Rate Of Venous Thromboembolic Events Research Articles

Venous Thromboembolic Events Following Revisional Gastric Bypass: An Analysis of the MBSAQIP Database from 2015 to 2019 Using Propensity Matching.

Primary bariatric surgery is associated with moderate-to-high risk of venous thromboembolic events (VTE); however, the risk for revisional surgery lacks granularity. Our primary objective was to define the risk of VTE following revisional Roux-en-Y gastric bypass (RYGB) compared to primary RYGB. Adults who underwent primary or revision/conversion RYGB between January 1, 2015, and December 31, 2019, with a BMI ≥ 35kg/m2 were identified in a bariatric specific database. VTE was defined as pulmonary embolus and/or deep venous thrombosis. Thirty-day VTE and transfusion rates were compared between the two groups using propensity score matching of 3:1. Primary RYGB was performed in 197,186 (92.4%) patients compared to 16,144 (7.6%) in the revisional group. Patients in the revisional group had fewer comorbidities than those undergoing primary RYGB. In the matched cohort of 64,258 procedures, there were 48,116 (74.9%) primary RYGB cases compared to 16,142 (25.1%) RYGB revisions. The rate of VTE was similar in the revisional surgery group compared to the propensity matched primary RYGB group (0.4% vs. 0.3%, p > 0.580); however, transfusion was more common in the revisional group (1.4% vs. 1.0%, p = 0.005). Revisional group had higher rates of readmission, reoperation, increased length of stay, and operation length ≥ 180min compared to matched primary RYGB group (p < 0.001). VTE rates for both primary and revisional RYGB are similar. Revisional RYGB cases impose increased risk of bleeding among other outcomes. Thus, identifying those at higher risk of complications is critical.

#1828 Venous thromboembolic events in ANCA associated vasculitis patients—data from Croatian referral center

Abstract Background and Aims Our aim was to investigate the prevalence of venous thromboembolic events (VTE) in a cohort of patients with ANCA-associated vasculitis (AAV) and define factors associated with the frequency of VTE considering there is data on high incidence of VTE in AAV patients. In these cohorts VTE occurred mostly early in the course of disease. Method This study included 114 consecutive AAV patients with biopsy proven renal involvement in the period from 2007-2017. Patients were classified according to clinical: granulomatosis with poliangitis (GPA), microscopic polingitis (MPA) and eosinophilic granulomatosis with poliangitis (EGPA) and serological phenotype: MPO-ANCA positive, PR3-ANCA positive, MPO- and PR3-ANCA positive and ANCA-negative. Ordinal variables were analysed using logistical regression test. Statistical analysis was done in MedCalc Statistical Software version 18.11.6 (MedCalc Software Bvba, Ostend, Belgium). Results In the cohort there were 64 (56%) females, mean age was 58 (IQR 16-84) with mean follow up time 46.9 months (IQR 1-127). Clinically there were 84 (73%) patients with MPA, 26 (22%) with GPA and 4 (5%) with EGPA. Serologically there were 20% PR3-ANCA, 54% MPO-ANCA, 8% MPO- and PR-3 ANCA positive patients and 18% ANCA-negative patients. Mean serum creatinine levels (SCr) was 380.9 μmol/l (IQR 65-1402). Mean BVAS (Brimingham vasculitis score) at the time of diagnosis of AAV was 17 (IQR 5-50) and at the time of VTE 0, 9 (0-22). Mean body weight was 71kg (IQR 48-110) and mean CRP was 84 mg/ml (IQR 0, 3-256). During the follow up 7 (6.14%) of the patients had VTE, with 4 having VTE in first month after the diagnosis and other two at month 14 and 19. Logistic regression showed the connection of weight (P = 0.0052) and CRP (0.0138) with VTE with odds ratio of 1,0829 for CRP (1.003-1.027) and 1.0150 for weight (1.0284-1.1736) respectively. There was no statistical significance for clinical or serological phenotype being associated with VTE nor for other clinical or laboratory parameters. Conclusion In our cohort patients with AAV were at risk of VTE, particularly within the first year following onset of disease. In this cohort the frequency of VTE did not depend of clinical or serological AAV phenotype, age or gender. Only CRP and body weight were associated significantly with VTE occurrence. Despite VTE rates in AAV patients, routine anticoagulation is not recommended in AAV patients, given the potential risk of bleeding complications. Prospective studies are needed to assess VTE risk stratification in AAV patients and to evaluate the both benefits and potential risks ratio of prophylactic anticoagulation in AAV patients.

Association of timing and agent for venous thromboembolism prophylaxis in patients with severe traumatic brain injury on venous thromboembolism events, mortality, neurosurgical intervention, and discharge disposition.

