Risk Of Venous Thromboembolic Events Research Articles

Association of timing and agent for VTE prophylaxis in patients with severe traumatic brain injury on VTE, mortality, neurosurgical intervention, and discharge disposition.

Trauma patients are at increased risk for venous thromboembolism events (VTE). The decision of when to initiate VTE chemoprophylaxis (VTEP) and with what agent remains controversial in patients with severe traumatic brain injury (TBI). This comparative effectiveness study evaluated the impact of timing and agent for VTEP on outcomes for patients with severe TBI (AIS Head = 3,4, or 5). Data was collected at 35 Level 1 and 2 trauma centers from January 1, 2017 to June 1, 2022. Patients were placed into analysis cohorts: No VTEP, low-molecular weight heparin (LMWH) ≤ 48 hours, LMWH>48 hours, Heparin≤48 hours, Heparin>48 hours. Propensity score matching accounting for patient factors and injury characteristics was used with logistic regression modeling to evaluate in-hospital mortality, VTE events, and discharge disposition. Neurosurgical intervention after initiation of VTEP was used to evaluate extension of intracranial hemorrhage. Of 12,879 patients, 32% had no VTEP, 36% LMWH, and 32% Heparin. Overall mortality was 8.3% and lowest among patients receiving LMWH≤48 hours (4.1%). VTE rates were lower with use of LMWH (1.6 vs 4.5%, OR 2.98, 95% CI 1.40-6.34, p = 0.005) without increasing mortality or neurosurgical interventions. VTE rates were lower with early prophylaxis (2.0 vs 3.5%, OR 1.76, 95% CI 1.15-2.71, p = 0.01) without increasing mortality (p = 1.0). Early VTEP was associated with more non-fatal intracranial operations (p < 0.001). However, patients undergoing neurosurgical intervention after VTEP initiation had no difference in rates of mortality, withdrawal of care, or unfavorable discharge disposition (p = 0.7, p = 0.1, p = 0.5). In patients with severe TBI, LMWH usage was associated with lower VTE incidence without increasing mortality or neurosurgical interventions. Initiation of VTEP≤48 hours decreased VTE incidence and increased non-fatal neurosurgical interventions without affecting mortality. LMWH is the preferred VTEP agent for severe TBI, and initiation ≤48 hours should be considered in relation to these risks and benefits. Therapeutic/Care Management, Level III.

Abstract PO2-01-09: Patient preferences for CDK4/6 inhibitor treatments in HR+/HER2− early breast cancer: a discrete choice survey study

