Increased Risk Of Venous Thromboembolism Research Articles

Joint effect of ischemic stroke and obesity on the risk of venous thromboembolism: the Tromsø Study

BackgroundPatients with ischemic stroke have increased risk of venous thromboembolism (VTE). Obesity is prevalent in stroke patients and a well-established risk factor for VTE. Whether obesity further increases the VTE risk in patients with stroke remains unclear. ObjectivesWe investigated the joint effect of ischemic stroke and obesity on the risk of incident VTE in a population-based cohort. MethodsParticipants (n = 29,920) were recruited from the fourth to sixth surveys of the Tromsø Study (1994-1995, 2001, and 2007-2008) and followed through 2014. Incident events of ischemic stroke and VTE during follow-up were recorded. Hazard ratios (HRs) of VTE with 95% CIs were estimated according to combined categories of ischemic stroke and obesity (body mass index ≥ 30 kg/m2), with exposure to neither risk factors as reference. ResultsDuring a median follow-up of 19.6 years, 1388 participants experienced ischemic stroke and 807 participants developed VTE. Among those with stroke, 51 developed VTE, yielding an incidence rate of VTE after stroke of 7.2 per 1000 person-years (95% CI, 5.5-9.5). In subjects without stroke, obesity was associated with a 1.8-fold higher VTE risk (HR, 1.76; 95% CI, 1.47-2.11). In nonobese subjects, stroke was associated with a 1.8-fold higher VTE risk (HR, 1.77; 95% CI, 1.27-2.46). Obese subjects with stroke had a 2-fold increased VTE risk (HR, 2.44; 95% CI, 1.37-4.36). ConclusionThe combination of obesity and ischemic stroke did not yield an excess risk of VTE. Our findings suggest that obese subjects with ischemic stroke do not have a more than additive risk of VTE.

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for fourweeks postoperatively. Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p=0.21). Most events were symptomatic (n=16, 62%) and were attributable to pulmonary emboli (n=16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p=0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p=0.98). A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

Improvement of thrombosis management in patients with cancer: a practical consensus document of recommendations for cancer-associated thrombosis patients' healthcare in Spain.

Cancer patients are at risk of venous thromboembolism (VTE), its recurrence, but also at risk of bleeding while anticoagulated. In addition, cancer therapies have been associated to increased VTE risk. Guidelines for VTE treatment in cancer patients recommend low molecular weight heparins (LMWH) or direct oral anticoagulants (DOAC) for the initial treatment, DOAC for VTE short-term treatment, and LMWH or DOAC for VTE long-term treatment. This consensus article arises from a collaboration between different Spanish experts on cancer-associated thrombosis. It aims to reach an agreement on a practical document of recommendations for action allowing the healthcare homogenization of cancer-associated thrombosis (CAT) patients in Spain considering not only what is known about VTE management in cancer patients but also what is done in Spanish hospitals in the clinical practice. The text summarizes the current knowledge and available evidence on the subject in Spain and provides a series of practical recommendations for CAT management and treatment algorithms to help clinicians to manage CAT over time.

Does hormone therapy exacerbate other venous thromboembolism risk factors?

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. 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. 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. 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.

Venous Thromboembolism in Patients Hospitalized for COVID-19 in a Non-Intensive Care Unit.

Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may contribute to venous thromboembolism (VTE) with adverse effects on the course of COVID-19. The purpose of this study was to investigate an incidence and risk factors for VTE in patients hospitalized for COVID-19 in a non-intensive care unit (non-ICU). Consecutive adult patients with COVID-19 hospitalized from November 2021 to March 2022 in the isolation non-ICU at our center were included in the study. Incidence of VTE including pulmonary embolism (PE) and deep vein thrombosis (DVT), clinical characteristics, and D-dimer plasma levels during the hospitalization were retrospectively evaluated. Among the 181 patients (aged 68.8 ± 16.2 years, 44% females, 39% Delta SARS-CoV-2 variant, 61% Omicron SARS-CoV-2 variant), VTE occurred in 29 patients (VTE group, 16% of the entire cohort). Of them, PE and DVT were diagnosed in 15 (8.3% of the entire cohort) and 14 (7.7%) patients, respectively. No significant differences in clinical characteristics were observed between the VTE and non-VTE groups. On admission, median D-dimer was elevated in both groups, more for VTE group (1549 ng/mL in VTE vs. 1111 ng/mL in non-VTE, p = 0.09). Median maximum D-dimer was higher in the VTE than in the non-VTE group (5724 ng/mL vs. 2200 ng/mL, p < 0.005). In the univariate analysis, systemic arterial hypertension and the need for oxygen therapy were predictors of VTE during hospitalization for COVID-19 (odds ratio 2.59 and 2.43, respectively, p < 0.05). No significant associations were found between VTE risk and other analyzed factors; however, VTE was more likely to occur in patients with a history of VTE, neurological disorders, chronic pulmonary or kidney disease, atrial fibrillation, obesity, and Delta variant infection. Thromboprophylaxis (83.4% of the entire cohort) and anticoagulant treatment (16.6%) were not associated with a decreased VTE risk. The incidence of VTE in patients hospitalized in non-ICU for COVID-19 was high despite the common use of thromboprophylaxis or anticoagulant treatment. A diagnosis of arterial hypertension and the need for oxygen therapy were associated with an increased VTE risk. Continuous D-dimer monitoring is required for the early detection of VTE.