Trauma patients are at increased risk for venous thromboembolism events (VTEs). The decision of when to initiate VTE chemoprophylaxis (VTEP) and with what agent remains controversial in patients with severe traumatic brain injury (TBI). This comparative effectiveness study evaluated the impact of timing and agent for VTEP on outcomes for patients with severe TBI (Abbreviated Injury Scale head score of 3, 4, or 5). Data were collected at 35 Level 1 and 2 trauma centers from January 1, 2017, to June 1, 2022. Patients were placed into analysis cohorts: no VTEP, low-molecular-weight heparin (LMWH) ≤48 hours, LMWH >48 hours, heparin ≤48 hours, and heparin >48 hours. Propensity score matching accounting for patient factors and injury characteristics was used with logistic regression modeling to evaluate in-hospital mortality, VTEs, and discharge disposition. Neurosurgical intervention after initiation of VTEP was used to evaluate extension of intracranial hemorrhage. Of 12,879 patients, 32% had no VTEP, 36% had LMWH, and 32% had heparin. Overall mortality was 8.3% and lowest among patients receiving LMWH ≤48 hours (4.1%). Venous thromboembolism event rates were lower with use of LMWH (1.6% vs. 4.5%; odds ratio, 2.98; 95% confidence interval, 1.40-6.34; p = 0.005) without increasing mortality or neurosurgical interventions. Venous thromboembolism event rates were lower with early prophylaxis (2.0% vs. 3.5%; odds ratio, 1.76; 95% confidence interval, 1.15-2.71; p = 0.01) without increasing mortality ( p = 1.0). Early VTEP was associated with more nonfatal intracranial operations ( p < 0.001). However, patients undergoing neurosurgical intervention after VTEP initiation had no difference in rates of mortality, withdrawal of care, or unfavorable discharge disposition ( p = 0.7, p = 0.1, p = 0.5). In patients with severe TBI, LMWH usage was associated with lower VTE incidence without increasing mortality or neurosurgical interventions. Initiation of VTEP ≤48 hours decreased VTE incidence and increased nonfatal neurosurgical interventions without affecting mortality. Low-molecular-weight heparin is the preferred VTEP agent for severe TBI, and initiation ≤48 hours should be considered in relation to these risks and benefits. Therapeutic/Care Management; Level III.

Pharmacologic Anticoagulation Is Associated With a Lower Risk of Recurrent Venous Thromboembolic Events During Janus Kinase Inhibitor Use for Patients With a Prior Thrombosis.

Janus kinase (JAK) inhibitors tofacitinib and upadacitinib are effective therapies for inflammatory bowel disease and rheumatologic disorders but currently possess a warning for increased venous thromboembolism (VTE) risk. Some patients with a history of VTE may benefit from a JAK inhibitor, but the risk of recurrent VTE with JAK inhibitor use is unclear. Our goal was to observe rates of new VTE events after starting JAK inhibitor therapy in patients with a prior VTE, and observe whether concurrent anticoagulation (AC) reduces this risk. We conducted a review of adults prescribed tofacitinib or upadacitinib between January 1, 2000, and June 30, 2023, with a prior history of VTE. Patient charts were reviewed for demographic data, disease type, and VTE date(s), and to verify duration of JAK inhibitor use along with any concurrent AC. VTEs following JAK inhibitor initiation were identified by International Classification of Diseases-Tenth Revision code and verified by physician documentation and imaging. We identified 79 patients with a documented VTE history before initiating JAK inhibitors, 47 of whom began a JAK inhibitor with concurrent AC. Of these, 15 patients discontinued AC while receiving JAK inhibitors. In total, 5 new VTE events were observed during 55.42 patient-years of JAK inhibitor treatment without concurrent AC (9.0 events per 100 patient-years), while no new VTE events occurred during 65.2 patient-years of JAK inhibitor treatment with concurrent AC, demonstrating a lower risk of recurrent VTE (P = .020). These results suggest that for patients with a prior VTE history there is a high risk for recurrent VTE while receiving JAK inhibitors. Concurrent use of AC with JAK inhibitors appears to be protective against recurrent VTEs in this population.

A collaborative multidisciplinary trauma program improvement team improves VTE chemoprophylaxis guideline compliance in non-operative stable TBI.

