. Further, inherited thrombophilia was associated with an HR of 2.05 (95% CI, 1.15-3.66) for post-COVID-19 VTE. In this population-based cohort study of patients with COVID-19, ambulatory COVID-19 was associated with a substantially increased risk of incident VTE, but this risk was greatly reduced in fully vaccinated people with breakthrough infection. Older age, male sex, and obesity were clinical risk factors for post-COVID-19 VTE; factor V Leiden thrombophilia was additionally associated with double the risk, comparable with the risk of 10-year aging. These findings may reinforce the need for vaccination, inform VTE risk stratification, and call for targeted VTE prophylaxis strategies for unvaccinated outpatients with COVID-19.

WE6.9 Enoxaparin venous thromboembolism prophylaxis in bariatric surgery: A best evidence topic update

Abstract Aim To examine the literature and identify the best dosing regimen of enoxaparin for perioperative venous thromboembolism (VTE) prophylaxis in patients undergoing bariatric surgery. This presentation reviewed publications from 2015 to 2021 to determine whether previous recommendations based on a similar examination of evidence conducted in 2015 needed to be updated, considering new evidence. Method A literature search was conducted in accordance with a structured format. One hundred and one papers were identified using a standardised literature search from 2015 to 2021 on Medline and EMBASE using the same search terms “bariatric surgery” AND “venous thromboembolism” AND “enoxaparin”. The author, date and country of publication, patient groups and VTE prophylaxis strategy, level of evidence, outcomes, key results and study weaknesses were tabulated. Results Three studies were selected as the best available evidence to answer the question. All three articles were non-randomised cohort studies analysing VTE and major bleeding rates following different bariatric thromboprophylaxis regimens. There was still no level 1 evidence available to answer this question. Conclusion Enoxaparin 40mg/day starting 12 hours after the operation, continuing for at least one week post-discharge may be the best enoxaparin dosing regimen for VTE prophylaxis in bariatric surgery patients based on the best evidence available to 2021. New evidence suggests that the previously recommended 40mg enoxaparin twice daily for in-hospital patients may increase major bleeding risk. A Randomised Controlled Trial would probably require 3500 patients in each arm to identify the best enoxaparin dosing regimen.

Obstetric venous thromboembolism: Evaluation of prophylactic approach based on risk scores, D-dimer levels, and ultrasonography findings in a tertiary hospital in Japan.

Pulmonary embolism remains a leading cause of maternal mortality in developed countries despite developments in venous thromboembolism prophylaxis strategies. This study aimed to evaluate the effectiveness of our approach involving risk-scoring, D-dimer level assessment, and ultrasonography for obstetric venous thromboembolism. This retrospective cohort study included women who delivered at 22-41 weeks of gestation in The University of Tsukuba Hospital, Japan between January and December 2020. Venous thromboembolism risk (determined according to Japanese guidelines) and D-dimer levels were evaluated within 20 weeks of gestation, 30-34 weeks of gestation, and during the pre-delivery period (36 weeks of gestation or any time before preterm delivery). Compression and color Doppler ultrasonography for lower extremity deep vein thrombosis were performed if D-dimer levels were ≥3.2 μg/mL (for those undergoing cesarean delivery, 1.0μg/mL). Of 1026 women, 6 women had deep vein thrombosis during pregnancy and 1 during the puerperium period. Pulmonary embolism was not observed. The D-dimer screening result was positive for 8 women (2%) within 20 weeks of gestation (deep vein thrombosis was confirmed in 3 of them), 87 women (10%) (no deep vein thrombosis) at 30-34 weeks of gestation, and 367 women (36%) during the pre-delivery period (asymptomatic deep vein thrombosis in one). Based on the Japanese guidelines, 1%, 11%, 33%, and 55% of women had high, intermediate, low, and no postpartum risk factors, respectively. Our approach appears useful for antenatal venous thromboembolism screening in the first trimester. For postpartum prophylaxis, more cost-effective strategies are needed.

