Risk Of Venous Thromboembolism Research Articles

Incidence of venous thromboembolism in newly diagnosed glioblastoma multiforme and associated risk factors: A retrospective chart review.

e14040 Background: Patients diagnosed with glioblastoma multiforme (GBM) are recognized as a population at high risk of developing venous thromboembolism (VTE) (1,2). A retrospective chart review of patients diagnosed with GBM at the Juravinski Cancer Centre (JCC) was performed with the primary objective to assess the incidence of the development of VTE in newly diagnosed GBM. The secondary objective was to identify patients who were at higher risk and who could benefit from prophylactic anticoagulation. Methods: This was a single-centre, retrospective cohort study. We reviewed the charts of 528 patients diagnosed with GBM at the JCC from an 8-year period from January 1, 2013 to December 31, 2020. Information on the following factors was collected: Body-mass index (BMI), comorbidities (hypertension, diabetes, dyslipidemia, smoking history), performance status, location and size of tumour, degree of resection, presence of and location of weakness, baseline blood counts, treatments administered, date of diagnosis and time to death or last follow-up. Results: Over the period of review, a total of 528 patients were identified. 111 patients (21%) were diagnosed with VTE. The location of VTE was as follows: 39 patients (35%) unilateral lower extremity deep venous thrombosis (DVT), 8 (7%) unilateral upper extremity DVT, 8 (7%) bilateral lower extremity DVT, 30 (27%) pulmonary embolism (PE), and 25 (23%) DVT and PE. Most VTE (87%) occurred within 12 months of diagnosis of GBM. On univariate and multivariate analysis, no factors were identified that contributed to an increased risk of VTE. Conclusions: Newly diagnosed patients with GBM have been shown to have a significant risk of developing VTE. The AVERT study (3) demonstrated the preventive benefit of administering a direct oral anticoagulant (DOAC) to cancer patients, including those with GBM, at high risk of developing VTE (3). Thus consideration should be given to treating patients with GBM with a DOAC at the time of diagnosis. The benefit of preventive treatment will need to be balanced against the risk of bleeding in these patients.

Tamoxifen for breast cancer prevention among survivors of pediatric lymphoma previously treated with chest radiation: Clinical benefits, harms and tradeoffs.

10025 Background: Survivors of pediatric lymphoma previously treated with chest radiation are at high risk for subsequent breast cancer. Although early initiation of breast cancer screening is recommended, the clinical benefits and harms of adding tamoxifen to reduce breast cancer deaths among these women are unknown. Methods: We adapted a Cancer Intervention and Surveillance Modeling Network (CISNET) breast model using data from the Childhood Cancer Survivor Study (CCSS) to reflect the elevated risks for breast cancer and competing mortality for 5-year survivors previously treated with chest radiation (RT). Breast cancer risk was based on age, chest RT field, timing of RT relative to menarche, menopause status, anthracycline exposure, and family history. Premature menopause risk varied by cumulative ovarian RT and alkylator dose. Based on the US Preventive Services Task Force 2019 Evidence Summary, we assumed tamoxifen (20mg daily for 5 years) reduced estrogen receptor positive (ER+) breast cancer risk by 42% (RR = 0.58 [0.42-0.81]) for 20 years and increased risks for venous thromboembolism, deep vein thrombosis, coronary heart disease, stroke and endometrial cancer during treatment. Strategies included no screening or tamoxifen, annual screening with mammography and MRI starting at age 25, annual screening with mammography and MRI starting at age 25 with the addition of tamoxifen at ages 25, 30 or 35. Model outcomes included cumulative breast cancer risk, number of childbearing years before age 45 (defined as years menstruating without tamoxifen use or a breast cancer diagnosis or having survived breast cancer for at least 3 years), and number of tamoxifen-related side-effects. Results: Among a cohort of 20-year-old 5-year lymphoma survivors previously treated with mediastinal RT without primary ovarian failure, an estimated 20% were projected to develop breast cancer and 2.6% would die from the disease before age 50 in the absence of screening or tamoxifen use. Survivors would have on average 22 childbearing years before age 45. Early initiation of breast cancer screening at age 25 would reduce breast cancer deaths before age 50 by 56.3%. Depending on age at initiation, tamoxifen would further reduce breast cancer deaths by 8.0 to 9.6 percentage points for an overall 64.3% to 65.9% reduction and reduce the average number of childbearing years by 17% to 21%. For each breast cancer death averted, a reduction of 1950 to 3740 childbearing life years and 11 to 20 side-effects would occur and varied by the tamoxifen start age compared to mammography and MRI screening. Conclusions: Tamoxifen use for primary breast cancer prevention among pediatric lymphoma survivors may further reduce breast cancer deaths but decisions might depend on survivor preferences for side effects vs. avoiding breast cancer and consideration of timing for childbearing.

