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Background: Recently, cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have emerged as a novel treatment strategy for breast cancer. However, increasing reports of CDK4/6i-associated venous thromboembolism (VTE) have garnered attention. This study assessed CDK4/6i-associated VTE in breast cancer, and examined the effect of CDK4/6i on platelet/coagulation function for the first time in vitro., Methods: PubMed and Embase databases were searched for studies published from the establishment of the database to December 31, 2022 for randomized controlled trials (RCTs) and real-world studies of CDK4/6i in patients with breast cancer, and the data obtained from the included studies were used for meta-analysis. A disproportionality analysis by extracting adverse drug reaction signals of CDK4/6i-associated VTE from the FDA Adverse Event Reporting System (FAERS) database was also conducted. Additionally, the in vitro effect of CDK4/6i on platelet function was assessed based on platelet aggregation tests and flow cytometry, and coagulation function was assessed based on the blood clotting function test., Findings: A total of 16,903 patients in 13 RCTs and 6,490 patients in 9 real-world studies were included in the meta-analysis. In RCTs, VTE occurred in 193 (2.1 %) and 55 (0.7 %) patients in the CDK4/6i and control groups, respectively. In real-world studies, the aggregate incidence rate of VTE was 4.2 % (95 % CI: 2.1, 6.3). The meta-analysis of RCTs revealed that abemaciclib (Odds ratio [OR]: 4.40 [95 % CI: 2.74,7.05], p < 0.001) and palbociclib (OR: 2.35 [95 % CI: 1.34, 4.12], p < 0.01) significantly increased the risk of VTE in patients with breast cancer compared to placebo. FAERS database analysis revealed that abemaciclib (reporting odds ratio [ROR]: 1.63 [95 % CI: 1.36, 1.97]; IC 025 : 0.67) and ribociclib (ROR: 1.17 [95 % CI: 1.0, 1.39]; IC 025 : 0.18) demonstrated a significantly increased signal of VTE. Similarly, findings from in vitro experiments demonstrated that abemaciclib enhanced agonist-induced platelet activation, especially when collagen was used as the inducer, and this effect became more prominent with increasing its concentration., Interpretation: Use of abemaciclib may increase the risk of VTE in patients with breast cancer, which may be partially attributed to the effect of abemaciclib on platelet function. Close monitoring of VTE occurrence is highly recommended while using abemaciclib, especially in patients at a high risk of VTE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, commonly used direct oral anticoagulant (DOAC), are widely used to prevent and treat stroke and venous thromboembolic events in patients with atrial fibrillation (AF). This study aimed to assess and compare reports of adverse events associated with rivaroxaban, apixaban, and edoxaban, including hemorrhagic and non-hemorrhagic events., Methods: Reporting odds ratio (ROR), proportional reporting ratio (PRR), Medications and Health Care Products Regulatory Agency (MHRA), and the information component (IC) were used to perform a risk assessment of adverse event reports in the FDA Adverse Event Reporting System (FAERS) database for the years 2018-2022., Results: Combined with disproportionality analysis in different backgrounds, the salient risks of the three-factor Xa inhibitors varied. Rivaroxaban had the most significant risk of hemorrhage, apixaban had a higher incidence and risk of death, cardiac and cerebral adverse events, and edoxaban showed a more prominent risk in the kidneys and urinary system., Conclusion: Hemorrhage is a common risk with factor Xa inhibitors, with rivaroxaban being the most significant. Apixaban and edoxaban also showed significant association with non-hemorrhagic adverse events, and increased attention to non-hemorrhagic adverse events is needed in clinical use.

Background: Venous thromboembolism (VTE) risk is higher among patients with non-small cell lung cancer (NSCLC) and specific subgroups, including the elderly, but little is known about the VTE risk of different generations of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and whether the risk differs by demographic characteristics. This study aims to compare the risk of VTE (deep venous thromboembolism [DVT]; pulmonary embolism [PE]) between a third-generation EGFR-TKI and first/second-generation EGFR-TKIs and stratify VTE risk by sex, age, and race/ethnicity in third-generation EGFR-TKI users., Methods: Via the 2006-2019 Surveillance, Epidemiology, and End Results-Medicare database, this retrospective cohort study included older patients (aged ≥65 years) with advanced NSCLC who initiated on a third-generation EGFR-TKI (n = 493) and first/second-generation EGFR-TKIs (n = 1036). We estimated the hazard ratio (HR) and its 95% confidence interval (95% CI) with the Cox proportional hazards model., Results: A third-generation EGFR-TKI had a significantly higher VTE risk than first/second-generation EGFR-TKIs (HR, 1.26 [95% CI, 1.01-1.57]; p = .037), with an elevated risk in males (HR, 2.16 [95% CI, 1.47-3.19]; p < .001), patients aged ≥75 years (HR, 1.38 [95% CI, 1.04-1.83]; p = .026), and non-Hispanic Whites (HR, 1.46 [95% CI, 1.10-1.95]; p = .010). Males consistently showed a significantly higher risk of DVT (HR, 2.49 [95% CI, 1.29-4.80]; p = .007) and PE (HR, 2.00 [95% CI, 1.29-3.11]; p = .002). A significantly higher risk of DVT (HR, 1.54 [95% CI, 1.00-2.37]; p = .050) and PE (HR, 1.47 [95% CI, 1.06-2.05]; p = .021) was shown in patients aged ≥75 years and non-Hispanic Whites, respectively. Among third-generation EGFR-TKI users, non-Hispanic Whites had a significantly higher risk of VTE (HR, 2.04 [95% CI, 1.03-4.02]; p = .041) and PE (HR, 2.88 [95% CI, 1.24-6.70]; p = .014) than non-Hispanic Asian/Pacific Islanders., Conclusions: Close monitoring of VTE events in high-risk patients is essential to promote early diagnosis and treatment., (© 2024 American Cancer Society.)

Introduction: Several risk scores have been proposed to predict venous thromboembolism (VTE) in hospitalized patients. However, their predictive performances in lung cancer patients receiving immune checkpoint inhibitors (ICIs) is unclear. We aimed to validate and compare their performances of the Caprini, Padua and Khorana risk scores in lung cancer patients receiving ICIs., Methods: This was a retrospective cohort study of patients with lung cancer treated with ICIs at West China Hospital between January 2018 and March 2022. The primary outcome was VTE during 12 months of follow-up from the first day of treatment with ICIs. The predictive performances of risk scores was determined using receiver operating characteristic (ROC) curve analysis., Results: Among the 1115 eligible patients with lung cancer who received ICIs, 105 patients (9.4%) experienced VTE during the 12-month follow-up period. There was a statistically significant difference in the cumulative incidence of VTE between the different risk levels as determined by Caprini and Padua scores (all P < 0.001). However, no significant difference was observed for the Khorana score (P = 0.488). The Caprini and Padua scores demonstrated good discriminative performances (AUC 0.743, 95% CI 0.688-0.799 for Caprini score; AUC 0.745, 95% CI 0.687-0.803 for Padua score), which were significantly better than that of the Khorana score (AUC 0.553, 95% CI, 0.493-0.613) (P < 0.05)., Conclusion: In our study, the Caprini and Padua risk scores had better discriminative ability than the Khorana score to identify lung cancer patients treated with ICIs who were at high risk of VTE., (© 2024. The Author(s).)

