Incidence Of Venous Thromboembolic Events Research Articles

Prevalence and clinical burden of venous thromboembolic events (VTEs) in contemporary total knee arthroplasties (TKAs) in US hospitals

IntroductionTotal knee arthroplasty (TKA) is a highly demanded procedure in orthopedic surgery, with over 1.3 million joint arthroplasties performed annually in the U.S. The increasing need for TKAs is driven by an aging population, rising obesity rates, and advances in surgical techniques. Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), significantly impacts TKA patients' mortality and morbidity. Despite advances in prophylaxis and Enhanced Recovery After Surgery (ERAS) protocols reducing VTE incidence, survival rates have not markedly improved. This study aims to identify preoperative predictors of PE and DVT in TKA patients and examine their impact on hospital stays and mortality. MethodsA retrospective observational study was conducted using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, focusing on 367,365 TKA patients from 2016 to 2021. Preoperative variables, including demographic factors, comorbidities, and functional status, were analyzed. Primary endpoints were PE and DVT predictors; secondary endpoints included 30-day mortality and prolonged hospital stay. Univariate and logistic regression analyses were performed using SPSS version 26. ResultsUnivariate analysis revealed significant associations of male gender, older age, Hispanic ethnicity, smoking, dyspnea, CHF, and COPD with DVT and PE. Multivariate analysis confirmed female sex, younger age, Hispanic ethnicity, and COPD as independent DVT predictors, and independent functional status, smoking, COPD, CHF, and metastatic malignancy as PE predictors. VTE prevalence was 1.09 % (0.67 % DVT, 0.42 % PE), with PE associated with higher mortality (0.78 %) and prolonged hospital stays. ConclusionDemographic and clinical variables significantly influence VTE risk post-TKA. Tailored interventions and comprehensive preoperative assessments are crucial for optimizing patient outcomes and reducing thrombotic risks.

Venous thromboembolism incidence and association with overall survival in pancreatic cancer: A Finnish nationwide cohort study.

Pancreatic cancer (PC) is associated with a high risk of venous thromboembolic events (VTEs). We investigated the incidence of VTE before and after the diagnosis of PC and its association with overall survival. We identified PC patients diagnosed in 2013-2016 from the Finnish Cancer Registry. Data on healthcare visits and death were collected, along with follow-up data through the end of 2020. We compared patients who underwent radical-intent surgery (RIS) to those who underwent palliative treatment (PT) alone. We identified 4086 PC patients, of whom 343 (8.4%) underwent RIS and 3743 (91.6%) received PT. VTE incidence within 1 year before a PC diagnosis was higher in the PT (4.2%, n = 156) than in the RIS group (0.6%, n = 2; p < 0.001). The cumulative incidence of VTE at 12 and 24 months after a PC diagnosis was 6% (n = 21) and 9% (n = 31), respectively, within the RIS group, and 8% (n = 286) and 8% (n = 304) within the PT group. In the PT group, a VTE within 1 year before a PC diagnosis was independently associated with a worse survival {hazard ratio, HR 1.9 [95% confidence interval (CI) 1.6-2.2]}. In both groups, VTE after a PC diagnosis was associated with a worse survival [RIS group: HR 2.6 (95%CI 1.8-3.7) vs. PT group: HR 2.2 (95%CI 1.9-2.4)]. A VTE within 1 year before a PC diagnosis more often occurred among PT PC patients than among patients who underwent RIS. VTE might serve as a diagnostic clue to detect PC at an earlier stage.

Subcutaneous amivantamab and lazertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Results from the phase 2 PALOMA-2 study.