Abstract Background: Patients (pts) with stage II/III HR+/HER2− early breast cancer (EBC) are at risk of recurrence that persists over years. The addition of a CDK4/6 inhibitor (CDK4/6i) to adjuvant endocrine therapy (ET) was investigated in monarchE, evaluating abemaciclib (ABE) in lymph node (LN)+ high-risk pts, and NATALEE, using ribociclib (RIB) in stage II/III disease, including pts with N0 disease. ABE was FDA approved in this indication in 2021, while NATALEE recently reported statistically significant iDFS results. Both efficacy and tolerability are relevant for pts treated in a curative setting. This prospective study evaluated the extent pts with EBC value different treatment (tx) attributes and how these may translate into preferences between the two CDK4/6i in the US. Methods: A web-based discrete choice experiment survey was conducted among pts with EBC between Jan and May 2023 before NATALEE results were available. Eligible pts were adult women in a US clinical practice setting with self-reported stage II/III HR+/HER2− EBC +/- prior chemotherapy receiving only adjuvant ET at the time of survey, who completed curative surgery 1-3 years ago. Pts selected the scenario that best reflected their preferences from a series of choice cards, each displaying a pair of hypothetical tx profiles. A total of 8 attributes related to efficacy (5-year iDFS), adverse events (AEs), monitoring requirements, tx duration, and schedule were included (Table 1). Attributes were included based on an initial pilot qualitative assessment that selected efficacy and safety attributes most relevant to pts, clinical input, and differentiating features between CDK4/6i. A conditional logit regression model was used to estimate preference weights and relative importance (RI) of each attribute. Utility scores, summarizing overall preference for CDK4/6i tx profiles, were estimated from the model, and various scenarios were tested. Subgroup analyses by menopausal status and BC stage will be presented. Results: 409 pts participated in the survey (median age, 53 years; White/Black/other race, 59%/23%/18%; BC stage II/III, 48%/52%; employed, 38%). Pt preferences for attributes that significantly impacted tx decision, in order of high to low RI, were higher efficacy (iDFS), lower risk of diarrhea, lower risk of fatigue, shorter tx duration, and lower risk of venous thromboembolic events. Attributes based on monitoring or schedule, including number of blood tests, number of EKGs, and tx schedule, did not affect tx choice (Table 2). Overall utility scores were consistently higher for reconstructed tx profiles that resembled RIB features, including under conservative scenarios where efficacy of RIB was assumed to be equivalent or lower than that of ABE. Conclusions: This study showed that, driven by strong preference for lower risk of AEs, pts with HR+/HER2− EBC prefer tx profiles that more closely resemble the clinical experience of receiving RIB. These pt preferences are important for shared decision making when discussing the addition of a CDK4/6i to adjuvant tx for eligible pts with HR+/HER2− EBC. Discrete Choice Experiment Attributes and Levels Estimated Preference Weight and Relative Importance Citation Format: Erica Mayer, Mary Lou Smith, Annie Guerin, Dominick Latremouille-Viau, Nisha C. Hazra, Yan Meng, Wendi Qu, Remi Bellefleur, Vaidyanathan Ganapathy, Liz Santarsiero, Robert Morlock, Maryam Lustberg. Patient preferences for CDK4/6 inhibitor treatments in HR+/HER2− early breast cancer: a discrete choice survey study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-09.

Long-term incidence, risk factors and complications for venous thromboembolism in patients with systemic lupus erythematosus.

To compare frequency, incidence rates (IR), risk factors and outcomes of a first venous thromboembolic event (VTE) between patients with systemic lupus erythematosus (SLE) and controls. Using state-wide longitudinal hospital data from Western Australia (WA), we recorded venous thrombosis (VT) and pulmonary embolism (PE) in patients with SLE (n = 1854, median age 40, 86% female) and matched hospitalised controls (n = 12,107, median age 40 years, females 88.6%) in the period 1985-2015. Results presented are medians, frequency, IR per 1000 person years (PY) and odds, rate, or adjusted hazard ratios (OR/RR/a-HR) with 95% confidence intervals (CI). Patients with SLE had significantly higher odds (12.8 vs 3.3%; OR 4.26, CI 3.60-5.05) and IR for a first VTE (10.09 vs 1.52; RR 6.64; CI 5.56-7.79). Over the three study decades, the IR for PE declined in patients with SLE from 7.74 to 3.75/1000 PY (p < .01) with no changes observed for VT or in controls. VTE recurred more frequently in patients with SLE (24.1% vs 10.2 %) (p < .01). Antiphospholipid antibodies (aPL) (a-HR 4.24, CI 2.50-7.19), serositis (a-HR 2.70, CI 1.86-3.91), lupus nephritis (a-HR 1.75 CI 1.25-2.33) and thrombocytopenia (a-HR 1.65 (1.10-2.49) were the strongest disease risk factors for VTE only in patients with SLE, while arterial hypertension, smoking and obesity were independent VTE risk factors for both groups. VTE was not associated with an increased risk for arterial events, but PE increased the risk for pulmonary hypertension (PH) in both patients with SLE (a-HR 6.47, CI 3.73-11.23) and controls (a-HR 9.09, CI 3.50-23.63). VTE increased the risk of death in both patients with SLE (a-HR 2.02, CI 1.50-2.70) and controls (a-HR 6.63, CI 5.21-8.42) after 10 years of follow-up. VTE affected 12.8% of patients with SLE at six times the VTE rate in controls with aPL as the strongest, but not the only risk factor in SLE. The risk of PH was increased in both groups following PE, but VTE did not associate with an increased risk of arterial events.