Objectives: To update the long-term safety profile of filgotinib, a Janus kinase-1 preferential inhibitor, in patients with moderate-to-severe rheumatoid arthritis., Methods: Data from seven trials were integrated (NCT01888874, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700 and NCT03025308). Patients received once-daily filgotinib 100 mg or 200 mg. Exposure-adjusted incidence rates (EAIRs)/100 patient-years of exposure (PYE) were calculated for treatment-emergent adverse events (TEAEs). Post hoc analyses assessed patients aged <65 and ≥65 years., Results: Patients (N=3691) received filgotinib for a median (maximum) of 3.8 (8.3) years (12 541 PYE). Rates of TEAEs of interest: serious infections, malignancies, major adverse cardiovascular events (MACE) and venous thromboembolism were stable over time and comparable between doses. In the overall population, numerically lower EAIR (95% CI)/100 PYE of herpes zoster was observed for filgotinib 100 mg versus 200 mg (1.1 (0.8 to 1.5) vs 1.5 (1.2 to 1.8)). Incidence of serious infections, herpes zoster, MACE, malignancies and all-cause mortality was higher in patients aged ≥65 versus <65 years. In patients aged ≥65 years, EAIRs (95% CI)/100 PYE for non-melanoma skin cancer (NMSC) (0.4 (0.1 to 1.1) vs 1.4 (0.8 to 2.2)), malignancies excluding NMSC (1.0 (0.5 to 1.9) vs 2.0 (1.3 to 2.9)) and all-cause mortality (1.3 (0.7 to 2.2) vs 1.6 (1.0 to 2.5)) were numerically lower for filgotinib 100 mg versus 200 mg., Conclusions: In the overall population, TEAEs of interest were stable over time and similar between filgotinib 100 mg and 200 mg dose groups, except for herpes zoster. A dose-dependent relationship between malignancies and all-cause mortality was suggested in patients ≥65 years old., Competing Interests: Competing interests: GRB reports consultancy fees from AbbVie, Amgen, BMS, Galapagos, Lilly, Pfizer and Sanofi; and speakers’ bureau fees from AbbVie, Amgen, BMS, Chugai, Galapagos, Lilly, Pfizer and Sanofi. J-EG reports consultancy fees from AbbVie, BMS, Galapagos, Gilead, Lilly, MSD, Novartis and Pfizer; and grant/research support from BMS and Pfizer. RC reports consultancy fees from AbbVie, Fresenius, Galapagos, Lilly, Pfizer, Novartis and UCB; speakers’ bureau fees from AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer and UCB. KLW reports consultancy fees from AbbVie, AstraZeneca, BMS, Eli Lilly & Company, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB; and grant/research support from BMS and Pfizer. YT has received speaker fees and/or honoraria from AbbVie, Asahi Kasei, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Taiho, Taisho and Pfizer; and research grants from Asahi Kasei, Chugai, Eisai, Mitsubishi Tanabe and Taisho. EVEO is a consultant for Galapagos. VR is a former employee of, and shareholder in, Galapagos. PVH is a consultant for AOP Health, Aspen and Galapagos; and a previous employee of Janssen, MSD and Schering-Plough. KVB is an employee of, and shareholder in, Galapagos. TT reports consultancy fees from AbbVie GK, Astellas, Chugai, Eli Lilly Japan, Gilead, Janssen Pharma K.K., Mitsubishi Tanabe and Pfizer Japan; speakers’ bureau fees from AbbVie GK, AYUMI, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Gilead, Janssen Pharma K.K., Mitsubishi Tanabe, Pfizer Japan and Sanofi K.K.; and research/grant support from AbbVie GK, Asahi Kasei, Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Mitsubishi Tanabe, Nippon Kayaku and UCB Japan. RW acted as an adviser and speaker for Celltrion, Galapagos and Gilead. DA reports consultancy fees, speakers’ bureau fees and grant/research support from AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz and Sanofi., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: Venous thromboembolism (VTE) poses a significant global health challenge, notably exacerbated by the use of combined oral contraceptives (COCs). Evidence mainly focuses on the type of progestogen used in COCs to establish the increased risk of VTE with less data assessed on the type of estrogen used. This meta-analysis aims to assess the risk of VTE associated with COCs containing synthetic estrogens like ethinylestradiol (EE) versus natural estrogens like estradiol (E2)., Methods: A systematic review and meta-analysis was conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searches were performed in December 2023 in MEDLINE and EMBASE to identify clinical studies comparing the VTE risk between COCs containing synthetic versus natural estrogens. Studies were selected through rigorous screening, and data extraction followed standardized protocols, with statistical analyses employing a random effects model., Results: The search yielded five relevant studies, involving over 560,000 women/time, demonstrating a significant 33% reduction in VTE risk among users of natural estrogen-based COCs compared to synthetic estrogen-based COCs (OR 0.67, 95% CI 0.51-0.87). Stratification analyses using adjusted hazard ratios (HR) of the main observationnal studies showed a 49% reduced VTE risk of E2-based pills compared to EE in association with levonorgestrel., Discussion and Conclusion: Despite the longstanding use of EE-based COCs, emerging evidence supports a lower thrombotic risk associated with natural estrogens. This meta-analysis substantiates the lower VTE risk associated with natural estrogen-based COCs compared to synthetic alternatives, advocating for a re-evaluation of contraceptive guidelines to prioritize patient safety and reduce thrombotic risks., Competing Interests: Authors JD, MD, ND, and LM were employed by company Qualiblood sa. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Douxfils, Raskin, Didembourg, Donis, Dogné, Morimont and Beaudart.)

Background: Increased risk of venous thromboembolism (VTE) is a life-threatening side effect for users of oral contraceptives (OCs) or hormone therapy (HT)., Objectives: To 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)., Methods: Use 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., Results: The 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)., Conclusion: The 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., Competing Interests: Declaration of competing interests T.N. receives speaking honoraria from Servier Finland and AstraZeneca. All other authors have no relevant disclosures., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Objectives: The ORAL Surveillance trial, a postmarketing safety clinical trial, found an increased risk of adverse cardiovascular events and venous thromboembolism (VTE) in patients treated with Janus Kinase (JAK) inhibitors compared to tumor necrosis factor (TNF) inhibitors. However, additional studies yielded mixed results and data on other JAK inhibitors are limited., Methods: A retrospective, pharmacovigilance study using the FDA adverse event reporting system (FAERS) to assess reporting of adverse cardiovascular events following treatment with JAK inhibitors in rheumatoid arthritis (RA) patients between January 2015 and June 2023. To identify disproportionately increased reporting, an adjusted reporting odds ratio (adj.ROR) was calculated with a multivariable logistic regression model., Results: We identified safety reports of 75,407 RA patients treated with JAK inhibitors (tofacitinib, n = 52,181; upadacitinib, n = 21,006; baricitinib, n = 2,220) and 303,278 patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs; TNF inhibitors, rituximab, and tocilizumab). The mean age was 61.2(±12) and 59.0(±13), respectively; 82 % and 81 % were women. Compared to bDMARDs, JAK inhibitors were associated with an increased reporting of VTE [n = 1,393, adj.ROR=2.11 (1.97-2.25)], stroke [n = 973, adj.ROR=1.25 (1.16-1.34)], ischemic heart disease [IHD, n = 999, adj.ROR=1.23 (1.13-1.33)], peripheral edema [n = 2699, adj.ROR=1.22 (1.17-1.28)], and tachyarrhythmias [n = 370, adj.ROR=1.15 (1.00-1.33)]. Most of the events occurred in the first year after treatment initiation. When different JAK inhibitors were compared, VTE, stroke, and IHD were more frequently reported with upadacitinib and baricitinib than tofacitinib. When stratified by age category, all safety signals were statistically significant in patients aged≤65 years., Conclusion: In this global postmarketing study, JAK inhibitors are associated with increased reporting of VTE, stroke, IHD, and tachyarrhythmias. These adverse events were reported following all JAK inhibitors that were studied, suggesting a class effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Second-generation antipsychotics (SGAs) are commonly prescribed medications used to treat a variety of mental health conditions. Recent data has correlated antipsychotic medications with venous thromboembolism (VTE). SGAs have diverse side effect profiles, which may contribute to differences in incidence of VTE. It is unknown which SGAs confer the most risk, and what the mechanism of increased risk is. Objective: Determine incidence of VTE in Veterans at Veterans Affairs North Texas Health Care System (VA-NTX HCS) between SGAs aripiprazole, olanzapine and risperidone. Methods: Retrospective chart review of adult Veterans at VA-NTX HCS between October 2015 to December 2019 prescribed aripiprazole, olanzapine, or risperidone. Results: Of 823 Veterans, incidence of VTE was lowest in aripiprazole group at .4%, increased to 1.7% in the olanzapine group, and was highest at 2.5% in the risperidone group . However, differences in incidence of VTE between SGAs were not statistically different, indicating no between-group differences. Conclusion: There was no difference in the incidence of VTE between risperidone, olanzapine, or aripiprazole. Given multiple limitations with this study, higher-powered studies should be conducted to investigate the possibility of differences in the incidence of VTE between the SGAs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Venous thromboembolism is associated with significant patient morbidity, mortality, and can lead to delays in treatment for patients with cancer. The objectives of this study were to identify the incidence of venous thromboembolism in patients with advanced ovarian cancer receiving neoadjuvant chemotherapy, and identify risk factors for venous thromboembolism., Methods: A systematic literature search of biomedical databases, including Ovid Medline, Web of Science, Scopus, CINAHL, and Embase was performed on December 6, 2022 and updated on December 21, 2023 for peer reviewed articles. Studies were included if they were cohort studies or randomized controlled trials that evaluated the incidence of venous thromboembolism for patients with ovarian cancer receiving neoadjuvant chemotherapy. Risk of bias assessment was performed using the Newcastle Ottawa Scale for cohort studies and the Cochrane risk of bias tool for randomized controlled trials. Random effects meta-analysis was used to pool results across studies., Results: A total of 2636 studies were screened, and 11 were included in the review. Ten were retrospective cohort studies, and one was a randomized controlled trial. The incidence of venous thromboembolism in the included studies ranged from 0% to 18.9%. The pooled incidence rate of venous thromboembolism was 10% (95% confidence interval (CI) 7% to 13%). This remained significant when restricted to only studies with a low risk of bias (pooled incidence of 11%, 95% CI 9% to 14%). Body mass index of ≥30 kg/m 2 was a significant risk factor for venous thromboembolism with a pooled odds ratio of 1.76 (95% CI 1.13 to 2.76) CONCLUSIONS: The results from this study demonstrated a 10% incidence of venous thromboembolism for patients with advanced ovarian cancer receiving neoadjuvant chemotherapy. This suggests that there may be a role for universal thromboprophylaxis in this population., Trial Registration: PROSPERO CRD42022339602., Competing Interests: Competing interests: SP has received consultancy fees from GSK., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM., (© 2024 Wiley Periodicals LLC.)

