Incidence Of VTE Research Articles

Prophylactic Enoxaparin Dosing Using Anti-Factor Xa Levels in Hepatic Surgery Patients: A Pilot Study.

This study examines the safety and efficacy of using peak anti-Xa levels to achieve prophylactic enoxaparin (Lovenox, Sanofi-Aventis) levels in patients who underwent hepatic surgery. Prospectively enrolled patients undergoing major and minor hepatic procedures received postoperative enoxaparin dosing. The enoxaparin dose was adjusted to attain a peak anti-Xa level ≥ 0.20U/ml. This group was compared to a historical cohort of patients who underwent similar procedures and received standard postoperative VTE chemoprophylaxis dosing. Inpatient postoperative VTE rates were higher in the control group when compared to the experimental group (0 patients [0.00%] vs 4 patients [8.16%]; P = .035). There was no statistically significant difference in number of postoperative blood transfusions, discharge hemoglobin, or in-hospital bleeding events. Adjusting enoxaparin dosing to achieve prophylactic peak anti-Xa levels of ≥0.20IU/ml was associated with a reduced incidence of symptomatic inpatient postoperative VTE in patients who underwent hepatic surgery without increasing postoperative bleeding events.

Venous and arterial thrombosis in patients with VEXAS syndrome

AbstractVEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, caused by somatic mutations in UBA1, is an autoinflammatory disorder with diverse systemic manifestations. Thrombosis is a prominent clinical feature of VEXAS syndrome. The risk factors and frequency of thrombosis in VEXAS syndrome are not well described, due to the disease’s recent discovery and the paucity of large databases. We evaluated 119 patients with VEXAS syndrome for venous and arterial thrombosis and correlated their presence with clinical outcomes and survival. Thrombosis occurred in 49% of patients, mostly venous thromboembolism (VTE; 41%). Almost two-thirds of VTEs were unprovoked, 41% were recurrent, and 20% occurred despite anticoagulation. The cumulative incidence of VTE was 17% at 1 year from symptom onset and 40% by 5 years. Cardiac and pulmonary inflammatory manifestations were associated with time to VTE. M41L was positively associated specifically with pulmonary embolism by univariate (odds ratio [OR]: 4.58, confidence interval [CI] 1.28-16.21, P = .02) and multivariate (OR: 16.94, CI 1.99-144.3, P = .01) logistic regression. The cumulative incidence of arterial thrombosis was 6% at 1 year and 11% at 5 years. The overall survival of the entire patient cohort at median follow-up time of 4.8 years was 88%, and there was no difference in survival between patients with or without thrombosis (P = .8). Patients with VEXAS syndrome are at high risk of VTE; thromboprophylaxis should administered be in high-risk settings unless strongly contraindicated.

Thrombosis in Critically Ill Influenza Patients: Incidence and Risk Factors.

Influenza infection is associated with a risk of thrombosis. Whether factors associated with reduced thrombosis might also be associated with reduced risk in patients with severe influenza is unknown. To investigate risk factors associated with thrombosis in patients with severe influenza. We used a cohort data set to identify adults diagnosed with severe influenza. Univariable and multivariable logistic regression models explored potential risk factors for thrombosis events in patients with severe influenza. Cox regression analysis was used to examine the risk factors for mortality in patients with severe influenza. A total of 854 patients with severe influenza were included in the analysis. The incidence of VTE was 9.37% (80/854). Multivariable regression analysis showed that previous aspirin medication (OR: 0.37; 95%CI: 0.14-0.84; P = .029) could reduce the risk factor of thrombosis in patients with severe influenza. Compared with patients in the non-thrombosis group, patients in the thrombosis group required more mechanical ventilation (P < .001), tracheostomy (P < .001), ECMO (P = .046), and high-frequency ventilation (P = .004). The incidence of co-infection was higher in the thrombosis group compared to the non-thrombosis group (P = .025). Univariable Cox regression analysis showed that previous aspirin medication (HR 0.52, 95%CI: 0.33-0.82, P = .005) and previous statin medication (HR 0.54, 95%CI: 0.34-0.87, P = .011) were risk factors for 60-day mortality in patients with severe influenza. Patients with severe influenza are at high risk for thrombosis. The effect of aspirin on thrombosis in patients with severe influenza needs further investigation.

