Higher Rate Of Venous Thromboembolism Research Articles

Aspirin is Not for Everyone: Discharge to Non-home Facilities After Total Hip and Knee Arthroplasty Increases Risk of Venous Thromboembolism

BackgroundPatients discharged to non-home facilities (NHD) after total hip arthroplasty (THA) and total knee (TKA) arthroplasty experience higher rates of adverse events and may require more aggressive venous thromboembolism (VTE) chemoprophylaxis. Our aim was to compare the rates of VTE in NHD patients and those discharged home (HD) after THA/TKA. Our secondary aim was to determine VTE rates within HD and NHD groups when stratified by chemoprophylactic regimen. MethodsA retrospective cohort of primary THA and TKA patients were stratified into HD and NHD, then allocated into groups by chemoprophylactic regimen on discharge: aspirin alone (AA), more aggressive (MA) chemoprophylaxis, and other regimens (other). The primary outcome was VTE. Rates of VTE in HD and NHD patients, as well as AA and MA regimens, were analyzed using a generalized linear regression model. ResultsSix thousand three hundred seventy-nine patients were included with 1.03% experiencing VTE. HD had lower rates of VTE compared to NHD (0.83% vs 2.17%, P < .001). AA had similar rates of VTE compared to MA (0.99% vs 1.08%, P = .82). NHD patients had a lower VTE rate with MA vs AA prophylaxis (1.47% vs 3.83%, P = .016). HD patients treated with AA vs MA had no difference in VTE rates (0.76% vs 0.96%, P = .761). ConclusionsNHD patients have higher rates of VTE than HD patients. However, NHD patients have significantly lower rates of VTE on MA chemoprophylaxis compared to those on AA. Providers should consider prescribing MA VTE chemoprophylaxis for NHD patients. Prospective, randomized studies are necessary to confirm these recommendations.

Incidence of Thrombosis in COVID-19 Patients Compared to Non-COVID-19 Sepsis Patients in the Intensive Care Unit.

Background/Objectives: The hypercoagulable state associated with COVID-19 infection is associated with adverse outcomes and mortality. Studies have also demonstrated high rates of venous thromboembolism (VTE) events among patients with sepsis. We aimed to evaluate how the increase in thrombotic events in critically ill patients with COVID-19 infection compares to that of critically ill patients with non-COVID-19 sepsis. Methods: A chart review was performed of patients 18 years or older admitted to the intensive care unit (ICU) at Tampa General Hospital between 1 January 2020 and 31 December 2020 diagnosed with COVID-19 or sepsis secondary to other pathogens. Non-COVID-19 sepsis patients and COVID-19 patients were propensity-matched 3:1 on the Charlson Comorbidity Index. Multivariate analyses adjusting for confounding were conducted to report odds ratio (OR) and 95% confidence intervals (95% CIs) of predictors for thrombotic events and overall mortality. Results: After propensity score matching, 492 sepsis patients and 164 COVID-19 patients were included in the analysis. COVID-19 patients were significantly older (p = 0.021) and showed higher BMI (p < 0.001) than sepsis patients. COVID-19 patients did not show significantly higher odds of thrombosis after adjustment for confounders (OR 0.85, 95% CI 0.42-1.72), but had significantly lower odds of mortality than sepsis patients (OR 0.33, 95% CI 0.16-0.66). Conclusions: Our results suggest that further study is required to lower the rate of VTE in COVID-19 and non-COVID-19 sepsis patients admitted to the ICU; it is also reasonable to consider similar thromboembolism practices between these two patient groups.

Risk Factors for Venous Thromboembolism and Eventual Amputation in Traumatic Femoral and Iliac Vein Injuries: A Trauma Quality Improvement Program Analysis.

Iliac and femoral venous injuries represent a challenging dilemma in trauma surgery with mixed results. Venous restoration of outflow (via repair or bypass) has been previously identified as having higher rates of VTE (venous thromboembolism) compared to ligation. We hypothesized that rates of VTE and eventual amputation were similar whether restoration of venous outflow vs ligation was performed at initial operation. Patients in the 2019-2021 National Trauma Data Bank with iliac and femoral vein injuries were abstracted and analyzed. The primary outcomes of interest were in-hospital lower extremity amputation and VTE. A total of 2642 patients with operatively managed iliac and femoral vein injuries were identified VTE was found in 10.8% of patients. Multivariable logistic regression was performed and identified bowel injury, higher ISS, older age, open repair, and longer time to VTE prophylaxis initiation as independent predictors of VTE. Amputation was required in 4.2% of patients. Multivariable logistic regression identified arterial or nerve injury, femur or tibia fracture, venous ligation, percutaneous intervention, fasciotomy, bowel injury, and higher ISS as independent factors of amputation. Venous restoration was not an independent predictor of VTE. Venous ligation on index operation was the only modifiable independent predictor of amputation identified on regression analysis.