A Three-year Retrospective Study Looking at Preventing Hospital Acquired Thrombosis.

Hospital-acquired venous thromboembolism (HA-VTE) is defined as cases of venous thromboembolism (VTE) that occur in a hospital and within ninety days of a hospital admission. Deep vein thromboses (DVTs) most commonly occur within the deep veins of the pelvis and legs. If the thrombus dislodges and travels to the lungs, it can result in a pulmonary embolus (PE). VTE is associated with significant morbidity and mortality, accounting for almost 10% of all hospital deaths. If risk factors are correctly identified and VTE prophylaxis is prescribed, VTE can be a preventable condition. In 2010, NHS England launched The National Venous Thromboembolism Prevention Programme. This included NICE guidance, and a VTE risk assessment tool, which must be completed for at least 95% of patients on admission. The National Thrombosis Survey, published by Thrombosis UK, studied how this program was implemented locally, and audited HA-VTE prevention strategies nationally. Using the Thrombosis Survey and NICE guidance as an aide, this study collects data about hospital-acquired DVT (HA-DVT) at the Queen Elizabeth Hospital in Gateshead (QEH) and aims to: 1. Identify cases of HA-DVT and understand the clinical circumstances surrounding these cases 2. Assess the quality of VTE preventative measures at QEH 3. Outline potential improvement in reducing the incidence of HA-VTE at this hospital Methods: This retrospective cohort study used electronic records to identify all cases of DVT between April 2019 and April 2022 at QEH. Cases of HA-DVT were defined as: a positive ultrasound doppler report and either the case occurring in the 90 days following an inpatient stay, or beyond two days into an admission. For these cases of HA-DVT, we recorded the: reason for admission; admitting specialty; presence of an underlying active cancer and deaths occurring within 90 days of diagnosis. We assessed the quality of VTE preventative measures, by recording the: completion of VTE risk assessments; prescription of weight-adjusted pharmacological VTE prophylaxis and provision of VTE prophylaxis on discharge. For HA-DVT cases occurring within 90 days of an inpatient stay, the preventative measures were assessed on the original admission. Electronic records were used to record the completion rate of the National VTE risk assessment tool for all inpatients during this time frame. The VTE risk assessment tool was completed for 98.5% of all admissions. One hundred and thirty-five cases of HA-DVT were identified between April 2019 and April 2022. Sixteen patients with HA-DVT did not have VTE prophylaxis prescribed on admission. Eleven of these patients had a clearly documented reason why anticoagulation was avoided. In HA-DVT cases where pharmacological VTE prophylaxis was prescribed, 23% were prescribed an inappropriate dose for their weight. If anticoagulation was required on discharge, this was prescribed appropriately in 94% of cases. About 31% of the patients with HA-DVT had an underlying active malignancy. Thirty-nine patients died within 90 days of the DVT being diagnosed; in only 1 case was VTE thought to be a contributing factor to death. The hospital exceeded the national standard of VTE risk assessment completion on admission (greater than 95%). For almost a quarter of patients with HA-DVT, the dose of thromboprophylaxis prescribed was not appropriate for weight. In five cases of HA-DVT, thromboprophylaxis was omitted with no clear justification. HA-DVT often affects the most clinically vulnerable patients and is associated with a high mortality.

