Venous Thromboembolic Events Research Articles

Epidemiology of clinically unsuspected venous thromboembolism in children with cancer: A population-based study from Maritimes, Canada.

Inconsistencies in the definition of clinically unsuspected venous thromboembolism (VTE) in pediatric patients recently led to the recommendation of standardizing this terminology. Clinically unsuspected VTE (cuVTE) is defined as the presence of VTE on diagnostic imaging performed for indications unrelated to VTE in a patient without symptoms or clinical history of VTE. The prevalence of cuVTE in pediatric cancer patients is unclear. Therefore, the main objective of our study was to determine the prevalence of cuVTE in pediatric cancer patients. All patients 0-18years old, treated at the IWK in Halifax, Nova Scotia, from August 2005 through December 2019 with a known cancer diagnosis and at least one imaging study were eligible (n=743). All radiology reports available for these patients were reviewed (n=18,120). The VTE event was labeled a priori as cuVTE event for radiology reports that included descriptive texts indicating a diagnosis of thrombosis including thrombus, central venous catheter-related, thrombosed aneurysm, tumor thrombosis, non-occlusive thrombus, intraluminal filling defect, or small fragment clot for patients without documentation of clinical history and or signs of VTE. A total of 18,120 radiology reports were included in the review. The prevalence of cuVTE was 5.5% (41/743). Echocardiography and computed tomography had the highest rate of cuVTE detection, and the most common terminologies used to diagnose cuVTE were thrombus and non-occlusive thrombus. The diagnosis of cuVTE was not associated with age, sex, and type of cancer. Future efforts should focus on streamlining radiology reports to characterize thrombi. The clinical significance of these cuVTE findings and their application to management, post-thrombotic syndrome, and survival compared to cases with symptomatic VTE and patients without VTE should be further studied.

Lipid lowering for prevention of venous thromboembolism: a network meta-analysis.

Studies have suggested that statins may be associated with reduced risk of venous thromboembolism (VTE). The aim of the current study was to assess the evidence regarding the comparative effect of all lipid-lowering therapies (LLT) in primary VTE prevention. After a systematic search of PubMed, CENTRAL, and Web of Science up until 2 November 2022, randomized controlled trials (RCT) of statins (high- or low-/moderate-intensity), ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were selected. An additive component network meta-analysis to compare VTE risk during long-term follow-up across different combinations of LLT was performed. Forty-five RCTs (n = 254 933 patients) were identified, reporting a total of 2084 VTE events. Compared with placebo, the combination of PCSK9i with high-intensity statin was associated with the largest reduction in VTE risk (risk ratio [RR] 0.59; 95% confidence interval [CI] 0.43-0.80), while there was a trend towards reduction for high-intensity (0.84; 0.70-1.02) and low-/moderate-intensity (0.89; 0.79-1.00) statin monotherapy. Ezetimibe monotherapy did not affect the VTE risk (1.04; 0.83-1.30). There was a gradual increase in the summary effect of VTE reduction with increasing intensity of the LLT. When compared with low-/moderate-intensity statin monotherapy, the combination of PCSK9i and high-intensity statin was significantly more likely to reduce VTE risk (0.66; 0.49-0.89). The present meta-analysis of RCTs suggests that LLT may have a potential for VTE prevention, particularly in high-intensity dosing and in combination therapy.

Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury

BackgroundThe effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear.MethodsWe randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale–Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months.ResultsA total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, −2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively.ConclusionsIn critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.)

Pregnancy, delivery, and neonatal outcomes among women with PCOS and endometriosis: a population database cohort.