Venous thromboembolism in pediatric patients with sickle cell disease: A north American survey on experience and management approaches of pediatric hematologists

BackgroundThere is a lack of pediatric-specific data to guide recommendations for prevention and management of venous thromboembolism (VTE) in sickle cell disease (SCD). Experience and expert opinion in this area have not been reported. ObjectivesTo characterize the management practices of pediatric hematologists in SCD-associated VTE. We hypothesized there is substantial variability in duration of therapy and prophylaxis preferences. MethodsElectronic survey among pediatric hematologists members of three international subspecialty societies/consortia. ResultsAmong 52 complete respondents (response rate, 42%), 47% of physicians reported treating 1–2 patients with SCD-associated VTE, while 20% treated 3–5 patients during the preceding 12 months. Most respondents (86%) estimated the risk of VTE recurrence at <5%. The vast majority (98%) of respondents prescribed anticoagulation for symptomatic VTE treatment. Duration of therapy varied by VTE type, 95% reported prescribing 6 weeks-3 months for provoked DVT, while 60% reported prescribing a similar duration for provoked PE with the remaining 40% reporting treating PE for longer duration. There was notable variation in the treatment practices for asymptomatic or unprovoked VTE. Lastly, half of physicians indicated to be “somewhat” (40%) and “not at all” (10%) confident making decisions regarding the duration and intensity of prophylactic anticoagulation. ConclusionsWe identified significant variability in practice, a lower than expected perceived risk of recurrence, and uncertainty regarding VTE prophylaxis strategies in pediatric SCD. Cooperative multicenter studies are needed to generate evidence for future treatment guidelines development, and to identify opportunities for interventions aimed at managing and preventing VTE in pediatric SCD.

Optimizing Thromboembolism Prophylaxis for the Contemporary Age of Multiple Myeloma.

Venous thromboembolism (VTE) is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma (MM) have a 9-fold increase in VTE risk, likely because of their malignancy, its treatments, and other additional patient-related factors. In MM, thromboembolism events tend to occur within 6 months of treatment initiation, regardless of treatment regimen; however, the use of immunomodulatory agents such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for VTE. Currently, official recommendations for VTE prophylaxis in MM outlined in various national guidelines or multidisciplinary society panels are based on expert opinion, because data from randomized controlled trials are scarce. Large studies which have mainly focused on the efficacy of thromboprophylaxis in patients with cancer at higher risk for VTE either had a very low representation of patients with MM, or excluded them all together, limiting our ability to draw evidence-based conclusions on how to effectively protect MM population from VTE. In this brief perspective, we highlight some of the greatest challenges that have hampered the field concerning the availability of high-quality clinical trial data for the formulation of best VTE prophylaxis strategies in patients with newly diagnosed MM, as well as the rationale for the latest updates in the NCCN Guidelines on this topic.

American Association for the Surgery of Trauma/American College of Surgeons-Committee on Trauma Clinical Protocol for inpatient venous thromboembolism prophylaxis after trauma.

Trauma patients are at increased risk of venous thromboembolism (VTE), which includes both deep vein thrombosis and pulmonary embolism. Pharmacologic VTE prophylaxis is a critical component of optimal trauma care that significantly decreases VTE risk. Optimal VTE prophylaxis protocols must manage the risk of VTE with the competing risk of hemorrhage in patients following significant trauma. Currently, there is variability in VTE prophylaxis protocols across trauma centers. In an attempt to optimize VTE prophylaxis for the injured patient, stakeholders from the American Association for the Surgery of Trauma and the American College of Surgeons-Committee on Trauma collaborated to develop a group of consensus recommendations as a resource for trauma centers. The primary goal of these recommendations is to help standardize VTE prophylaxis strategies for adult trauma patients (age ≥15 years) across all trauma centers. This clinical protocol has been developed to (1) provide standardized medication dosing for VTE prophylaxis in the injured patient; and (2) promote evidence-based, prompt VTE prophylaxis in common, high-risk traumatic injuries. Therapeutic/Care Management; Level V.

Utilization Patterns, Efficacy, and Complications of Venous Thromboembolism Prophylaxis Strategies in Revision Hip and Knee Arthroplasty as Reported by American Board of Orthopaedic Surgery Part II Candidates