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.

Racial Distribution and Associated Outcomes for Patients With and Without Severe-Isolated Traumatic Brain Injuries Following Venous Thromboembolism Prophylaxis.

Disparities in venous thromboembolism (VTE) incidence and prophylaxis have been observed across racial groups. This study investigates the relationship between race, injury type, and the timing of VTE prophylaxis in severe trauma patients, both with and without isolated traumatic brain injuries. The primary goal is to analyze how these factors interact and their potential impact on clinical outcomes. A retrospective cohort study of the American College of Surgeons Trauma Quality Program Participant Use File (ACS-TQIP-PUF) from 2018 to 2021. Patient demographics, injury categories, VTE prophylaxis timing, injury severity, and in-hospital complications were collected. Multivariable regression models explored associations between race, injury type, VTE prophylaxis, and in-hospital mortality. Groups were analyzed by injury profile (isolated TBI vs non-TBI) and then by VTE prophylaxis timing (early ≤24hours, late >24hours). Of 68,504 trauma patients analyzed, the majority were non-Hispanic or Latino (83.3%), White (71.2%), and male (69.6%). Patients receiving late VTE prophylaxis had higher rates of DVT and PE across race groups than patients with early prophylaxis. Logistic regression showed Asian patients with TBI receiving early prophylaxis were significantly more likely to have in-hospital mortality (OR 16.27, CI = 1.11-237.43, P = .04) than other races. Patients who received late prophylaxis had higher VTE rates than early prophylaxis, independent of injury pattern or race. Additionally, assessing the implications of race in early VTE prophylaxis for isolated TBI showed that adult Asian patients had 16 times higher odds of in-hospital mortality compared to other races.

Venous thromboembolism prophylaxis and multiple myeloma patients in real-life: Results of a large survey and clinical guidance recommendations from the IFM group

Venous thromboembolism (VTE) remains a critical issue in the management of patients with multiple myeloma (MM), particularly when immunomodulatory drugs (IMiDs) combined with dexamethasone therapy are being prescribed as first-line and relapse therapy. One possible explanation for the persistent high rates of VTE, is the use of inappropriate thromboprophylaxis strategies for patients starting antimyeloma treatment. To tackle the issue, the Intergroupe francophone du myélome (IFM) offered convenient guidance for VTE thromboprophylaxis in MM patients initiating systemic therapy. This guidance is mainly supported by the results of a large survey on the clinical habits regarding VTE of physicians who are substantially involved in daily care of MM patients. VTE prophylaxis should be considered for all patients treated with IMiDs in combination with dexamethasone, in the absence of significant comorbidities, such as renal failure or bleeding risk. Anticoagulant should be preferred to antiplatelet agents for thromboprophylaxis. Despite the absence of large randomized controlled trials comparing those attitudes/options, available data on direct oral anticoagulants, which are already used in daily management of MM patients, are consistent with their potential usefulness for VTE prophylaxis in such patients. However, in order to implement a personalized continuous improvement strategy, clinicians must to be organized to collect all the data regarding this management. In other situations, thromboprophylaxis should be evaluated by using risk models and after careful evaluation of the risk/benefit ratio.

Impact of Genetic Variations on Thrombotic Risk in Saudis with Sickle Cell Disease