PCOS and endometriosis are independent risk factors for perinatal outcomes. Little research has evaluated the concomitant effects of these conditions, nor have studies been conducted on a population database. We sought to identify the pregnancy, delivery, and neonatal outcomes in women with polycystic ovary syndrome (PCOS) and endometriosis vs. PCOS without endometriosis. A retrospective population-based cohort study was performed extracting data using ICD-9 codes from the HCUP-NIS Database from 2004 to 2014. Endometriosis in women with PCOS represented the study group (n = 163), and the remaining PCOS, non-endometriosis patients constituted the reference group (n = 14,719). Subjects were included once per delivery. Demographics were compared using chi-squared tests. Confounding effects in pregnancy outcomes were controlled using binary logistic regression analysis. Concomitant endometriosis and PCOS patients were more likely to be white (88.5% vs.71.0%, p < 0.001), with BMI < 30kg/m2 (87.1% vs.77.8%, p < 0.004) and from lower income quartiles (27.1% vs.17.1%, p < 0.017) when compared to PCOS without endometriosis. Comparing pregnancy complication rates, placental abruption (p < 0.018, aOR 3.01, 95% CI 1.21-7.50), Cesarean section (p < 0.003, aOR 1.75, 95% CI 1.21-2.53), deep venous thromboses (p < 0.002, aOR 74.31, 95% CI 4.57-1209.21), and venous thromboembolic events (p < 0.031, aOR 10.40, 95% CI 1.24-87.37), were increased in the study group compared to the reference group. Women with PCOS and endometriosis were more likely to be white, of lower socioeconomic status, lean, and experience abruptio-placenta, cesarean deliveries, and venous thromboembolisms. Since little was previously known about the combined outcomes of PCOS and endometriosis, it is difficult to counsel patients on risks. Our findings can help clinicians manage pregnant PCOS patients with endometriosis to minimize complications such as abruptio placenta and VTE.

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 .

Total Hip Arthroplasty in Patients Who Have Factor V Leiden: Elevated Risks Isolated to Venous Thromboembolism Events

BackgroundTotal hip arthroplasty (THA) is a common procedure that requires consideration of preexisting comorbidities. Factor V Leiden (FVL), an inherited thrombophilia, is one such condition that predisposes patients to venous thromboembolism (VTE, deep vein thrombosis, and pulmonary embolism). The present study aimed to characterize the risks associated with FVL patients undergoing THA and evaluate the effect of VTE chemoprophylactic agents on these risks. MethodsA total of 544,022 adult patients who underwent primary THA for osteoarthritis indications between 2010 and October 2021 were identified in an administrative claims database. Of these, FVL was identified in 1,138 (0.21%). Patients who had and did not have FVL were matched at a 1:4 ratio (1,131 with FVL and 4,519 without FVL) based on age, sex, and Elixhauser comorbidity index. Univariable and multivariable analyses were assessed for 90-day complications. Implant survival at 5 years was assessed and compared with log-rank tests. The relative use of different chemoprophylactic agents, including aspirin, warfarin, heparin, or direct oral anticoagulant (DOAC), was assessed. Bleeding events and VTE were compared for those prescribed either aspirin or warfarin, heparin, or DOAC. A Bonferroni correction was applied. ResultsOn multivariable analysis, FVL patients were found to have increased odds of 90-day deep vein thrombosis (odds ratio (OR) = 9.20), pulmonary embolism (OR = 6.89), and aggregated severe and all adverse events (OR = 4.74 and 1.98, respectively), but not elevated risk of other perioperative adverse events or 5-year reoperations. More potent chemoprophylactic agents (warfarin, heparin, DOAC) reduced, but did not completely eliminate, the increased VTE risks (without increasing bleeding events). ConclusionsThis study quantified the significantly elevated VTE risk associated with FVL patients undergoing THA. The lack of difference in other specific adverse events and 5-year reoperations is reassuring. Clearly, chemoprophylactic agents are important in this population and may need further attention.

Thromboembolic incidents in prostate cancer patients: A nationwide propensity-matched study.

e23082 Background: Venous thromboembolic events (VTE) are a major cause of morbidity and mortality in cancer patients. We aim to investigate the outcome and incidence of acute DVT and PE in prostate cancer compared to all other malignancies. Methods: The National Readmission Database (2016-2020) was utilized to identify all-cause admissions for patients with a history of prostate cancer. A Propensity Score Matching (PSM) model, matched such patients with subjects having any type of other malignancies. Pearson’s x2 test was applied to the PSM-2 matched cohorts to compare outcomes. Results: Among 3.2 million all-cause hospitalizations of prostate cancer patients, about 3.3% suffered a VTE. The majority had acute DVT (1.6%), followed by PE (1.1%) &amp; DVT with PE (0.6%). On a propensity-matched &amp; multivariate analysis, patients with prostate cancer have a lower incidence of acute PE (1.1% vs 1.9%, aOR: 0.57), DVT (1.9% vs 2.8%, aOR: 0.65) &amp; combined DVT with PE (0.6% vs 1%, aOR: 0.62) [p &lt; 0.001] as compared to other malignancies. Among different VTEs, the mortality was highest for Acute PE (aOR: 2.69), followed by DVT with PE (aOR: 1.68) &amp; DVT (aOR: 1.55) [p &lt; 0.001] in prostate cancer. Resource utilization is also higher in prostate cancer hospitalizations complicated by VTE, with patients suffering a DVT having the highest LOS (9 vs 3 days) &amp; total cost of hospitalization ($20,425 vs $14,452) [p &lt; 0.001] followed by DVT with PE and only PE [p &lt; 0.05]. Interestingly, patients with DVT have higher readmission rates as compared to PE at 30 days (16.6% vs 13.5%, p &lt; 0.001) and subsequently at 90-day intervals. Conclusions: The odds of venous thromboembolism were lower in prostate cancer when compared to all other patients with active cancer. The mortality was highest for PE in this cohort, while healthcare-related burden and readmission rates were higher for DVT. [Table: see text]