LBA8612 Background: Amivantamab (ami), an EGFR-MET bispecific antibody with immune cell-directing activity, is approved as an intravenous (IV) formulation. IV ami + lazertinib (laz), a 3rd-generation EGFR TKI, demonstrated superior progression-free survival (PFS) in patients (pts) with treatment-naïve, advanced EGFR-mutated NSCLC vs osimertinib (Cho Ann Oncol 2023). Subcutaneous (SC) ami substantially reduced infusion-related reactions (16% vs 67%) and administration time (≤7 mins vs 2–4 hours) vs historical IV experience (Minchom JCO 2023). PALOMA-2 (NCT05498428) evaluated the efficacy, safety, and pharmacokinetics (PK) of first-line SC ami+laz. Methods: Cohorts 1 and 6 enrolled pts with treatment-naïve, EGFR Ex19del or L858R-mutated advanced NSCLC. Prophylactic anticoagulation for the first 4 months (mo) of treatment was recommended in cohort 1 and mandatory in cohort 6. SC ami was administered by manual injection in the abdomen at 1600 mg (≥80 kg: 2240 mg) weekly for the first 4 weeks and every 2 weeks thereafter. Laz was dosed orally at 240 mg daily. The primary endpoint was objective response rate (ORR) as assessed by the investigator per RECIST v1.1. Results: As of 6 Jan 2024, 68 and 58 pts were enrolled in cohorts 1 and 6, respectively. Overall, median age was 59 years, 60% were female, and 68% Asian. The median follow-up was 10 mo for cohort 1 and 6 mo for cohort 6. ORR (confirmed responses) in cohort 1 was 68% (95% CI, 55–79) by investigator and 72% (95% CI, 60–82) by independent central review. ORR in cohort 6 was 64% (95% CI, 49–78) and 73% (95% CI, 58–85), respectively. At data cutoff, 40/46 responders in cohort 1 and 29/29 responders in cohort 6 were receiving ongoing treatment. Best overall response rates (includes unconfirmed responses) were 81% (95% CI, 70–89) for cohort 1 and 76% (95% CI, 61–87) for cohort 6. Median time to response was 2 mo (range, 1.4–5.3). Median duration of response, PFS, and overall survival were not estimable. Administration-related reactions (ARRs) were reported in 13 (19%) pts in cohort 1 and 6 (11%) pts in cohort 6, all grade 1–2. EGFR- and MET-related AEs were primarily grade 1–2. Total of 71% of pts in cohort 1 and 100% in cohort 6 received prophylactic anticoagulation. Venous thromboembolic events (VTE) were reported in 18% and 7% of pts in cohorts 1 and 6, respectively. There were no dose reductions or discontinuations due to VTE. Rate of bleeding was 2% among pts receiving anticoagulation. Mean ami concentrations on cycle 2 day 1 were 328 µg/mL (n=49) in cohort 1 and 371 µg/mL (n=41) in cohort 6, consistent with historic IV levels. Conclusions: SC ami+laz showed a response rate similar to historic IV ami+laz in first-line EGFR-mutated NSCLC, with an improved safety profile that included significantly lower ARR rates. Further, prophylactic anticoagulation can be safely implemented and reduced incidence of VTE. Clinical trial information: NCT05498428 .

Incidence of Venous Thromboembolism after Primary Total Hip Arthroplasty with Mechanical Prophylaxis in Hong Kong Chinese.

The incidence of deep vein thrombosis (DVT) following total hip arthroplasty (THA) without chemoprophylaxis could be as high as 50% in Caucasians. However, according to several subsequent studies, the incidence of venous thromboembolic events (VTE) in Asians was much lower. The routine use of chemoprophylaxis, which could potentially cause increased bleeding, infection, and wound complications, has been questioned in low-incidence populations. The objective of this study is to determine the incidence of VTE after primary THA without chemoprophylaxis in an Asian population using a fast-track rehabilitation protocol and to verify the safety profile for use of 'mechanical prophylaxis alone' in patients with standard risk of VTE. This is a retrospective cohort study of 542 Hong Kong Chinese patients who underwent primary THA without chemoprophylaxis. All patients received intermittent pneumatic compression and graduated compression stockings as mechanical prophylaxis. Multimodal pain management was applied in order to facilitate early mobilisation. Routine duplex ultrasonography was performed between the fourth and seventh postoperative day for detection of proximal DVT. All patients were Chinese (mean age, 63.0±11.9 years). Six patients developed proximal DVT (incidence rate, 1.1%). None of the patients had symptomatic or fatal pulmonary embolism. The incidence of VTE after primary THA without chemical prophylaxis can be low in Asian populations when following a fast-track rehabilitation protocol. Mechanical prophylaxis alone can be regarded as a reasonably safe practice in terms of a balanced benefit-to-risk ratio for Asian patients with standard risk of VTE.

#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.

Cumulative Incidence of Venous Thromboembolic Events In-Hospital, and at 1, 3, 6, and 12 Months After Metabolic and Bariatric Surgery: Systematic Review of 87 Studies and Meta-analysis of 2,731,797 Patients.