Risk factors for incident venous thromboembolism in patients with renal tumor and inferior vena cava tumor thrombus: a retrospective case-control study.

Venous thromboembolism (VTE) is a principal cause of mortality and adverse oncologic outcomes in patients with renal tumor and inferior vena cava tumor thrombus (RT-IVCTT). However, the preoperative thrombotic risk factors in these patients remain not fully characterized. To identify preoperative thrombotic risk factors in patients with RT-IVCTT. Two hundred fifty-seven consecutive postsurgical patients with RT-IVCTT aged 18-86 years were enrolled between January 2008 and September 2022. Clinicopathological variables were retrospectively reviewed. A multivariate logistic regression model was performed. Preoperative hemoglobin, neutrophils, and serum albumin levels were analyzed as both continuous and categorical variables. VTE was identified in 63 patients (24.5%). On both continuously and categorically coded variables, advanced IVC thrombus (OR 3.2, 95% CI: 1.4-7.0; OR 2.7, 95% CI: 1.2-6.1), renal sinus fat invasion (OR 3.4, 95% CI: 1.6-7.0; OR 3.7, 95% CI: 1.8-7.7), IVC wall invasion (OR 3.6, 95% CI: 1.6-7.9; OR 4.3, 95% CI: 1.9-10.0), IVC blockage status of greater than 75% (OR 5.2, 95% CI: 1.7-15.8; OR 6.1, 95% CI: 1.9-19.7), and higher neutrophils (OR 1.3, 95% CI: 1.0-1.7; OR 2.4, 95% CI: 1.1-5.4) were significantly associated with increased VTE risk in patients with RT-IVCTT. Except hemoglobin, categorically coded serum albumin (OR 0.36, 95% CI: 0.17-0.75) was validated as an independent risk factor for VTE. This study provided an insight of risk factors contributing to preoperative VTE in patients with RT-IVCTT, which may be beneficial for optimizing strategies to manage VTE in clinical practice.

Venous Thromboembolism in Patients with Inflammatory Bowel Disease.

Patients diagnosed with inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, experience chronic inflammation of the gastrointestinal tract. Those with IBD face a higher risk of developing venous thromboembolism (VTE) compared to individuals without IBD. This escalated risk is associated with various factors, some modifiable and others non-modifiable, with disease activity being the primary concern. Interestingly, Janus Kinase inhibitors approved for the treatment of IBD may be associated with an increased risk of VTE but only in patients that have other underlying risk factors leading to an overall increased VTE risk. Several recognized medical societies have recommended the use of VTE prophylaxis for hospitalized individuals with IBD. The association between VTE and IBD and the need for pharmacologic prophylaxis remains under-recognized. Increased awareness of this complication can hopefully protect patients from a potentially deadly complication.

Neoadjuvant Chemotherapy is Associated with Increased Risk of Postoperative DVT After Distal Pancreatectomy for Pancreatic Adenocarcinoma: a NSQIP Analysis.