The impact of venous thromboembolism before open or minimally-invasive radical cystectomy in the USA: insurance claims data on perioperative outcomes and healthcare costs.

The relationship between venous thromboembolism (VTE) and solid malignancy has been established over the decades. With rising projected rates of bladder cancer (BCa) worldwide as well as increasing number of patients experiencing BCa and VTE, our aim is to assess the impact of a preoperative VTE diagnosis on perioperative outcomes and health-care costs in BCa cases undergoing radical cystectomy (RC). Patients ≥18 years of age with BCa diagnosis and undergoing open or minimally invasive (MIS) RC were identified in the Merative™ Marketscan® Research Databases between 2007 and 2021. The association of previous VTE history with 90-day complication rates, postoperative VTE events, rehospitalization, and total hospital costs (2021 USA dollars) was determined by multivariable logistic regression modeling adjusted for patient and perioperative confounders. Sensitivity analysis on VTE degree of severity (i.e., pulmonary embolism [PE] and/or peripheral deep venous thrombosis [DVT]) was also examined. Out of 8759 RC procedures, 743 (8.48%) had a previous positive history for any VTE including 245 (32.97%) PE, 339 (45.63%) DVT and 159 (21.40%) superficial VTE. Overall, history of VTE before RC was strongly associated with almost any worse postoperative outcomes including higher risk for any and apparatus-specific 90-days postoperative complications (odds ratio [OR]: 1.21, 95% CI, 1.02-1.44). Subsequent incidence of new VTE events (OR: 7.02, 95% CI: 5.93-8.31), rehospitalization (OR: 1.25, 95% CI: 1.06-1.48), other than home/self-care discharge status (OR: 1.53, 95% CI: 1.28-1.82), and higher health-care costs related to the RC procedure (OR: 1.43, 95% CI: 1.22-1.68) were significantly associated with a history of VTE. Preoperative VTE in patients undergoing RC significantly increases morbidity, post-procedure VTE events, hospital length of stay, rehospitalizations, and increased hospital costs. These findings may help during the BCa counseling on risks of surgery and hopefully improve our ability to mitigate such risks.

An analysis of post-operative thromboembolic events in patients diagnosed with gastro-esophageal cancer.

e16123 Background: Venous thromboembolism (VTE) commonly manifests as a postoperative complication of gastroesophageal cancer (GEC) surgery. However, guidelines seldom differentiate preventive approaches for postoperative VTE based on cancer types. Furthermore, there is a lack of research evaluating factors associated with the risk of thrombosis for patients diagnosed with GEC who undergo surgery. Herein, we aim to determine the incidence of VTE after GEC surgery and the clinical characteristics of the patients associated with VTE events. Methods: We retrospectively reviewed the charts of patients diagnosed with GEC and underwent gastrectomy/esophagectomy at Cleveland Clinic, OH, and Weston, FL, between 2005 and 2022. Patients who had non-malignant diseases or did not undergo invasive surgery were excluded. Of the 437 patients who underwent GEC surgery, only 375 met the inclusion criteria. Patients who developed a VTE event diagnosed by imaging studies within one year of GEC surgery were considered positive for the event. DVT prophylaxis (DDPX) was defined as the administration of anticoagulants, such as heparin and enoxaparin. The average length of DVT prophylaxis was 7 days. The chi-square test was used to assess the significant differences among the groups based on VTE status. Results: In this cohort of 375 patients, 54 (14.4%) patients experienced VTE. 43 patients (79.60%) who experienced a VTE event received DDPX, whereas 10 patients (18.50%) with VTE did not receive DDPX. Of the 321 patients who did not develop VTE, 251 patients (78.20%) received DDPX, while 66 patients (20.60%) did not receive DDPX. DDPX administration in both cohorts was not significantly different (p 0.868). Notably, 36 (66.7%) of the patients developed VTE events within 30 days following GEC surgery, with a subsequent significant decrease in VTE incidence beyond this timeframe (9.3%, 7.4%, 11.1%, and 5.5% in the 30-60-, 60-90, 90–180, and 180-365-day intervals, respectively, p &lt; 0.001). Among the patients who presented with gastrointestinal stromal and neuroendocrine tumors (7.50%), none of the patients developed a VTE event. Nevertheless, 19.35% of the 31 patients diagnosed with squamous cell carcinoma had a VTE within one year of GEC. Patients with Stage IV disease had a higher risk of VTE compared to lower-stage disease (25.95%, p 0.032). However, factors such as BMI, smoking status, type of surgery, treatment regimens, and ECOG score were not significantly associated with VTE. Conclusions: Patients diagnosed with GEC who underwent surgical intervention demonstrated a significant propensity for VTE, particularly within 30 days post-surgery. The rate of VTE incidence was not significantly different among the DPPX and non-DPPX cohorts, which could be attributed to the short duration of anticoagulation. Further studies are warranted to investigate the optimal duration of DDPX.