Cervical Spine Surgery Following COVID-19 Infection: When is it Safe to Proceed?

Retrospective. We utilized the NIH National COVID Cohort Collaborative (N3C) database to characterize the risk profile of patients undergoing spine surgery during multiple time windows following the COVID-19 infection. While the impact of COVID-19 on various organ systems is well documented, there is limited knowledge regarding its effect on perioperative complications following spine surgery or the optimal timing of surgery after an infection. We asked the National COVID Cohort Collaborative for patients who underwent cervical spine surgery. Patients were stratified into those with an initial documented COVID-19 infection within 3 time periods: 0-2 weeks, 2-6 weeks, or 6-12 weeks before surgery. A total of 29,449 patients who underwent anterior approach cervical spine surgery and 46,379 patients who underwent posterior approach cervical spine surgery were included. Patients who underwent surgery within 2 weeks of their COVID-19 diagnosis had a significantly increased risk for venous thromboembolic events, sepsis, 30-day mortality, and 1-year mortality, irrespective of the anterior or posterior approach. Among patients undergoing surgery between 2 and 6 weeks after COVID-19 infection, the 30-day mortality risk remained elevated in patients undergoing a posterior approach only. Patients undergoing surgery between 6 and 12 weeks from the date of the COVID-19 infection did not show significantly elevated rates of any complications analyzed. Patients undergoing either anterior or posterior cervical spine surgery within 2 weeks from the initial COVID-19 diagnosis are at increased risk for perioperative venous thromboembolic events, sepsis, and mortality. Elevated perioperative complication risk does not persist beyond 2 weeks, except for 30-day mortality in posterior approach surgeries. On the basis of these results, it may be warranted to postpone nonurgent spine surgeries for at least 2 weeks following a COVID-19 infection and advise patients of the increased perioperative complication risk when urgent surgery is required.

Venous thromboembolism in patients with acute myeloid leukemia: development of a predictive model.

Patients with acute myeloid leukemia (AML) are at increased risk of venous thromboembolic events (VTE). However, thromboprophylaxis is largely underused. This study aimed to determine possible VTE development risk factors and to develop a novel predictive model. We conducted a retrospective cohort study of adult patients with newly diagnosed AML. We used univariate and multivariable logistic regression to estimate binary outcomes and identify potential predictors. Based on our final model, a dynamic nomogram was constructed with the goal of facilitating VTE probability calculation. Out of 626 eligible patients with AML, 72 (11.5%) developed VTE during 6 months of follow-up. Six parameters were independent predictors: male sex (odds ratio [OR] 1.82, 95% confidence interval [CI]: 1.077-2.065), prior history of thrombotic events (OR 2.27, 95% CI: 1.4-4.96), international normalized ratio (OR 0.21, 95% CI: 0.05-0.95), Eastern Cooperative Oncology Group performance status (OR 0.71, 95% CI: 0.53-0.94), and intensive therapy (OR 2.05, 95% CI: 1.07-3.91). The C statistics for the model was 0.68. The model was adequately calibrated and internally validated. The decision-curve analysis suggested the use of thromboprophylaxis in patients with VTE risks between 8 and 20%. We developed a novel and convenient tool that may assist clinicians in identifying patients whose VTE risk is high enough to warrant thromboprophylaxis.

Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after cancer surgery: a systematic review and meta-analysis.

Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.

Thrombotic and bleeding complications in patients with AL amyloidosis.