Background Sickle cell disease (SCD) is a Mendelian disease characterised by multigenic phenotypes. Previous reports indicated a higher rate of venous thromboembolism (VTE) in SCD patients. A number of candidate polymorphisms in certain genes (e.g. FVL, PRT, and MTHFR) were previously reported as risk factors for VTE in different clinical conditions. This study aimed to genotype these genes and other loci predicted to underlay VTE in SCD patients. Methodology A genome-wide association study involving Saudi SCD adult patients with a history of VTE (n=65) and control patients without VTE history (n=285) was performed. Genotyping used the 10x Affymetrix Axiom array which includes 683,030 markers. Results No associations were identified between the targeted single nucleotide polymorphisms (SNPs) [FVL (rs6025), PRT (rs1799963), and MTHFR (rs1801133)] and VTE episodes in SCD patients. In contrast, GWAS analysis showed two genome-wide significant signals (P&amp;lt;5×10 -8) on chromosome (Chr) 11. These SNPs, rs35390334 and rs331532, are in strong linkage equilibrium (LD, r 2=0.97). A total of 35 other markers had an association threshold of P&amp;lt;5×10 -6. Four of these variants are located in olfactory receptor genes [OR51B5 (rs147062602), OR51V1 (rs7933549), OR51A1P (rs80034548), and OR52A5 (rs2472530)]. Conclusion No association between FVL, PRT, and MTHFR genes and VTE episodes was seen in Saudis with SCD. In contrast, two markers (rs35390334 and rs331532) showed significant genome-wide associations and less significant associations (P&amp;lt;5×10 -6) were identified for 35 other variants (24 of them are located on Chr 11). Further replication of these findings is needed.

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.

Derivation of a Risk Prediction Model for Venous Thromboembolism in Adult Patients with Acute Myeloid Leukemia

Background: Venous thromboembolism (VTE) is a well-established complication of malignancy associated with high morbidity. Many validated scoring systems exist to predict risk of VTE in patients with solid tumors. However, there are no models that can prospectively identify patients at high risk for the development of VTE in acute myeloid leukemia (AML). The purpose of this study was to determine risk factors for the development of VTE in a large cohort of AML patients and to develop a risk stratification model to predict VTE risk in this patient population. Methods: Adult patients presenting to the University of Wisconsin-Madison with newly-diagnosed AML from 1/1/2010 through 12/31/2021 were included in this retrospective cohort study. The primary end point was VTE within one year of diagnosis. Univariate logistic regression models were used to assess the association of each variable with development of VTE. Multivariate analysis was then completed using 16 candidate variables including demographics (sex, race, age at diagnosis), comorbidities (hypertension, diabetes, coronary artery disease, asthma/COPD), body mass index (BMI), Eastern Cooperative Oncology Group performance status (ECOG PS), history of solid organ or hematologic malignancy, smoking status, indwelling venous catheter, history of VTE, and baseline laboratory values (white blood cell count, hemoglobin, platelet count). Non-normally distributed continuous candidates were log10-transformed, then stepwise selection was used on a training set to choose predictive variables to construct a risk score to predict VTE within one year of AML diagnosis. Results: 326 patients with AML were included in the analysis. The median age at diagnosis was 60 years (range 19-92 years), 55% of the study population was male, and 94% were Caucasian race. 59 patients (18%) experienced VTE within one year of diagnosis. Age at diagnosis (OR 0.98, 95% CI, 0.963-0.998, p=0.033), BMI (OR 1.058, 95% CI, 1.02-1.10, p=0.005), hypertension (OR 0.522, 95% CI, 0.29-0.96, p=0.035) and platelets (OR 3.16, 95% CI, 1.44-6.94, p = 0.004) were individually associated with VTE. In a subgroup analysis of 278 patients with next generation sequencing data available, mutations in DNA methylation genes (DNMT3A, DNMT1, IDH1, IDH2, TET2) were associated with an increased risk of VTE (OR 1.911, 95% CI 1.017-3.591, p=0.0442, Table 1). A multivariate logistic regression model identified six independent predictors of VTE including platelet count &amp;gt;150,000 (OR 1.64, 95% CI 0.65-4.14, p=0.2953), BMI &amp;gt;25 (OR 3.10, 95% CI 1.22-7.86, p=0.0173), hypertension (OR 2.17, 95% CI 1.03-4.55, p=0.0410), history of other cancer (OR 1.72, 95% CI, 0.74-4.01, p=0.2109), diabetes (OR 2.05, 95% CI 0.73-5.73, p=0.1718), and ECOG PS (OR 1.33, 95% CI, 0.66-2.65, p=0.4263). Subsequently, a risk score was constructed from the multivariable model (3*platelets&amp;gt;150 + 8*BMI&amp;gt;25 + 5*NoHTN + 3*NoOtherCancer + 4*Diabetes + 1*ECOG0). Patients were categorized into three groups: low (score&amp;lt;9), moderate (9score&amp;lt;12), and high (score) risk of developing VTE (Table 2). Rates of VTE within one year of AML diagnosis were 3.2%, 16.4%, and 23.6% in the low, moderate, and high risk groups respectively. The model had an external AUC=0.704 when applied to our test set. Conclusions: Our study demonstrates a high rate of early VTE in patients with AML at 18%, highlighting the importance of identifying those at higher risk which would allow for early screening, patient education, and consideration of thromboprophylaxis. On multivariable analysis, we found that normal or elevated platelet count &amp;gt;150, BMI 25, and diabetes were associated with an increased risk of early VTE. Surprisingly, higher ECOG PS, history of malignancy, and hypertension were associated with a decreased risk of early VTE in our cohort. A risk prediction model incorporating these findings was able to identify patients with low, moderate, and high risk of VTE. This model may help with clinical decision making, such as the consideration of thromboprophylaxis for patients with a moderate or high risk score. However, prospective validation of this model in a larger cohort of patients is needed. In summary, we propose a risk prediction model for the development of VTE in AML that can now be validated in order to provide optimal supportive care for this patient population.