Venous thromboembolism (VTE) remains a persistent source of postoperative morbidity despite prevention and mitigation efforts. Cancer, surgery, and chemotherapy are known risk factors for VTE. Existing literature suggests that neoadjuvant therapy (NAT) may contribute to increased VTE risk in the postoperative period, but few authors specifically examine this relationship in distal pancreatic adenocarcinoma (PDAC). In this study, we analyze the association of NAT and postoperative VTE in patients who underwent distal pancreatectomy (DP) for PDAC. Using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database, we analyzed the Procedure Targeted files for pancreatectomy from 2014 to 2020. Adults with PDAC who underwent DP were grouped by receipt of NAT. The primary outcome was the rate of deep venous thrombosis (DVT) and the secondary outcome was the rate of pulmonary embolism (PE). We performed univariate and multivariate logistic regression analysis to determine risk factors associated with postoperative DVT. There were 4327 patients with PDAC who underwent DP. Of these, 1414 (32.7%) had NAT. Receipt of NAT was significantly associated with postoperative DVT requiring therapy (3.5% vs. 2.3%, p = 0.02), but was not associated with PE (p = 0.42). On MVA, NAT was associated with a 73% greater chance of developing postoperative DVT [odds ratio (OR) 1.73, 95% CI 1.18-2.55]. Patients who receive NAT prior to DP for PDAC are 73% more likely to develop postoperative DVT compared with upfront resection. As NAT becomes more commonplace, these high-risk patients should be prioritized for guideline-recommended extended duration prophylaxis.

Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomization analysis.

People with cancer experience high rates of venous thromboembolism (VTE). Risk of subsequent cancer is also increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer. We used data from large genome-wide association study meta-analyses to perform bidirectional Mendelian randomization analyses to estimate causal associations between genetic liability to VTE and risk of 18 different cancers. We found no conclusive evidence that genetic liability to VTE was causally associated with an increased incidence of cancer, or vice versa. We observed an association between liability to VTE and pancreatic cancer risk [odds ratio for pancreatic cancer: 1.23 (95% confidence interval: 1.08-1.40) per log-odds increase in VTE risk, P = 0.002]. However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence to suggest a causal relationship. These findings do not support the hypothesis that genetic liability to VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesize evidence for these mechanisms.

Hormonal Contraception and Menopausal Hormone Therapy: A Reference for Orthopaedic Surgeons

BACKGROUND: Exogenous estrogen is a double-edged sword in the realm of orthopaedic surgery, providing many musculoskeletal health benefits to menopausal women yet adding an additional risk of venous thromboembolism (VTE) in the perioperative setting for patients using certain forms of hormonal contraception and menopausal hormone therapy (MHT). The primary objective of this review is to summarize the known literature regarding the VTE risks of perioperative medications containing exogenous estrogen among orthopaedic patients. A secondary objective is to provide guidance to orthopaedic surgeons regarding perioperative management of commonly encountered forms of hormonal contraception and MHT. METHODS: A summative review of existing literature regarding VTE risk of various forms of hormonal contraception and MHT is provided, with emphasis on perioperative VTE risk surrounding major and minor orthopaedic surgery. RESULTS: Increased risk of VTE has been identified after arthroscopic knee procedures in patients utilizing oral contraceptive pills and after major lower extremity surgery in patients using MHT, yet there is not a clear standard of care as to how to manage these medications after surgery or how and when to adjust VTE prophylaxis. Regardless of the mode of delivery (pills, patches, vaginal rings), hormonal contraception with exogenous estrogen carries some associated VTE risk that can be compounded by surgery. Depo-Provera has also demonstrated increased risk. Forms of hormonal contraception without elevated VTE risk are progestin only pills and intrauterine devices (IUDs) as well as Nexplanon. MHT with systemic level doses of exogenous estrogen delivered orally has associated VTE risk. While systemic transdermal and transvaginal formulations of estrogen have not been shown to increase VTE risk in the non-surgical state, the risk when combined with the perioperative state after major operations is not yet known. Local estrogen therapies for vaginal symptoms of menopause do not increase risk of VTE. CONCLUSION: Given the frequent utilization of hormonal contraception and MHT, orthopaedic surgeons should consider the use of medications containing exogenous estrogen in the perioperative VTE risk assessment of patients. Further discussion toward the perioperative management of these medications and standardization of care for patients with increased VTE risks should be encouraged.