P1151 Incidence and risk factors of thromboembolic events in Pediatric-Onset Inflammatory Bowel Disease: a population-based study

Abstract Background Patients with inflammatory bowel disease (IBD) are known to be more susceptible to thromboembolic events. However, limited data on the incidence and risk factors for both venous (VTE) and arterial thromboembolic events (ATE) have been documented at the population level, especially in pediatric-onset IBD. Methods All patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) before the age of 17 years from 1988 to 2011 in a prospective population-based registry were retrospectively followed until 2013. Every VTE and ATE occurring during the follow-up period were included. Cox proportional hazard models with hazard ratio (HR) were performed using time dependent variable except for patient’s characteristics at diagnosis. Results A total of 1,344 patients diagnosed with IBD between 1988 and 2011, including 1,007 (75%) patients with CD and 337 (25%) with UC, with a median age at diagnosis of 14.3, IQR [11.7-16.0] years were included. After a median follow-up of 8.3, IQR [4.3–13.9] years, 15 (1.1%) VTE and 2 (0.15%) ATE occurred at a median age of 20.4, IQR [16.6-24.5] years (younger age: 14.8 years). The global incidence rate for both VTE and ATE was 1.32 per 1000 person-years, 95%CI [0.77 - 2.11]. In CD patients, the incidence of VTE was 1.41 per 1000 person-years, 95%CI [0.77 - 2.37], whereas it stood at 0.33 per 1000 person-years, 95%CI [0.01 - 1.85] in UC patients. The risk of VTE and ATE did not change over the study period. Periods of active disease (HR 8.4 [2.3-30.5], p=0.0002), the 3-months postoperative period (HR 16.4 [5.2-52.3], p=0.0002) and hospitalization (HR 21.7 [7.5-62.9], p&amp;lt;0.0001) were found to be associated with an increased risk of VTE. Conclusion The risk of both arterial and venous thromboembolism was low in this pediatric-onset IBD population-based cohort. VTE were strongly associated with active disease, surgery and hospitalization among IBD patients.

P1137 Long-term trend of cumulative incidence of venous thromboembolism in Korean patients with inflammatory bowel disease: A nationwide population-based cohort study

Abstract Background Venous thromboembolism (VTE) is a serious extraintestinal manifestation of inflammatory bowel disease (IBD). However, limited research has been conducted on the cumulative incidence of VTE in patients with IBD. Therefore, this study aimed to observe the trend of cumulative incidence of VTE after IBD diagnosis. Methods From 2005 to 2016, a population-based cohort study was conducted using health administration claims data from South Korea. IBD and VTE were defined by ICD-10 codes. Incidence density and cumulative incidence rate were analysed. The risk of variables including age, sex, and IBD subtype was comparatively analysed. Results A total of 35,508 newly diagnosed patients with IBD between 2005 and 2015 were followed up until 2016. Among them, 634 (1.8%) experienced VTE (619 adults and 15 children). The incidence densities of VTE per 10,000 person-year were 28.90 (range, 27.75–32.54) for overall IBD, 30.07 (range, 27.75–32.54) for adult IBD, and 11.08 (range, 6.20–18.27) for PIBD, respectively. The cumulative incidences of VTE at 0, 1-, 3-, 5-, and 10 years post-diagnosis were 0.01%, 0.30%, 0.80%, 1.30%, and 3.0%, respectively (Figure 1-A). Adulthood, female sex, and ulcerative colitis were associated with an increased risk of VTE (Figure 1-B, C, D). Conclusion The study showed a steady and gradual increase in the cumulative incidence of VTE in patients with IBD over a follow-up period of up to 11 years, with a slightly more rapid increase after 8 or 9 years. This trend was even more pronounced in children. This suggests that vigilant monitoring of VTE is necessary in the management of patients with IBD.

Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California

IntroductionVenous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis (‘late VTE’) is scarce, particularly in young survivors. MethodsWe examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15–39 years) diagnosed with cancer (2006–2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses. ResultsAmong 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80–2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86–12.22), second primary cancer (HR = 2.58, CI:2.01–3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84–3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer. ConclusionsVTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.

Development of a Risk Assessment Tool for Venous Thromboembolism among Hospitalized Patients in the ICU.