Association of baseline characteristics with adverse events (AEs) in the PROpel trial of olaparib (ola) plus abiraterone (abi) as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC).

e17030 Background: The PROpel trial (NCT03732820) met its primary endpoint and showed a statistically significant radiographic progression-free survival benefit (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P&lt;0.0001) with ola + abi vs placebo + abi in 1L mCRPC; whilst not statistically significant, overall survival (OS) was numerically prolonged (median 42.1 vs 34.7 months; HR 0.81, 95% CI 0.67–1.00; P=0.0544). To further inform clinical decision making, we provide exploratory post hoc analysis investigating the relationship between selected patient baseline characteristics and AEs for ola + abi. Methods: Anemia and venous thromboembolism events (VTEs) were identified as the only grade (Gr) ≥3 AEs or AEs of special interest reported in &gt;20 (&gt;5.0%) patients (pts) in the ola + abi arm (data cutoff 12 Oct 2022). Baseline characteristics were correlated with AEs using Cox regression by backwards elimination and analysis with AEs as dependent variables. Baseline characteristics assessed included: age (&lt;70 or ≥70 y), time since diagnosis (&lt;median or ≥median) , ECOG status (0 or 1), metastatic sites (visceral [yes or no], bone only [yes or no]), number of bone metastases (0, 1–4, 5‒9, 10‒20 or &gt;20), Gleason score (&lt;9 or 9–10), homologous recombination repair mutation status (HRRm, non-HRRm or unknown), race (white or non-white), prior docetaxel at metastatic hormone-sensitive prostate cancer (yes or no), pain (symptomatic or asymptomatic/mildly symptomatic), type of progression (prostate-specific antigen [PSA], radiographic or both), prior radiotherapy (yes or no) and albumin, creatinine, lactate dehydrogenase, alkaline phosphatase (ALP), hemoglobin (10&lt;12 or ≥12) and log PSA levels. Results: 398 pts received ola + abi. 64 (16.1%) had Gr ≥3 anemia and 34 (8.5%) a VTE. Baseline characteristics correlated significantly with increased risk of these AEs as shown (Table); characteristics not shown were not associated with AEs. Conclusions: These results provide insight into which baseline characteristics correlate with the risk of Gr ≥3 anemia. Pts with abnormal ALP, pre-existing anemia, ECOG PS 1 or age ≥70 years could be at higher risk and the development of Gr ≥3 anemia during treatment with ola + abi should be monitored. Clinical trial information: NCT03732820 . [Table: see text]

In-depth analysis of responders in the phase 3 PhALLCON trial of ponatinib vs imatinib in newly diagnosed Ph+ ALL.