Haemostatic abnormalities and deregulated coagulation are common complications in AL amyloidosis. The relevant risks of thromboembolic and haemorrhagic events have not been thoroughly evaluated. To describe clinically significant thrombotic/haemorrhagic events in 450 consecutive patients with AL amyloidosis. Venous thromboembolic events (VTEs) were reported in 6% and arterial embolic events (AEEs) in 5% of patients, respectively, during a 55-month median follow-up. Lower albumin, lower eGFR, higher BM infiltration, soft tissue involvement, IMiD-based therapy and prior thrombosis were associated with VTE risk. Prior thrombosis was the only independent prognostic variable (HR 9.3, p = 0.001). Coronary arterial disease, prior AEE, 24-h proteinuria and higher platelet counts were associated with AEE risk. Significant bleeding events were reported in 9%, and associated mortality was 19%. Liver involvement, higher serum creatinine and higher baseline VWF:Ag levels were linked to bleeding risk. Using competing risk analysis, the cumulative probability of thrombosis/bleeding was higher during the first year following diagnosis, but a stable lower risk for both events remained for the duration of follow-up. In AL amyloidosis patients, the risk of thrombotic/arterial embolic events is significant, but the bleeding risk is also high. A multiparametric assessment is required to initiate anti-thrombotic or anti-platelet therapy appropriately.

Risk of Venous Thromboembolic Events After Surgery for Cancer

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

Role of thromboprophylaxis during neoadjuvant chemotherapy before radical cystectomy in patients with bladder cancer: Results of a multicenter retrospective cohort study.

598 Background: Patients undergoing radical cystectomy are at risk of developing venous thromboembolic events (VTE), with most VTEs occurring during neoadjuvant chemotherapy. The ASCO Clinical Practice Guideline Update recommends thromboprophylaxis in cancer patients with a high risk of VTE and a low risk of bleeding. However, the risks of VTE and bleeding with or without thromboprophylaxis in bladder cancer patients scheduled for radical cystectomy have not been well evaluated. Methods: We conducted a retrospective cohort study of patients with non-metastatic bladder cancer undergoing cystectomy across 28 centers in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis during neoadjuvant chemotherapy on VTE and bleeding. Results: Of 4886 patients, 4631 (95%) received neither thromboprophylaxis nor anticoagulation during chemotherapy. Thromboprophylaxis during neoadjuvant chemotherapy was prescribed in 151 (3%) patients mainly being enoxaparin (80%) with a median duration of 94 (range 38 to 104) days. In inverse probability weighting analyses, patients with thromboprophylaxis compared to patients without thromboprophylaxis during chemotherapy had not only a lower VTE (HR 0.32 [95% CI, 0.12 to 0.81], p-value = 0.016) but also a lower bleeding risk (HR 0.03 [95% CI, 0.09 to 0.12], p-value: &lt;0.0001). Conclusions: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomized trials in other malignancies. Our data suggests thromboprophylaxis seems protective against VTEs during neoadjuvant chemotherapy in bladder cancer patients planned for cystectomy. The ASCO guidelines recommending thromboprophylaxis during chemotherapy should therefore also be regarded as a standard of care in patients treated with neoadjuvant chemotherapy before cystectomy.

Pulmonary Thromboembolism in the Intermediate PostOperative Period of Laparoscopic Adrenalectomy for an Adrenocortical Adenoma with Cushing’s Syndrome

Introduction: Cushing’s Syndrome is a constellation of clinical features resulting from chronic exposure to excess glucocorticoids. This is suggested to induce hypercoagulability, which results in a 10-fold increase in the risk for venous thromboembolic events. It results from an increased production of procoagulant factors and impaired fibrinolytic, leading to decreased activated partial thromboplastin time and increased clot lysis time. However, reported events are quite rare and majority of which occur in the post-operative setting. A systematic review done in 2009 by Zaane, et al., discussed that there is up to a 1.5% incidence of venous thromboembolism after transsphenoidal surgery and 0.3-3% after laparoscopic adrenalectomy. Despite this, it is still up to debate whether thromboprophylaxis should be instituted post-operatively among these patients. Discussion: The case is a 42-year-old Filipino, female, with Cushing’s Syndrome readmitted because of generalized body weakness, seven days after laparoscopic adrenalectomy of a left adrenocortical adenoma. After correction of electrolytes and further evaluation, findings suggested the possibility of an infection of the post-operative site. This was confirmed with a whole abdominal CT scan with contrast. She was then managed conservatively with antibiotics. The study was repeated four days after for surveillance of the abscess site. It showed incidental findings of diffuse thromboembolism on the right main pulmonary artery and its segmental branches, right common iliac vein, internal iliac vein, superior gluteal vein, and left ovarian vein. No hypotension, dyspnea, syncope, leg pain, or swelling was noted during this period. Findings were confirmed through CT Angiography of Pulmonary Arteries. Furthermore, no right ventricular dysfunction was noted on 2D echo. She was then treated with loading dose of Rivaroxaban and eventually sent home well after resolution of infection and maintained on anticoagulation

Thrombo-inflammatory response in hospitalised patients with COVID-19: a single institution experience.