BackgroundThe optimum venous thromboembolism (VTE) prophylaxis strategy to minimize risk of VTE and bleeding complications following revision total hip and knee arthroplasty (rTHA/rTKA) is controversial. The purpose of this study is to describe current VTE prophylaxis patterns following revision arthroplasty procedures to determine efficacy, complication rates, and prescribing patterns for different prophylactic strategies. MethodsThe American Board of Orthopaedic Surgery Part II (oral) examination case list database was analyzed. Current Procedural Terminology codes for rTHA/rTKA were queried and geographic region, VTE prophylaxis strategy, and complications were obtained. Less aggressive prophylaxis patterns were defined if only aspirin and/or sequential compression devises were utilized. More aggressive VTE prophylaxis patterns were considered if any of low-molecular-weight heparin (enoxaparin), warfarin, rivaroxaban, fondaparinux, or other strategies were used. ResultsIn total, 6387 revision arthroplasties were included. The national rate of less aggressive VTE prophylaxis strategies was 35.3% and more aggressive in 64.7%. Use of less aggressive prophylaxis strategy was significantly associated with patients having no complications (89.8% vs 81.9%, P < .001). Use of more aggressive prophylaxis patterns was associated with higher likelihood of mild thrombotic (1.2% vs 0.3%, P < .001), mild bleeding (1.7% vs 0.6%, P < .001), moderate thrombotic (2.6% vs 0.4%, P < .001), moderate bleeding (6.2% vs 4.0%, P < .001), severe bleeding events (4.4% vs 2.4%, P < .001), infections (6.4% vs 3.8%, P < .001), and death within 90 days (3.1% vs 1.3%, P < .001). There were no significant differences in rates of fatal pulmonary embolism (0.1% vs 0.04%, P = .474). Subgroup analysis of rTHA and rTKA patients showed similar results. ConclusionThe individual rationale for using a more aggressive VTE prophylaxis strategy was unknown; however, more aggressive strategies were associated with higher rates of bleeding and thrombotic complications. Less aggressive strategies were not associated with a higher rate of thrombosis. Level of EvidenceTherapeutic Level III.

A Real-Life Survey of Venous Thromboembolic Events Occurring in Myeloma Patients Treated in Third Line with Second-Generation Novel Agents.

Compared to the general population, patients with multiple myeloma (MM) have a nine-fold increased risk of developing venous thromboembolism (VTE). Little is known about VTE prophylaxis in relapsed/refractory (RR) MM patients treated with next generation anti-myeloma drugs, such as pomalidomide (Poma) and carfilzomib (K), and monoclonal antibodies daratumumab (Dara) and elotuzumab (Elo), alone or in combination with dexamethasone at high- (D, 40 mg/week) or low-dose (d, 20 mg/week). Here, we describe the incidence of VTE in a retrospective cohort of 112 consecutive relapsed and refractory myeloma (RRMM) patients who received a third line of treatment from April 2013 to February 2020. Anti-MM regimens included combinations of pomalidomide and dexamethasone (PomaD, N = 61), carfilzomib, lenalidomide and dexamethasone (KRd, N = 31), and elotuzumab, lenalidomide and dexamethasone (EloRd, N = 10), while the remaining 10 patients received daratumumab as a single agent. According to National Comprehnsive Cancer Network (NCCN), International Myeloma Working Group (IMWG) and 2015 European Myeloma Network (EMN) guidelines, 42 patients (38%) were classified as high-risk patients. According to the IMPEDE VTE score, 32 patients (28%) were classified as low-risk, with a score ≤ 3 (most of them in the PomaD and Dara group), 70 (63%) were classified as intermediate-risk, with a score of 4–7 (most of them in PomaD and KRd group), and 10 (9%) were classified as high-risk, with a score ≥8 (most of them in the PomaD group). All patients received a prophylaxis, consisting generally of low-doses of acetylsalicylic acid. VTE was recorded in 9% of our patients, all of them with an intermediate or high-risk IMPEDE score, treated with low doses aspirin (ASA). No VTE occurred in patients treated with daratumumab. Thus, our real-life experience documents that (1) in RRMM patients treated with continuative regimens of third line, the incidence of VTE is similar to the setting of newly-diagnosed patients; (2) many patients in real-life received prophylaxis with ASA, irrespective of the risk classification; (3) the IMPEDE VTE score seems to be more appropriate to define the risk categories. Randomized clinical trials are required to better define the VTE prophylaxis strategy in the RRMM setting.