Systematic review/meta-analysis of cumulative incidences of venous thromboembolic events (VTE) after metabolic and bariatric surgery (MBS). Electronic databases were searched for original studies. Proportional meta-analysis assessed cumulative VTE incidences. (PROSPERO ID:CRD42020184529).A total of 3066 records, and 87 studies were included (N patients = 4,991,683). Pooled in-hospital VTE of mainly laparoscopic studies = 0.15% (95% CI = 0.13-0.18%); pooled cumulative incidence increased to 0.50% (95% CI = 0.33-0.70%); 0.51% (95% CI = 0.38-0.65%); 0.72% (95% CI = 0.13-1.52%); 0.78% (95% CI = 0-3.49%) at 30 days and 3, 6, and 12 months, respectively. Studies using predominantly open approach exhibited higher incidence than laparoscopic studies. Within the first month, 60% of VTE occurred after discharge. North American and earlier studies had higher incidence than non-North American and more recent studies. This study is the first to generate detailed estimates of the incidence and patterns of VTE after MBS over time. The incidence of VTE after MBS is low. Improved estimates and time variations of VTE require longer-term designs, non-aggregated reporting of characteristics, and must consider many factors and the use of data registries. Extended surveillance of VTE after MBS is required.

Real-world comparative effectiveness of dalteparin and enoxaparin for venous thromboembolism prophylaxis.

Venous thromboembolism (VTE) is a preventable cause of significant morbidity and mortality in hospitalized patients world-wide. In Australia, the low-molecular weight heparins (LMWHs) enoxaparin or dalteparin are usually used as first-line prophylaxis for VTE, though there is uncertainty whether dalteparin has the same effectiveness as enoxaparin in real-world settings. This is relevant because dalteparin is less renally cleared and may be more cost effective than enoxaparin. The aim of this study was to explore VTE event incidence in a general cohort of hospitalized adult inpatients who were prescribed enoxaparin or dalteparin for VTE prophylaxis. A retrospective observational study was conducted at a quaternary hospital in Brisbane, Australia, of patients who had experienced a hospital-acquired VTE from 1 September 2021 to 1 March 2023. Patients were identified from routinely collected data following an in-hospital VTE event, and further data was retrieved retrospectively from the integrated electronic Medical Record (ieMR). Incidence and type of VTE events, LMWH-prescribing patterns, and risk factors were assessed. The incidence of VTE events were similar across the dalteparin and enoxaparin cohorts (42.1 events/10 000 patients vs. 34.4 events/10 000 patients, respectively), although patients prescribed enoxaparin had a higher number of risk factors, particularly obesity and active cancer. Our research indicates comparable incidence of VTE in patients prescribed dalteparin compared with enoxaparin in an Australian hospital general cohort of adult inpatients. Dalteparin may be as effective as enoxaparin for VTE prophylaxis in a real-world cohort of patients, and as such dalteparin may be considered a suitable alternative to enoxaparin for VTE prophylaxis. Further research including large randomized controlled trials are required to confirm these results.

534 - Incidence of venous thromboembolic events and atherosclerotic cardiovascular disease risk factors in adolescents and adults with atopic dermatitis in Denmark: a population-based cohort study