6533 Background: Ponatinib, a third-generation BCR::ABL TKI, has potent activity against all clinically relevant BCR::ABL1 variants, including T315I. PhALLCON (NCT03589326), a phase 3 trial comparing frontline TKIs in adults with Ph+ ALL, met its primary endpoint with a higher rate of minimum residual disease–negative (MRD-neg) complete remission (CR) at end of induction (EOI) with ponatinib vs imatinib (34.4%/16.7%; P=0.002). Here, we report response rates of MRD-neg at any time and PFS by age and BCR::ABL1 variant subgroups. Methods: Adults with newly diagnosed Ph+ ALL were randomized 2:1 to ponatinib (30 mg QD reduced to 15 mg QD upon MRD-neg CR at or after EOI) or imatinib (600 mg QD) plus 20 cycles of reduced-intensity chemotherapy (induction: 3 cycles; consolidation: 6 cycles; maintenance: 11 cycles), followed by single-agent ponatinib or imatinib until disease progression or unacceptable toxicity. Hematopoietic stem cell transplant (HSCT) was per investigator’s discretion. Post hoc analyses compared MRD-neg ( BCR:: ABL1IS ≤0.01%; MR4) at any time and PFS (any-cause death, failure to achieve CR by EOI, relapse from CR, or failure to achieve/loss of MRD-neg) by age (&lt;/≥65 y) and BCR:: ABL1 variant (p190/p210). Data cutoff: Aug 12, 2022. Results: In the population of randomized patients (pts) with p190/p210 confirmed by central lab (n=232; 154/78 ponatinib/imatinib; median follow-up 20.1 mo), 68% vs 50% in the ponatinib vs imatinib arms were MRD-neg at any time, with similar benefit of ponatinib across age and variant subgroups (Table). Median PFS was more than twice as long with ponatinib vs imatinib across subgroups (Table). Pts achieving MRD-neg at any time were less likely to have HSCT with ponatinib vs imatinib (32%/56%). Among 107/42 pts without HSCT, exposure was &gt;2-fold longer in the ponatinib vs imatinib arms (median 12.8/5.1 mo) with comparable rates of arterial occlusive (3%/2%) and venous thromboembolic events (11%/12%), and discontinuations due to TEAEs (13%/14%). Conclusions: Ponatinib was superior to imatinib in combination with reduced-intensity chemotherapy for frontline treatment of Ph+ ALL, with higher rates of MRD-neg at any time, substantially longer PFS across age and BCR::ABL1 variant subgroups, and a safety profile comparable to imatinib. Clinical trial information: NCT03589326 . [Table: see text]

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.

Angiogenesis inhibitors and cardiovascular outcomes in cancer: Real-world, population-based, matched cohort study.

e24024 Background: Angiogenesis inhibitors (AI) have vascular side effects and are now recognized forcardiovascular adverse events (CVAEs). Clinical trial outcomes can underestimate treatment-related adverse events due to restrictive eligibility criteria, limited sample size, and failure to anticipate specific toxicities. In contrast, observational studies have small sample sizes and insufficient adjustment of confounding covariates. In addition, prospective high-quality evidence in real-world settings is scarce. We evaluated the incidence of CVAEs in real-world populations on AI therapy. Methods: This large retrospective cohort study was conducted using the TriNetX database and included adult patients ( &gt; 18 years) with new cancer diagnoses. We performed 1:1 propensity score matching (PSM) for demographics, BMI, nicotine dependence, comorbidities, cancer type, and medications to similar controls as cancer patients never treated with AIs. The primary outcome was the new incidence of CVAEs-like heart failure (HF), major adverse cardiovascular events (MACE; coronary artery intervention myocardial infarction, or unstable angina), arrhythmia, ischemic heart disease (IHD), venous thromboembolism (VT), and cerebrovascular events (CVE cerebral infarction, carotid intervention, stroke, transient ischemic attack). Sensitivity analysis assessed statistical robustness. Hazard ratios (HR) were calculated to compare the AI therapy association with incident CVAEs. Results: We identified 1,170,667 patients with diagnoses of colorectal, cervical, kidney, liver, nonsmall cell lung, or ovarian cancer between 2010 and 2022. Among these, 59,890 had an AI treatment history, and 110,777 did not, with a median follow-up time of 3.1 years. After PSM, both cohorts (59545 each) were well-matched. In the adjusted analysis, AI therapy was associated with higher risks of MACE (HR, 1.23; 95% CI 1.16 -1.31), HF (HR, 1.16; 95% CI 1.08 - 1.25), and VT (HR 2.07; 95% CI 1.95 - 2.19), IHD (HR 1.23; 95% CI 1.16- 1.31), arrhythmias (HR 1.19; 95% CI 1.12-1.27), CVEs (HR, 1.30; 95% CI 1.21- 1.40) at 1 year of exposure. These outcomes were still significantly higher “increased,” suggesting causation; this is an association at follow-up by increasing the lag exposure. Sensitivity analysis results were consistent, and all statistically significant associations remained unchanged. Conclusions: Angiogenesis inhibitor treatment was associated with a significantly higher risk of CVAEs and various malignancies. The increased risk ranges from approximately 1.16 to 2.07 fold, indicating a substantial elevation in risk. These findings highlight the importance of risk stratification and cardiovascular monitoring during and after AI therapy. There is an unmet need to define strategies for CVAE prevention in this high-risk population.