Venous Thromboembolism in Hospitalized COVID-19 Patients: Systematic Review

BackgroundCoagulopathy associated with COVID-19 infection and venous thromboembolism (VTE) have emerged as significant contributors to morbidity among patients infected with SARS-CoV-2.ObjectiveWe performed a systematic review to estimate VTE incidence in hospitalized patients and to analyze characteristic factors in the VTE cohort.MethodsWe searched PubMed and Google Scholar using specified title search terms “SARS-CoV-2” or “COVID-19” and “venous thromboembolism” and “anticoagulation” among others to identify peer-reviewed journal articles published between June 22, 2019, and June 22, 2020. Data were systematically extracted and synthesized using Microsoft Excel for analysis. The main outcome was VTE incidence, and measures included patient characteristics, anticoagulation, and clinical outcomes with assessment for associations.ResultsIn total, 14 studies were included comprising 1677 patients. Most patients (n=1306, 82.4%) received anticoagulation (either VTE prophylaxis or treatment). VTE incidence was 26.9% (SE 3.1; 95% CI 20.8-33.1) and was correlated with systematic screening (r2=0.34, P=.03) and study duration (r2=–0.33, P=.03). D-dimer was higher for the VTE cohort (5.62 [SD 0.9] vs 1.43 [SD 0.6]; P<.001). Odds of VTE were higher at the intensive care unit (odds ratio [OR] 6.38, 95% CI 3.67-11.11; P<.001) but lower with anticoagulation (OR 0.58, 95% CI 0.36-0.92; P=.02).ConclusionsDespite the utilization of background anticoagulation, VTE incidence was historically high. Future studies are needed to provide additional data to guide optimal VTE prophylaxis and diagnostic strategies.

Venous thromboembolism prophylaxis in ambulatory cancer patients initiating chemotherapy: A cost-effectiveness analysis.

7074 Background: Venous thromboembolism (VTE) is a major cause of morbidity and mortality among cancer patients. The Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) randomized controlled trial concluded that apixaban is a safe and effective option for VTE prophylaxis in high-risk ambulatory cancer patients initiating a new chemotherapy regimen. We performed a cost-effectiveness analysis from a health system perspective to determine if apixaban is a feasible prophylactic strategy for this population. Methods: A decision model was created from a third party payer perspective with a time horizon of 6 months, based on the treatment arms of the AVERT trial: (1) apixaban 2.5 mg twice daily for 6 months during active chemotherapy versus (2) placebo. Rates of VTE (4.2% apixaban vs 10.2% placebo), major bleeding (3.5% vs 1.8%) and clinically relevant nonmajor bleeding (CRNMB) (7.3% vs 5.5%) were modeled from the results of the AVERT trial. Cost estimates for treatments and events were obtained from wholesale drug costs, previously published studies and Medicare reimbursement data, and adjusted for inflation to 2018 dollars. Quality adjusted life years were calculated based on previously published utility values for the health states of advanced cancer, DVT, PE, and major bleeding events. An exploratory analysis was performed comparing prophylactic aspirin to no prophylaxis assuming a VTE rate of 7.2%, major bleeding rate of 3.5%, and CRNMB rate of 7.3%, based on the conservative assumptions that while aspirin may not be as effective at preventing VTE, the rate of clinically significant bleeding events would be similar or greater than that of apixaban. Results: In the base case model, apixaban is more costly and more effective than placebo (ICER = $5,013,190/QALY), and the cost per VTE prevented in the apixaban arm is $33,000. In one-way sensitivity analysis, if the cost of apixaban were reduced by 40% from $3,197 to $1,250 for a 6 month course, this could potentially be a cost-effective prophylaxis strategy with an ICER less than $100,000/QALY. In the alternative analysis, aspirin dominates placebo as it is both more effective and less expensive, and remains cost-effective even when the rate of clinically recognized bleeding with aspirin exceeds 15%. Conclusions: Further investigation into less costly prophylactic options such as generic direct oral anticoagulants (once available) and aspirin is warranted prior to broader implementation of a VTE prophylaxis strategy in this population.

1086 Venous Thromboembolism Trends and Impact in Patients With Cirrhosis: Analysis of the National Inpatient Sample Database 2003-2014