Age- and sex- specific rate of venous thromboembolism in cancer survivors: a nationwide cohort study

Abstract Background Patients with cancer have an increased risk of venous thromboembolism (VTE) initially, then to decrease over time. VTE might be potentially preventable with pharmacologic prophylaxis, particularly in high-risk patients. The long-term risk of VTE among cancer survivors, however, has not been reported. Purpose We investigated the rate of VTE in survivors of various cancers 5 years out from diagnosis, overall and according to age and sex. Methods Using Danish nationwide registries, five-year survivors of 20 cancers (diagnosed between 1994 and 2013; &amp;gt;15 years at diagnosis) were matched on age and sex with four non-cancer controls from the general population. Rates of VTE in the cancer and non-cancer groups were compared with Cox regression models, overall and according to age (i.e., 15-39, 40-64, and &amp;gt;65 years) and sex. Results In total, 197,702 five-year cancer survivors (median age at diagnosis 63 years [IQR: 53 – 71 years]; 38.5% men) were matched with 790,808 non-cancer controls. During a median follow-up of 6.2 years, cancer survivors overall had a higher associated rate of incident VTE than non-cancer controls (incidence rate per 1,000 person-years 5.6 [95% CI, 5.5-5.8] and 3.3 [3.3-3.4] for cancer survivors and non-cancer controls, respectively; adjusted hazard ratio [aHR] 1.77 [1.72-1.83]). The increased rate of VTE in cancer survivors, compared with matched controls, was statistically significant for all 20 cancer subtypes and was more pronounced in multiple myeloma and lung cancer [Figure 1]. The relatively higher rate of VTE in cancer survivors was more pronounced in women, and the younger patients (age group: 15-39 years) (PInteraction&amp;lt;0.01). Though, VTE was more prevalent in men (per 1,000 person-years 6.7 [95% CI, 6.4-6.9]) than in women (5.2 [95% CI, 5.0-5.3]), and in older patients (8.5 [95% CI, 8.2-8.7]) compared with younger patients (2.2 [95% CI, 1.9-2.4]) [Figure 2]. Conclusions Compared with the general population, five-year cancer survivors had higher associated rates of VTE, irrespective of age and sex. The increased relative rate of VTE was more pronounced in the younger individuals and women.Hazard ratios of venous thromboembolismVenous thromboembolism by age and sex

Persistent underuse of extended venous thromboembolism prophylaxis in patients undergoing major abdominal cancer operations.

Guidelines recommend extended venous thromboembolism (VTE) prophylaxis for high-risk populations undergoing major abdominal cancer operations. Few studies have evaluated extended VTE prophylaxis in the Medicare population who are at higher risk due to age. We performed a retrospective study using a 20% random sample of Medicare claims, 2012-2017. Patients ≥65 years with an abdominal cancer undergoing resection were included. Primary outcome was the proportion of patients receiving new extended VTE prophylaxis prescriptions at discharge. Secondary outcomes included postdischarge VTE and hemorrhagic events. The study included 72 983 patients with a mean age of 75. Overall, 8.9% of patients received extended VTE prophylaxis. This proportion increased (7.2% in 2012, 10.6% in 2017; p < 0.001). Incidence of postdischarge hemorrhagic events was 1.0% in patients receiving extended VTE prophylaxis and 0.8% in those who did not. The incidence of postdischarge VTE events was 5.2% in patients receiving extended VTE prophylaxis and 2.4% in those who did not. Adherence to guideline-recommended extended VTE prophylaxis in high-risk patients undergoing major abdominal cancer operations is low. The higher rate of VTE in the prophylaxis group may suggest we captured some therapeutic anticoagulation, which would mean the actual rate of thromboprophylaxis is lower than reported herein.