Background: This study aimed to measure and present a comprehensive overview of the association of antipsychotic drugs and venous thromboembolism (VTE) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Method: All VTE cases treated with antipsychotic drugs as primary suspected medicines were extracted from the FAERS database from 2004 to 2021. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC)., Results: In the FAERS system, 4,455 VTE cases associated with antipsychotics were identified. The VTE signal was detected with olanzapine, haloperidol, paliperidone, and quetiapine. The RORs and 95% confidence intervals (95% CI) of olanzapine, haloperidol, paliperidone, and quetiapine were (ROR = 2.53 95% Cl 2.38-2.69 IC = 1.31 95% Cl 1.11-1.52), (ROR = 2.17 95% Cl 1.91-2.46 IC = 1.1 95% Cl 0.66-1.52), (ROR = 1.6 95% Cl 1.4-1.83 IC = 0.67 95% Cl 0.22-1.11), and (ROR = 1.37 95% Cl 1.28-1.47 IC = 0.45 95% Cl 0.23-0.67). Pulmonary embolism occurred in more than 50% of VTE events (2760 cases, 52.84%)., Conclusion: The data mining of FAERS suggested an association between VTE and antipsychotic drugs, which reminds medical workers to pay attention to the serious adverse drug effects of antipsychotic drugs leading to venous thromboembolism.

Background: In 2019, the Food and Drug Administration issued a black box warning for increased risk of venous thromboembolism in patients with rheumatoid arthritis exposed to tofacitinib. There are limited data regarding postoperative venous thromboembolism risk in patients with ulcerative colitis exposed to tofacitinib., Objective: To assess whether preoperative exposure to tofacitinib is associated with increased odds of postoperative venous thromboembolism., Design: Retrospective review., Settings: Tertiary academic medical center., Patients: Consecutive patients exposed to tofacitinib within 4 weeks before total abdominal colectomy or total proctocolectomy, with or without ileostomy, from 2014 to 2021, matched 1:2 for tofacitinib exposure or no exposure., Intervention: Tofacitinib exposure versus no exposure., Main Outcome Measures: Ninety-day postoperative venous thromboembolism rate., Results: Forty-two patients with tofacitinib exposure and 84 case-matched patients without tofacitinib exposure underwent surgery for medically refractory ulcerative colitis. Nine (22.0%) tofacitinib-exposed patients and 7 (8.5%) unexposed patients were diagnosed with venous thromboembolism within 90 days of surgery. In univariate logistic regression, patients exposed to tofacitinib had 3.01 times increased odds of developing venous thromboembolism within 90 days after surgery compared to unexposed patients ( p = 0.04; 95% CI, 1.03-8.79). Other venous thromboembolism risk factors were not significantly associated with venous thromboembolisms. Venous thromboembolisms in both groups were most commonly portomesenteric vein thromboses (66.7% in the tofacitinib-exposed group and 42.9% in the unexposed group) and were diagnosed at a mean of 23.2 days (range, 3-90 days) postoperatively in the tofacitinib-exposed group and 7.9 days (1-19 days) in the unexposed group. There were no statistically significant differences in location or timing between the 2 groups., Limitations: Retrospective nature of the study and associated biases. Reliance on clinically diagnosed venous thromboembolisms may underreport the true incidence rate., Conclusions: Tofacitinib exposure before surgery for medically refractory ulcerative colitis is associated with 3 times increased odds of venous thromboembolism compared with patients without tofacitinib exposure. See Video Abstract ., Tofacitinib Se Asocia Con Un Mayor Riesgo De Tromboembolismo Venoso Postoperatorio En Pacientes Con Colitis Ulcerosa: ANTECEDENTES:En 2019, la FDA emitió una advertencia de recuadro negro sobre un mayor riesgo de tromboembolismo venoso en pacientes con artritis reumatoide expuestos a tofacitinib. Hay datos limitados sobre el riesgo de tromboembolismo venoso postoperatorio en pacientes con colitis ulcerosa expuestos a tofacitinib.OBJETIVO:Evaluar si la exposición preoperatoria a tofacitinib se asocia con mayores probabilidades de tromboembolismo venoso postoperatorio.DISEÑO:Revisión retrospectiva.LUGARES:Centro médico académico terciario.PACIENTES:Pacientes consecutivos expuestos a tofacitinib dentro de las 4 semanas previas a la colectomía abdominal total o proctocolectomía total, con o sin ileostomía, entre 2014 y 2021, emparejados 1:2 para exposición a tofacitinib o ninguna exposición.INTERVENCIÓN(S):Exposición a tofacitinib versus ninguna exposición.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de tromboembolismo venoso posoperatorio a los 90 días.RESULTADOS:Cuarenta y dos pacientes con exposición a tofacitinib y 84 pacientes de casos similares sin exposición a tofacitinib se sometieron a cirugía por colitis ulcerosa médicamente refractaria. Nueve (22,0%) pacientes expuestos a tofacitinib y 7 (8,5%) pacientes no expuestos fueron diagnosticados con tromboembolismo venoso dentro de los 90 días posteriores a la cirugía. En la regresión logística univariada, los pacientes expuestos a tofacitinib tuvieron 3,01 veces más probabilidades de desarrollar un tromboembolismo venoso dentro de los 90 días posteriores a la cirugía en comparación con los no expuestos ( p = 0,04, IC del 95 %: 1,03-8,79). Otros factores de riesgo de tromboembolismo venoso no se asociaron significativamente con el tromboembolismo venoso. Los tromboembolismos venosos en ambos grupos fueron más comúnmente trombosis de la vena portomesentérica (66,7% en los expuestos a tofacitinib y 42,9% en los no expuestos) y se diagnosticaron en una media de 23,2 días (rango, 3-90 días) después de la operación en los expuestos a tofacitinib y 7,9 días. (1-19 días) en los grupos no expuestos, respectivamente. No hubo diferencias estadísticamente significativas en la ubicación o el momento entre los dos grupos.LIMITACIONES:Carácter retrospectivo del estudio y sesgos asociados. La dependencia de tromboembolismos venosos diagnosticados clínicamente puede subestimar la tasa de incidencia real.CONCLUSIONES:La exposición a tofacitinib antes de la cirugía para la colitis ulcerosa médicamente refractaria se asocia con probabilidades 3 veces mayores de tromboembolismo venoso en comparación con los pacientes sin exposición a tofacitinib. (Traducción-Dr. Mauricio Santamaria )., (Copyright © The ASCRS 2024.)

Background: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin., Methods: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) twice daily or 81 mg of aspirin twice daily for thromboprophylaxis. The duration of the thromboprophylaxis, including post-discharge prescription, was based on hospital protocols. The study outcomes included patient satisfaction with and out-of-pocket costs for their thromboprophylactic medication measured on ordinal scales., Results: The trial enrolled 12,211 patients (mean age and standard deviation [SD], 45 ± 18 years; 62% male), 9725 of whom completed the question regarding their satisfaction with the medication and 6723 of whom reported their out-of-pocket costs. The odds of greater satisfaction were 2.6 times higher for patients assigned to aspirin than those assigned to low-molecular-weight heparin (odds ratio [OR]: 2.59; 95% confidence interval [CI]: 2.39 to 2.80; p < 0.001). Overall, the odds of incurring any out-of-pocket costs for thromboprophylaxis medication were 51% higher for patients assigned to aspirin compared with low-molecular-weight heparin (OR: 1.51; 95% CI: 1.37 to 1.66; p < 0.001). However, patients assigned to aspirin had substantially lower odds of out-of-pocket costs of at least $25 (OR: 0.15; 95% CI: 0.12 to 0.18; p < 0.001)., Conclusions: Use of aspirin substantially improved patients' satisfaction with their medication after orthopaedic trauma. While aspirin use increased the odds of incurring any out-of-pocket costs, it protected against costs of ≥$25, potentially improving health equity for thromboprophylaxis., Level of Evidence: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This study was funded by the Patient-Centered Outcomes Research Institute (PCS-1511-32745 and DI-2022C3-29701). The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H893 )., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Purpose: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis., Methods: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons., Results: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM., Conclusion: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated., (© 2024. Crown.)