Delays in initiating venous thromboembolism (VTE) prophylaxis in patients suffering from traumatic brain injury (TBI) persist despite guidelines recommending early initiation. We hypothesized that the expansion of a Trauma Program Performance Improvement (PI) team will improve compliance of early (24-48 hours) initiation of VTE prophylaxis and will decrease VTE events in TBI patients. We performed a single-center retrospective review of all TBI patients admitted to a Level I trauma center before (2015-2016,) and after (2019-2020,) the expansion of the Trauma Performance Improvement and Patient Safety (PIPS) team and the creation of trauma process and outcome dashboards. Exclusion criteria included discharge or death within 48 hours of admission, expanding intracranial hemorrhage on CT scan, and a neurosurgical intervention (craniotomy, pressure monitor, or drains) prior to chemoprophylaxis initiation. A total of 1,112 patients met the inclusion criteria, of which 54% (n = 604) were admitted after Trauma PIPS expansion. Following the addition of a dedicated PIPS nurse in the trauma program and creation of process dashboards, the time from stable CT to VTE prophylaxis initiation decreased (52 hours to 35 hours; p < 0.001) and more patients received chemoprophylaxis at 24 hours to 48 hours (59% from 36%, p < 0.001) after stable head CT. There was no significant difference in time from first head CT to stable CT (9 vs. 9 hours; p = 0.15). The Contemporary group had a lower rate of VTE events (1% vs. 4%; p < 0.001) with no increase in bleeding events (2% vs. 2%; p = 0.97). On multivariable analysis, being in the Early cohort was an independent predictor of VTE events (adjusted odds ratio, 3.74; 95% confidence interval, 1.45-6.16). A collaborative multidisciplinary Trauma PIPS team improves guideline compliance. Initiation of VTE chemoprophylaxis within 24 hours to 48 hours of stable head CT is safe and effective. Therapeutic/Care Management; Level IV.

Is extended venous thromboprophylaxis required in patients undergoing ileal pouch procedure for ulcerative colitis?

Venous thromboembolic events (VTEs) are relatively common adverse surgical complications. Extended VTE prophylaxis for 4 weeks is recommended after colorectal cancer surgery, but its use in inflammatory bowel disease surgery lacks high-quality evidence. This retrospective study aimed to assess and characterize VTEs within the first 30 days after ileal pouch-anal anastomosis (IPAA) procedures and subtotal colectomies (STCs) for ulcerative colitis (UC). All patients who underwent IPAA for UC between 1 January 2017 and 31 December 2021 were included. VTE rates after IPAA, in-hospital or at-home occurrences, utilization of in-hospital thromboprophylaxis, and prescribed anticoagulant treatment were evaluated. Retrospectively, the same variables were analysed if patients of the cohort underwent STC before the IPAA construction. In all, 204 patients underwent IPAA (61.8% men, 73% laparoscopic), with an average hospital stay of 6.8 days. Among them, 116 patients underwent STC prior to IPAA. Thirteen patients (6.3%) experienced VTEs after IPAA, with 76.9% (10/13) of cases occurring during hospitalization and under adequate thromboprophylaxis. The VTE rate after STC was 10.3% (12/116), with 58.2% (7/12) occurring in hospital and under appropriate thromboprophylaxis. No reoperations or mortality were attributed to thrombotic events. The type and duration of anticoagulant treatment varied considerably. The VTE rate after IPAA for UC was 6.3%, with the majority of events occurring in hospital and under adequate thromboprophylaxis. These findings suggest that routine use of extended VTE prophylaxis in our cohort may not be supported. Further research is needed to clarify the optimal VTE prophylaxis strategy for inflammatory bowel disease surgery.

Rates of Adverse Events in Patients With Ulcerative Colitis Undergoing Colectomy During Treatment With Tofacitinib vs Biologics: A Multicenter Observational Study.

Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.

P508 Pre-operative exposure to tofacitinib is as safe as biologics in patients with ulcerative colitis undergoing colectomy: a multicentre observational study

Abstract Background Patients with ulcerative colitis (UC) receiving immunomodulators are at substantial risk of colectomy. Since robust evidence regarding the post-operative outcomes of patients treated with anti-JAKs in the pre-operative phase is lacking, we aimed to assess the risk of complications of tofacitinib exposure prior to colectomy in comparison with anti-TNFs, vedolizumab, and ustekinumab. Methods A multicentre, retrospective, observational study was conducted across 27 European Centres. Patients with active UC who underwent a total colectomy for medically refractory disease were included. Patients were considered exposed to tofacitinib when they had received the last dose within 4 weeks of surgery and exposed to biologics when they had received the last dose within 12 weeks of surgery. Primary outcome was the occurrence of any complications within 30 days (early) and 90 days (late) after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications (SSC), venous thromboembolic events (VTE), hospital re-admissions and re-do surgery within the same timepoints. Results In total, 301 patients were recruited, whose baseline characteristics are reported in Table 1A. No significant differences were found in any outcome across the groups, except for a significantly higher rate of early VTE with anti-TNFs (P=0.047) and of late VTE with VDZ (P=0.03) (Table 1B). In the multivariate analysis, drug class was not associated with a significantly higher risk of any complications both at 30 and 90 days. However, urgent surgery provided a higher risk of any early complications (OR 3.04, 95%CI 1.33-6.96) and late complications (OR 4.57, 95%CI 1.31-15.91), early hospital re-admission (OR 9.90, 95%CI 2.23-43.95) and early re-do surgery (OR 6.86, 95%CI 1.40-33.47). A steroid dose higher than 20 mg of oral prednisone increased the risk of any early complications (OR 2.42, 95%CI 1.14-5.13), early SSC (OR 2.38, 95%CI 1.02-5.55), and early re-do surgery (OR 7.70, 95%CI 1.59-37.14). A higher Charlson comorbidity index increased the risk of any early complications (OR 1.40, 95%CI 1.06-1.84), early infections (OR 1.67, 95%CI 1.17-2.37), early sepsis (OR 2.67, 95%CI 1.46-4.90), and early SSC (OR 1.38, 95%CI 1.04-1.84). Conclusion Pre-operative tofacitinib treatment demonstrated a post-operative safety profile comparable to that of biologicals in patients with UC undergoing colectomy. No warning signals were found, with particular regard to VTE and infections. Due to its fast wash-out, tofacitinib could represent an appealing strategy in severe cases in which likelihood of urgent surgery is increased.