ICU patients have a high incidence of VTE. The American College of Chest Physicians antithrombotic practice guidelines recommend assessing the risk of VTE in all ICU patients. Although several VTE risk assessment tools exist to evaluate the risk factors among hospitalized patients, there is no validated tool specifically for assessing the risk of VTE in ICU patients. A retrospective corhort study was conducted between June 2018 and October 2022. We obtained data from the electronic medical records of patients with a variety of diagnoses admitted to a mixed ICU. Multivariable logistic regression analysis was used to evaluate the independent risk factors of VTE. Receiver operating characteristic (ROC) curves were used to analyse the predictive accuracy of different tools. A total of 566 patients were included, and VTE occurred in 89 patients (15.7%), 62.9% was asymptomatic VTE. A prediction model (the ICU-VTE prediction model) was derived from the independent risk factors identified using multivariate analysis. The ICU-VTE prediction model included eight independent risk factors: history of VTE (3 points), immobilization ≥4 days (3 points), multiple trauma (3 points), age ≥70 years (2 points), platelet count >250 × 103/μL (2 points), central venous catheterization (1 point), invasive mechanical ventilation (1 point), and respiratory failure or heart failure (1 point). Patients with a score of 0-4 points had a low (1.81%) risk of VTE. Patients were at intermediate risk, scoring 5-6 points, and the overall incidence of VTE in the intermediate-risk category was 17.1% (odds ratio [OR], 11.1; 95% confidence interval [CI], 4.2-29.4). Those with a score ≥7 points had a high (44.1%) risk of VTE (OR, 42.6; 95% CI, 16.4-110.3). The area under the curve (AUC) of the ICU-VTE prediction model was 0.838, and the differences in the AUCs were statistically significant between the ICU-VTE prediction model and the other three tools (ICU-VTE score, Z = 3.723, P < 0.001; Caprini risk assessment model, Z = 6.212, P < 0.001; Padua prediction score, Z = 7.120, P < 0.001). We identified eight independent risk factors for acquired VTE among hospitalized patients in the ICU, deriving a new ICU-VTE risk assessment model. The model aims to predict asymptomatic VTE in ICU patients. The new model has higher predictive accuracy than the current tools. A prospective study is required for external validation of the tool and risk stratification in ICU patients.

External Validation of the ICU-Venous Thromboembolism Risk Assessment Model in Adult Critically Ill Patients.

Currently, no universally accepted standardized VTE risk assessment model (RAM) is specifically designed for critically ill patients. Although the ICU-venous thromboembolism (ICU-VTE) RAM was initially developed in 2020, it lacks prospective external validation. To evaluate the predictive performance of the ICU-VTE RAM in terms of VTE occurrence in mixed medical-surgical ICU patients. We prospectively enrolled adult patients in the ICU. The ICU-VTE score and Caprini or Padua score were calculated at admission, and the incidence of in-hospital VTE was investigated. The performance of the ICU-VTE RAM was evaluated and compared with that of Caprini or Padua RAM using the receiver operating curve. We included 269 patients (median age: 70 years; 62.5% male). Eighty-three (30.9%) patients experienced inpatient VTE. The AUC of the ICU-VTE RAM was 0.743 (95% CI, 0.682-0.804, P < 0.001) for mixed medical-surgical ICU patients. Comparatively, the performance of the ICU-VTE RAM was superior to that of the Pauda RAM (AUC: 0.727 vs 0.583, P < 0.001) in critically ill medical patients and the Caprini RAM (AUC: 0.774 vs 0.617, P = 0.128) in critically ill surgical patients, although the latter comparison was not statistically significant. The ICU-VTE RAM may be a practical and valuable tool for identifying and stratifying VTE risk in mixed medical-surgical critically ill patients, aiding in managing and preventing VTE complications.

Comparison of different intervention methods to reduce the incidence of venous thromboembolism: study protocol for a cluster-randomized, crossover trial

BackgroundVenous thromboembolism (VTE) remains a priority challenge among orthopedic trauma patients. It is crucial to further improve the prophylaxis against VTE in routine orthopedic treatment. This study aims to compare the efficacy of two low molecular weight heparin (LMWH) regimens and additional intermittent pneumatic compression in preventing VTE among orthopedic trauma patients.Methods and analysisThis is a cluster-randomized crossover clinical study conducted in four hospitals in Shanghai from December 2019 to December 2023. The unit of randomization is orthopedic wards, and each ward will define a cluster. All clusters will implement four diverse intervention measures and one control measure in a given random sequence. Perioperative orthopedic trauma patients aged ≥ 18 years with stable vital signs, Caprini score > 2, and no contraindication of anticoagulation or intermittent pneumatic compression (IPC) devices will be eligible. The sample size will be determined to be 2590, considering cluster effect, period effect, and interactions. We will generally use the intention-to-treat (ITT) at the subject level for each outcome. For the primary outcome of the study, the incidence of VTE will be presented as risk ratio and 95% CIs. Generalized estimating equation (GEE) will be deployed to compare differences and adjust cluster effect, period effect, and interaction among interventions and periods if applicable.DiscussionVTE is a complication that cannot be underestimated after major orthopedic surgery. Early identification, early assessment, and early prevention can significantly reduce the incidence of VTE. Most guidelines recommend both medical and physical prevention, and we hope to demonstrate how they would affect the incidence among perioperative orthopedic patients. We want to explore if there is a difference between the two types of LWMH with or without an IPC device to provide more evidence for future guidelines and prevent more patients from the threat of VTE.Ethics and disseminationThe study received approval from the IRB of the coordinating center and all participating hospitals. Findings will be disseminated through peer-reviewed publications and conference presentations.Trial registrationChiCTR1900027659. Registered on 17 November 2019