•The risk of venous thromboembolism (VTE) is not increased in women using long-acting reversible contraceptive methods (LARCs) with progestogens. •Oral contraceptives with levonorgestrel or norgestimate confer half the risk of VTE compared to oral contraceptives containing desogestrel, gestodene or drospirenone. •Progestogen-only pills do not confer an increased risk of VTE. •Women using transdermal contraceptive patches and combined oral contraceptives (COCs) are at an approximately eight times greater risk of VTE than non-users of hormonal contraceptives (HCs), corresponding to 9.7 events per 10,000 women/years. •Vaginal rings increase the risk of VTE by 6.5 times compared to not using HC, corresponding to 7.8 events per 10,000 women/years. •Several studies have demonstrated an increased risk of VTE in transgender individuals receiving hormone therapy (HT). •Hormone therapy during menopause increases the risk of VTE by approximately two times, and this risk is increased by obesity, thrombophilia, age over 60 years, surgery and immobilization. •The route of estrogen administration, the dosage and type of progestogen associated with estrogen may affect the risk of VTE in the climacteric. •Combined estrogen-progesterone therapy increases the risk of VTE compared to estrogen monotherapy. •Postmenopausal HT increases the risk of thrombosis at atypical sites., Competing Interests: Conflicts of interest: none to declare.

Background: Intimate partner violence (IPV) targeting women is probably underestimated during a woman's lifetime. Venous thromboembolism (VTE) is a multifactorial disease associated with haemostasis-activating conditions. Minor injuries can trigger VTE., Objectives: We aimed to look for an association between VTE and IPV in women taking combined oral contraceptives (COCs) METHODS: We performed a multicentric, international, matched case-control study. Patients were women with a first VTE associated with COC intake. Controls were women taking COCs undergoing regular gynaecological check-ups. Patients and Controls were matched for country, age, length of COC intake and type (997 pairs). IPV was evaluated using the WAST self-administrated questionnaire., Results: IPV, defined as a WAST score value at least 5, was diagnosed in 33 Controls (3.3 %) and 109 patients (10.9 %), conditional odds ratio (OR): 3.586, 95 % confidence interval (2.404-5.549), p < 0.0001. After multivariate analysis, the adjusted OR was 3.720 (2.438-5.677), p < 0.0001. Sensitivity analysis using increasing WAST score thresholds confirmed the association., Conclusions: A first VTE in women taking COCs is associated with IPV. This association can have strong human consequences but also raises significant medical issues, for instance on the haemorrhagic risk of anticoagulant treatments in abused women. Pathophysiological studies are warranted., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: The incidence of venous thromboembolism (VTE) is notably high in lung cancer patients, particularly among those treated with immune checkpoint inhibitors (ICIs). Previous studies have focused on the relationship between Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) and VTE risk in immune checkpoint inhibitor therapy, but available evidence is inconsistent., Methods: The clinical data of lung cancer patients treated with ICIs were collected and analyzed from West China Hospital between January 2018 and March 2022. ECOG PS score was measured on admission. The primary outcome was the incidence of VTE, encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE). Multivariate logistic regression analysis was conducted to calculate the odds ratio (OR) and 95% confidence interval (95% CI)., Results: A total of 1115 lung cancer patients receiving ICIs were eligible for this study, VTE developed in 105 (9.4%) during the 12-month follow-up, of which 95 (8.5%) had DVT,14 (1.3%) had definite PE. Poor ECOG PS (PS ≥ 2) was associated with an increased risk for VTE (OR = 5.405, 95% CI = 3.067-9.525, P < 0.001), DVT (OR = 4.669, 95% CI = 2.588-8.427, P < 0.001) and PE (OR = 8.413, 95% CI = 2.565-27.600, P < 0.001) after multivariable adjustment in the study cohort., Conclusion: VTE occurred in 9.4% of lung cancer patients treated with ICIs, and poor performance status was associated with an increased risk of VTE., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial, and its mechanisms are yet to be fully understood. Thus, in this study, we aim to determine the associations of antipsychotic drugs with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), and their potential mechanisms., Methods: We first mined the adverse event signals of VTE, DVT, and PE caused by antipsychotic drugs in Food and Drug Administration Adverse Event Reporting System (FAERS). Next, we used two-sample Mendelian randomization (MR) method to investigate the association of antipsychotic drug target gene expression with VTE, DVT, and PE, using single-nucleotide polymorphisms as genetic instruments. We not only used the expression of all antipsychotic drug target genes as exposure to perform MR analyses but also analyzed the effect of single target gene expression on the outcomes., Results: In the FAERS, 1694 cases of VTE events were reported by 16 drugs. However, using the MR approach, no significant association was determined between the expression of all antipsychotic target genes and VTE, DVT, or PE, either in blood or brain tissue. Although the analysis of single gene expression data showed that the expression of nine genes was associated with VTE events, these targets lacked significant pharmacological action., Conclusions: Adverse event mining results have supported the claim that antipsychotic drugs can increase the risk of VTE. However, we failed to find any genetic evidence for this causal association and potential mechanisms. Thus, vigilance is still needed for antipsychotic drug-related VTE despite the limited supporting evidence.

Introduction: There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE)., Materials and Methods: We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg., Results: The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81-1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08-1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84-1.51, P = 0.41)., Conclusions: Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoshito Ogihara reports a relationship with Bayer Healthcare that includes: funding grants and speaking and lecture fees. Yoshito Ogihara reports a relationship with Daiichi Sankyo Co Ltd. that includes: funding grants and speaking and lecture fees. Yoshito Ogihara reports a relationship with Bristol Myers Squibb that includes: speaking and lecture fees. Yoshito Ogihara reports a relationship with Pfizer that includes: speaking and lecture fees. Yugo Yamashita reports a relationship with Bayer Healthcare that includes: funding grants and speaking and lecture fees. Yugo Yamashita reports a relationship with Daiichi-Sankyo that includes: funding grants and speaking and lecture fees. Yugo Yamashita reports a relationship with Bristol Myers Squibb that includes: speaking and lecture fees. Yugo Yamashita reports a relationship with Pfizer that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Daiichi Sankyo that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Japan Lifeline that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Kowa that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Kyocera that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Novartis that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Toray that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Sanofi that includes: consulting or advisory. Kazuhisa Kaneda reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Kazuhisa Kaneda reports a relationship with Pfizer that includes: speaking and lecture fees. Kazuhisa Kaneda reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Pfizer that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Nobutaka Ikeda reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Nobutaka Ikeda reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Nobutaka Ikeda reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Satoshi Ikeda reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Satoshi Ikeda reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Satoshi Ikeda reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Norimichi Koitabashi reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Norimichi Koitabashi reports a relationship with Pfizer that includes: funding grants. Kaoru Dohi reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Kaoru Dohi reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Kaoru Dohi reports a relationship with Pfizer that includes: speaking and lecture fees. Kaoru Dohi reports a relationship with Daiichi Sankyo that includes: funding grants and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Vascular involvement in Behçet's disease (BD) occurs in up to 50% of patients. The main mechanism of thrombosis is inflammation. Thus, immunosuppressants (IS) are the mainstay of therapy, and adding anticoagulation (AC) is controversial. In daily practice, we observed that patients who received AC in combination with IS experienced less recurrent thrombosis and decided to investigate our BD patients retrospectively. We hypothesized that adding AC to immunosuppressive therapy may lower the risk of recurrent thrombosis. Treatment at the time of first or recurrent thrombotic events was recorded. Events under the only IS and IS + AC treatments were compared. There were 40 patients (33 males). The most common types of first vascular events were deep vein thrombosis (77.5%) followed by pulmonary embolism (PE) (52.5%). One patient did not receive any treatment. Among the 39 patients, 32 received glucocorticoid and at least one of the azathioprine, or cyclophosphamide, anti-TNF, 5 received monotherapy with azathioprine, 1 received monotherapy with corticosteroid, and the remaining 1 received monotherapy with cyclophosphamide. In total, 22 patients (55%) experienced 27 recurrent venous thromboembolism (VTE) events. Two (7.4%) events while only on AC, 2 (7.4%) events while on AC + IS, and 15 (55.5%) events occurred while on only IS. Eight (19.6%) patients were not receiving any treatment during relapses. The recurrence rate was statistically significantly lower in the IS + AC treatment group compared to IS alone. In conclusion, IS are the mainstay of treatment for BD, and adding AC may help to lower the recurrence risk of thrombotic events., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Menopausal hormone therapy (MHT) is known to increase the risk of venous thromboembolism (VTE), which includes deep vein thrombosis, pulmonary embolism, and less frequently cerebral vein thrombosis, but the absolute risk for a given patient is very low. After starting MHT, the risk of VTE seems to be at its highest, declining to the non-HRT user baseline level of risk after stopping. Whether estrogen-only or estrogen-progestin HRT combination is linked to a similar risk of VTE is unclear from the available evidence. The aim of this study is to evaluate the risks of developing VTE in relation to different types as well as different modes of administration of MHT through a database search including PubMed, MEDLINE, Google Scholar, Cochrane Library, and others in order to provide the women carers with the up-to-date and evidence-based guidelines and recommendations while counseling the post-menopausal women enquiring on use of hormonal therapies either to alleviate the menopausal symptoms or to prevent the long-term sequelae of estrogen deficiency., Competing Interests: The Authors declared no conflict of interest, (African Journal of Reproductive Health © 2024.)