Abstract Background Atopic dermatitis (AD) is associated with substantial impairment in quality of life, including sleep disturbances, anxiety, and depression, which may increase the risk of cardiovascular disease (CVD). However, the association between CVD and AD is not well established. Objectives To evaluate incidence rates (IRs) of venous thromboembolism (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE) in patients with and without AD in a population-based cohort study in Denmark, and to assess IRs of malignancies, major adverse cardiovascular events (MACE), VTE, and the distribution of Atherosclerotic Cardiovascular Disease (ASCVD) risk factors in patients with AD and rheumatoid arthritis (RA) in a nested cohort analysis. Methods Data from all individuals aged ≥12 years (≥18 years in the nested cohort analysis) between January 1, 2000, and December 31, 2018, were extracted from the Danish National Patient Registry. Patients with ≥1 AD diagnosis during the study period were matched on sex and age with 10 individuals from the general population. The nested cohort analysis included patients diagnosed with RA as an additional comparison population. In the overall cohort, IRs of VTE, DVT, and PE were assessed; the nested cohort analysis evaluated the distribution of ASCVD risk factors and incidence of malignancies, MACE, and VTE in patients with and without ASCVD risk factors (age ≥65 years, and history of smoking, coronary artery disease, stroke, DVT, PE, and malignancy). The follow-up period was from the first diagnosis during the study period until the occurrence of death or an endpoint, the first instance of migration, or December 31, 2018. IRs are shown per 100 patient-years (PY) of exposure with 95% confidence intervals. Results The population-based cohort comprised 190,751 patients, including 17,341 patients with AD and 173,410 age- and sex-matched controls. The IR/100 PY of VTE was similar between the AD cohort (0.14 [95% CI, 0.12-0.16]) and the general population (0.11 [0.11-0.12]). The IR/100 PY for VTE was higher in patients with AD aged ≥65 years (0.71 [0.56-0.90]) than the age-matched general population (0.50 [0.46-0.54]) and lower in the younger AD cohorts (12 to &amp;lt;18 years, 0.02 [0.00-0.08]; 18 to &amp;lt;65 years, 0.12 [0.09-0.13]). The IRs/100 PY of DVT and PE were comparable between the AD cohort (DVT, 0.08 [0.06-0.09]; PE, 0.06 [0.05-0.08]) and the general population (DVT, 0.06 [0.06-0.07]; PE, 0.05 [0.05-0.05]).. The nested cohort analysis comprised 195,807 patients, including 13,432 with AD, 48,055 with RA, and 134,320 age- and sex-matched controls. Distribution of risk factors for malignancies (excluding nonmelanoma skin cancer [NMSC]), MACE, and VTE was comparable in the AD cohort and general population, but higher in patients with RA. The IR/100 PY for malignancies (excluding NMSC) was higher in patients with AD with a history of malignancy (11.41 [9.83-13.25]) than those without (0.44 [0.40-0.48]), and in those aged ≥65 years (3.09 [2.75-3.48]) versus &amp;lt;65 years (0.36 [0.33-0.40]). Similarly, the IR/100 PY for MACE was higher in patients with AD aged ≥65 years (2.30 [2.01-2.63]) versus &amp;lt;65 years (0.15 [0.13-0.17]), and patients with a history of ASCVD (5.02 [4.37-5.76]) versus without (0.15 [0.13-0.18]). Patients with AD with a history of VTE (including DVT/PE) and inherited thrombophilia had a greater risk of VTE than patients without these risk factors. Conclusions In these 2 large cohort studies of adults and adolescents with AD, IRs of VTE, DVT, and PE were comparable with the general Danish population. The risk of VTE, malignancy, and MACE was higher in patients with AD with a history of risk factors for ASCVD. This underscores the need for appropriate monitoring and reporting of cardiovascular events in patients with AD, and active management of risk factors with early and effective therapeutic intervention.

Risk of Venous Thromboembolic Events After Surgery for Cancer

The risks and benefits of thromboprophylaxis therapy after cancer surgery are debated. Studies that determine thrombosis risk after cancer surgery with high accuracy are needed. To evaluate 1-year risk of venous thromboembolic events after major cancer surgery and how these events vary over time. This register-based retrospective observational matched cohort study included data on the full population of Sweden between 1998 and 2016. All patients who underwent major surgery for cancer of the bladder, breast, colon or rectum, gynecologic organs, kidney and upper urothelial tract, lung, prostate, or gastroesophageal tract were matched in a 1:10 ratio with cancer-free members of the general population on year of birth, sex, and county of residence. Data were analyzed from February 13 to December 5, 2023. Major surgery for cancer. The main outcome was incidence of venous thromboembolic events within 1 year after the surgery. Crude absolute risks and risk differences of events within 1 year and adjusted time-dependent cause-specific hazard ratios (HRs) of postdischarge events were calculated. A total of 432 218 patients with cancer (median age, 67 years [IQR, 58-75 years]; 68.7% women) and 4 009 343 cancer-free comparators (median age, 66 years [IQR, 57-74 years]; 69.3% women) were included in the study. The crude 1-year cumulative risk of pulmonary embolism was higher among the cancer surgery population for all cancers, with the following absolute risk differences: for bladder cancer, 2.69 percentage points (95% CI, 2.33-3.05 percentage points); for breast cancer, 0.59 percentage points (95% CI 0.55-0.63 percentage points); for colorectal cancer, 1.57 percentage points (95% CI, 1.50-1.65 percentage points); for gynecologic organ cancer, 1.32 percentage points (95% CI, 1.22-1.41 percentage points); for kidney and upper urinary tract cancer, 1.38 percentage points (95% CI, 1.21-1.55 percentage points); for lung cancer, 2.61 percentage points (95% CI, 2.34-2.89 percentage points); for gastroesophageal cancer, 2.13 percentage points (95% CI, 1.89-2.38 percentage points); and for prostate cancer, 0.57 percentage points (95% CI, 0.49-0.66 percentage points). The cause-specific HR of pulmonary embolism comparing patients who underwent cancer surgery with matched comparators peaked just after discharge and generally plateaued 60 to 90 days later. At 30 days after surgery, the HR was 10 to 30 times higher than in the comparison cohort for all cancers except breast cancer (colorectal cancer: HR, 9.18 [95% CI, 8.03-10.50]; lung cancer: HR, 25.66 [95% CI, 17.41-37.84]; breast cancer: HR, 5.18 [95% CI, 4.45-6.05]). The hazards subsided but never reached the level of the comparison cohort except for prostate cancer. Similar results were observed for deep vein thrombosis. This cohort study found an increased rate of venous thromboembolism associated with cancer surgery. The risk persisted for about 2 to 4 months postoperatively but varied between cancer types. The increased rate is likely explained by the underlying cancer disease and adjuvant treatments. The results highlight the need for individualized venous thromboembolism risk evaluation and prophylaxis regimens for patients undergoing different surgery for different cancers.