BILATERAL PULMONARY EMBOLISM MIMICKING ACUTE CHEST SYNDROME IN A PATIENT WITH SICKLE CELL DISEASE: ACASE REPORT AND REVIEW OF THE LITERATURE

Abstract This case report discusses a 24-year-old female with sickle cell disease (SCD) who developed bilateral pulmonary embolism (PE), mimicking acute chest syndrome (ACS) following a cholecystectomy. Despite initial treatment for ACS, the patient\\\'s condition deteriorated, leading to a diagnosis of massive bilateral PE via chest CT angiography. The report underscores the importance of considering PE in SCD patients with respiratory symptoms unresponsive to standard ACS treatment. It highlights the hypercoagulable state in SCD, which increases the risk of venous thromboembolism, including PE. The case emphasizes the necessity for heightened clinical suspicion and appropriate diagnostic measures to improve patient outcomes. Unfortunately, the patient succumbed to septic shock despite aggressive management. This report advocates for comprehensive evaluation strategies in similar clinical scenarios to prevent misdiagnosis and improve survival rates.

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.

Edoxaban, Rivaroxaban, or Apixaban for Cancer-Associated Venous Thromboembolism in the Real World: Insights from the COMMAND VTE Registry-2.

Real-world data on clinical characteristics and outcomes related to the use of different direct oral anticoagulants (DOACs) for cancer-associated venous thromboembolism (VTE) is lacking. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive patients with acute symptomatic VTE from 31 centers in Japan from January 2015 to August 2020. Our study population comprised 1,197 patients with active cancer who were divided into the edoxaban (N = 643, 54%), rivaroxaban (N = 297, 25%), and apixaban (N = 257, 22%) groups. The cumulative 5-year incidence of recurrent VTE (9.3, 10.2, and 8.5%, respectively, p = 0.82) and all-cause death (67.5, 66.8, and 63.8%, respectively, p = 0.22) did not differ among the groups. Despite adjusting for confounders, the risks of recurrent VTE and all-cause death did not differ significantly among the groups. The cumulative 5-year incidence of major and clinically relevant bleeding was significantly lower in the rivaroxaban group than those in the other groups (22.6, 14.0, and 22.8%, p = 0.04; and 37.6, 26.8, and 38.3%, p = 0.01, respectively). After adjusting for confounders, in the rivaroxaban group, the risk for major bleeding was numerically lower (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.40-1.01) and that of clinically relevant all bleeding was significantly lower (HR: 0.67, 95% CI: 0.48-0.92) than those in the edoxaban group. The risks of recurrent VTE and all-cause death did not differ significantly among the different DOACs ; however, the risk of bleeding events could differ, with a potentially lower risk of bleeding with rivaroxaban.

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.

The Association between Obstructive Sleep Apnea and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study.

Despite previous observational studies linking obstructive sleep apnea (OSA) to venous thromboembolism (VTE), these findings remain controversial. This study aimed to explore the association between OSA and VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), at a genetic level using a bidirectional two-sample Mendelian randomization (MR) analysis. Utilizing summary-level data from large-scale genome-wide association studies in European individuals, we designed a bidirectional two-sample MR analysis to comprehensively assess the genetic association between OSA and VTE. The inverse variance weighted was used as the primary method for MR analysis. In addition, MR-Egger, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for complementary analyses. Furthermore, a series of sensitivity analyses were performed to ensure the validity and robustness of the results. The initial and validation MR analyses indicated that genetically predicted OSA had no effects on the risk of VTE (including PE and DVT). Likewise, the reverse MR analysis did not find substantial support for a significant association between VTE (including PE and DVT) and OSA. Supplementary MR methods and sensitivity analyses provided additional confirmation of the reliability of the MR results. Our bidirectional two-sample MR analysis did not find genetic evidence supporting a significant association between OSA and VTE in either direction.