Thrombo-inflammatory response in hospitalised patients with COVID-19: a single institution experience.

Severe COVID-19 causes acute inflammation, which is complicated by venous thromboembolism events (VTE). However, it is unclear if VTE risk has evolved over time since the COVID-19 outbreak. To determine markers of thrombo-inflammation and rates of symptomatic VTE in patients hospitalised for COVID-19 in a metropolitan hospital in Sydney, Australia. A retrospective, single-centre, cohort study was performed by reviewing electronic medical records of consecutive patients admitted to Royal Prince Alfred Hospital between March 2020 and September 2021. This period included three waves of COVID-19 outbreaks in Australia with the ancestral, alpha and delta variants. Standard coagulation assays and inflammatory markers were recorded over 4 weeks. A total of 205 patients were consecutively admitted during the study period. Activated partial thromboplastin time, neutrophil count and C-reactive protein (CRP) were significantly increased in patients hospitalised in the intensive care unit (ICU) compared with non-ICU patients. The use of anti-inflammatory medication increased in 2021 compared with 2020. The mortality rate was 7.3% in our cohort. Ninety-four per cent of patients received anticoagulation with 6.3% of patients developing VTE. We observed lower rates of VTE compared to the internationally reported rate for the same period. We conclude that in the setting of controlled hospital admission rate and standard anticoagulation guidelines, COVID-19 resulted in similar thrombo-inflammatory response and VTE rates over the first 1.5 years of the pandemic.

The changing landscape of cardiac co-morbidities and in-hospital cardiac complications mediating Covid-19 mortality between 2020 and 2021

BackgroundCardiac co-morbidities and in-hospital cardiac complications significantly contribute to COVID-19 mortality. However, their influence on mortality between 2021 and 2020 may differ due to the availability of vaccines, different viral strains, and therapeutic advancements. MethodsWe performed a retrospective chart review and individual patient analysis of all COVID-19 associated in-patient deaths in 2020 (n = 346) and 2021(n = 527) in a large Minneapolis health system. Cause of death was adjudicated by at least two health care providers, including one cardiologist. ResultsPatients who died in 2021 were younger, of similar race/ethnicity, and body mass index compared to 2020. In 2021, 24 % of the cohort was full or partially vaccinated, while none were vaccinated in 2020. Patients who died in 2021 had significantly fewer cardiovascular co-morbidities and major adverse cardiovascular events prior to COVID-19 infection, resulting in significantly fewer in-hospital cardiac adverse events compared to patients who died in 2020, including myocardial infarction, stroke, and atrial fibrillation. In contrast, patients in 2021 had significantly higher rates of venous thromboembolic events. ConclusionPatients who died from COVID-19 in 2021 had significantly fewer cardiovascular co-morbidities and in-hospital cardiovascular complications compared to patients who died in 2020. Sixteen percent of patients stipulated as dying from COVID-19 actually die from other causes.