Venous Thromboembolism in Total Hip and Total Knee Arthroplasty

The optimal pharmacologic thromboprophylaxis agent after total hip and total knee arthroplasty is uncertain and consensus is lacking. Quantifying the risk of postoperative venous thromboembolism (VTE) and bleeding and evaluating comparative effectiveness and safety of the thromboprophylaxis strategies can inform care. To quantify risk factors for postoperative VTE and bleeding and compare patient outcomes among pharmacological thromboprophylaxis agents used after total hip and knee arthroplasty. This retrospective cohort study used data from a large health care claims database. Participants included patients in the United States with hip or knee arthroplasty and continuous insurance enrollment 3 months prior to and following their surgical procedure. Patients were excluded if they received anticoagulation before surgery, received no postsurgical pharmacological thromboprophylaxis, or had multiple postsurgery thromboprophylactic agents. In a propensity-matched analysis, patients receiving a direct oral anticoagulant (DOAC) were matched with those receiving aspirin. Aspirin, apixaban, rivaroxaban, enoxaparin, or warfarin. The primary outcome was 30-day cumulative incidence of postdischarge VTE. Other outcomes included postdischarge bleeding. Among 29 264 patients included in the final cohort, 17 040 (58.2%) were female, 27 897 (95.2%) had inpatient admissions with median (IQR) length of stay of 2 (1-2) days, 10 948 (37.4%) underwent total hip arthroplasty, 18 316 (62.6%) underwent total knee arthroplasty; and median (IQR) age was 59 (55-63) years. At 30 days, cumulative incidence of VTE was 1.19% (95% CI, 1.06%-1.32%) and cumulative incidence of bleeding was 3.43% (95% CI, 3.22%-3.64%). In the multivariate analysis, leading risk factors associated with increased VTE risk included prior VTE history (odds ratio [OR], 5.94 [95% CI, 4.29-8.24]), a hereditary hypercoagulable state (OR, 2.64 [95% CI, 1.32-5.28]), knee arthroplasty (OR, 1.65 [95% CI, 1.29-2.10]), and male sex (OR, 1.34 [95% CI, 1.08-1.67]). In a propensity-matched cohort of 7844 DOAC-aspirin pairs, there was no significant difference in the risk of VTE in the first 30 days after the surgical procedure (OR, 1.14 [95% CI, 0.82-1.59]), but postoperative bleeding was more frequent in patients receiving DOACs (OR, 1.36 [95% CI, 1.13-1.62]). In this cohort study of patients who underwent total hip or total knee arthroplasty, underlying patient risk factors, but not choice of aspirin or DOAC, were associated with postsurgical VTE. Postoperative bleeding rates were lower in patients prescribed aspirin. These results suggest that thromboprophylaxis strategies should be patient-centric and tailored to individual risk of thrombosis and bleeding.

Risk of Venous Thromboembolic Events Among Obese Hormonal Contraceptive Users

Background: Obesity and hormonal contraception (HC) are independent risk factors for venous thromboembolism (VTE). Thirty eight percent of women in the United States (US) are obese, and the prevalence of childhood obesity in the US is among the highest in the world. Obesity (BMI&amp;gt;30 kg/m2), increases VTE risk via several mechanisms, and the VTE risk in obese individuals is 2.5 times higher than that of their non-obese peers. More than half of women aged 15-49 years use some form of contraception, and 14% report using oral contraceptive pills specifically. The overall VTE risk with combined hormonal contraception (CHC) is approximately two-fold higher than an individual's baseline risk, with further increase depending on the type/dose of progesterone and estrogen, and route of administration. To date case-control and cohort studies have demonstrated an increased VTE risk among obese contraceptive users. But these data do not include adolescents and were derived from populations with relatively low rates of obesity. This study aimed to assess and compare the VTE risk among obese females, age 10-44 years, who were prescribed HC compared to non-obese HC users and obese non-users utilizing a national electronic-medical record database. Using a large national database allowed the inclusion of females from diverse ethnic, economic, and geographic background. Methods: Population level data was collected from TriNETX, LLC, an administrative database that contains comprehensive inpatient and outpatient data from 56 tertiary care hospitals in US. Prevalence data regarding the type and dose of progesterone and estrogen and mode of administration was assessed. Data on females ages 10-44 years from 1/1/2000 to 12/30/2022, who received a new prescription for any HC as identified by the prescription name in pharmaceutical claims and procedure codes was analyzed. Recorded BMI was used to divide the cohort into obese and non-obese individuals as per CDC guidelines. VTE events were defined as presence of ≥1 ICD 9 or 10 codes for VTE diagnosis and presence of a prescription for an anticoagulant drug within the first year after hormonal prescription. Data was summarized descriptively and VTE rates were calculated. Results: Of the 97,026,002 females who met inclusion criteria, 1,370,481 were obese and 2,649,987 were non-obese. The overall rate of VTE for obese vs. non-obese users was 0.9% vs. 0.5% (p&amp;lt;-0.001) and obese HC users vs. obese non-users was 0.9 and 1.06% (p&amp;lt;0.05). VTE rates among obese users versus non-obese users was significantly higher for most progesterone only options (p&amp;lt;0.001), excluding drospirenone only pills and high dose norethindrone (Table 1). A similar pattern of higher VTE rates in obese vs non-obese users was observed for the majority of CHC preparations with few exceptions (p&amp;lt;0.001). (Table 1) In general, VTE rates were higher among obese non-users compared to obese users. However, the rate of VTE was significantly higher among obese users of oral norethindrone 5mg and all medroxyprogesterone acetate users (p&amp;lt;0.001). (Table 2) Discussion: Utilizing the data from a large inpatient/outpatient administrative database, our study shows that obese HC users have a higher VTE rate within one year of initiating HC when compared to non-obese HC users, for progesterone only options (excluding drospirenone, high dose norethindrone) and most CHCs. With few exceptions, obese HC non-users had a higher rate of VTE when compared to obese users. This observation is likely due to confounding by indication bias as prescribers may avoid HC in individuals with underlying risk factors for VTE. Applying propensity score analysis and examining different subcategories of obesity may help overcome this bias in future analysis. Our study highlights the utility of large databases to study healthcare outcomes of VTE risk in females with and without obesity and HC users and non-users. Although limited by the use of administrative claims data and acknowledging that all statistically significant results may not be clinically significant, our study suggests obesity as a VTE risk factor in females for most HCs.