Venous thromboembolism (VTE) is a massive clinical challenge, annually affecting millions of patients globally. VTE is a particularly consequential pathology, as incidence is correlated with extremely common risk factors, and a large cohort of patients experience recurrent VTE after initial intervention. Altered hemodynamics, hypercoagulability, and damaged vascular tissue cause deep-vein thrombosis and pulmonary embolism, the two permutations of VTE. Venous valves have been identified as likely locations for initial blood clot formation, but the exact pathway by which thrombosis occurs in this environment is not entirely clear. Several risk factors are known to increase the likelihood of VTE, particularly those that increase inflammation and coagulability, increase venous resistance, and damage the endothelial lining. While these risk factors are useful as predictive tools, VTE diagnosis prior to presentation of outward symptoms is difficult, chiefly due to challenges in successfully imaging deep-vein thrombi. Clinically, VTE can be managed by anticoagulants or mechanical intervention. Recently, direct oral anticoagulants and catheter-directed thrombolysis have emerged as leading tools in resolution of venous thrombosis. While a satisfactory VTE model has yet to be developed, recent strides have been made in advancing in silico models of venous hemodynamics, hemorheology, fluid-structure interaction, and clot growth. These models are often guided by imaging-informed boundary conditions or inspired by benchtop animal models. These gaps in knowledge are critical targets to address necessary improvements in prediction and diagnosis, clinical management, and VTE experimental and computational models., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Anti-myelin-associated glycoprotein (MAG) neuropathy is a debilitating demyelinating polyneuropathy with no approved therapies. Our primary objective was to ascertain lenalidomide safety and maximum tolerated dose (MTD) in anti-MAG neuropathy., Methods: This phase 1b, open-label, single-arm, dose-finding trial was conducted from 2019 through 2022. The original design included a dose-escalation/extension phase followed by a dose-expansion phase. Three doses of lenalidomide were evaluated: 10, 15, and 25 mg. The main outcome was the MTD., Results: Eleven patients enrolled (10 men), with a mean age of 67.6 years (SD = 6.18, range 58-77 years) and mean disease duration of 8.5 years (SD = 10.9, range 1-40 years). The study terminated early due to higher-than-expected non-dose-limiting toxicity venous thromboembolism (VTE) events. The calculated MTD was 25 mg (posterior mean of toxicity probability was 0.01 with a 95% credible interval of 0.00, 0.06), but a recommended phase 2 dose of 15 mg was advised. For secondary exploratory outcomes, only EQ-5D (-0.95, 95% CI -1.81 to -0.09) and total IgM (-162 mg/dL, 95% CI -298 to -26) showed signs of improvement by month 12., Conclusions: Lenalidomide was associated with higher-than-expected VTE events in anti-MAG neuropathy patients, despite a calculated MTD of 25 mg. A recommended phase 2 dose of 15 mg was advised. Lenalidomide did not improve disability or impairment at 12 months, although this study was not powered for efficacy. The risks of long term lenalidomide may outweigh benefit for patients with anti-MAG neuropathy. Any future efficacy study should address VTE risk, as current myeloma guidelines appear inadequate., Trial Registration: Lenalidomide in Anti-MAG Neuropathy: Phase 1b Study, ClinicalTrials.gov Identifier: NCT03701711, https://clinicaltrials.gov/ct2/show/NCT03701711. First submitted October 10, 2018. First patient enrolled in January 2019., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

This pooled analysis compared the risk of venous thromboembolism (VTE) associated with combined oral contraceptives (COCs) containing estradiol (E2) valerate-dienogest with those containing ethinyl E2-levonorgestrel. Data were retrieved from two large, prospective, observational cohort studies. Propensity score subclassification was applied to balance baseline parameters between the COC user cohorts. Crude and adjusted hazard ratios (HRs) were calculated based on the extended Cox model. The pooled data set included 11,616 E2 valerate-dienogest users and 18,681 ethinyl E2-levonorgestrel users, contributing 17,932 and 29,140 women-years of observation, respectively. A significantly decreased VTE risk in E2 valerate-dienogest COCs compared with ethinyl E2-levonorgestrel COCs was observed (propensity score-stratified HR 0.46, 95% CI, 0.22-0.98). This pooled analysis expands data from a previous postauthorization safety study and provides valuable real-world safety information on the relative safety of current COCs., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Evolving evidence suggests that patients receiving Janus kinase-signal transducer and activator of transcription inhibitors (JAK-STATi) may be at higher risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE). Most existing literature has focused on indications that may confer a higher MACE and VTE risk than that among patients with isolated dermatological indications., Objective: To evaluate risk of MACE, VTE, serious adverse events (SAEs), and tolerability of systemic JAK-STATi compared with placebo, in those with a dermatologic indication., Data Sources: A systematic review of the literature was carried out to June 2023, using databases Embase, MEDLINE, SCOPUS, Cochrane Library of Registered Trials, and registered Clinical Trials. The analysis was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The analysis itself took place in June 2023., Study Selection: Placebo-controlled randomized clinical trials that compared systemic JAK-STATi with placebo, and investigated the safety in patients with alopecia areata, psoriasis, vitiligo, atopic dermatitis, lichen planus or hidradenitis suppurativa., Data Extraction and Synthesis: Study selection and data extraction by 2 authors working independently using a standardized template. Crude numbers for MACE, VTE, SAEs, and study discontinuation due to treatment emergent adverse events (TEAEs) were pooled and underwent meta-analysis., Main Outcomes and Measures: Incidence of MACE, VTE, SAE, and study discontinuation due to TEAEs. Analysis of these values against person exposure years to determine the incidence rate (IR). Risk ratios (RRs) compared incidence rates among treatment and placebo comparator arms., Results: Forty-five randomized clinical trials were eligible for inclusion, with 12 996 patients receiving active JAK-STATi therapy and 4925 allocated to placebo treatment. Meta-analysis found no significant increase in MACE (I2 = 0.00%; RR, 0.47; 95% CI, 0.28-0.80) or VTE (I2 = 0.00%; RR, 0.46; 95% CI, 0.26-0.80) between placebo and JAK-STATi comparator arms. There was also no significant difference in SAEs (I2 = 12.38%; RR, 0.92; 95% CI, 0.72-1.20) and discontinuations between JAK-STATi and placebo (I2 = 23.55%; RR, 0.94; 95% CI, 0.76-1.19)., Conclusions and Relevance: This meta-analysis did not identify a significant increase in the risk of MACE and VTE in dermatology patients receiving JAK-STATi for median duration of 16 weeks. The results of this review suggest there is insufficient evidence that JAK-STATi confer an increased risk of cardiovascular complications in dermatological patients, especially when used for short time frames.