Predictors and Timing of Venous Thromboembolism in Lung Cancer

Introduction Venous thromboembolism (VTE) is a common complication in lung cancer, but its risk factors and incidence have not been fully characterized. While prophylactic anticoagulation is recommended for some patient with cancer to prevent VTE, the thrombosis-risk prediction Khorana score considers lung cancer intermediate risk for development of VTE and combines all subtypes of lung cancer into a single entity. There are also limited data on the impact of therapy-type on VTE risk in patients with lung cancer. This study aimed to identify the incidence of VTE and its associated risk factors in patients with lung cancer at our university cancer center. Methods Using data from our tumor registry, we identified patients diagnosed with lung cancer between 2018 and 2022 who received first therapy beyond surgery alone after date of first contact. Using automated text search from our electronic medical record (EPIC®) combined with natural language processing review, VTE events were identified from 90-days before and up to one year(y) after initiation of systemic therapy. VTE events, including lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), were captured by physician investigators, with final, secondary adjudication by one of us (GAS). We report time to event analysis and survival analysis using Kaplan-Meier curve. The study was censored at one year. Univariate and multivariate analyses were performed using COX-regression model. We evaluated the effect of lung cancer subtype, stage, age, sex, race, ethnicity, white blood cell count, hemoglobin, and platelet count. Results A total of 635 lung cancer patients were included in the study with a median age of 65 years. The median white blood cell count (WBC) was 8.8 × 109/L, median hemoglobin (Hgb) was 12.7 g/dL, and platelets (Plt) was 284 × 109/L. Other patient characteristics can be seen in Table 1. The overall 12-month incidence of VTE (lower extremity DVT and/or PE) was 10.1% (n=64). Of the 64 VTE events, 20 were identified before the start of therapy. Univariate analysis revealed that age &amp;lt;60 and WBC &amp;gt;= 11 were associated with a higher risk of VTE (p&amp;lt;0.05), which remained significant after multivariate analysis including age, stage, WBC, and surgery. There was a trend towards a higher risk of VTE in patients receiving chemoimmunotherapy, compared with chemotherapy alone, (HR 1.22), although this trend did not reach significance. Targeted therapy was associated with a lower trend (HR = 0.89), but that also was not significant. The median overall survival was 18 months. Univariate analysis showed that VTE was associated with an increased risk of death (HR 2.05, p&amp;lt;0.001). Other parameters associated with reduced Overall Survival (OS) were age &amp;gt;=60, male sex, stage III-IV, WBC, Hgb, and Plt. After multivariate analysis considering age, sex, stage, lung cancer histology, Hgb, Plt, WBC, surgery, therapy type, and VTE, age &amp;gt;=60, stage III-IV, WBC &amp;gt;=11, Hgb &amp;lt;10, and VTE remained significant predictors of death. Discussion In a retrospective study of more than 600 patients with lung cancer, there was a significant risk of VTE. Every subgroup of patients analyzed in this study retained a high risk of VTE after multivariate analysis. The only hematologic parameter from the Khorana score significantly associated with VTE after multivariate analysis was WBC. WBC and Hgb were associated with increased risk of death. Age &amp;lt;= 60 was associated with increased risk of VTE, while age &amp;gt;60 was associated with increased mortality. There was a trend towards a higher risk of VTE in patients receiving chemoimmunotherapy compared with chemotherapy alone. There were too few immunotherapy-only patients to allow for any interpretation. The development of thrombosis was associated with a significantly decreased overall survival, although we do not have data on the potential contribution of VTE to death. These findings were derived from a single-center data set, and further validation using independent data sets is warranted. If confirmed, a prospective study re-evaluating the risk of VTE and benefits of prophylactic anticoagulation specifically in contemporary patients with lung cancer receiving systemic therapy regardless of histology, treatment, or other factors described here may be indicated. Our findings do not support limiting any such study to any specific sub-group of patients with lung cancer.