Apixaban Is Effective and Safe in Reducing Venous Thromboembolism (VTE) in Obese Patients with Newly Diagnosed Pediatric Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (ALL/LL) a Sub-Study Analysis of the Prevapix-ALL/Children's Oncology Group ACCL1333 Trial

Background: Pediatric patients with ALL/LL are at increased risk for VTE and obesity further increases VTE risk. Pediatric ALL/LL patients experiencing VTE have increased risk for mortality as compared to ALL/LL patients without VTE. Therefore, effective and safe pharmacologic VTE prevention options are urgently needed. The PREVAPIX-ALL trial was a multi-center, multinational, randomized, open-label, controlled trial assessing the safety and efficacy of primary prophylaxis using apixaban for the prevention of VTE in pediatric patients with ALL/LL. PREVAPIX-ALL was a collaboration between the Bristol Myers Squibb/Pfizer Alliance and the Children's Oncology Group. Patients with ALL/LL undergoing induction chemotherapy containing asparaginase therapy were randomized to either apixaban or standard of care (SOC - no anticoagulation). The objective of the current study was to separately analyze obese patients as a subgroup of the PREVAPIX-ALL trial. Aims: To assess the efficacy and safety of prophylactic apixaban vs. SOC for VTE prevention during induction chemotherapy in obese pediatric patients with ALL/LL. Methods: Obesity was defined as ≥ 95 th percentile for age and sex specific body mass index as per the Centers for Disease Control and Prevention childhood obesity definition. Patients newly diagnosed with ALL/LL, ages ≥ 1 to &amp;lt; 18 years, with a central venous line, and on induction chemotherapy with asparaginase were randomized to apixaban vs. SOC. Apixaban thromboprophylaxis was administered at a fixed dose per body weight until the end of induction when participants were screened for VTE. The primary efficacy outcome was a composite of symptomatic and asymptomatic VTE. The primary safety outcome was major bleeding, and the secondary safety outcome was a composite of major and clinically relevant non-major (CRNM) bleeding. Results: Out of 512 PREVAPIX-ALL participants, 498 (97.2%) were age 24 months or older with weight and height available. Of those, 82 were obese. Forty-two were randomized to apixaban and 40 were randomized to SOC (Table 1). For the primary efficacy outcome there was a statistically significant decrease in VTE events in the apixaban arm, 1/42 (2.4%) compared to the SOC arm 10/40 (25%) [RRR 91% (95% CI 3%, 99%) p 0.0067] (Table 2). No statistically significant difference was observed in bleeding between the two groups (Table 2). The mean apixaban exposure was similar among the obese and non-obese groups: obese apixaban mean exposure (SD) 23.4 days (5.55) and non-obese 23.5 days (6.44). No statistical difference was observed in the median steady-state area under the curve (AUC-TAU ng.h/mL) drug exposure between obese and non-obese categories stratified by age group on a linear scale: obese (n=38) 686.94 ng.h/mL (95% CI 397.8-1314.6) and non-obese (n=186) 663.50 ng.h/mL (95% CI 319.1-1090.9). Conclusion: Apixaban VTE prophylaxis in obese ALL/LL patients receiving asparaginase during induction chemotherapy resulted in a statistically significant 91% RRR in VTE compared to SOC. No statistical difference was observed in apixaban exposure days and AUC/TAU between obese and non-obese patients. Bleeding events were not increased in the apixaban arm as compared to SOC. Primary prophylaxis using apixaban safely reduces VTE in obese ALL/LL pediatric patients receiving induction chemotherapy containing asparaginase.