Purpose: Bevacizumab has evolved as an integral treatment option for patients with high-grade gliomas. Little is known about clinical risk factors that predispose patients with high-grade gliomas receiving bevacizumab to VTE or ICH. We sought to characterize the clinical risk factors associated with risk of either event., Methods: In this multi-institutional retrospective study, we first evaluated patients with high-grade gliomas who were treated with bevacizumab at University of Texas MD Anderson Cancer Center from 2015-2021. We compared clinical and treatment-related factors among three cohorts: those who developed VTE, ICH, or neither. We further compared survival outcomes of these patients from the time of bevacizumab initiation. Then to further confirm our results in a non-cancer center hospital setting we evaluated patients from two Ascension Seton Hospitals in Austin, Texas which are affiliated with Dell Medical School at the University of Texas at Austin from 2017-2022., Results: We found that the presence of cerebral macrobleeding, defined as a magnetic susceptibility of > 1 cm 3 on magnetic resonance imaging, was highly associated with risk of developing ICH after initiation of bevacizumab. Development of ICH was significantly associated with poorer survival outcomes. We did not find a statistically significant effect of VTE on survival after bevacizumab initiation., Conclusion: In order to stratify the risk for developing ICH before the initiation of bevacizumab, we recommend to assess for the presence of cerebral macrobleeding as it is associated with ICH development., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To assess bleeding risk of patients treated by oral anticoagulants, several scores have been constructed to assist physicians in the evaluation of the benefit risk. Most of these scores lack a strong enough level of evidence for use in family practice., Objective: To assess the predictive prognostic accuracy of 13 scores designed to assess the risk of major or clinically relevant non-major (CRNM) bleeding events in a French ambulatory cohort receiving Vitamin-K antagonists (VKA) or direct oral anticoagulants (DOACs) in a family practice setting., Methods: CACAO (Comparison of Accidents and their Circumstances with Oral Anticoagulants) was a multicentre prospective cohort of ambulatory patients prescribed oral anticoagulants. We selected patients from the cohort who had received an oral anticoagulant because of non-valvular atrial fibrillation (NVAF) and/or venous thromboembolism (VTE) to be followed during one year by their GP. The following scores were calculated: mOBRI, Shireman, Kuijer, HEMORR2HAGES, ATRIA, HAS-BLED, RIETE, VTE-BLEED, ACCP score, Rutherford, ABH-Score, GARFIEL-AF, and Outcomes Registry for Better InformedTreatment of Atrial Fibrillation (ORBIT). Prognostic accuracy was assessed by using receiver operating characteristic curves and c-statistics., Results: During 1 year, 3,082 patients were followed. All of the scores demonstrated only poor to moderate ability to predict major bleeding or CRNM in NVAF patients on DOACs (c-statistic: 0.41-0.66 and 0.45-0.58), respectively. The results were only slightly better for patients prescribed VKA (0.47-0.66 and 0.5-0.55, respectively) in this indication. The results were also unsatisfactory in patients treated for VTE., Conclusion: None of the scores demonstrated satisfactory discriminatory ability when used in family practice., Clinical Trial Registration: ClinicalTrials.gov NCT02376777., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Tranexamic acid (TXA) is a life-saving treatment for traumatic hemorrhage, but the optimal dosing regimen remains unknown. Different doses and treatment strategies have been proposed, including single bolus, repeated bolus, or bolus plus infusion. The aim of this study was to determine the effect of different TXA dosing strategies on clinical outcomes in bleeding trauma patients., Methods: Secondary analysis of a perpetual cohort study from a UK Level I trauma center. Adult patients who activated the local major hemorrhage protocol and received TXA were included. The primary outcome was 28-day mortality. Secondary outcomes were 24-hour mortality, multiple organ dysfunction syndrome, venous thromboembolism, and rotational thromboelastometry fibrinolysis., Results: Over an 11-year period, 525 patients were included. Three dosing groups were identified: 1 g bolus only (n = 317), 1 g bolus +1 g infusion over 8 hours (n = 80), and 2 g bolus (n = 128). Demographics and admission physiology were similar, but there were differences in injury severity (median Injury Severity Score, 25, 29, and 25); and admission systolic blood pressure (median Systolic Blood Pressure, 99, 108, 99 mm Hg) across the 1-g, 1 g + 1 g, and 2-g groups. 28-day mortality was 21% in each treatment group. The incidence of multiple organ dysfunction syndrome was significantly higher in the bolus plus infusion group (84%) vs. 1 g bolus (64%) and 2 g bolus (62%) group, p = 0.002, but on multivariable analysis was nonsignificant. Venous thromboembolism rates were similar in the 1-g bolus (4%), 2 g bolus (8%) and bolus plus infusion groups (7%). There was no difference in rotational thromboelastometry maximum lysis at 24 hours: 5% in both the 1-g and 2-g bolus groups vs. 4% in bolus plus infusion group., Conclusion: Clinical outcomes and 24-hour fibrinolysis state were equivalent across three different dosing strategies of TXA. Single bolus administration is likely preferable to a bolus plus infusion regimen., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2023 American Association for the Surgery of Trauma.)

Aims: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have off-target effects on haemoconcentration and anti-inflammation. The impact of SGLT-2i on the risk of venous thromboembolism (VTE) in patients with diabetes mellitus (DM) remains unclear. This study aimed to evaluate the risk of newly diagnosed VTE in patients with DM using SGLT-2i in comparison to dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA)., Materials and Methods: In this nationwide retrospective cohort study, we used data from Taiwan's National Health Insurance Research Database. Patients with diabetes aged 20 years or older who received SGLT-2i, DPP-4i, or GLP-1RA between 1 May 2016, and 31 December 2020, were included. The risks of VTE in SGLT-2i users were compared with those of DPP-4i and GLP-1RA users. A Cox regression model with stabilised inverse probability of treatment weighting was used to calculate hazard ratio (HR) for VTE risk. Additionally, a meta-analysis of relevant articles published before 23 May 2023, was conducted., Results: Data from 136,530 SGLT-2i, 598,280 DPP-4i, and 5760 GLP-1RA users were analysed. SGLT-2i use was associated with a lower risk of VTE than DPP-4i (HR, 0.70; 95% CI, 0.59-0.84; p < 0·001), but not with GLP-1RA (HR, 1.39; 95% CI, 0.32-5.94; p = 0.66). Our meta-analysis further supported these findings (SGLT-2i vs. DPP-4i: HR, 0.71; 95% CI, 0.62-0.82; p < 0·001; SGLT-2i vs. GLP-1RA: HR, 0.91; 95% CI, 0.73-1.15; p = 0.43), suggesting the robustness of our retrospective analysis., Conclusions: In patients with DM, SGLT-2i was associated with a lower risk of VTE compared to DPP-4i, but not GLP-1RA., (© 2023 John Wiley & Sons Ltd.)

Purpose: To evaluate whether the thromboembolic risk and contraceptive effectiveness of NOMAC-E2 observed in the PRO-E2 study can be extended to each participating country, as lifestyle, cardiovascular risk factors and prescribing habits may differ geographically. This analysis was performed on the PRO-E2 Italian subpopulation, where smoking habit and women over 35 years were more prevalent compared with the overall study population., Materials and Methods: Data from NOMAC-E2 or levonorgestrel-containing COCs (COC LNG ) new users were descriptively analysed. Incidence rates of thrombosis (events/10,000 women-years [WY]) and the Pearl Index (pregnancies/100 WY) were calculated., Results: Overall, 11,179 NOMAC-E2 and 8,504 COC LNG users were followed up to 2 years (34,869 WY). The NOMAC-E2 cohort included more women over 35 vs. COC LNG (37.7% vs. 31.8%; p  = 0.001). A comparable low risk of combined deep venous thrombosis of lower extremities (DVT) and pulmonary embolism (PE) was observed in NOMAC-E2 (1.7/10,000 WY; 95% CI: 0.21-6.2) and COC LNG users (6.6/10,000 WY; 95% CI: 2.4-14.4). Similar results were obtained by considering all thromboembolic events (VTE). Unintended pregnancies did not differ between NOMAC-E2 (0.12/100 WY; 95% CI: 0.06-0.21) and COC LNG (0.15/100 WY; 95% CI: 0.08-0.26) cohorts., Conclusion: Despite the higher age and tobacco use, findings from the Italian subpopulation were broadly consistent with overall PRO-E2 results, confirming a similar low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 and COC LNG ., Short Condensation: This subgroup analysis of the PRO-E2 study provides comprehensive epidemiological data on the use of combined oral contraceptives in a large Italian cohort, with a higher prevalence of women over 35 years and smokers. The study confirms the low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 pill.

Objective: Postmenopausal symptoms in women at higher risk for venous thromboembolism (VTE) due to comorbidities are often undertreated because of concerns that hormone therapy (HT) may increase VTE risk; however, it is unclear how much HT impacts risk of VTE when compared with other risk factors., Methods: This is a case-control study in a commercial claims database from 2007 to 2019. Women aged 50 to 64 years (n = 223,949) were classified as cases if they had an International Classification of Diseases code indicating an acute VTE plus a filled prescription for an anticoagulant, placement of intravascular vena cava filter, or death within 30 days of diagnosis. Controls were matched 10:1 to each case by index date and age. Risk factors and comorbidities present within the year before index were examined. Exposure was defined as a HT prescription within 60 days before index., Results: There were 20,359 VTE cases and 203,590 matched controls. A conditional logistic regression indicated that the greatest risks for VTE were from metastatic cancer (odds ratio [OR], 13.66; 95% CI, 12.64-14.75), hospitalization/surgery (OR, 8.51; 95% CI, 8.09-8.96), trauma (OR, 3.52; 95% CI, 3.32-3.73), comorbidity burden (OR, 3.51; 95% CI, 3.34-3.69), history of hypercoagulable condition (OR, 3.10; 95% CI, 2.87-3.36), and varicose veins (OR, 2.87; 95% CI, 2.56-3.22). Regarding hormone exposure, we observed ORs of 1.51 (95% CI, 1.43-1.60) for any recent hormone exposure; 1.13 (95% CI, 1.04-1.23; number needed to harm, 4,274) for unopposed estrogen menopausal HT; 1.23 (95% CI, 1.10-1.38; number needed to harm, 2,440) for combined menopausal HT; and 5.22 (95% CI, 4.67-5.84) for combined hormonal contraceptives compared with no recent HT exposure., Conclusions: Hormone therapy exposure did not appear to adversely influence other risk factors, and exposure generally played a minor role in VTE risk. Contraceptives, however, were a strong risk factor., Competing Interests: Financial disclosure/conflict of interest: John W. Davis receives ongoing funding from GE Healthcare and Novartis AG for consulting. The other authors have nothing to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The Menopause Society.)