Bleeding and Thrombosis in Patients with Cancer and Acute Venous Thromboembolism Requiring Urgent Procedures

BACKGROUND There are limited data of outcomes in patients who require anticoagulation interruption for a surgical procedure shortly after an acute VTE, especially in patients with cancer who are at higher risk for both hemorrhage and recurrent thrombosis. Our goal was to assess the incidence of recurrent thrombosis or major hemorrhage at 60-days following an urgent surgical procedure in patients with acute VTE (within one month prior to surgery). METHODS We performed a retrospective cohort study of patients with cancer at Memorial Sloan Kettering Cancer Center (from January 1 st 2021 to December 31 st 2022). Patients were eligible for inclusion if they were diagnosed with a new acute deep vein thrombosis or pulmonary embolism and underwent surgical procedure within 30-days following the acute VTE diagnosis. Recurrent VTE was defined as symptomatic new deep-vein thrombosis or pulmonary embolism, incidental new deep-vein thrombosis or pulmonary embolism involving segmental or more proximal pulmonary arteries, or fatal pulmonary embolism or unexplained death for which pulmonary embolism could not be ruled out as the cause. Major hemorrhage was characterized according to ISTH definition. Competing risk framework was used to estimate cumulative incidences of major hemorrhage, VTE and death at 30 and 60-days. RESULTS A total of 90 patients were included in this analysis. The median age was 73 years and 62% were female (Table 1). Surgical procedures were classified by their risk of bleeding with 64 patients undergoing lower bleeding risk procedures and 26 high-risk procedures (Table 1). There were 10 recurrent or new VTE within 60-days of surgery (60-day cumulative incidence of 8.9%, 95% CI 4.1-16%). The recurrent sites were deep venous (N=7) and new PE (N=3). There were 12 major hemorrhagic events within 60 days (cumulative incidence of 12%, 95% CI 6.5-20%). The most common sites of hemorrhage were the lower gastrointestinal tract and genitourinary system. The competing risk framework is shown graphically in Figure 1. Among patients who received IVC filters the incidence of recurrent VTE was 1.1% and major hemorrhage was 2.2%. The 60-day cumulative incidence of death following surgical procedure was 19% (95% 12-28%). There were no fatal VTE and 3 fatal hemorrhagic events. CONCLUSION Among patients with cancer undergoing surgical procedures within 30-days of an acute VTE, the rates of recurrent VTE and major hemorrhage are substantively higher than reported in non-surgical acute VTE cohorts. Placement of temporary IVC filters may improve short-term bleeding and thrombotic outcomes.

Bleeding and Thrombotic Outcomes in Adults with Cancer-Associated Splanchnic Vein Thrombosis and Thrombocytopenia

Introduction: Splanchnic vein thrombosis (SVT) can arise as a complication in patients with underlying cancers, especially gastrointestinal malignancies, as well as other comorbidities such as liver disease. In patients with cancer-associated thrombosis, thrombocytopenia is a common co-occurrence that can complicate management decisions around anticoagulation. Data on the optimal management of SVT in patients with malignancies is limited, and the risk of bleeding and recurrent thrombosis in patients with cancer-associated SVT and thrombocytopenia is unclear. Methods: We identified patients with radiographic diagnosis of cancer-associated SVT at our institution between 2010 and 2021. Exclusion criteria included squamous and basal cell carcinomas and myeloproliferative neoplasms. We manually reviewed all medical records to determine baseline clinical data and clinical outcomes. We performed log-binomial regression to identify independent risk factors for major bleeding, using age at thrombosis (continuous), gender, prior major bleed, baseline creatinine (continuous), use of antiplatelets, and use of anticoagulants as covariates. We present these data as adjusted risk ratios (RR) and 95% confidence intervals (CI). We subsequently used Cox models with inverse probability of treatment weighting with propensity scores for thrombocytopenia (platelet count less than 100,000/uL within 15 days before or after diagnosis of SVT) to calculate hazard ratios (HR) and 95% CIs for our outcomes of interest. Independent variables used in propensity scoring included all variables included in the adjusted models plus type of cancer (hematologic, solid tumor). Outcomes included major bleeding, clinically relevant non major bleeding (CRNMB), clinically relevant bleeding (major bleeding + CRNMB), progression and recurrence of SVT, and development of usual-site VTE (DVT or PE) up to one year following the initial SVT. Progression was defined as extension of the thrombus contiguously into a new vein, and recurrence was defined as a new interval thrombus which was non-contiguous with the initial thrombus. Results: A total of 581 patients with cancer and SVT were identified. Baseline demographics, clinical history, laboratory data, and details of SVT are shown in Table 1. Of note, 44.2% of patients had cirrhosis, and the most common cancer types were hepatobiliary (55.2%) and pancreatic (22.0%); 40.7% of patients had metastatic disease. Of 512 patients with available platelet count data, 39.5% of patients had platelet count &amp;lt;100,000/uL; of these 512, 14.1% were &amp;lt;75,000/uL, and 12.7% were &amp;lt;50,000/uL. Most (70.6%) SVT were bland thrombi based on radiology interpretation, 19.9% were tumor thrombi, and 5.5% were mixed type, with the remainder being of uncertain etiology. Survival at one year was 41.5%, and median follow-up time was 5.5 months (interquartile range: 1.4-22.2). Only 4.0% of patients received a thrombectomy, and 39.2% were treated with anticoagulation within two weeks of diagnosis. The cumulative incidence of major bleeding event within one year of SVT diagnosis was 11.0% (95% CI: 8.5-13.5). This was primarily upper GI bleeding (70.3% of major bleeds). Multivariate regression analysis identified only male gender as an independent predictor of major bleeding (aRR: 0.91, 95% CI: 0.84-0.99), as shown in Table 2. In the propensity score-weighted Cox models, thrombocytopenia was not associated with an increased risk of major bleeding within one year (aHR: 1.65, 95% CI: 0.32-8.41). The cumulative incidence of CRNMB at one year was 6.7% (95% CI: 4.7-8.7), and cumulative incidence of clinically relevant bleeding was 17.7% (95% CI: 14.6-20.8). The cumulative incidence of progression or recurrence of SVT at one year was 16.3% (95% CI: 13.3-19.3). In the weighted Cox models, patients with thrombocytopenia did not impact the risk of progression or recurrence of SVT (aHR: 1.15, 95% CI: 0.58-2.26). The cumulative incidence of usual-site VTE at one year was 5.7% (95% CI: 3.8-7.5). Conclusion: Thrombocytopenia was a common co-occurrence in cancer-associated SVT. Major bleeding- especially upper GI bleeding- was a common complication of cancer-associated SVT. Recurrent or progressive SVT was also frequent, which highlights the challenges of optimal management in this high-risk population. We found that thrombocytopenia was not an independent risk factor for major bleeding in this population.