Management of Catheter-Related Upper Extremity Deep Vein Thrombosis in Patients with Cancer: A Systematic Review and Meta-Analysis

Background: Patients with cancer commonly require a central venous catheter (CVC) for delivery of cancer therapies and/or supportive care. The presence of a CVC is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. Objective: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding complications in patients with cancer and catheter-related upper extremity DVT. Methods: We searched MEDLINE, Embase, Scopus, and CENTRAL (Cochrane) from inception to June 2, 2023. We aimed to include randomized controlled trials (RCTs) (if any), prospective and retrospective cohort studies, and case-control studies (including ≥ 10 patients) evaluating adult patients with cancer and catheter-related upper extremity DVT. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding as defined by individual studies. Secondary outcomes included clinically relevant non-major bleeding, total bleeding events, and all-cause mortality. By using R software (version 4.0.3), the incidence rates (with 95% confidence interval [CI]) of recurrent VTE and bleeding outcomes at different time points were pooled using random effects model. Results: After screening 4,264 records, we included 29 studies (N=2,848 patients) in the systematic review. There were no RCTs, 5 prospective cohort studies (including 260 patients), and 24 retrospective cohort studies. Most studies had modest sample size (N&amp;lt;100). Overall from 24 studies with reported tumor types, the most common malignancy was hematological malignancy (50.4%), followed by gastrointestinal (13.6%), breast (10.2%), and lung (5.5%) cancers. The median or mean follow-up duration varied widely from 1 to 20 months. Duration of anticoagulation also varied considerably with median or mean duration of 20 days to 6 months. The main long-term anticoagulant used was low-molecular-weight heparin (58.1%), followed by direct oral anticoagulants (24.3%). Only two studies (N=87 patients) specifically reported the management and associated outcomes after catheter removal. Thirteen studies (N=1105 patients) reported a 3-month recurrent VTE rate, with the pooled rate of 1% (95% CI 0-3%, I 2 = 0%) (Figure 1). Nine studies (N=811 patients) reported a 3-month major bleeding rate, with the pooled rate of 2% (95% CI 1-5%, I 2 = 0%) (Figure 2). We were unable to pool event rates beyond 3 months given high degree of heterogeneity in the follow-up duration, bleeding definition, and duration of anticoagulation. Conclusions: Our systematic review and meta-analysis demonstrated relatively low rates of recurrent VTE and major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months, and available data are poor to guide treatment strategies and duration of anticoagulation. The optimal management after catheter removal was also unclear. Future large prospective studies are needed.

Thrombocytopenia and venous thromboembolic events after BNT162b2, CoronaVac, ChAdOx1 vaccines and SARS-CoV-2 infection: a self-controlled case series study

This study assessed the association between COVID-19 vaccines, SARS-CoV-2 infection and the risk of thrombocytopenia and venous thromboembolism (VTE). This self-controlled case series study used hospital records between 1st February 2021 and 28th February 2022 linked to the national immunisation registry and COVID-19 surveillance data in Malaysia. Conditional Poisson regression was used to estimate incidence rate ratios (IRR) of events in the risk period (day 1–21 post-exposure) relative to control period with the corresponding 95% confidence interval (CI) adjusted for calendar period. We found no significant increased risk of thrombocytopenia in 1–21 days following BNT162b2, CoronaVac and ChAdOx1 vaccines while the risk was increased following SARS-CoV-2 infection (IRR 15.52, 95% CI 13.38–18.00). Similarly, vaccination with BNT162b2, CoronaVac, or ChAdOx1 was not associated with an increased risk of VTE during the 1–21 days risk period. SARS-CoV-2 infection was associated with increased risk of VTE (IRR 39.84, 95% CI 27.45–32.44). Our findings showed low event rates of thrombocytopenia and VTE following booster vaccination with comparable safety profiles between those who received homologous and heterologous booster combinations. Our findings showed the risk of thrombocytopenia and VTE was not increased after COVID-19 vaccination while the risks were substantially higher after SARS-CoV-2 infection.

High Rates of Thrombotic Events in Newly Diagnosed Multiple Myeloma Patients Enrolled on the Maia Trial