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment are of interest in oncology due to ease of administration and lack of need for therapeutic monitoring compared to other anticoagulants. Data supporting their use in patients with hematologic malignancies post-hematopoietic stem cell transplant (HCT) are limited. The purpose of the study is to characterize DOAC use in HCT patients. This multicenter, retrospective cohort analysis included allogeneic and autologous HCT recipients. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB)/minor bleeding and VTE recurrence. Of 126 patients, 91 (72.2%) patients received an autologous HCT, and 35 (27.8%) patients received an allo-HCT. No major bleeding occurred in either transplant recipient groups. In autologous HCT recipients, CRNMB/minor bleeding occurred in four (4.4%) patients and VTE recurrence occurred in one (1.1%) patient. For allogeneic HCT recipients, CRNMB/minor bleeding occurred in five (14.3%) patients and VTE recurrence occurred in two (5.7%) patients. For patients that experienced a CRNMB, five (100%) of the allogeneic HCT and two (50%) of the autologous HCT recipients were thrombocytopenic at the time of bleeding. Only 38.5% of patients who experienced a drug-drug interaction requiring DOAC dose adjustment received the appropriate dose adjustment. DOACs were associated with low rates of recurrent VTE and no major bleeding events, similar to published data on DOAC use in the general cancer patient population. This suggests that DOACs may be safe therapeutic options with proactive management of drug interactions and careful monitoring for bleeding events, especially in the allogeneic HCT population where minor bleeding rates were slightly higher., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

In the context of the COVID-19 pandemic, this study investigates the potential correlation between the increased use of antipsychotic medications and the rising incidence of venous thromboembolism (VTE). As psychiatric disorders surged, the consequential escalation in antipsychotic drug use raised concerns about thrombotic risks. We conducted a comprehensive literature review using PubMed, focusing on articles that intersected COVID-19, antipsychotic medication, and thrombosis. This approach allowed for a nuanced examination of the historical and recent data on antipsychotic drugs and their association with thrombotic events. Our findings reveal a notable link between the use of antipsychotic medications, particularly second-generation antipsychotics, and an increased risk of VTE, including pulmonary embolism and deep vein thrombosis. This association was evident, despite variations in study designs and populations. The study underscores the need for cautious medication management in psychiatric care, especially during pandemic conditions like COVID-19, to mitigate thrombotic risks. It advocates a personalized approach to prescribing antipsychotics, considering individual patient factors and comorbidities, to balance the benefits against potential thrombotic complications.

Abstract: The persistence of risk of venous thromboembolism (VTE) due to combined hormonal contraceptives (CHCs), after their cessation, is unknown but important to guide clinical practice. The objective of this prospective cohort study was to define the time until normalization of estrogen-related thrombotic biomarkers after CHC cessation. We enrolled women aged 18 to 50 years who had decided to stop their CHC, excluding those with a personal history of VTE, anticoagulation, or pregnancy. The study started before cessation of CHC, with 6 visits afterwards (at 1, 2, 4, 6, and 12 weeks after cessation). Primary outcomes were normalized sensitivity ratios to activated protein C (nAPCsr) and to thrombomodulin (nTMsr), with sex hormone-binding globulin (SHBG) as a secondary end point. We also included control women without CHC. Among 66 CHC users, from baseline until 12 weeks, average levels of nAPCsr, nTMsr, and SHBG decreased from 4.11 (standard deviation [SD], 2.06), 2.53 (SD, 1.03), and 167 nmol/L (SD, 103) to 1.27 (SD, 0.82), 1.11 (SD, 0.58), and 55.4 nmol/L (SD, 26.7), respectively. On a relative scale, 85.8%, 81.3%, and 76.2% of the decrease from baseline until 12 weeks was achieved at 2 weeks and 86.7%, 85.5%, and 87.8% at 4 weeks after CHC cessation, respectively. Levels were not meaningfully modified throughout the study period among 28 control women. In conclusion, CHC cessation is followed by a rapid decrease in estrogen-related thrombotic biomarkers. Two to 4 weeks of cessation before planned major surgery or withdrawal of anticoagulants in patients with VTE appears sufficient for the majority of women. The trial is registered at www.clinicaltrials.gov as #NCT03949985., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Venous thromboembolism is a multifactorial dis ease and major cause of morbidity and mortality. Absolute risk of venous thromboembolism is less than 1 per 10,000 per year in women of reproductive age. Hormonal contraception is a common risk situation for venous thromboembolism in this part of the population. The risk of venous thrombosis depends on many factors, mainly female characteristics and also the type of contraception. Hematologists can help with the choice of contraception in females with inherited thrombophilia and females experiencing thrombosis. Intrauterine devices with levonorgestrel seem to be the best option in these settings.

Background: Data on complications after upper extremity vein thrombosis (UEVT) are limited and heterogeneous., Methods: The aim of the present study was to evaluate the pooled proportions of venous thromboembolism (VTE) recurrence, bleeding, and post-thrombotic syndrome (PTS) in patients with UEVT. A systematic literature review was conducted of PubMed, Embase, and the Cochrane Library databases from January 2000 to April 2023 in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. All studies included patients with UEVT and were published in English. Meta-analyses of VTE recurrence, bleeding, and of PTS after UEVT were performed to compute pooled estimates and associated 95% confidence intervals (CIs). Subgroup analyses of cancer-associated UEVT and catheter-associated venous thrombosis were conducted. Patients with Paget-Schroetter syndrome or effort thrombosis were excluded., Results: A total of 55 studies with 15,694 patients were included. The pooled proportions for VTE recurrence, major bleeding, and PTS were 4.8% (95% CI, 3.8%-6.2%), 3.0% (95% CI, 2.2%-4.0%), and 23.8% (95% CI, 17.0%-32.3%), respectively. The pooled proportion of VTE recurrence was 2.7% (95% CI, 1.6%-4.6%) for patients treated with direct oral anticoagulants (DOACs), 1.7% (95% CI, 0.8%-3.7%) for patients treated with low-molecular-weight heparin (LMWH), and 4.4% (95% CI, 1.5%-11.8%) for vitamin K antagonists (VKAs; P = .36). The pooled proportion was 6.3% (95% CI, 4.3%-9.1%) for cancer patients compared with 3.1% (95% CI, 2.1%-4.6%) for patients without cancer (P = .01). The pooled proportion of major bleeding for patients treated with DOACs, LMWH, and VKAs, was 2.1% (95% CI, 0.9%-5.1%), 3.2% (95% CI, 1.4%-7.2%), and 3.4% (95% CI, 1.4%-8.4%), respectively (P = .72). The pooled proportion of PTS for patients treated with DOACs, LMWH, and VKAs was 11.8% (95% CI, 6.5%-20.6%), 27.9% (95% CI, 20.9%-36.2%), and 24.5% (95% CI, 17.6%-33.1%), respectively (P = .02)., Conclusions: The results from this study suggest that UEVT is associated with significant rates of PTS and VTE recurrence. Treatment with DOACs might be associated with lower PTS rates than treatment with other anticoagulants., Competing Interests: Disclosures None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions., Objective: To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions., Data Sources: PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023., Study Selection: This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded., Data Extraction and Synthesis: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO., Main Outcomes and Measures: Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE., Results: The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04)., Conclusions and Relevance: In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.