Trends in deep vein thrombosis prophylaxis after total hip arthroplasty: 2016 to 2021

IntroductionVenous thromboembolism (VTE) has long been acknowledged as a potential complication of total hip arthroplasty (THA) contributing to heightened patient morbidity, mortality, and substantial healthcare costs. We aimed to: 1) assess trends in VTE prophylaxis utilization between 2016 and 2021; 2) determine the incidence of postoperative VTE and transfusions; and 3) identify independent risk factors for 90-day VTE and transfusion risks following THA in relation to the use of aspirin, dabigatran, enoxaparin, rivaroxaban, and warfarin. MethodsA national, all-payer database was queried from January 1, 2016 and December 31, 2022. Use trends for aspirin, enoxaparin, rivaroxaban, dabigatran, and warfarin as thromboprophylaxis following THA was assessed. Incidence of ninety-day postoperative outcomes assessed included rates of 90-day postoperative VTE and transfusion. ResultsFrom 2016 to 2021, aspirin (n = 36,346) was the most used agent for VTE prophylaxis after THA, followed by dabigatran (n = 13,065), rivaroxaban (n = 11,790), enoxaparin (n = 11,380), and warfarin (n = 6326). Independent risk factors for 90-day VTE included CKD, COPD, CHF, obesity, dabigatran, enoxaparin, rivaroxaban, and warfarin (all p < 0.05). ConclusionAspirin was used with increasing frequency and demonstrated lower rates of VTE and transfusion following THA, compared to dabigatran, enoxaparin, rivaroxaban, and warfarin. These findings seem to indicate that the increasing use of aspirin in VTE prophylaxis has been accomplished in appropriately selected patients.

Adjudicated thrombotic events in a cotemporary multicenter cohort of patients with COVID-19: findings from the CORONA-VTE Registry

Abstract Background Venous thromboembolism (VTE) and arterial thrombosis emerged among the main serious complications of coronavirus disease 2019 (COVID-19) in the early post-infection period and during convalescence. Data are less consistent about how the event rates may have changed over time considering the change in viral variants and COVID-19 therapies, and vaccination status. Purpose To report VTE and arterial thrombotic events in patients with COVID-19, and assess results by vaccination status and over time from a large multicenter patient-level US registry. Methods Adult patients with polymerase chain reaction-confirmed COVID-19 who received inpatient or outpatient care at Mass-General Brigham (MGB) Health system, the largest health system in the Massachusetts that serves 1.5 million patients, were eligible. Data elements were entered into a centralized database by trained research staff. Thrombotic events were adjudicated by two independent physicians. Outcomes were assessed at 30- and 90-day follow-up. Findings were pre-specified to be assessed separately for patients who were hospitalized with COVID-19 vs outpatients. Vaccination status was ascertained for subgroup analysis. Results The study included 4,123 patients from the MGB Health System from 3/13/2020 through 06/03/2022 (age: 53.5 ± 18 years; 55.9% female, Table). Among hospitalized patients, the cumulative incidence of VTE was 7.7% at day 90 (95% CI: 6.2-9.2%). Respective 30-day event rates for arterial thrombosis among hospitalized patients were 4.4% (95% CI: 3.2%-5.5%). Event rates were lower for outpatients (Figure, Panel A). Thirty-day cumulative incidence of VTE and arterial thrombosis/thromboembolism based on history of vaccination (restricted to cohort from 12/14/2020 onward) are presented in Panel B. Conclusions In this multicenter study 30-day adjudicated thrombotic events were frequent in patients with COVID-19, albeit lower among vaccinated patients. Follow-up for 90-day outcomes are being finalized and will be presented at ESC 2023.