Increased risk of venous thromboembolism in young and middle-aged individuals with hereditary angioedema: a family study

AbstractHereditary angioedema (HAE), caused by C1 inhibitor protein deficiency, was recently shown to be associated with an increased risk for venous thromboembolism (VTE). To our knowledge, this is the first national family study of HAE, which aimed to determine the familial risk of VTE. The Swedish Multi-Generation Register was linked to the Swedish National Patient Register for the period of 1964 to 2018. Only patients with HAE with a validated diagnosis were included in the study and were linked to their family members. Hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE were calculated for patients with HAE in comparison with relatives without HAE. Among 2006 individuals (from 276 pedigrees of 365 patients with HAE), 103 individuals were affected by VTE. In total, 35 (9.6%) patients with HAE were affected by VTE, whereas 68 (4.1%) non-HAE relatives were affected (P < .001). The adjusted HR for VTE among patients with HAE was 2.51 (95% CI, 1.67-3.77). Patients with HAE were younger at the first VTE than their non-HAE relatives (mean age, 51 years vs 63 years; P < .001). Before the age of 70 years, the HR for VTE among patients with HAE was 3.62 (95% CI, 2.26-5.80). The HR for VTE for patients with HAE born after 1964 was 8.29 (95% CI, 2.90-23.71). The HR for VTE for patients with HAE who were born in 1964 or earlier was 1.82 (95% CI, 1.14-2.91). HAE is associated with VTE among young and middle-aged individuals in Swedish families with HAE. The effect size of the association is in the order of other thrombophilias. We suggest that HAE may be considered a new rare thrombophilia.

Glass bead-activated clotting time (gb-ACT) for monitoring the anticoagulation effects in elderly patients with high risk of venous thromboembolism (VTE)

ABSTRACT Background To find a new bedside method to monitor the anticoagulation effects of low-molecular-weight heparins (LMWHs) in patients with a high risk of venous thromboembolism (VTE). Research design and methods A total of 32 hospitalized patients (aged ≥60 years) who were at high risk of VTE were assigned to receive subcutaneous LMWH for 5 to 14 days. Plasma anti-factor Xa (anti-Xa) activity was conducted by a chromogenic method, and the glass bead-activated whole blood clotting time (gb-ACT) value was obtained by a Sonoclot Analyzer. Results A correlation between the gb-ACT values and the anti-Xa levels was suggested (R = 0.447, p = 0.002), and it was stronger in the older group aged 80 years above (R = 0.467, p = 0.008) and in the group of patients with an eGFR of 30 ~ 60 mL/min (R = 0.565, p = 0.005). The area under the curve (AUC) for gb-ACT by receiver operating characteristic (ROC) curve evaluation was 0.725 (p = 0.011), and the gb-ACT >282.5s provided a sensitivity of 60% and specificity of 74% for anti-Xa >0.800 IU/ml. Conclusions The gb-ACT values detected by a Sonoclot Analyzer could act as a novel bedside method in the monitoring of LMWH anticoagulation.

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.

Thrombin Generation Profile Using ST-Genesia after PEG-asparaginase in Pediatric Patients with Acute Lymphoblastic Leukemia.

Venous thromboembolism (VTE) etiology in children with acute lymphoblastic leukemia (ALL) is multifactorial. The use of global assays of hemostasis as a thrombin generation test (TGT) is useful to individualize VTE risk in adult patients. This prospective cohort study aimed to evaluate the usefulness of an automated TGT to evaluate VTE risk during ALL treatment in children. TGT (automated analyzer ST Genesia; ThromboScreen) and pro- and anticoagulant plasma proteins were analyzed during ALL treatment in pediatric patients following LAL-SEHOP-PETHEMA-2013 guidelines. Results were compared with a series of pediatric normal controls and evaluated according to pegylated asparaginase PEG-ASP administration and to VTE risk factors. The study included 67 patients: males n = 35, B-ALL (n = 60). None had a VTE during the evaluated period. Compared to healthy controls, the normalized endogenous thrombin potential (N-ETP) ratio in patients was higher and ETP inhibition (ETP-inh) was lower, especially after PEG-ASP administration. Plasmatic protein C and protein S levels decreased after PEG-ASP administration, but antithrombin mean level did not. A bivariant analysis showed that ETP-inh was lower in patients >10 years old (p = 0.05) and in those with non-O blood type (p = 0.005). A linear mixed model also showed a higher TGT prothrombotic profile in patients with inherited thrombophilia. TGT could be a biomarker of a high VTE risk in ALL pediatric patients. Non-O blood group and inherited thrombophilia were associated with a significantly higher thrombotic profile, and an increased profile was also observed after administration of PEG-ASP.