FRI205 Splenic Infarct: A Rare Presentation Of Cushing Syndrome

Abstract Disclosure: G. Virella: None. Splenic Infarct: A Rare Presentation of Cushing Syndrome Geover, Virella M.D. 1,2, Carlos Santiago Botero Suarez, M.D.1,2, Alfredo Palomino Abella, M.D. 1,2, Mustafa Kinaan, M.D. 1,2 1) University of Central Florida HCA Healthcare GME, Greater Orlando, Florida2) Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, Florida Disclaimer: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.Introduction Cushing’s syndrome (CS) is associated with a hypercoagulable state leading to increased incidence of thromboembolic events. The mechanism behind this phenomenon is due to an imbalance between activity of pro- and anticoagulant pathways. We report a case of newly diagnosed CS in a patient presenting with acute splenic and inferior vena cava (IVC) infarcts. Case Description A 59-year-old woman with no significant medical history presents with acute left upper quadrant pain. She denied other symptoms. Physical examination was remarkable for tachycardia, left upper quadrant tenderness, and centripetal adiposity with BMI of 19. Labs showed marked leukocytosis (WBC 26 x 109/L) and thrombocytopenia (platelet 96,000 cells/uL). She was also found to be diabetic (HgA1C 12.5%). Abdominal CT imaging showed a wedge-shaped 4.3 x 3.1 x 2.3 cm splenic infarction, peri-splenic abscess, and thrombosis of the left renal and gonadal veins extending into the IVC. Additionally, there was a left adrenal incidentaloma measuring 4.5 x 3.8 x 2.9 cm. MRI of the left adrenal gland was consistent with an adenoma. The right adrenal gland was unremarkable. Screening for pheochromocytoma and hyperaldosteronism was normal. A morning serum cortisol was 33.4 mcg/dL, and ACTH level of &amp;lt; 1.5 pg/mL. An overnight 1-mg dexamethasone suppression test revealed post-dexamethasone cortisol of 4.58 mcg/dL. These findings were consistent with Cushing syndrome secondary to adrenal cause. The patient was initially treated with heparin infusion and underwent a successful thrombectomy of the IVC and gonadal vein. She later underwent a successful laparoscopic left adrenalectomy and splenectomy. Pathology reports confirmed an adrenocortical adenoma. A random post-surgical cortisol was 22.8. The patient had an uneventful postoperative course and was discharged home with outpatient endocrine follow-up planned to evaluate for hypercortisolism resolution and management of diabetes. Conclusion Cushing Syndrome patients have been shown to have an almost 18-fold higher rate of venous thromboembolism (VTE). This is an often-overlooked complication of hypercortisolism. The pathogenesis is not fully understood but is believed to be related to shortening of activated partial thromboplastin time (aPTT), increased clot lysis time, and glucocorticoid-induced increase in procoagulant factors such as fibrinogen, von Willebrand factor, and factor VIII. Our case will closely demonstrate the link between hypercortisolism and hypercoagulability. Presentation: Friday, June 16, 2023

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis

The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Erasmus MC.

COMPASS-CAT versus Khorana risk assessment model for predicting venous thromboembolic events in patients with non-small cell lung cancer on active treatment with chemotherapy and/or immunotherapy, the CK-RAM study.