Background. Patients with newly diagnosed multiple myeloma (NDMM) have a nine-fold increased risk of developing venous thromboembolism (VTE). Despite the availability of the IMWG and NCCN VTE prophylaxis guidelines and updated risk stratification models such as SAVED and IMPEDE, the optimal thromboprophylaxis strategy is unknown, especially in the age of modern daratumumab-containing regimens. To continue highlighting the importance of appropriate thromboprophylaxis for patients with NDMM, we performed a post-hoc analysis of the randomized phase 3 MAIA trial to identify rates of venous and arterial thromboembolism. Methods. This retrospective study, carried out under YODA Project #2021-4663, used data from the randomized phase 3 MAIA trial that investigated lenalidomide and dexamethasone (Rd) with or without daratumumab (DRd) in 733 transplant ineligible (TIE) patients obtained from the Yale University Open Data Access (YODA) Project, which has an agreement with JANSSEN RESEARCH &amp; DEVELOPMENT, L.L.C.. Thrombotic events (TE), including both venous and arterial events (V/ATE) were examined with VTE events including deep vein thrombosis (DVT), pulmonary embolism (PE), and superficial thrombophlebitis (SVT). Arterial events (ATE) included cerebrovascular accidents (CVA) defined as hemorrhagic, ischemic, or verebrobasilar strokes. The incidence and time to event of V/ATE were calculated and graded using the CTCAE v4, with Grade 1 representing nonactionable venous thrombosis, Grades 2-4 representing TEs requiring increasing higher levels of medical intervention, and Grade 5 indicating death was a result of the TE. Rates and time to events were compared between the DRd and Rd arms. Results. Of the included patients, median age was 72 years (range 64-72) and 48% were female. There was no signficant difference between baseline characteristics of sex, race, myeloma subtype, presence of high-risk cytogenetics, or ISS staging between patients that experienced a V/ATE event and those that did not. All grade V/ATE events were 18% (66/363) and 19% (70/365) in the DRd and Rd arms, respectively. Of these, most were VTE events in both arms (16%), with G2-4 actionable VTE event rate of 14.9% vs 14.8% for the DRd and Rd arms, respectively. G5 VTE events were 0.2% in both arms (no G5 ATEs). ATE were 2.2% and 2.7% in the DRd and Rd group, respectively, overall constituting a minority of events. The overall PE rate was higher in the DRd than Rd arm, 6.3% vs 4.7%, DVT was more frequent in the Rd arm, 9.6% vs 7.7%, and rates of SVT rates were similar between both arms at 1.9% and 2.2% for the DRd vs Rd arms, respectively (Table 1). Median time to onset of cumulative TEs was longer in DRd vs Rd arm, 7.15 (0.27 - 63.0) vs 4.65 (0.03 - 58.0) months, respectively. Among these, median time to onset of VTE was similar among the groups [6.57 (0.27 - 63.0) vs 4.48 (0.03 - 52.9) months, respectively] while the median time to onset of ATEs was longer in DRd vs Rd arm, 19.8 (1.70 - 26.6) vs 8.3 (0.67 - 58.5) months. The incidence of VTE events persisted past 24 months and incidence of ATE events increased over time (Figure 1). Analysis regarding prophylactic anticoagulation use and rates of TE based on prophylactic regimen are ongoing. Conclusion. This retrospective study reveals the highest reported rates of VTE in any modern therapy dataset. In patients with transplant ineligible NDMM, we show that the TE risk persists past 24 months of treatment in patients on DRd or Rd therapy. Similar to observations in the GRIFFIN trial, the addition of daratumumab did not increase the risk of TE. Our report highlights the critical need for further investigation of optimal prophylactic strategies and their duration for patients with NDMM.

MACE and VTE across upadacitinib clinical trial programmes in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

ObjectivesTo provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing...

Comparison of Venous Thromboembolism Outcomes after COVID-19 and Influenza Vaccinations.

Background Published data on the risk of venous thromboembolism (VTE) with coronavirus disease 2019 (COVID-19) vaccines are scarce and inconclusive, leading to an unmet need for further studies. Methods A retrospective, multicentered study of adult patients vaccinated for one of the three approved COVID-19 vaccines in the United States of America and a pre-COVID-19 cohort of patients vaccinated for influenza at two institutions: Mayo Clinic Enterprise sites and the Medical College of Wisconsin, looking at rate of VTE over 90 days. VTE was identified by applying validated natural language processing algorithms to relevant imaging studies. Kaplan-Meier curves were used to evaluate rate of VTE and Cox proportional hazard models for incident VTE after vaccinations. Sensitivity analyses were performed for age, sex, outpatient versus inpatient status, and type of COVID-19 vaccine. Results A total of 911,381 study subjects received COVID-19 vaccine (mean age: 56.8 [standard deviation, SD: 18.3] years, 55.3% females) and 442,612 received influenza vaccine (mean age: 56.5 [SD: 18.3] years, 58.7% females). VTE occurred within 90 days in 1,498 (0.11%) of the total 1,353,993 vaccinations: 882 (0.10%) in the COVID-19 and 616 (0.14%) in the influenza vaccination cohort. After adjusting for confounding variables, there was no difference in VTE event rate after COVID-19 vaccination compared with influenza vaccination (adjusted hazard ratio: 0.95 [95% confidence interval: 0.85-1.05]). No significant difference in VTE rates was observed between the two cohorts on sensitivity analyses. Conclusion In this large cohort of COVID-19-vaccinated patients, risk of VTE at 90 days was low and no different than a pre-COVID-19 cohort of influenza-vaccinated patients.