Hyperhomocysteinemia is associated with the risk of venous thromboembolism in patients with mental illness: a case-control study.

The risk of venous thromboembolism in patients with mental illness has been insufficiently addressed. This study aimed to assess the correlation between hyperhomocysteinemia and venous thromboembolism prevalence among this population. Patients with a diagnosis of mental illness and concurrent venous thromboembolism, admitted to Sir Run Run Shaw Hospital at Zhejiang University School of Medicine between January 2014 and December 2021, were included in the venous thromboembolism group. The control group, approximately twice the size, comprised individuals with mental illness but without venous thromboembolism. Basic clinical data were gathered for both cohorts. In psychiatric patients, elevated D-dimer levels(OR=5.60,95% CI 3.28-10.00), hyperhomocysteinemia (OR=2.37,95% CI 1.10-5.14), and hyperprolactinemia(OR= 2.68,95% CI 1.12-6.42)were significant risk factors for venous thromboembolism. According to further subgroup analyses, hyperhomocysteinemia is a significant risk factor associated with pulmonary embolism, with an OR of 5.08 (95% CI 1.20-21.48). An interaction effect between gender and homocysteine level was found, with a p-interaction of 0.022.A subsequent analysis confirmed the association between hyperhomocysteinemia and venous thromboembolism in female psychiatric patients, with an OR of 3.34 (95% CI 1.68-6.65), indicating that hyperhomocysteinemia is a significant risk factor for venous thromboembolism in women. Patients with psychiatric disorders were found to have an elevated risk of venous thromboembolism, which was associated with increased levels of D-dimer, hyperprolactinemia, and hyperhomocysteinemia. A strong correlation between hyperhomocysteinemia and pulmonary embolism was identified in patients with mental illnesses. Furthermore, the study revealed that female psychiatric patients with hyperhomocysteinemia constituted a high-risk group for venous thromboembolism. This finding holds significant clinical implications, suggesting that early preventative measures could be implemented for this high-risk population to reduce the incidence of thromboembolic events during hospitalization for psychiatric patients.

Risk of recurrent venous thromboembolism and bleeding in patients with acute isolated subsegmental pulmonary embolism

IntroductionApproximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood. MethodsThis is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE. ResultsOverall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer. ConclusionsMost patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer.

Adverse cardiovascular events in rheumatoid arthritis patients treated with JAK inhibitors: An analysis of postmarketing spontaneous safety reports

ObjectivesThe 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. MethodsA 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. ResultsWe 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. ConclusionIn 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.

An insight into the causal relationship between sarcopenia-related traits and venous thromboembolism: A mendelian randomization study.

As a geriatric syndrome, sarcopenia has a high prevalence in the old population and represents an impaired state of health with adverse health outcomes. A strong clinical interest in its relationship with venous thromboembolism (VTE), which is a complex trait disease with a heterogeneous annual incidence rate in different countries, has emerged. The relationship between sarcopenia and venous thromboembolism has been reported in observational studies but the causality from sarcopenia to VTE remained unclarified. We aimed to assess the causal effect of sarcopenia on the risk of VTE with the two-sample Mendelian randomization (MR) method. Two sets of single-nucleotide polymorphisms (SNPs), derived from two published genome-wide association study (GWAS) meta-analyses and genetically indexing muscle weakness and lean muscle mass separately, were pooled into inverse variance weighted (IVW), weighted median and MR-Egger analyses. No evidence was found for the causal effect of genetically predicted muscle weakness (IVW: OR = 0.90, 95% CI = 0.76-1.06, p = 0.217), whole body lean mass (IVW: OR = 1.01, 95% CI = 0.87-1.17, p = 0.881) and appendicular lean mass (IVW: OR = 1.13, 95% CI = 0.82-1.57, p = 0.445) on the risk of VTE. However, both genetically predicted whole-body lean mass and appendicular lean mass can causally influence diabetes mellitus (IVW of whole-body lean mass: OR = 0.87, 95% CI = 0.78-0.96, p = 0.008; IVW of appendicular lean mass: OR = 0.71, 95% CI = 0.54-0.94, p = 0.014) and hypertension (IVW of whole-body lean mass: OR = 0.92, 95% CI = 0.87-0.98, p = 0.007; IVW of appendicular lean mass: OR = 0.84, 95% CI = 0.73-0.96, p = 0.013). Genetically predicted sarcopenia does not causally influence VTE directly, but it might still have an indirect effect on VTE incidence via diabetes mellitus and hypertension.