P616 Prescribing practices of tofacitinib and preferences amongst high-risk patients in the UK

Abstract Background Tofacitinib was licensed for use in patients with ulcerative colitis in August 2018. Because it is administered orally, has a rapid onset of action and is relatively inexpensive, it was quickly adopted in real-world practice. Safety warnings linking high-dose tofacitinib use to venous thromboembolic events (VTE) and death followed. Further warnings were issued linking its use to an increased risk of malignancy and adverse cardiovascular events in patients: over 65 years, with a history of diabetes, current or past smokers, and those with a history of coronary vascular disease. The most recent Medicines and Healthcare products Regulatory Agency (MHRA) statement advised against the use of all commercially available JAKi in this high-risk cohort unless a suitable alternative is unavailable (MHRA 2023). We sought to define the number of patients who had, or were, being treated with tofacitinib who were in this high-risk group and the proportion who opted to switch therapy once we had outlined their risk-status and the MHRA advice to them. Methods We conducted a retrospective observational cohort study of 131 patients with UC and IBD-U (61% male [80/131]; median age 43 years [range 16-85]; 46% [60/131] patients had previously had at least one biologic agent) treated with tofacitinib from October 2018 to December 2022 in our centre with at least 3 months follow-up. Patients were categorised as high-risk according to the MHRA statement if they had at least one of the criteria above. Results Overall, about one-third, 31.3% [41/131] patients that we had treated with tofacitinib were classified in the MHRA high-risk group. Rates of treatment discontinuation were similar in the high-risk versus no risk group. In the high-risk group ten patients (24.4% [10/41]) had discontinued treatment due to lack of response (4) or an adverse event (6). The most common adverse events were herpes zoster infections (14.6%), malignancy (3.3%) and infections requiring hospitalisation (3.3%). Two patients died while on treatment (one due to complications following cervical spinal surgery and the other due to ischaemic heart disease). There were no incidences of VTE. We clinically reviewed 29 high risk patients who were being treated with tofacitinib after a median of 2.4 years (range 0.6-4.56) of treatment. 25/29 high-risk patients decided on continuing their treatment in spite of the health care warnings and alternative therapies being available. Conclusion About one-third of our tofacitinib-treated patients were classified as at high-risk. The majority of high-risk patients opted to continue therapy even though alternative therapies were available.

The Application of Existing Risk Assessment Models (RAMS) to Predict the Occurrence of Venous Thromboembolic Events among Patients with Classic Hodgkin Lymphoma.

Background: A majority of patients included in risk assessment models (RAMs) developed to predict venous thromboembolic events (VTE) in lymphoma were non-Hodgkin lymphoma. Our study aims to evaluate the incidence and predictors of VTE, utilizing different RAMs, in patients with classic Hodgkin lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). Methods: Adult patients with cHL, treated and followed at our center, were included. Correlations between different variables, Khorana score, and thrombosis in lymphoma (ThroLy) RAMs with VTE were examined using Fisher's exact test and logistic regression analysis. Results: A total of 321 patients were included, with a median age of 29 (range: 18-83) years. Of them, 169 (52.6%) had advanced-stage disease. Combined modality treatment was given to 169 (52.6%) patients. A total of 52 (16.2%) patients had relapsed or refractory disease. VTE were reported in 15 (4.7%) patients and were mostly during the administration of first-line (n = 8, 53.3%), or salvage chemotherapy (n = 6, 40.0%). There was no correlation between a Khorana score > 2 (p = 0.689) or ThroLy score > 3 (p = 0.335) and VTE. Older age (p = 0.014) and relapsed or refractory disease (p = 0.003) significantly correlated with VTE. Conclusions: VTE are uncommon in cHL. The commonly used RAMs failed to predict VTE. However, older age and relapsed or refractory disease significantly increased this risk.