Season of delivery and risk of venous thromboembolism during hospitalization among pregnant women.

Seasons were found to be related to the occurrences of venous thromboembolism (VTE) in hospitalized patients. No previous study has explored whether seasons were associated with VTE risk in pregnant women. This study aimed to investigate the relationships between the season of delivery and VTE risk during hospitalization among pregnant women. This is a multi-center retrospective cohort study of pregnant women. Participants were those who delivered at seven designated sites in Hubei Province, China, during the period from January 2017 to December 2022. They were categorized according to their season/month of delivery. Information on new-onset VTE during hospitalization was followed. Approximately 0.28% (104/37,778) of the pregnant women developed new-onset VTE during hospitalization for delivery. After adjustment, compared with participants in the spring group, participants in the summer, autumn, and winter groups had an increased risk of VTE during hospitalization. The ORs were 2.59 [1.30, 5.15], 2.83 [1.43, 5.60], and 2.35 [1.17, 4.75] for the summer, autumn, and winter groups, respectively. Pregnant women in the combined group (summer + autumn + winter) had an increased risk of VTE during hospitalization than those in the spring group (OR, 2.59 [1.39, 4.85]). By restricting the analyses among pregnant women without in vitro fertilization, gestational diabetes mellitus, and preterm, the results still remained robust. Compared with participants who delivered in March, April, and May, participants who delivered in June, July, September, November, December, and February had a higher risk of VTE during hospitalization. This study demonstrated that pregnant women who delivered in summer, autumn, and winter had an increased VTE risk during hospitalization compared with those who delivered in spring.

Perioperative Cerebrospinal Fluid Drain Placement Does Not Increase Venous Thromboembolism Risk After Thoracic and Fenestrated Endovascular Aortic Repair

Venous thromboembolism (VTE) incidence after thoracic and fenestrated endovascular aortic repair (TEVAR/FEVAR) is high (up to 6-7%) relative to other vascular procedures; however, the etiology for this discrepancy remains unknown. Notably, patients undergoing TEVAR/FEVAR commonly receive cerebrospinal fluid drains (CSFDs) for neuroprotection, requiring interruption of perioperative anticoagulation and prolonged immobility. We hypothesized that CSFDs are a risk factor for VTE after TEVAR/FEVAR. Consecutive TEVAR/FEVAR patients at a single center were reviewed (2011-2020). CSFDs were placed based on surgeon preference preoperatively or for spinal cord ischemia (SCI) rescue therapy postoperatively. The primary end-point was VTE occurrence, defined as any new deep venous thrombosis (DVT) or pulmonary embolism (PE) confirmed on imaging within 30-days postoperatively. Routine postoperative VTE screening was not performed. Patients with and without VTE, and subjects with and without CSFDs were compared. Logistic regression was used to explore associations between VTE incidence and CSFD exposure. 897 patients underwent TEVAR/FEVAR and 43% (n=387) received a CSFD at some point during their care (preoperative: 94%[n=365/387]; post-operative SCI rescue therapy: 6%[n=22/387]). CSFD patients were more likely to have previous aortic surgery (44% vs. 37%; p=.028) and received more postoperative blood products (780 vs. 405mL; p=.005). The overall VTE incidence was 2.2% (n=20). 70% (14) patients with VTE had DVT, 50% (10) had PE, and 20% (4) had DVT and PE. Among TEVAR/FEVAR patients with VTE, 65% (n=13) were symptomatic. Most VTEs (90%, n=18) were identified in-hospital and the median time to diagnosis was 12.5 (IQR 7.5-18) days postoperatively. Patients with VTE were more likely to have non-elective surgery (95% vs. 41%; p<.001), had higher ASA classification (4.1 vs. 3.7; p<.001), required longer ICU admission (24 vs. 12-days; p<.001), and received more blood products (1386 vs. 559mL; p<.001). VTE incidence was 1.8% in CSFD patients compared to 3.5% in non-CSFD patients (OR 0.70 [95% CI 0.28-1.78, p = .300). However, patients receiving CSFDs postoperatively for SCI rescue therapy had significantly greater VTE incidence (9.1% vs. 1.1%; p=.044). CSFD placement was not associated with an increased risk of VTE in patients undergoing TEVAR/FEVAR. VTE risk was greater in patients undergoing nonelective surgery and those with complicated perioperative courses. VTE risk was greater in patients receiving therapeutic CSFDs compared to prophylactic CSFDs, highlighting the importance of careful patient selection for prophylactic CSFD placement.