Disparities in the prevalence of acute pulmonary embolism in patients with ovarian cancer: A nationwide analysis.

e17560 Background: Ovarian cancer is the leading cause of death among gynecological cancers. It is highly thrombogenic and is associated with increased venous thromboembolism events. We conducted a retrospective analysis to study the prevalence and disparities in the association of Acute Pulmonary embolism(PE) with ovarian cancer. Methods: National Inpatient Sample (2017-2020) was used to identify the patients with primary diagnosis of Acute PE and was stratified into those with and without concurrent diagnosis of Ovarian cancer ( regional and advanced metastatic disease). Basic demographic variables were analyzed to identify disparities in the prevalence of Acute PE among ovarian cancer patients.Multivariate logistic regression analysis was conducted to examine the association between Acute PE and Ovarian cancer. Results: A total of 651435 patients were hospitalized with a primary diagnosis of Acute PE, and 2980 (0.46%) had a secondary diagnosis of Ovarian cancer. The ovarian cancer group had a greater percentage of white (73.4% vs.71.93%), Hispanics (7.98% vs. 6.04%), and fewer Black patients (15.78% vs. 19.86), p=0.021. Compared to the white, Black population with ovarian cancer (OR=0.77(0.6-0.9); p=0.04) had a decreased likelihood of developing Acute PE without any difference noted in the Hispanics (OR=1.13 (0.81-1.58); p=0.44) and other races (OR=1.11 (0.67-1.83); p=0.67). Patients in the high income groups were more likely to be admitted due to acute PE ($65,000-$85,999: OR=1.35 (1.05-1.73), p=0.018; &gt;$86,000: OR=1.24 (1.14-1.62), p=0.01). A greater percentage of patients with ovarian cancer had private insurance (35.2% vs. 28.91%), while a greater percentage of patients without ovarian cancer had Medicare (54.38% vs. 50.34%) and Medicaid (11.9% vs. 12.5%), p=0.003. Patients with private insurance were more likely to be admitted due to acute PE (OR=1.73(1.36-2.22); p&lt;0.001). Patients with a Charlson comorbidity index of 3 or more had higher odds of Acute PE (OR=1.3(1.12-3.4); p=0.02). A greater percentage of Acute PE patients with ovarian cancer were admitted to large (54.03% vs. 47.86%; p=0.014), urban (95.3% vs. 90.35%; p&lt;0.001), and teaching hospitals (79.87% vs. 69.15%; p&lt;0.001). Teaching hospitals had higher odds of admissions due to acute PE in ovarian cancer patients (OR=1.37(1.07-1.75); p=0.01). On multivariate regression analysis, Ovarian cancer patients had higher odds of Acute PE (OR=1.88 (1.73-2.05); p&lt;0.001). Conclusions: Ovarian cancer patients with Black race and private insurance showed a significantly increased likelihood of admissions due to acute pulmonary embolism. Additionally, urban and teaching hospitals demonstrated higher odds of encountering cases of acute pulmonary embolism. Further prospective studies are necessary to validate the findings presented in our study.

Hospital acquired venous thromboembolism in children with sickle cell disease

Sickle cell disease (SCD) is well recognized as a hypercoagulablestate, however, it remains unclear whether a subgroup of children with SCD at higher risk of venous thromboembolic event (VTE) during hospitalization may benefit from thromboprophylaxis. Our objectives were to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients with SCD younger than 21 years. This was a single center retrospective study. Data regarding demographics, reason for admission, location of VTE, risk factors like central venous catheter (CVC), intensive care unit (ICU) admission among others were extracted from electronic medical records over a 10-year study period (2011–2021). Recurrence of VTE at 1 and 5 years was assessed. Descriptive statistics were used as indicated. We identified a total of 20 VTE events over the 10-year study period. Six of these events occurred in those younger than 12 years of age. Fourteen (70%) VTE events occurred in the HbSS or HbSβThal0 genotypes compared to 6 (30%) in HbSC. Most common VTE was isolated pulmonary embolism (PE) (n = 10, 50%). VTE were most often associated with acute chest syndrome (ACS) (n = 14, 70%), ICU admissions (n = 10, 50%) and CVC (n = 5/9, 55%). One patient died from the VTE event. One patient with additional underlying risk factors had a recurrent VTE at 13 months. Our study suggests that ICU admission, ACS and presence of CVC increases the risk of VTE in children and young adults with SCD, but larger studies are indicated to validate our findings.