Abstract 13121: Incidence, Predictors, and Outcomes of Venous and Arterial Thrombosis in COVID-19: A Nationwide Analysis

Introduction: Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous (VTE) and arterial (ATE) thromboembolism. However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. We evaluated the incidence, associated factors, and mortality outcomes of VTE and ATE in COVID-19 infection. Hypothesis: COVID-19 is associated with a higher risk of thrombosis and mortality. Methods: Hospitalized patients with COVID-19 during 2020 were identified from the National Inpatient Sample database and data was retrieved regarding clinical characteristics, incident VTE and ATE and mortality outcomes. Multivariate regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients. Results: Overall, 1,583,135 COVID-19 inpatients were identified out of which patients with thrombosis were 41% females with a mean age 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1%, including VTE 4.8%, ATE 3.0%, and in-hospital mortality rate was 13.4%. The main factors associated with overall thrombosis, VTE and ATE were paralysis, ventilation, solid tumors without metastasis, and metastatic cancer. Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p&lt;0.001) compared to patients without thrombosis, along with comorbidities like complicated diabetes mellitus and congestive heart failure, and acute presentations like septic shock, acute respiratory distress syndrome and acute kidney injury. Symptomatic and severe COVID-19 disease were associated with a higher risk of thrombosis (OR 1.37 (1.31-1.43) and OR 1.62 (1.49-1.76), respectively, p&lt;0.001) and VTE (OR 1.40 (1.33-1.46) and OR 1.66 (1.52-1.80) respectively, p&lt;0.001). Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p&lt;0.001), they were not significant in multivariate analyses. Conclusions: Overall, thrombosis, especially VTE was found in approximately 5% of COVID-19 inpatients, while ATE was rare, with important associated factors identified, however they were not independently associated with higher in-hospital mortality.

A Real-World, Single Institution, Post-Market Comparison of Pegaspargase and Calasparagase Pegol-Mknl Therapeutic Drug Monitoring and Toxicity