Causal inference of sex hormone-binding globulin on venous thromboembolism: evidence from Mendelian randomisation

BackgroundPrevious cohort studies have shown that exogenous sex hormone use, such as testosterone replacement therapy and oestrogen-containing contraceptives, can increase the risk of venous thromboembolism (VTE). However, the relationship between endogenous sex hormone levels and VTE remains unclear. The goal of the present study was to explore the causal roles of endogenous sex hormones, including hormone-binding globulin (SHBG), bioactive testosterone (BT), and total testosterone (TT), in VTE and its two subgroups, deep vein thrombosis (DVT) and pulmonary embolism (PE).MethodsWe used a genome-wide association study of sex hormones as exposure data and Finnish VTE data as the outcome. Inverse variance weighting, MR-Egger, and weighted median were used for two-sample Mendelian randomisation (MR). Sensitivity analyses included MR-Egger, MR-PRESSO, Cochrane Q test, MR Steiger, leave-one-out analysis, and funnel plot, combined with multivariate MR and replicated MR analyses using larger VTE data from the global biobank meta-analysis initiative. Linkage disequilibrium score regression (LDSC) was used to determine genetic associations and estimate sample overlap.ResultsOur findings genetically predicted that an increase in serum SHBG levels by one standard deviation (SD) caused 25% higher odds for VTE (OR: 1.25, 95% CI: 1.01−1.55) and 58% higher odds for PE (OR: 1.58, 95% CI: 1.20−2.08). LDSC supported the genetic correlation between these two traits and replicated analyses confirm SHBG’s genetic effect on VTE in both sexes (OR: 1.46, 95% CI: 1.20−1.78) and in females (OR: 1.49, 95% CI: 1.17−1.91). In addition, an increase in serum TT levels by one SD caused 32% higher odds for VTE (OR: 1.32, 95% CI: 1.08−1.62) and 31% higher odds for DVT (OR: 1.31, 95% CI: 1.01−1.69); however, LDSC and replicated analyses did not find a genetic correlation between TT and VTE or its subtypes. No significant correlation was observed between BT and all three outcome traits.ConclusionOur study provides evidence that elevated serum SHBG levels, as predicted by genetics, increase VTE risk. However, the causal effect of testosterone levels on VTE requires further investigation.

Withholding of Hormone Replacement Therapy Prior to Total Joint Arthroplasty Surgery to Reduce the Risk of Postoperative Thromboembolic Events: Is It Justified?—A Systematic Review of Clinical Practice Guidelines

BackgroundHormone replacement therapy (HRT), menopausal hormone therapy (MHT), and estrogen-containing medications are frequently withheld before elective lower limb arthroplasty, based on a perceived risk of venous thromboembolism (VTE). However, evidence linking HRT, MHT, and an increased VTE risk is equivocal. This systematic review evaluated the concordance of international clinical practice guidelines (CPGs) on the withholding of HRT or MHT. MethodsThe PubMed, Google Scholar, Cochrane, and Ovid databases were searched for CPGs for the preoperative, perioperative, and postoperative management of patients on HRT and MHT undergoing elective lower limb arthroplasty. This was supplemented by an internet search. There were 7 international CPGs in English, from Europe and North America, published between January 2000 and February 2023 reviewed against the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE-II) criteria, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. ResultsThe guidelines reviewed revealed a mixed picture on HRT or MHT withdrawal and use in arthroplasty, with some featuring detailed advice on the preoperative and postoperative management of HRT or MHT (Scottish Intercollegiate Guidelines Network), while others featured no guidance (American College of Chest Physicians). The evidence referenced in these guidelines highlighted studies showing HRT or MHT to play a limited role in increasing VTE risk, with most studies from the 1990s and 2000s. ConclusionsBased on current evidence, non-estrogen-containing transdermal HRT or MHT should not be withheld in patients undergoing elective joint arthroplasty, though further evidence is required to justify withholding estrogen-containing forms.