Cancer patients are at higher risk for venous thromboembolism (VTE). Several risk assessment models (RAM), including the Khorana and COMPASS-CAT, were developed to help predict the occurrence of VTE in cancer patients on active anti-cancer therapy. We aim to study the prevalence and predictors of VTE among patients with non-small cell lung cancer (NSCLC) and compare both RAMs in predicting VTE in patients with NSCLC were retrospectively reviewed. Variables known to increase the risk of VTE were collected and risk of VTE was assessed using both Khorana and COMPASS-CAT RAM. A total of 508 patients (mean age ± SD, 58.4 ± 12.2 years) were enrolled. Most (n = 357, 70.3%) patients had adenocarcinoma, and 333 (65.6%) patients had metastatic disease. VTE were confirmed in 76 (15.0%) patients. Rates were higher among patients with metastatic disease (19.8%, p < 0.001), adenocarcinoma (17.4%, p = 0.01) and those treated with immunotherapy (23.5%, p = 0.014). VTE rates were 21.2%, 14.1% and 13.9% among those with high (n = 66), intermediate (n = 341) and low (n = 101) Khorana risk scores, respectively (p = 0.126). On the other hand, 190 (37.4%) were classified as high risk by the COMPASS-CAT RAM; 52 (27.4%) of them had VTE compared to 24 (7.5%) of the remaining 318 (62.6%) classified as Low/Intermediate risk level, p < 0.001. In conclusion, patients with NSCLC are at high risk for VTE, especially those with adenocarcinoma, metastatic disease and when treated with immunotherapy. Compared to Khorana RAM, COMPASS-CAT RAM was better in identifying more patients in high-risk group, with higher VTE rate.

High rates of venous thromboembolism among deliveries complicated by cancer

BackgroundVenous thromboembolism (VTE) risk is increased independently by both cancer and pregnancy. ObjectivesTo estimate VTE risk in the postpartum period among patients delivering with a cancer diagnosis, stratified by cancer type and delivery route. MethodsWe performed a retrospective cohort study utilizing the large, all-payer Nationwide Readmissions Database from October 2015 through December 2020. We identified delivery hospitalizations, cancer diagnoses, and VTE using patient demographics and diagnosis codes. The primary outcome was VTE incidence at 42 and 330 days from delivery admission date, comparing patients with and without cancer diagnoses. A secondary analysis included VTE risk stratified by cancer diagnosis and delivery route. Outcomes were compared using inverse probability-weighted survival curves. ResultsThe study population included 9 793 503 delivery hospitalizations (weighted estimate, 18 207 346), with a weighted estimate of 10 428 (0.06%) pregnant patients with cancer. Individuals with cancer were older, with higher rates of comorbid conditions, than those without cancer. VTE incidence in individuals with cancer at 42 and 330 days was 1.11% and 2.19%, respectively, vs 0.11% and 0.14%, respectively, in those without cancer. At 330 days, this finding was significant in both unadjusted (relative risk, 15.52; 95% CI, 11.54-19.51) and adjusted (relative risk, 9.68; 95% CI, 7.18-12.18) models. Stratification by cancer type and delivery route demonstrated elevated VTE risk across cancer types, with cesarean delivery conferring a greater risk. ConclusionCancer in pregnancy confers excess thromboembolic risk extending beyond the immediate postpartum period. Further study is needed to identify optimal VTE prophylactic strategies for this population.

Venous thromboembolism risk in cancer patients receiving first-line immune checkpoint inhibitor versus chemotherapy.

It remains unclear if immune checkpoint inhibitor (ICI) therapy is associated with higher rate of venous thromboembolism (VTE) compared with cytotoxic chemotherapy (chemo) in patients with comparable cancer type, staging, and comorbidities. Using the national Veterans Affairs healthcare system database from 2016 to 2021, we performed a propensity score (PS)-weighted retrospective cohort study to compare the incidence of VTE in patients with selected stage III/IV cancer receiving first-line ICI versus chemo. The PS model utilized overlap weights to balance age, sex, race, treatment year, VTE history, paralysis/immobilization, prolonged hospitalization, cancer type, staging, time between diagnosis and treatment, and National Cancer Institute comorbidity index. Weighted Cox regressions with robust standard error were used to assess the hazard ratio (HR) and 95% confidence interval (CI). We found that among comparable advanced cancers, first-line ICI (n = 1823) and first-line chemo (n = 6345) had similar rates of VTE (8.49% for ICI and 8.36% for chemo at 6 months). The weighted HR was 1.06 (95% CI 0.88-1.26) for ICI versus chemo. In a subgroup analysis restricted to lung cancers, first-line ICI/chemo (n = 828), ICI monotherapy (n = 428), and chemo monotherapy (n = 4371) had similar rates of VTE (9.60% for ICI/chemo, 10.04% for ICI, and 8.91% for chemo at 6 months). The weighted HR was 1.05 (95% CI 0.77-1.42) for ICI versus chemo, and 1.08 (95% CI 0.83-1.42) for ICI/chemo versus chemo. In conclusion, ICI as a systemic therapy has a similarly elevated risk as cytotoxic chemo for VTE occurrence in cancer patients. This finding can inform future prospective studies exploring thromboprophylaxis strategies.