Management of Neurologic Complications in Patients with Brain and Spine Tumors.

Patients with brain and spine tumors represent a distinct population with unique needs. We provide a practical review of neurologic care in this group with an emphasis on familiarizing the general neurologist to the nuances of neuro-oncologic supportive care. We review the management of cerebral edema, steroid dosing, and pertinent side effects. We discuss seizure management, including choice of anticonvulsants, putative antitumor effects, and important seizure mimics like drop attacks. We review the presentation and symptomatology of stroke-like migraine attack after radiation therapy (SMART syndrome). We describe the signs and symptoms that should prompt concern for metastatic spinal cord compression, as well as both acute and definitive treatment options. Finally, we discuss the underappreciated incidence of venous thromboembolic events, particularly in patients with gliomas, and review the data on management.

Prevalence of chronic venous insufficiency and deep vein thrombosis in cirrhotic patients.

People with cirrhosis of the liver are at risk for complications that can worsen their quality of life and increase morbidity and mortality. Contrary to previous beliefs, cirrhosis does not protect against the development of thromboembolic events, and cirrhotic patients may have higher rates of deep vein thrombosis (DVT). The study of chronic venous disease and its impact on patients with cirrhosis is unknown in the literature and may be an important fact since this condition also had impact on quality of life and morbidity. The aim of this study is to evaluate the prevalence of DVT (Deep Venous thrombosis) in outpatients with cirrhosis and the degree of chronic venous insufficiency, evaluating possible correlations between clinical and laboratory aspects of cirrhotic patients with these pathologies. Patients with cirrhosis were evaluated in the outpatient clinic of the Liver Transplantation and Hepatology Service of HC-FMUSP from November 2018 to November 2022, with clinical evaluation, venous disease questionnaires, data collection of imaging and laboratory tests, and venous color Doppler ultrasound. The information was analyzed by the University of São Paulo (USP) Statistics Department. There was a prevalence of 7.6% of DVT in studied patients, VCSS score 6.73 and severe CEAP classification (C4-6) 32.1%. There was no association of DVT with qualitative variables by the Fisher test such as Child Turcotte Pugh Scale (CTP) (p = 0.890), dichotomized INR values (p = 0.804), etiology of cirrhosis (p = 0.650) and chronic kidney disease (p > 0.999), nor with quantitative variables by t-student's such as age (p = 0.974), Body Mass Index (BMI) (p = 0.997), MELD score (p = 0.555), Albumin (p = 0.150) and Platelets (p = 0.403). We found that as the severity of ascites increases, there is an increase in the proportion of patients classified in the category indicating more severe clinical manifestations of chronic venous disease (C4 to C6). The mean age (54 years) was higher in patients with DVT than in those without. The mean BMI of patients without DVT (25.7 kg/m2) is lower than that of patients with DVT (27.0 kg/m2). The prevalence of DVT is higher in patients with thrombophilia (20.0%) than in those without (7.0%). This suggests an association between the two variables. The descriptive measures of the MELD score, the cirrhosis scale used for liver transplant waiting lists, did not indicate an association of this scale with the occurrence of DVT. The incidence of VTE (Venous Thromboembolic Events) and CVD (Chronic Venous Disease) within the sample surpassed that of the general population; nevertheless, more studies are required to validate these results. Concerning venous thromboembolism, no correlation was observed between the variables within the sample and the augmented risk of VTE. Regarding chronic venous disease, studies have shown that edema and orthostatism are correlated with increased severity of CVD on the VCSS scales. Statistical dispersion methods suggest that patients with higher BMI and more severe liver disease (according to the Child-Pugh score) are more likely to experience worsening of CVD. About chronic venous disease, studies have shown that edema and orthostatism are correlated with increased severity of CVD on the VCSS scales.

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.

Clinical outcome of open ankle fractures in patients above 70 years of age.