Venous Thromboembolism Chemoprophylaxis Adherence Rates After Major Cancer Surgery

Venous thromboembolism (VTE) represents a major source of preventable morbidity and mortality and is a leading cause of death in the US after cancer surgery. Previous research demonstrated variability in VTE chemoprophylaxis prescribing, although it is unknown how these rates compare with performance in the Veterans Health Administration (VHA). To determine VTE rates after cancer surgery, as well as rates of inpatient and outpatient (posthospital discharge) chemoprophylaxis adherence within the VHA. This retrospective cohort study within 101 hospitals of the VHA health system included patients aged 41 years or older without preexisting bleeding disorders or anticoagulation usage who underwent surgical treatment for cancer with general surgery, thoracic surgery, or urology between January 1, 2015, and December 31, 2022. The VHA Corporate Data Warehouse, Pharmacy Benefits Management database, and the Veterans Affairs Surgical Quality Improvement Program database were used to identify eligible patients. Data analysis was conducted between January 2022 and July 2023. Inpatient surgery for cancer with general surgery, thoracic surgery, or urology. Rates of postoperative VTE events within 30 days of surgery and VTE chemoprophylaxis adherence were determined. Multivariable Poisson regression was used to determine incidence-rate ratios of inpatient and postdischarge chemoprophylaxis adherence by surgical specialty. Overall, 30 039 veterans (median [IQR] age, 67 [62-71] years; 29 386 men [97.8%]; 7771 African American or Black patients [25.9%]) who underwent surgery for cancer and were at highest risk for VTE were included. The overall postoperative VTE rate was 1.3% (385 patients) with 199 patients (0.7%) receiving a diagnosis during inpatient hospitalization and 186 patients (0.6%) receiving a diagnosis postdischarge. Inpatient chemoprophylaxis was ordered for 24 139 patients (80.4%). Inpatient chemoprophylaxis ordering rates were highest for patients who underwent procedures with general surgery (10 102 of 10 301 patients [98.1%]) and lowest for patients who underwent procedures with urology (11 471 of 17 089 patients [67.1%]). Overall, 3142 patients (10.5%) received postdischarge chemoprophylaxis, with notable variation by specialty. These findings indicate the overall VTE rate after cancer surgery within the VHA is low, VHA inpatient chemoprophylaxis rates are high, and postdischarge VTE chemoprophylaxis prescribing is similar to that of non-VHA health systems. Specialty and procedure variation exists for chemoprophylaxis and may be justified given the low risks of overall and postdischarge VTE.

Comparison of Standard Versus Intermediate Prophylaxis Dose for Venous Thromboembolism Prophylaxis in Patients Hospitalized With COVID-19 Infection.

Background: COVID-19 infection is associated with a high risk of venous thromboembolism (VTE) events. VTE prophylaxis reduces the risk of these events. The optimal dose of VTE prophylaxis however remains uncertain. Objectives: To compare the incidence of VTE in patients treated with either standard dose VTE versus intermediate dose VTE prophylaxis. Methods: In this retrospective cohort study, we analyzed data from 1786 adult patients admitted into the hospital with polymerase chain reaction confirmed COVID-19 infection between April 2020 to September 2021. For analysis, patients were divided into 2 cohorts: either standard dose prophylaxis treatment group (patients who received either unfractionated heparin 5000units 3 times a day or enoxaparin 30-40 mg daily subcutaneously) or intermediate dose VTE prophylaxis group (patients received either unfractionated heparin 7500 units 3 times daily or enoxaparin 30-40 mg twice a day subcutaneously). The primary outcome was incidence of VTE events described as either deep vein thrombosis (DVT) or pulmonary embolism (PE). Secondary outcome was bleeding events. Results: During the study period, 398 (22%) patients were primarily treated with standard dose VTE prophylaxis, whereas 1388 (78%) patients were treated with intermediate dose VTE prophylaxis. There was a significantly higher incidence of venous thromboembolism events noted in the standard dose prophylaxis treatment group when compared with the intermediate dose prophylaxis group (25/398 (6.3%) vs 35/1388 (2.5%) P < .001, [Odds Ratio 2.6197, 95% confidence interval = 1.5482-4.4327]). Multivariable-adjusted logistic regression, adjusting for age, obesity, and smoking, with the intermediate dose prophylaxis treatment group as the referent category revealed higher odds for incident venous thromboembolism events in the standard dose prophylaxis group. There was no statistically significant difference in bleeding events between the 2 treatment groups (9 (2.3%) for standard dose prophylaxis group vs 46 (3.3%) for intermediate dose prophylaxis group P = .26). Conclusions: Among patients hospitalized with COVID-19 infection, patients receiving intermediate dose VTE prophylaxis experienced lower incident rates of venous thromboembolism events compared to those receiving standard dose VTE prophylaxis without a statistically significant increase in the risk of bleeding events.

Revisiting Anticoagulation in Spine Surgery: Balancing Venous Thromboembolic Events and Epidural Hematoma.