Severe COVID-19 causes acute inflammation, which is complicated by venous thromboembolism events (VTE). However, it is unclear if VTE risk has evolved over time since the COVID-19 outbreak. To determine markers of thrombo-inflammation and rates of symptomatic VTE in patients hospitalised for COVID-19 in a metropolitan hospital in Sydney, Australia. A retrospective, single-centre, cohort study was performed by reviewing electronic medical records of consecutive patients admitted to Royal Prince Alfred Hospital between March 2020 and September 2021. This period included three waves of COVID-19 outbreaks in Australia with the ancestral, alpha and delta variants. Standard coagulation assays and inflammatory markers were recorded over 4 weeks. A total of 205 patients were consecutively admitted during the study period. Activated partial thromboplastin time, neutrophil count and C-reactive protein (CRP) were significantly increased in patients hospitalised in the intensive care unit (ICU) compared with non-ICU patients. The use of anti-inflammatory medication increased in 2021 compared with 2020. The mortality rate was 7.3% in our cohort. Ninety-four per cent of patients received anticoagulation with 6.3% of patients developing VTE. We observed lower rates of VTE compared to the internationally reported rate for the same period. We conclude that in the setting of controlled hospital admission rate and standard anticoagulation guidelines, COVID-19 resulted in similar thrombo-inflammatory response and VTE rates over the first 1.5 years of the pandemic.

The Role of KRAS Mutation in Colorectal Cancer-Associated Thrombosis

Venous thromboembolic events (VTE) are common in patients with colorectal cancer (CRC) and represent a significant contributor to morbidity and mortality. Risk stratification is paramount in deciding the initiation of thromboprophylaxis and is calculated using scores that include tumor location, laboratory values, patient clinical characteristics, and tumor burden. Commonly used risk scores do not include the presence of molecular aberrations as a variable. This retrospective study aims to confirm the link between KRAS-activating mutations and the development of VTE in CRC. A total of 166 patients were included in this study. They were split into two cohorts based on KRAS mutational status. We evaluated the frequency and mean time to VTE development stratified by the presence of KRAS mutations. Patients with mutant KRAS had an odds ratio (OR) of 2.758 for VTE compared to KRAS wild-type patients, with an increased risk of thrombosis being maintained in KRAS mutant patients even after adjusting for other known VTE risk factors. Taking into account the results of this study, KRAS mutation represents an independent risk factor for VTE.

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.

Risk Factors for Thrombosis in Pregnant People with Sickle Cell Disease: A Multinational Study.