Open fractures of the ankle are complex injuries requiring multidisciplinary input and are associated with significant morbidity and mortality. However, data on the clinical outcomes of open ankle fracture management in patients older than 70 is minimal. To evaluate the clinical outcomes following open ankle fracture management in patients older than 70. Our secondary aim is to look at predictors of poor outcomes. Following local research and audit department registration, 22 years of prospectively collated data from an electronic database in a district general hospital were assessed. All patients older than 70 years of age with an open ankle fracture requiring surgical intervention were identified. Demographic information, the nature, and the number of surgical interventions were collated. Complications, including surgical site infection (SSI), venous thromboembolic events (VTEs) during hospital stay, and mortality rate, were reviewed. A total of 37 patients were identified (median age: 84 years, range: 70-98); n = 30 females median age: 84 years, range: 70-97); n = 7 males median age: 74 years, range: 71-98)) who underwent surgical intervention after an open ankle fracture. Sixteen patients developed SSIs (43%). Superficial SSIs (n = 8) were managed without surgical intervention and treated with antibiotics and regular dressing changes. Deep SSIs (n = 8; 20%) required a median of 3 (range: 2-9) surgical interventions, with four patients requiring multiple washouts and one patient having metalwork removed. VTE incidence was 5% during the hospital stay. Eight patients died within 30 d, and mortality at one year was 19%. The 10-year mortality rate was 57%. The presence of a history of stroke, cancer, or prolonged inpatient stay was found to be predictive of lower survivorship in this population (log-rank test: cancer P = 0.008, stroke P = 0.001, length of stay > 33 d P = 0.015). The presence of a cardiac history was predictive of wound complications (logistic regression, P = 0.045). Age, number of operations, and diabetic history were found to be predictive of an increase in the length of stay (general linear model; age P < 0.001, number of operations P < 0.001, diabetes P = 0.041). An open ankle fracture in a patient older than 70 years has at least a 20% chance of requiring repeated surgical intervention due to deep SSIs. The presence of a cardiac history appears to be the main predictor for wound complications.

The Role of EGFR Amplification in Deep Venous Thrombosis Occurrence in IDH Wild-Type Glioblastoma

Introduction: Glioblastoma (GBM) patients have a 20-30 incidence of venous thromboembolic events. EGFR is a widely used prognostic marker for many cancers. Recent lung cancer studies have described relationships between EGFR amplification and an increased incidence of thromboembolic complications. We aim to explore this relationship in glioblastoma patients. Methods: Two hundred ninety-three consecutive patients with IDH wild-type GBM were included in the analysis. The amplification status of EGFR was measured using fluorescence in situ hybridization (FISH). Centromere 7 (CEP7) expression was recorded to calculate the EGFR-to-CEP7 ratio. All data were collected retrospectively through chart review. Molecular data were obtained through the surgical pathology report at the time of biopsy. Results: There were 112 subjects who were EGFR-amplified (38.2%) and 181 who were non-amplified (61.8%). EGFR amplification status was not significantly correlated with VTE risk overall (p = 0.2001). There was no statistically significant association between VTE and EGFR status after controlling for Bevacizumab therapy (p = 0.1626). EGFR non-amplified status was associated with an increased VTE risk in subjects greater than 60 years of age (p = 0.048). Conclusions: There was no significant difference in occurrence of VTE in patients with glioblastoma, regardless of EGFR amplification status. Patients older than 60 years of age with EGFR amplification experienced a lower rate of VTE, contrary to some reports on non-small-cell lung cancer linking EGFR amplification to VTE risk.

Abstract #1403021: HIV Status in a Patient on Testosterone Therapy: Confounder or Modifier to Venous Thromboembolism?

The association between venous thromboembolic events (VTE) and testosterone therapy has been controversial. Some studies showed an increased risk of VTE with testosterone use, while few studies showed none. Furthermore, some data suggest HIV can also predispose patients to a hypercoagulable state due to immune dysregulation. A 60-year-old male presented with right leg pain and dyspnea. He was on an aromatase inhibitor and testosterone replacement therapy (TRT) for aromatase excess syndrome, and on bictegravir, emtricitabine and tenofovir alafenamide for HIV infection with normal CD4 count and undetectable viral load. Hospital course revealed right mid-femoral deep vein thrombosis and right-sided pulmonary embolism. He was managed conservatively with IV heparin and eventually discharged on a direct oral anticoagulant. Existing literature on the correlation between VTE and TRT is inconclusive. A case-control study in the USA showed no increased risk of VTE in those on TRT. However, another population-based case-control study in the UK showed that TRT had an increased incidence of VTE compared to general population, with peak risk noted at 6 months. Possible reasons for the higher risk of VTE in patients requiring TRT included increased hematocrit, platelet aggregation, and blood viscosity. A recent case-crossover study that included more VTE-exposed cases showed that TRT patients had greater short-term risk of VTE, especially in the immediate period after initiation of therapy. Another important factor to consider in this patient’s predisposition to VTE is his HIV status which promotes a prothrombotic state and predisposes patients to venous and arterial thromboembolism. Likely due to immune dysregulation secondary to chronic inflammation and immune activation. It usually happens in patients with low CD4 counts and high viral loads. But, in HIV patients with well-controlled viral load and CD4 counts, data suggests that VTE incidence is close to that of general population. In our patient, who was on TRT chronically with no previous VTE, it is hard to assess if his current HIV status was a confounder to his hypercoagulable state or a modifier to an existing risk. With subgroups of TRT-using patients like the transgender population having an increased incidence of HIV, concurrent infection may heighten clinical risk. It is essential to further explore the confounding versus modifying effect that HIV may have on VTE incidence. Currently, there are no large-scale clinical trial data available to identify the true association of VTE with TRT.