Outcomes in infants with unprovoked venous thromboembolism: A retrospective cohort study

BackgroundAlthough children aged <1 year have a relatively high rate of venous thromboembolism (VTE) compared to older children, most have additional prothrombotic risk factors. Unprovoked VTE is rare, and little is known about this population, particularly the risk of recurrent VTE. ObjectivesWe aimed to determine the rate of recurrent VTE in infants with prior unprovoked VTE and evaluate long-term, end-organ outcomes for infants with renal and intracranial vein thrombosis. MethodsInfants <1 year of age with an unprovoked VTE between 2003 and 2021 at a single institution were included. Time to recurrent event and anticoagulation duration were summarized using the Kaplan-Meier estimator. Neurologic outcomes were summarized with the pediatric stroke outcome measure for infants with cerebral sinovenous, medullary, or cortical vein thrombosis. Kidney outcomes were summarized with estimated glomerular filtration rates for infants with renal vein thrombosis. Anticoagulation was summarized. ResultsForty infants with intracranial, renal, portal, and extremity VTE met the inclusion criteria and were followed for a median of 4.7 years (IQR, 2.1-8.5). Most VTE events occurred during the first month of life. There was 1 recurrent event in 237 person-years of follow-up (incidence rate, 4 per 1000 [95% CI, 0.6-29.9] person-years). In outpatient follow-up, 40% of infants with intracranial thrombosis met criteria for moderate or severe neurologic outcomes and two-thirds of infants with a prior renal vein thrombosis had abnormal kidney function (estimated glomerular filtration rate < 90 mL/min/1.73 m2). ConclusionThere is a low rate of recurrent VTE but significant end-organ morbidity in infants with unprovoked VTE.

MP43-08 VENOUS THROMBOEMBOLISM RISK IN TESTOSTERONE TREATED MEN WITH AND WITHOUT KLINEFELTER SYNDROME

You have accessJournal of UrologyCME1 Apr 2023MP43-08 VENOUS THROMBOEMBOLISM RISK IN TESTOSTERONE TREATED MEN WITH AND WITHOUT KLINEFELTER SYNDROME Christopher Lau, Yunzhe Zhang, Bethany Gabriel, Jesufikunayomi Ifeoluwa, and Tet Yap Christopher LauChristopher Lau More articles by this author , Yunzhe ZhangYunzhe Zhang More articles by this author , Bethany GabrielBethany Gabriel More articles by this author , Jesufikunayomi IfeoluwaJesufikunayomi Ifeoluwa More articles by this author , and Tet YapTet Yap More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003289.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is a higher risk of VTE in Klinefelter syndrome (KS) (∼17%) compared to the general population (∼0.1%). The risk of venous thromboembolism (VTE) as an adverse effect of testosterone therapy (TT) has been hypothesised, however there is limited data on this. TT is a common treatment for symptom management in KS, and is potentially a factor in higher VTE rates seen in KS. This study aims to evaluate the association between TT in both men with and without KS and VTE. METHODS: A literature review was performed following PRISMA guidelines, using sites such as BMJ, PubMed and ScienceDirect. Study searches, selection, data collection and analysis were carried out by four researchers independently and cross reviewed. 27 studies were selected and results from 6, which were specific to TT and VTE, were included [Table 1]. Significance level was set at p≤0.05. To assess risk of bias, tools such as Newcastle-Ottawa scale were used, and heterogeneity was found. RESULTS: The incidence of VTE in non-KS on TT ranged from 0.6-5.6% (n=2224). The incidence of VTE in KS on TT ranged from 31.3-40.0% (n=135). The background risk was 0.12% and 17.0% for the non-KS and KS groups respectively. Overall, there was a statistically significant increase in incidence of VTE in men taking TT both in the KS [χ2 = 9.95, p<.05] and non-KS [χ2 = 545.66, p<.05] patient groups. However, no statistically significant difference in VTE between the different routes of administration of TT in both the KS [χ2 = 0.12, p=.729485] and non-KS [χ2 = 7.29, p=.06309] patient groups. CONCLUSIONS: Overall, a significant increase in incidence of VTE was observed in men taking TT both in the KS and non-KS patient groups. However, similar rates of VTE between the different routes of administration of TT. Owing to the highly variable follow up period of testosterone treated men, a transient increase in risk of VTE in the first 6 months of initiating treatment was observed by a case control study. It is possible that this change was also observed in the results and therefore more data would be required exploring the long term use of TT and VTE risk. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e604 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christopher Lau More articles by this author Yunzhe Zhang More articles by this author Bethany Gabriel More articles by this author Jesufikunayomi Ifeoluwa More articles by this author Tet Yap More articles by this author Expand All Advertisement PDF downloadLoading ...