Background People with sickle cell disease (SCD) have exceptionally high rates of maternal morbidity, including increased risk for venous thromboembolic events (VTE). Data from the National Inpatient Sample shows that VTE risk in hospitalized Black pregnant people with SCD is 14 times that of unaffected Black and non-Black pregnant people. 1 There is little disease-specific data to inform anticoagulation (AC) use during pregnancy. 2 The purpose of this study is to describe VTE events in a SCD pregnancy cohort and to identify risk factors for VTE during pregnancy and compare maternal-fetal outcomes for subjects with or without VTE in pregnancy. Methods The Mount Sinai Hospital (MSH) Research Ethics Board and The Johns Hopkins Hospital (JHH) Institutional Review Board approved this retrospective study of pregnant people with SCD of ≥ 20 weeks gestation cared for at MSH, Toronto (1990-2017) or JHH (2000-2021). At MSH and JHH, all pregnant people with SCD and VTE history are prescribed antenatal prophylactic LMWH and for 6-weeks postpartum. At MSH, but not JHH, all receive AC prophylaxis for 6-weeks postpartum. At both centers, hospitalized pregnant people receive prophylactic AC. We stratified subjects by VTE occurrence during pregnancy. First, we described the cohort with VTE during pregnancy, including subject characteristics, VTE recurrence and pregnancy outcomes. Second, we compared cases with a first pregnancy with VTE to controls without VTE. We excluded repeat pregnancies in both groups. We compared cases and controls by SCD characteristics, medication use before pregnancy, and pregnancy outcomes. Painful events were defined as pain requiring acute care or hospital admission. Chronic transfusion therapy (CTT) was defined as pregnancies treated with scheduled, prophylactic transfusion; opioid use was defined as receiving an outpatient opioid prescription during pregnancy. We used the Chi-squared test for categorical variables and Wilcoxon signed-rank tests for continuous variables. A p-value of &amp;lt;0.05 was considered significant. Results There were 290 singleton pregnancies in 199 subjects. Half of the pregnancies were first pregnancies (142/290), with fewer second (51/290), third (2/290), fourth (3/290) or fifth (1/290) pregnancies. The cohort comprised of 58% subjects with HbSS/HbSβ 0, while 42% had HbSC/HbSβ+ genotype (Table 1). VTE occurred in 7% of pregnancies (20/290) including deep vein thrombosis (DVT, N=9), pulmonary embolism (PE, N=8), DVT+PE (N=3). Median age was 27 years (IQR 23,30). Before pregnancy, most VTE subjects received hydroxyurea (N=10). During pregnancy, six received CTT. Fourteen subjects had VTE in a single pregnancy; three had VTE recurrence in subsequent pregnancies. All three had HbSS/HbSβ 0. Two subjects had VTE history outside of pregnancy. One had DVT in two consecutive pregnancies and was prescribed AC in both pregnancies due to history of VTE. VTE occurred in first (N=4), second (N=8), third (N=4), fourth (N=1) and fifth (N=4) pregnancies. Most VTE occurred at JHH (11 JHH vs 6 MSH, p=0.008). To investigate SCD-specific risk factors for VTE in pregnancy, we compared characteristics in VTE subjects (N=17) to no-VTE subjects (N=182) by first study pregnancy with an event or first study pregnancy while enrolled in the study. VTE was associated with markers of disease severity including history of VTE before pregnancy (6/17 VTE vs 8/182 no-VTE, p&amp;lt;0.001), ACS during pregnancy (7/17 VTE vs 19/182 no-VTE, p&amp;lt;0.001), painful events requiring acute care during pregnancy (16/17 VTE vs 119/182 no-VTE, p=0.015) and hydroxyurea use before pregnancy (10/17 VTE vs 35/184 no-VTE, p&amp;lt;0.001). There was no difference in age or genotype. VTE was associated with earlier delivery and c-section delivery (Table 1). Conclusion In this study, 7% of cohort pregnancies had VTE. This rate exceeds reports from administrative datasets. 1 This may be due to the acuity of patients cared for at our centers and/or reflect undercounting of VTE in administrative datasets. In pregnant people with SCD, VTE is associated with VTE history, intrapartum painful events and ACS. Interventions to reduce acute events in pregnancy may help reduce VTE risk. While AC can be beneficial in preventing thrombotic events, careful assessment is essential to manage bleeding risks. Prospective data is needed to define the subpopulation of pregnant SCD patients who would benefit from AC prophylaxis antenatally.