Systematic search for the UBA1 mutation in men after a first venous thrombotic episode

VEXAS syndrome (acronym for Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is an autoinflammatory disease, described in adults in 2020, caused by a somatic mutation of the Ubiquitin like modifier activating enzyme 1 (UBA1) gene located on the X chromosome. VEXAS syndrome is mainly described in men after 50 years of age with a systemic inflammatory disease associated with febrile episodes, but also hematological, pulmonary, cutaneous, vascular, cartilaginous and articular involvement. Thrombotic complications have been reported in approximately 40% of VEXAS patients, with a predominance of venous thromboembolic events (VTE) rather than arterial thromboembolic events. Among the VTEs, deep vein thrombosis (DVT) was more frequent than pulmonary embolism (PE). The pathophysiology of VTE in VEXAS remains unknown. The objective of the study was to determine the frequency of UBA1 mutations in a cohort of men over 50 years of age with a first VTE. Our study included male patients aged > 50 years included in our center between January 2003 and January 2009, as part of the multicenter FARIVE study. The FARIVE case-control study included consecutive patients treated as inpatients or outpatients for a first episode of proximal DVT and/or PE. All patients were sampled for genetic study. In this study, exon 3 of UBA1 was sequenced. A total of 97 patients were included with a median age of 65 years and a median body mass index of 25.5. Of the patient cohort, 49 (50.5%) presented with an unprovoked VTE. Thrombophilia testing was available for 56 (57.7%) of the 97 patients and no severe thrombophilia was diagnosed among the patients tested. In the end, no UBA1 mutations were detected among the 97 patients (Table 1). VEXAS syndrome is associated with a high incidence of VTE but our study does not encourage its investigation in all men over 50 years of age with a first VTE without considering other clinical symptoms related to VEXAS. Routine screening for UBA1 exon 3 mutations should not be recommended after a first VTE.

328 Incidence and Number of Missed Chemical Venous Thromboembolic Event Prophylactic Doses Predict the Development of Venous Thromboembolic Events in Traumatic Brain Injury Patients

INTRODUCTION: Venous thromboembolic events (VTE) are a major concern in trauma and intensive care, with traumatic brain injury (TBI) patients at an elevated risk. Chemical VTE prophylaxis is used to prevent VTE development. Concerning TBI patients, achieving a fine balance between the risk of worsening hemorrhage and clot development is important. To date, there has been no correlation between the number of missed doses and VTE development in this population. METHODS: Data were retrospectively collected among 818 TBI patients admitted to a level I trauma center between 2015-2020. RESULTS: Overall VTE incidence was 9% (7.6% DVT; 3.2% PE; 1.7% both). Median time to DVT and PE was 7 (IQR: 4-11) and 5 days (IQR: 3-12), respectively. VTE occurred in 37.8% of patients who missed prophylactic doses and 28.4% who did not (p = 0.089). In patients who experienced a VTE, compared to non-VTE patients, missed chemical prophylaxis dosing was primarily due to a pending invasive procedure (44.8% vs. 25.2%, p = 0.02) and the presence of additional bleeding (13.8% vs. 2.8%, p = 0.005). Non-VTE patients missed prophylactic dosing primarily from patient or family refusal (42.1% vs. 3.4%, p &lt; 0.001). VTE incidence was higher in patients receiving invasive neurosurgery (45.9% vs. 30.5%, p = 0.007). Univariate analysis demonstrated 4-6 total missed doses as predicting the highest VTE risk (OR 4.08, 95% CI: 1.53-10.86, p = 0.005). No VTE were seen in &gt;7 missed doses, presumably due to an overall high mortality rate of 13.5%. CONCLUSIONS: This study is novel in showing the incidence and number of missed chemical VTE prophylaxis to predict an increased VTE risk in TBI patients. Our study suggests a threshold of 4 missed doses to be particularly important in this critical patient population.