Assessment of the Risk of Venous Thromboembolism in Nonhospitalized Patients With COVID-19

Patients hospitalized with COVID-19 have higher rates of venous thromboembolism (VTE), but the risk and predictors of VTE among individuals with less severe COVID-19 managed in outpatient settings are less well understood. To assess the risk of VTE among outpatients with COVID-19 and identify independent predictors of VTE. A retrospective cohort study was conducted at 2 integrated health care delivery systems in Northern and Southern California. Data for this study were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Participants included nonhospitalized adults aged 18 years or older with COVID-19 diagnosed between January 1, 2020, and January 31, 2021, with follow-up through February 28, 2021. Patient demographic and clinical characteristics identified from integrated electronic health records. The primary outcome was the rate per 100 person-years of diagnosed VTE, which was identified using an algorithm based on encounter diagnosis codes and natural language processing. Multivariable regression using a Fine-Gray subdistribution hazard model was used to identify variables independently associated with VTE risk. Multiple imputation was used to address missing data. A total of 398 530 outpatients with COVID-19 were identified. The mean (SD) age was 43.8 (15.8) years, 53.7% were women, and 54.3% were of self-reported Hispanic ethnicity. There were 292 (0.1%) VTE events identified over the follow-up period, for an overall rate of 0.26 (95% CI, 0.24-0.30) per 100 person-years. The sharpest increase in VTE risk was observed during the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% CI, 0.51-0.67 per 100 person-years vs 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days). In multivariable models, the following variables were associated with a higher risk for VTE in the setting of nonhospitalized COVID-19: age 55 to 64 years (HR 1.85 [95% CI, 1.26-2.72]), 65 to 74 years (3.43 [95% CI, 2.18-5.39]), 75 to 84 years (5.46 [95% CI, 3.20-9.34]), greater than or equal to 85 years (6.51 [95% CI, 3.05-13.86]), male gender (1.49 [95% CI, 1.15-1.96]), prior VTE (7.49 [95% CI, 4.29-13.07]), thrombophilia (2.52 [95% CI, 1.04-6.14]), inflammatory bowel disease (2.43 [95% CI, 1.02-5.80]), body mass index 30.0-39.9 (1.57 [95% CI, 1.06-2.34]), and body mass index greater than or equal to 40.0 (3.07 [1.95-4.83]). In this cohort study of outpatients with COVID-19, the absolute risk of VTE was low. Several patient-level factors were associated with higher VTE risk; these findings may help identify subsets of patients with COVID-19 who may benefit from more intensive surveillance or VTE preventive strategies.

High rate of venous thromboembolism in severe pediatric intestinal failure.

To quantify the rate of venous thromboembolism (VTE) in patients with pediatric intestinal failure and identify associated risk factors. We performed a retrospective cohort study in pediatric patients (<21years old) with severe pediatric intestinal failure (≥90 consecutive days of parenteral nutrition) secondary to short bowel syndrome who were treated from 2014 to 2021 at an interdisciplinary intestinal rehabilitation program. The primary outcome was the incidence of VTE. Multivariable regression was performed to identify independent clinical predictors of VTE. A total of 263 patients (59.7% male) met the criteria for inclusion. The cumulative incidence of VTE was 28.1%, with a rate of 0.32 VTEs per 1000 catheter-days. On univariate analysis, the number of catheter days, number of catheters, and history of central line-associated blood stream infection were associated with VTE. On multivariable logistic regression, a higher number of catheters was an independent risk factor for VTE (aOR, 1.17; 95% CI, 1.06-1.29). Additionally, earlier gestational age was a risk factor for VTE such that every week decrease in gestational age conferred a 9% increased risk of VTE (aOR, 1.09; 95% CI, 1.02-1.16). In this retrospective study, 28.1% of patients with severe pediatric intestinal failure developed VTE; the number of catheters and early gestational age were noted to be independent risk factors for VTE. This high incidence of VTE highlights the need to investigate VTE in pediatric intestinal failure prospectively, including the potential benefit of prophylactic anticoagulation.