INTRODUCTION: Despite the decreased synthesis of coagulation factors and high bleeding risk in patients with cirrhosis, they are not free of venous thromboembolism (VTE) risk. The impact of VTE in patients with cirrhosis is not well understood, even less so the impact of acute VTE during hospitalization. This study set out to establish the impact of inpatient VTE occurrence in mortality, bleeding, length and cost of hospitalization in patients with cirrhosis. METHODS: We identified individuals ≥ 18 years old from the 2003-2014 National Inpatient Sample database with a diagnosis of cirrhosis using ICD-9-CM codes. Cirrhosis, acute deep vein thrombosis of extremities and acute pulmonary embolism diagnoses were allocated if present among the top 10 admission diagnoses. Demographics and inpatient outcomes of patients with VTE were compared to those without VTE. We used SPSS 25 to calculated odds ratios (OR) with confidence intervals (CI), and trend analysis. RESULTS: A total of 1,165,369 cirrhotic patients were included (weighted cases = 5,594,565). 11,049 (0.9%) VTE cases were diagnosed. Patients with VTE were older (61.9 vs 58.4 years, P &lt; 0.0001), and less likely females (36.8% vs 39%, P &lt; 0.0001). Patients with VTE were more likely to die during the hospitalization (OR 1.6 [CI 95% 1.5-1.71, P &lt; 0.0001]), to have intracranial bleeding (OR 1.3 [CI 95% 1.03–1.64, P = 0.02]), retroperitoneal bleeding (OR 2.36 [CI 95% 1.68–3.3, P &lt; 0.0001]), had longer inpatient stay (9.6 vs 6.0 days, P &lt; 0.0001), and higher costs (72,434 vs 41,670 USD, P &lt; 0.0001). There was an increasing trend of inpatient VTE per year (0.27% 2003 vs 1.16% 2014, P &lt; 0.0001) but a decreasing trend in inpatient mortality per year in cirrhotic patients with VTE (17.6% 2003 vs 9.2% 2014, P = 0.0001). CONCLUSION: VTE occurrence is associated with increased inpatient mortality, intracranial bleed, retroperitoneal bleed, length and cost of hospitalization. More thorough VTE prophylaxis strategies may need to be implemented in patients with cirrhosis.

Venous thromboembolism prophylaxis strategies for people undergoing elective total knee replacement: a systematic review and network meta-analysis

Hospital-associated venous thromboembolism is a major patient safety concern. Provision of prophylaxis to patients admitted for elective total knee replacement surgery has been proposed as an effective strategy to reduce the incidence of venous thromboembolism. We aimed to assess the relative efficacy and safety of all available prophylaxis strategies in this setting. We did a systematic review and Bayesian network meta-analyses of randomised controlled trials to assess the relative efficacy and safety of venous thromboembolism prophylaxis strategies and to populate an economic model that assessed the cost-effectiveness of these strategies and informed the updated National Institute for Health and Care Excellence (NICE) guideline recommendations for patients undergoing elective total knee replacement surgery. The Cochrane Library (CENTRAL), Embase, and Medline were last searched on June 19, 2017, with key terms relating to the population (venous thromboembolism and total knee replacement) and the interventions compared, including available pharmacological and mechanical interventions. Outcomes of interest were deep vein thrombosis (symptomatic and asymptomatic), pulmonary embolism, and major bleeding. Risk of bias was assessed, and relevant data extracted from the included randomised controlled trials for the network meta-analyses. Relative risks (RR; with 95% credible intervals [95% CrI]) compared to no prophylaxis, median ranks (with 95% CrI), and the probability of being the best intervention were calculated. The study was done in accordance with PRISMA guidelines. 25 randomised controlled trials were included in the network meta-analyses. 23 trials (19 interventions; n=15 028) were included in the deep vein thrombosis network, 12 in the pulmonary embolism network (13 interventions; n=15 555), and 19 in the major bleeding network (11 interventions; n=19 797). Risk of bias ranged from very low to high. Rivaroxaban ranked first for prevention of deep vein thrombosis (RR 0·12 [95% CrI 0·06-0·22]). Low molecular weight heparin (LMWH; standard prophylactic dose, 28-35 days) ranked first in the pulmonary embolism network (RR 0·02 [95% CrI 0·00-3·86]) and LMWH (low prophylactic dose, 10-14 days) ranked first in the major bleeding network (odds ratio 0·08 [95% CrI 0·00-1·76]), but the results for pulmonary embolism and major bleeding are highly uncertain. Single prophylaxis strategies are more effective in prevention of deep vein thrombosis in the elective total knee replacement population than combination strategies, with rivaroxaban being the most effective. The results of the pulmonary embolism and major bleeding meta-analyses are uncertain and no clear conclusion can be made other than what is biologically plausible (eg, that no prophylaxis and mechanical prophylaxis strategies should have the lowest risk of major bleeding). National Institute for Health and Care Excellence.

Venous thromboembolism prophylaxis strategies for patients undergoing elective total knee replacement

Venous thromboembolism prophylaxis strategies for patients undergoing elective total knee replacement