Risk of recurrent venous thromboembolism in cancer patients after discontinuation of anticoagulant therapy

Anticoagulant therapy is recommended for cancer-related venous thromboembolism (VTE). Recurrent VTE prevention is the main goal of this treatment. The majority of evidence-based practice guidelines recommend anticoagulant treatment for at least 6 months. Based on individual assessment of potential benefits and risks, tolerability, drug availability, patient preference, and cancer activity, active cancer patients should continue anticoagulant treatment beyond the 6-month course. When cancer is no longer active or the risk outweighs the benefit, anticoagulant therapy is usually stopped after 3-6 months. Until recently, there was little data on the risk of recurrent VTE in cancer-associated VTE patients after stopping anticoagulants. New results and evidence synthesis have emerged in the last 3 years. Recurring VTE occurs in over 30% in the 5 years after treatment discontinuation. In the first six months, recurrence rates are 10-15%. Recurrences reach 31% at 2 years and stabilize between 2 and 5. Duration of prior anticoagulation does not affect cumulative recurrence. The high risk of recurrent VTE after discontinuing treatment supports guidelines to continue anticoagulant treatment if cancer is active. Stopping anticoagulants after 3-6 months may not be ideal, so randomized clinical trials should be conducted quickly. This review highlights the need to improve cancer patients' primary VTE prevention efforts.

Trends and updates on the epidemiology of cancer-associated thrombosis: a systematic review

For cancer patients, cancer-associated thrombosis (CAT) is a serious complication. An updated epidemiology of CAT over the last ten years is summarized in this review. A comprehensive analysis of pertinent population cohort research released between 2011 and 2024 was carried out. In patients with unselected cancers, the 12-month incidence of CAT is roughly 3-5% (9-fold increase vs to the matched non-cancer population); however, in patients with advanced cancers requiring systemic therapy, the risk rises to 6-8% (20-fold increase vs. to the matched non-cancer population). Anticoagulation use and adherence have improved, but the risk of recurrence is still high, at 5-8% at 6 months and 7-15% at 12 months. The type, stage, and treatment of cancer, a history of venous thromboembolism (VTE), prolonged hospitalization or immobilization, and obesity are significant clinical predictors of the development of CAT. The modified Vienna-CATS and EHR-CAT have the best performance (area under the curve 0.68-0.71) among the clinical risk prediction scores for CAT using the original Khorana score backbone that has been externally validated. However, additional research is required to guarantee appropriate implementation and utilization of these models. Even with contemporary antineoplastic treatments, CAT is still a major complication for cancer patients. We encourage interdisciplinary partnerships among hematologists, data scientists, epidemiologists, and oncologists to guarantee the integration of customized VTE risk evaluation into standard oncologic treatment.

Identifying novel biomarkers using proteomics to predict cancer-associated thrombosis.

Comprehensive protein analyses of plasma are made possible by high-throughput proteomic screens, which may help find new therapeutic targets and diagnostic biomarkers. Patients with cancer are frequently affected by venous thromboembolism (VTE). The limited predictive accuracy of current VTE risk assessment tools highlights the need for new, more targeted biomarkers. Although coagulation biomarkers for the diagnosis, prognosis, and treatment of VTE have been investigated, none of them have the necessary clinical validation or diagnostic accuracy. Proteomics holds the potential to uncover new biomarkers and thrombotic pathways that impact the risk of thrombosis. This review explores the fundamental methods used in proteomics and focuses on particular biomarkers found in VTE and cancer-associated thrombosis.

Reducing Patient's Refusal of Anticoagulant Medication to Decrease Venous Thromboembolism Risk.

Reducing Patient's Refusal of Anticoagulant Medication to Decrease Venous Thromboembolism Risk.