Estrogen depletion following menopause predisposes to increased risk of cardiovascular disease (CVD), mainly due to ischemic heart disease. This is mostly evident in cases with premature menopause. The pathophysiological basis for this atherosclerotic process is the accumulation of several risk factors, such as abdominal obesity, atherogenic dyslipidemia, insulin resistance and arterial hypertension. The presence of vasomotor symptoms may further augment this risk, especially in women younger than 60 years. Menopausal hormone therapy (MHT) exerts many beneficial effects on lipid profile and glucose homeostasis as well as direct arterial effects, and may reduce CVD risk if initiated promptly (i.e.,<60 years or within ten years of the final menstrual period). Transdermal estradiol and micronized progesterone or dydrogesterone are the safest regimens in terms of venous thromboembolic events (VTE) and breast cancer risk. In any case, an individualized approach, taking into account the patient's total CVD, VTE and breast cancer risk, is recommended., Competing Interests: Conflict of interest statement Dr. Anagnostis declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The antifibrinolytic tranexamic acid (TXA) may reduce death in trauma; however, outcomes associated with TXA use in patients without proven hyperfibrinolysis remain unclear. We analyzed the associations of empirically administered TXA, hypothesizing that TXA use would correlate to lower transfusion totals but increased thromboembolic complications., Methods: This retrospective cohort study compared trauma patients started on massive transfusion protocol at a Level I trauma center from 2016 to 2021 who either did or did not receive TXA. Our primary outcome was in-hospital mortality. Venous thromboembolism (VTE; pulmonary embolism or deep vein thrombosis), transfusion volumes, and coagulation measures were considered secondarily. Descriptive statistics, univariate analyses, and multivariable logistic regression were used to evaluate differences in outcomes., Results: TXA patients presented with lower systolic blood pressure (100 versus 119.5 mmHg, P = 0.009), trended toward higher injury severity (ISS of 25 versus 20, P = 0.057), and were likelier to have undergone thoracotomy or laparotomy (89 versus 71%, P = 0.002). After adjusting for age, mechanism, presenting vitals, and operation, TXA was not significantly associated with mortality or VTE. TXA patients had larger volumes of packed red blood cells, platelets, and plasma transfused within 4- and 24-h (P ≤ 0.002). No differences in clot stability, captured via thromboelastography, were noted., Conclusions: Despite no differences in mortality or VTE between patients who did and did not receive TXA, there were significant differences in transfusion totals. TXA patients had worse presenting physiology and likely had more severe bleeding. This absence of adverse outcomes supports TXA's safety. Nevertheless, further inquiry into the precise mechanism of TXA may help guide its empiric use, allowing for more targeted application., (Copyright © 2023 Elsevier Inc. All rights reserved.)

INTRODUCTION: A recent finding of a deep venous thrombosis during spaceflight has prompted the need to clarify mechanisms and risks of venous thromboembolism (VTE). In turn, mitigation countermeasures, diagnostic modalities, and treatment options must be explored. The objective of this review was to synthesize current evidence on VTE in spaceflight. METHODS: A literature review was performed from inception to April 2023 pertaining to VTE in the context of spaceflight or ground-based analogs with human participants. PubMed was searched for papers written in English using the terms "spaceflight" or "weightlessness" and "thrombotic" or "embolism" or "thromboembolism" in "venous" or "veins". Papers using cellular or animal models were excluded. RESULTS: There were 63 papers captured; 7 original scientific studies, 3 narrative reviews, 2 systematic reviews, and 3 commentaries discussed VTE in spaceflight. Reference lists were screened. Important themes included: altered venous hemodynamics, increased fibrinogen and coagulation markers, hypoalbuminemia, and immune dysfunction. Additional risk factors may be seen in women, such as the use of oral contraceptives. DISCUSSION: Venous stasis and decreased shear stress secondary to fluid shifts may induce inflammatory changes in the venous system, resulting in endothelial damage and upregulation of the coagulation cascade. Additionally, women in space are subject to physiological factors increasing their VTE risk, such as the use of oral contraceptives, inducing increased blood viscosity and hypoalbuminemia. Efforts should also be placed in optimizing sensitivity and specificity of imaging markers, payload, and training ability, notably the use of vector flow imaging, and improving point-of-testing biomarkers, such as albumin and p-selectin. Levasseur S, Purvis N, Trozzo S, Chung SH, Ades M, Drudi LM. Venous thromboembolism in exploration class human spaceflight . Aerosp Med Hum Perform. 2024; 95(1):45-53.

Problem Identification: The risk of venous thromboembolism (VTE) in patients with lymphoma may be overlooked because patients often experience thrombocytopenia from the disease or chemotherapy. A meta-analysis was conducted to identify the prevalence of and risk factors for VTE in patients with lymphoma., Literature Search: A systematic search of Embase®, Web of Science, PubMed®, and Cochrane Library databases was conducted to identify relevant studies investigating VTE in patients with lymphoma., Data Evaluation: The methodologic quality of the eligible observational studies was assessed using the Newcastle-Ottawa Scale. Stata, version 12.0, was used to perform the meta-analysis., Synthesis: Female sex, older age, history of VTE, a diagnosis of diffuse large B-cell lymphoma, Ann Arbor stage III-IV disease, a higher performance status score, bulky disease, central nervous system involvement, a white blood cell count greater than 11 × 109/L, a D-dimer level greater than 0.5 mg/L, central venous catheterization, and treatment with doxorubicin were significant risk factors for VTE., Implications for Practice: This meta-analysis identified risk factors for VTE, which may provide a theoretical foundation for clinical staff to conduct early assessment and identification of high-risk VTE groups, allowing for timely intervention.

Background: Venous thromboembolic disease (VTE) is characterized by obstruction of venous blood flow by a thrombus. Survival data, frequency of disease recurrence, and bleeding rate in patients on anticoagulant therapy with warfarin compared to rivaroxaban in the Latin American population are limited in VTE., Methods: A retrospective cohort study with propensity score matching analysis was conducted in patients with pulmonary embolism and/or deep vein thrombosis anticoagulated with warfarin or rivaroxaban treated. Survival analysis was performed using a Kaplan-Meier curve for each of the intervention groups, and it was compared using a Log Rank test., Results: Of 2193 potentially eligible patients with a suspected diagnosis of VTE, 505 patients entered the analysis; of these, 285 subjects were managed with warfarin and 220 anticoagulated with rivaroxaban. Major bleeding at 12 months occurred in 2.7% (6/220) of patients treated with Rivaroxaban, compared to 10.2% (29/285) in the Warfarin group in the unmatched population (p = 0.001). In the matched population, bleeding at 12 months occurred in 2.9% (6/209) of patients on Rivaroxaban and in 11.0% (23/209) of patients on Warfarin (p = 0.001). The survival rates at 6 months were 97.1% for Rivaroxaban and 97.6% for Warfarin (p = 0.76). At 12 months, the survival rates were 94.7% for Rivaroxaban and 95.7% for Warfarin (p = 0.61)., Conclusion: In the treatment of VTE, there is no differences on 6 and 12-month survival or a reduction in the occurrence of new thromboembolic events when comparing rivaroxaban to warfarin. However, a lower risk of major bleeding is observed at 12 months with Rivaroxaban., (© 2023. The Author(s).)

Venous thromboembolism (VTE) is a multifactorial disease, and its risk depends on exposure to risk factors and predisposing conditions. Based on their strength of association with a VTE episode, risk factors are classified as major or minor and determined using a temporal pattern to be transient or persistent. All patients with VTE should receive anticoagulant treatment for at least 3 months in the absence of an absolute contraindication. Beyond this period, selected patients may be candidates for an extended phase of anticoagulation aimed at secondary VTE prevention. The risk of recurrent VTE if anticoagulation is discontinued is probably the main driver of decision-making regarding extended treatment. The risk of recurrence after VTE associated with major risk factors is low if the risk factor is no longer present. In this case, treatment can be discontinued. If the major risk factor is persistent, anticoagulation should be continued. After VTE occurring in the absence of risk factors, anticoagulation should probably be continued indefinitely if the risk for bleeding is low and preferably with minimal effective doses of anticoagulants. VTE occurring after exposure to minor risk factors is probably the most challenging situation, especially if the clinical manifestation was acute pulmonary embolism. Understanding the actual role of minor risk factors in the occurrence of VTE helps in estimating the risk of recurrence and avoiding the dangers associated with unnecessary anticoagulation. The availability of safer strategies for anticoagulation could allow personalized strategies for secondary prevention of VTE., (Copyright © 2023 by The American Society of Hematology.)

Pulmonary embolism (PE) is associated with significant morbidity and mortality in the absence of properly prescribed anticoagulant treatment. Direct oral anticoagulants (DOACs) are currently the anticoagulant treatment of first choice. The quality of anticoagulation in the acute phase of PE is a major determinant of patients' prognosis. The dose regimens for the initiation phase must therefore be rigorously respected to ensure the efficacy of the treatment. For the maintenance phase, the reduced doses used in atrial fibrillation are not applicable in venous thromboembolism (VTE) except for edoxaban. Finally, for long-term secondary prevention in patients at risk of VTE recurrence, reduced dose DOACs are currently a very interesting option in terms of benefit-risk balance for the majority of patients., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.