Association of total cholesterol variability with risk of venous thromboembolism: A nationwide cohort study.

The effects of total cholesterol (TC) on coagulation and hemostatic systems could contribute to the development of venous thromboembolism (VTE). We investigated this possible association using TC variability. From the Korean NHIS-HEALS database, 1,236,589 participants with health screenings between 2003 and 2008 were included. TC variability was assessed using various parameters, including the coefficient of variation (CV), standard deviation (SD), and variability independent of mean (VIM). Occurrence of VTE was established by identifying at least two medical claims with a diagnostic code including various types of VTE: deep vein thrombosis (DVT) (I80.2-80.3), pulmonary embolism (PE) (I26, I26.0, I26.9), intraabdominal VTE (I81, I82, I82.2-82.3), and other VTE (I82.8-82.9). Throughout the study's median follow-up period of 12.4 years (interquartile range 12.2-12.6) years, TC levels were assessed a total of 5,702,800 times. VTE occurred in 11,769 (1.08%) patients (DVT (4,708 (0.43%)), PE (3,109 (0.29%)), intraabdominal VTE (5,215 (0.48%)), and other VTE (4,794, (0.44%)). As a result, there was gradual association was observed between higher TC variability and occurrence of VTE. Multivariable analysis showed that quartile of TC variability using CV showed a positive correlation with the occurrence of VTE (adjusted hazard ratio (the highest versus lowest quartile), 1.14, 95% confidence interval, 1.08-1.20, p < 0.001). This result remained consistent applying to SD and VIM. In addition, higher quartile of TC variability was consistently associated with the development of various types of VTE in subgroup analysis. Increased TC variability may be associated with increased VTE risk. This analysis highlights the importance of maintaining stable TC levels to prevent the development of VTE.

Thrombophilia gene mutations predict venous thromboembolism in ambulatory cancer patients receiving chemotherapy

BackgroundInherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear. ObjectivesOur objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy. MethodsWe conducted a post hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (prothrombin factor [F] II G20210A, FXI, fibrinogen gamma, serpin family A member 10, FV K858R, FXIII, FV Leiden [FVL], and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used to compare heterozygous and homozygous mutations (combined) to wild-type. VTE rates, bleeding rates, and risk differences for mutations stratified by prophylactic anticoagulation use were calculated. ResultsOf the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type (odds ratio [OR]: 5.2; 95% CI: 1.9-14.7 and OR: 2.7; 95% CI: 1.2-6.1, respectively). The use of anticoagulation prophylaxis resulted in complete protection in FVL patients, whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding. ConclusionOur results indicate that FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.

Venous Thromboembolism Risk in Patients With Newly Diagnosed Multiple Myeloma Treated with Carfilzomib or Bortezomib in Combination With Lenalidomide and Dexamethasone

BackgroundMultiple myeloma (MM), as well as some treatments for MM, increase the risk of venous thromboembolism (VTE). Prior literature suggests carfilzomib, lenalidomide, and dexamethasone (KRd) may have a higher incidence of thromboembolic events compared with bortezomib, lenalidomide, and dexamethasone (VRd). We aimed to evaluate VTE risk with KRd induction compared to VRd at a large academic medical center in the United States. Materials and MethodsWe retrospectively reviewed patients with newly diagnosed MM presenting at a single institution. Patients were followed for objectively diagnosed VTE events for 6 months following the start of induction therapy. ResultsA total of 209 patients were included, with 69 (33%) receiving KRd and 140 (67%) receiving VRd. Overall, 18 patients (9%) had a VTE event, with 5 (7%) in the KRd cohort and 13 (9%) in the VRd cohort (P = .80). Treatment with KRd was not associated with an increased risk of VTE compared to VRd (HR 0.74; 95% CI 0.26-2.08; P = .57). ConclusionIn this cohort, KRd was not associated with an increase in VTE risk compared to VRd, contrary to prior literature.