Sickle Cell Trait Is Associated with Adverse Clinical Outcomes in a Matched Case-Control Study at a Tertiary Care Center

Background: Sickle cell trait (SCT) is a common condition affecting more than 300 million individuals worldwide and 3 million in the United States. Although generally believed to be an asymptomatic condition, there is growing data to suggest potential associations with morbidity, including risk for venous-thromboembolic events and chronic kidney disease. Methods: We conducted this retrospective cohort study using electronic health record data from the University of Colorado Health Data Compass data warehouse. Patients with a coded diagnosis of SCT were analyzed for SCT-related clinical outcomes compared against a 1:1 randomized matched sample of controls without a history of SCT (matched on age, race, sex). Individuals with sickle cell disease, Sickle-cell/Hb-C disease, sickle-thalassemia, other sickle cell disorders, and hemolytic anemias were excluded from both case and control groups. Outcomes included chronic kidney disease (CKD), deep vein thrombosis (DVT), pulmonary embolism (PE), hematuria, rhabdomyolysis, and splenic infarction. Multivariate logistic regression was used to examine the association of each condition based on SCT carrier status, adjusting for age, sex, and race. Results: We included 1447 SCT patients with complete demographic data, along with 1447 matched controls (n = 2894). There were 1019 (70.4%) women and 428 (29.6%) men in each case and control group. A majority (72.7%) were black or African American. The median age of the cohort was 36 years (IQR = 28 - 47). We found significant associations for CKD (OR = 2.95, 95% CI: 2.03 - 4.30), DVT (2.54, 95% CI: 1.42 - 4.54), PE (OR=4.25, 95% CI: 2.43 - 7.45), and hematuria (OR= 2.28, 95% CI: 1.57 - 3.31). (Table) Despite few overall events and wide confidence intervals, association remained significant for rhabdomyolysis (OR=3.32, 95% CI 1.07 - 10.24) and splenic infarction (OR=44.9, 95% CI 6.15 - 328.00). Male sex was strongly associated with splenic infarction (OR = 8.70, 95% CI 4.11 - 18.41) and rhabdomyolysis (OR = 19.14, 95% CI 4.35 - 84.18). Conclusion: In this case-control cohort study we found significantly increased risk for CKD, DVT, PE, hematuria, rhabdomyolysis, and splenic infarction for patients with sickle cell trait with odds ratios similar to those seen in other study cohorts. The significant morbidity associated with this common genotype warrants further research into primary prevention of SCT associated adverse outcomes.

Anti-tumor Necrosis Factor Alpha Versus Corticosteroids: A 3-fold Difference in the Occurrence of Venous Thromboembolism in Inflammatory Bowel Disease－A Systematic Review and Meta-analysis

Abstract Background and Aims Patients with inflammatory bowel disease [IBD] have a more than two fold higher risk of venous thromboembolic events [VTE] than the general population. The aetiology is complex, and the role of medication is not precisely defined. We aimed to assess the effects of anti-tumor necrosis factor alpha [anti-TNFα] drugs and conventional anti-inflammatory therapy, namely corticosteroids [CS], immunomodulators [IM], and 5-aminosalicylates [5-ASA] on VTE in IBD. Methods A systematic search was performed in five databases on November 22, 2022. We included studies reporting VTE in the distinct categories of medications, determined the proportions, and calculated the odds ratios [OR] with 95% confidence intervals [CI], using the random-effects model. The risk of bias was evaluated with the Joanna Briggs Institute Critical Appraisal Checklist and the Risk of Bias in Non-randomized Studies of Interventions tool. Results The quantitative analysis included 16 observational studies, with data from 91 322 IBD patients. Patients receiving anti-TNFα medication had significantly less VTE [proportion: 0.05, CI: 0.02–0.10], than patients treated with CS [proportion: 0.16, CI: 0.07–0.32], with OR = 0.42 [CI: 0.25–0.71]. IMs resulted in similar proportions of VTE compared with biologics [0.05, CI: 0.03–0.10], with OR = 0.94 [CI: 0.67–1.33]. The proportion of patients receiving 5-ASA having VTE was 0.09 [CI: 0.04–0.20], with OR = 1.00 [CI: 0.61–1.62]. Conclusions Biologics should be preferred over corticosteroids in cases of severe flare-ups and multiple VTE risk factors, as they are associated with reduced odds of these complications. Further studies are needed to validate our data.