Retrospective Cohort Study. Venous thromboembolic events (VTE) and post-operative epidural hematoma (EDH) are significant complications after spine surgery. Guidelines for chemoprophylaxis are controversial and variability amongst surgeons remains. The objective of this study was to establish the incidence of clinical VTE and EDH at our institution and evaluate the association of chemoprophylaxis with clinical VTE and EDH. We conducted a retrospective cohort study of patients undergoing spine surgery at a high-volume tertiary care center in Seattle, WA between January 2016 and December 2019. The Premier Health Care Database and Agency for Healthcare Research and Quality (AHRQ) patient indicators PSI-9 (Perioperative hemorrhage and hematoma) and PSI-12(Perioperative PE or DVT) were used to identify patients experiencing VTE and/or post-operative EDH. The primary outcome was the incidence of clinical VTE and EDH in post-operative spine patients. Secondary outcomes included the association of chemoprophylaxis with clinical VTE and EDH. From 2016 to 2019, 4587 patients underwent spine surgery, totaling 4764 hospital stays. The incidence of clinical VTE was .21% (10/4764) and the incidence of EDH was .10% (5/4764). Most hemorrhages occurred prior to the initiation of chemoprophylaxis. One patient with EDH received chemoprophylaxis prior to hemorrhage. The rate of post-operative clinical VTE and EDH in spine surgery is low. Despite early initiation of chemoprophylaxis after major spine surgery we did not appreciate a high rate of EDH. We attribute our low rate of clinical VTE to multimodal prophylaxis with SCDs, early mobilization and chemoprophylaxis on post-operative day 1.

Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial

PurposeThis study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage.MethodsTOP-ART, a randomized, blinded, placebo-controlled, phase IIa trial, was conducted at a London major trauma center in adult trauma patients who activated the major hemorrhage protocol. Participants received artesunate or placebo (2:1 randomization ratio) as an intravenous bolus dose (2.4 mg/kg or 4.8 mg/kg) within 4 h of injury. The safety outcome was the 28-day serious adverse event (SAE) rate. The primary efficacy outcome was the 48 h sequential organ failure assessment (SOFA) score. The per-protocol recruitment target was 105 patients.ResultsThe trial was terminated after enrolment of 90 patients because of safety concerns. Eighty-three participants received artesunate (n = 54) or placebo (n = 29) and formed the safety population and 75 met per-protocol criteria (48 artesunate, 27 placebo). Admission characteristics were similar between groups (overall 88% male, median age 29 years, median injury severity score 22), except participants who received artesunate were more shocked (median base deficit 9 vs. 4.7, p = 0.042). SAEs occurred in 17 artesunate participants (31%) vs. 5 who received placebo (17%). Venous thromboembolic events (VTE) occurred in 9 artesunate participants (17%) vs. 1 who received placebo (3%). Superiority of artesunate was not supported by the 48 h SOFA score (median 5.5 artesunate vs. 4 placebo, p = 0.303) or any of the trial’s secondary endpoints.ConclusionAmong critically ill trauma patients, artesunate is unlikely to improve organ dysfunction and might be associated with a higher VTE rate.

Comparison of the Efficacy and Safety of Rivaroxaban and Low Molecular Heparin in Preventing Venous Thromboembolism in Inpatient Cancer Patients.

There are few studies on using rivaroxaban and low molecular heparin (LMWH) to prevent venous thromboembolism (VTE) in hospitalized cancer patients. We conducted a retrospective study to evaluate the efficacy and safety of rivaroxaban versus LMWH for the primary prevention of VTE in inpatient cancer patients. Information on patients was collected through 6-month follow-up and medical record inquiries. Clinical outcomes included VTE, total bleeding, thrombosis, major bleeding, minor bleeding, all-cause death, and a composite endpoint of bleeding, thrombosis, and death. A total of 602 hospitalized cancer patients were included in this study. During 6 months of follow-up, there were 26 VTE events (8.6%), 42 total bleeding events (7.0%), 62 all-cause deaths (10.3%), and 140 composite endpoints (23.3%). After adjusting for various confounding factors, there were no significant differences between the rivaroxaban and LMWH for VTE events (OR = 0.851, 95% CI [0.387-1.872], P=0.688), total bleeding (OR = 1.690, 95% CI [0.768-3.719], P = 0.192], thrombosis events (OR = 0.919, 95% CI [0.520-1.624], P = 0.772], major bleeding (OR = 0.276, 95% CI [0.037-2.059], P = 0.209), all-cause death (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), and composite endpoints (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), while minor bleeding (OR = 3.661 95% CI [1.000-7.083], P = 0.050) was significantly higher in the rivaroxaban than in the LMWH. In thromboprophylaxis in inpatient cancer patients, rivaroxaban has a similar rate of VTE and bleeding events as LMWH. Our results may provide a reference for the clinical use of rivaroxaban to prevent VTE in hospitalized cancer patients.