Risk Factors for Thromboembolism in the Population of Cancer and Hospice Patients

Venous thromboembolism (VTE) is a significant cause of death among palliatively treated patients. So far, numerous studies have been conducted on the general population. As a result, special scales were created to assess the risk of VTE or the probability of its occurrence. Among patients with terminal disease, there are much fewer publications discussing the problem of VTE. Hospice care patients constitute a special group due to their epidemiological structure and accompanying diagnoses. The most common are malignant tumors and heart failure. For this reason, they are particularly vulnerable to VTE events. This article reviews the literature on risk scales such as The Padua Risk Assessment Scale, Khoran score, Wells scale, PVFS scale and VTE-BLEED scale. W also present risk factors which contribute to the development of the VTE as well as to a more serious course of VTE. We discuss the epidemiological structure of patients, the impact of cancer as well as the chemotherapy used to treat it. We discuss the epidemiological structure of patients, the impact of cancer as well as the chemotherapy used in its treatment. We describe how the presence of a catheter and immobilization contribute to the development of VTE. We focus particularly on scales and risk factors to which a patient with a terminal disease is exposed. More research is needed in the future to better predict VTE in hospice patients. We hope that this work will increase awareness and encourage researchers to expand knowledge in this area.

The Use of Aspirin for Venous Thromboembolism Prophylaxis in Patients Who Have Morbid Obesity Undergoing Primary and Revision Total Joint Arthroplasty

BackgroundVenous thromboembolism (VTE) poses a major clinical concern due to its life-threatening nature, and obese and morbidly obese patients are thought to be at an increased risk for VTE. The aims of this study were twofold; first, to explore VTE rates in patients who have a body mass index (BMI) > 40 undergoing primary and revision total joint arthroplasty, and second, to investigate aspirin (ASA) efficacy and safety. MethodsWe identified all patients (n = 4,672) who had a BMI > 40 who underwent primary and revision total joint arthroplasty from 2016 to 2022 at a single academic tertiary care center. Patients were stratified by BMI groups: 40 to 44.9 (n = 3,462), 45 to 49.9 (n = 935), and 50+ (n = 275). The primary outcome was any VTE event within 90 days postoperatively. The secondary outcome consisted of wound complications within 90 days postoperatively. ResultsThe total VTE rate was 0.4% (n = 21) and did not differ statistically between the BMI groups (0.4 versus 0.4 versus 0.7%, P = .669). The VTEs consisted of 6 deep venous thromboses (DVTs), 14 pulmonary embolisms, and one concomitant deep venous thrombosis and pulmonary embolism. The VTE rates were not statistically different between patients who received aspirin 325 mg 0.5% (n = 9), aspirin 81 mg 0.2% (n = 1), aspirin + anticoagulant (AC) 0.5% (n = 6), and AC alone 0.4% (n = 5) (P = .954). In addition, wound complications did not differ significantly between patients who received ASA 325 mg, ASA 81mg, ASA + AC, or AC alone (1.6 versus 1.0 versus 1.8 versus 1.1%, P = .351). ConclusionsThe use of aspirin 325 and 81 mg was found to have similar VTE rates as aspirin + ACs and ACs alone, with no significant increase in wound complications. In patients who have a BMI > 40, the use of aspirin is a safe option for VTE prophylaxis and should be prescribed in the context of the patient who has other risk factors for 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.

#873 Membranous nephropathy has higher all-cause mortality rate in comparison to focal segmental glomerulosclerosis and IgA nephropathy: a long-term study