Intra-abdominal pressure increases peri-operatively in patients undergoing deep inferior epigastric perforator flap reconstruction: A prospective study linking high intra-abdominal pressure to non-fatal lung embolism within one patient

The deep inferior epigastric perforator (DIEP) flap is the gold standard for autologous breast reconstruction. The procedure and peri-operative period are associated with the risk of severe post-operative complications, like venous thromboembolic events (VTE) and lung embolism. Whether the intra-abdominal pressure (IAP) increases after the closure of the abdominal defect, thereby potentially affecting the venous backflow and the risk of VTE, is currently not known. The primary aim is to test if the closure of the abdominal donor site increases the IAP in women undergoing secondary DIEP flap breast reconstruction. By using a Unometer, we measured the intravesical pressure as a surrogate marker for the IAP, at baseline, immediately after, and 24h after abdominal skin closure, for 13 patients. The mean IAP increased from 6.1mmHg (95% CI 4.6-7.7) at baseline to 9.0mmHg (95% CI 8.0-10.0) immediately after skin closure [mean diff. 2.9 (95% CI 1.0-4.8) (p=0.007)] and further up to 11.7mmHg (95% CI 9.0-14.5) 24h after closure [mean diff. 5.3 (95% CI 1.4-9.1) (p=0.012)]. We found that IAP varies among the patients, regardless of the tightness of abdominal closure or rectus plication (n=3). Immediately after closure, none of the isolated patients showed abnormal levels of IAP (>12mmHg), while eight out of 12 isolated patients (67%) showed IAP levels above the normal range after 24h. One patient developed a non-fatal lung embolism. The mean IAP increases significantly over the post-operative period after DIEP flap reconstruction, although abnormal IAP values are only seen 24h after the closure of the skin.

Low molecular weight heparin use and thrombotic complications in upper gastrointestinal resection for malignancy in a multi-ethnic Asian population

ObjectiveEpidemiological studies showed substantially lower venous thromboembolic event risk among Asians compared to Caucasians. Yet no Asian guidelines addresses thromboprophylaxis following major surgery for upper gastrointestinal (UGI) malignancy. We aim to evaluate effects of LMWH on thromboembolic and bleeding events in our population. MethodsA retrospective study of all UGI resections for malignancy performed in a tertiary institution in Singapore between 2008 and 2018 was performed. Demographics, clinicopathological data and treatment outcome data were collected and analyzed. ResultsA total of 399 patients were included in the study. 210 (52.6%) received postoperative LMWH. Basic demographics-age, gender, BMI, smoking status were comparable. Most patients had cancers stage III or above (42.5% vs 34.6%) cancers. Patients who had open surgery were more likely to receive postoperative LMWH (81.8% vs 67.2%, p = 0.002).Postoperative mortality (3.2% vs 2.9%) and venous thromboembolic events (1.6% vs 1.4%) were similar. However, LMWH use was associated with increased blood transfusion (29.0% vs 12.7%, p < 0.001). ConclusionIncidence of venous thromboembolism was low and similar irrespective of postoperative LMWH use. However, LMWH use was associated with increased postoperative bleeding. Hence, we do not support routine LMWH for Asian patients undergoing UGI resection for malignancy.

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

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

Patient-Specific Venous Thromboembolic Event Prophylaxis in Total Joint Arthroplasty - Literature-Supported Guidelines.

Following total joint arthroplasty (TJA), venous thromboembolic events (VTE) are a known complication that may result in increased hospitalization cost as well as morbidity. Numerous investigations have documented patient-specific factors that place an individual at increased risk of VTE after TJA. Potential risk factors for VTE include genetic predisposition, history of a prior VTE event, revision surgery and patient comorbidity factors. The American Academy of Orthopedic Surgeons and The American College of Chest Physicians have both provided recommendations for VTE prophylaxis after orthopedic surgery. However, among orthopedic surgeons, there remains a lack of consensus regarding the appropriate agent and time course for prophylactic anticoagulation after TJA. In this study, we review the evidence-supported patient-specific factors that confer an increased risk of VTE in the TJA postoperative period. Furthermore, we describe the VTE prophylaxis regimen used at our home institution after TJA for low- and high-risk patients as well as a recommendation for cessation or continuation of anticoagulation regimens that patients were on preoperatively for comorbid conditions.