Abstract Background and Aims Membranous nephropathy, focal segmental glomerulosclerosis (FSGS) and IgA nephropathy are the most frequent types of primary glomerulonephrites in the adulthood. Glomerulonephritides may progress into end-stage renal disease despite appropriate treatment. Both the manifestations of the glomerulonephritides and medications for treatment might yield cardiovascular events such as venous thromboembolism, coronary artery disease and stroke. The purpose of this study is to compare three different types of primary glomerulonephritides in terms of all-cause mortality, kidney-related and cardiovascular outcomes. Method All patients who underwent kidney biopsy between 01.01.2000 and 01.06.2022 in Hacettepe University Hospital were screened and cases with primary glomerulonephritis and follow-up data were enrolled. Data regarding baseline demographics, laboratory and kidney pathology reports and outcomes were obtained. The primary end-point was defined as all-cause mortality. Kidney related and cardiovascular outcomes were determined as secondary end-points. Results population was 39 (18-81) years. Membranous nephropathy was present in 36.5% (n = 172), focal segmental glomerulosclerosis was present in 25.9% (n = 122) and IgA nephropathy was present in 37.6% (n = 177) of the cases. Age (p &amp;lt; 0.001), frequency of diabetes (p = 0.004) and smoking history (p = 0.020) were significantly higher in patients with membranous nephropathy than both FSGS and IgA nephropathy. Serum albumin levels were lower (p &amp;lt; 0.001), while total cholesterol (p &amp;lt; 0.001), LDL cholesterol (p &amp;lt; 0.001) and proteinuria levels (p &amp;lt; 0.001) were higher both in patients with membranous nephropathy than the other two groups and in patients with FSGS than IgA nephropathy. Median duration of follow-up was 120.2 (1.7-273.3) months (Table 1). All-cause mortality rate was significantly higher in patients with membranous nephropathy than the other two groups (p = 0.005); however the type of glomerulonephritides was not found to be related to all-cause mortality (HR: 1.07; 95% CI: 0.65-1.77; p = 0.770). Age (HR: 1.079; 95% CI: 1.05-1.10; p &amp;lt; 0.001), serum creatinine (HR: 1.35; 95% CI: 1.10-1.66; p = 0.003) and serum albumin (HR: 0.60; 95% CI: 0.38-0.95; p = 0.030) levels were found to be associated with all-cause mortality in patients with primary glomerulonephritides. The rates of ischemic stroke, atrial fibrillation and steroid induced diabetes were similar between all of the glomerulonephritides subgroups. Acute coronary syndrome (p = 0.015), coronary revascularization (p = 0.021) and venous thromboembolic events were more frequent in patients with membranous nephropathy than IgA nephropathy. There was no difference in terms of cardiovascular outcomes between the patients with FSGS and IgA nephropathy (Table 1). Although the remission rate was significantly higher in patients with membranous nephropathy than the other two groups (p &amp;lt; 0.001); there was not a distinct difference in relapse rates. Progression to end-stage renal disease was prominently lower in patients with membranous nephropathy than the other groups (p = 0.003) and loss of glomerular filtration rate per year was significantly higher in cases with FSGS compared to other groups (p = 0.021). Conclusion All-cause mortality risk was higher in patients with membranous nephropathy because of higher age at diagnosis and accompanying higher burden of comorbidities including diabetes and dyslipidemia. FSGS had a worse prognosis in terms of kidney related outcomes compared to other glomerulonephritides due to higher loss of glomerular filtration rate per year and increased rates of progression to end-stage renal disease. Intensive cardiovascular risk reduction strategies should be applied especially in patients with membranous nephropathy due to increased mortality rates.

Genome-wide investigation of exogenous female hormones, genetic variation, and venous thromboembolism risk

BackgroundIncreased risk of venous thromboembolism (VTE) is a life-threatening side effect for users of oral contraceptives (OCs) or hormone therapy (HT). ObjectivesTo investigate the potential for genetic predisposition to VTE in OC or HT users, we conducted a gene-by-environment case-only meta-analysis of genome-wide association studies (GWAS). MethodsUse or nonuse of OCs (7 studies) or HT (8 studies) at the time of the VTE event was determined by pharmacy records or self-report. A synergy index (SI) was modeled for each variant in each study and submultiplicative/supramultiplicative gene-by-environment interactions were estimated. The SI parameters were first meta-analyzed across OC and HT studies and subsequently meta-analyzed to obtain an overall estimate. The primary analysis was agnostic GWAS and interrogated all imputed genotypes using a P value threshold of <5.0 × 10−8; secondary analyses were candidate-based. ResultsThe VTE case-only OC meta-analysis included 2895 OC users and 6607 nonusers; the case-only HT meta-analysis included 2434 HT users and 12 793 nonusers. In primary GWAS meta-analyses, no variant reached genome-wide significance, but the smallest P value approached statistical significance: rs9386463 (P = 5.03 × 10−8). We tested associations for 138 candidate variants and identified 2 that exceeded statistical significance (0.05/138 = 3.62 × 10−4): F5 rs6025 (P = 1.87 × 10−5; SI, 1.29; previously observed) and F11 rs2036914 (P = 2.0 × 10−4; SI, 0.91; new observation). ConclusionThe candidate variant approach to identify submultiplictive/supramultiplicative associations between genetic variation and OC and HT use identified a new association with common genetic variation in F11, while the agnostic interrogations did not yield new discoveries.