Introduction: Calaspargase pegol-mknl (CalPEG) was FDA-approved in December 2018 as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia/lymphoma (ALL/LLy) in pediatric patients and adolescent and young adults (AYA). It has recently been incorporated into national pediatric ALL consortia clinical trials. The pharmacokinetics and toxicity profiles were reported in two clinical trials (AALL07P4; Angiolillo et al, J Clin Oncol, 2014 and DFCI 11-001; Vrooman et al, J Clin Oncol, 2021), with similar safety profiles to historical pegaspargase (PEGasp). There is a paucity of published data regarding serum asparaginase activity (SAA) level variation or toxicity between CalPEG and PEGasp since FDA-approval. This is timely given the recent transition in asparaginase product availability, which may impact resource utilization, comprehensive drug safety monitoring, and clinical practice guidelines. Methods: We conducted a single institution retrospective review of children and AYA with ALL/LLy who received an asparaginase product during upfront or relapse therapy between January 2022 to June 2023 as part of our chemotherapy quality and safety monitoring (Table). Patients received either PEGasp, CalPEG, and/or asparaginase Erwinia chrysanthemi recombinant (Rylaze) and had correlative SAA documented by a validated assay (NEXT Molecular Analytics; Chester, VA). The Common Terminology Criteria for Adverse Events version 5.0 was used to retrospectively grade asparaginase-related toxicities, including pancreatitis (≥ grade 3), venous thromboembolism (VTE; ≥ grade 2), hyperbilirubinemia (total bilirubin ≥ 5 mg/dL), allergy (≥ grade 3), and silent inactivation (SI, SAA &amp;lt; 0.025 IU/mL within 7 days post-treatment without allergic symptoms). Fisher's exact and Wilcoxon rank-sum tests were used to compare patient characteristics and toxicity incidence with pairwise post-hoc comparisons. P values were two-sided and considered significant if &amp;lt; 0.05. Generalized linear modeling (GLM) was used to model SAA over time and interactions among asparaginase product, toxicity, and immunophenotype. Results: One hundred twenty-five patients received either PEGasp, CalPEG, and/or Rylaze. (Table). Frequency of total asparaginase-related toxicity was comparable between CalPEG (27.7%) and PEGasp (27.4%). However, the incidence of pancreatitis was significantly higher in patients who received CalPEG (12.8%) compared to PEGasp (2.4%), P=0.025, with an Odds Ratio (OR) 5.91. T-ALL/LLy patients who received CalPEG had an increased incidence of both pancreatitis and VTE (33.3% each), with statistically significant pairwise interactions to PEGasp and/or B-ALL cohorts. Conversely, allergy was significantly higher in PEGasp (17.9%) compared to CalPEG (4.3%), P=0.03, with an OR 4.46. SI was found in 5.8% of PEGasp with none yet identified in CalPEG patients. The median peak SAA level over the first 10 days was not different among patients with adverse events; nor were median SAA levels higher in CalPEG patients, despite increased incidence in treatment-related toxicity (Figure). GLM fit slopes were predictably less negative in CalPEG compared to those of PEGasp; patients with toxicity had a larger modeled area under the curve. In 6 patients who were dose-capped to 3750 IU for body mass index (BMI) ≥ 40, all exhibited therapeutic SAA without any asparaginase-related toxicity. Conclusions: To our knowledge this is the first single-institution post-market retrospective quality and safety analysis comparing CalPEG and PEGasp therapeutic drug monitoring and toxicity. Interestingly, the incidence of pancreatitis and VTE is significantly higher in patients receiving CalPEG and disproportionately higher in T-lineage. Median peak SAA levels were not predictive of toxicity, though GLM may help provide a predictive model. The rate of SI emphasizes the need for continued resource utilization of SAA monitoring. Our observed differences in CalPEG and PEGasp toxicity are discordant with two previously published clinical trials used for FDA approval of CALPEG (AALL07P4 and DFCI 11-001). Larger analyses of CalPEG SAA and toxicities are necessary to determine if these trends are reproducible. This information will help establish optimal utilization of SAA safety monitoring with the broader goal of identifying necessary practice changes in CalPEG clinical management.

Prothrombotic Profile in Patients with Active Multiple Myeloma and the Impact of Immunomodulators: The Roadmap-MM Study

Backround: Thromboembolism occurs in about 10% of patients with multiple myeloma (MM). The incidence of VTE is higher in newly diagnosed MM patients as compared to those with relapsed or refractory disease and it is higher during the first 3 to 6 months after the initial diagnosis and treatment initiation. Some of the treatments administered to patients with MM are independent risk factors for VTE. Immunomodulatory agents (IMiDs) among anti-myeloma treatments stand out as having a considerable prothrombotic effect. Recognizing the significant risk associated with the use of immunomodulatory agents (the International Myeloma Working Group (IMWG) 2014 statement, and the European Myeloma Network Guidelines in 2015 both included guidance on the prevention of VTE in MM patients who receive IMiDs. The prospective, longitudinal observational study ROADMAP-MM CAT was designed to explore alternative strategies for the development of risk stratification tools in patients with multiple myeloma. To this target we evaluated the baseline profile of hypercoagulability in multiple myeloma patients with various disease status. Blood borne hypercoagulabity partly consisted of enhanced thrombin generation, a common phenomenon in patients with malignancies . It remains to be seen whether this phenomenon appears for multiple myeloma patients during the physical course of the disease. Aim: We conducted a study to explore the relationship between stages of MM and alterations of various thrombosis-related biomarkers in patients with MM and their relationship with MM therapy. Materials and Methods Patients with MM (n=162) were recruited and stratified to the following groups: 59 newly diagnosed treatment-naïve patients (ND), 49 patients receiving IMiDs (IM), 52 in complete remission (CR) and 12 patients in partial remission on IMiDs (PR/IM). Patients on anticoagulant treatment were excluded from the study. The control group (CG) consisted of 30 healthy age and sex-matched individuals. Samples of platelet-poor plasma (PPP) were assessed for thrombin generation (TG) with the TF 5pM PPP-Reagent® on Calibrated Automated Thrombogram (Diagnostica Stago, France). Plasminogen activator inhibitor-1 (PAI-1), soluble endothelial protein C receptor (sEPCR), and soluble vascular cell adhesion molecule-1 (sVCAM-1), Procoag-PPL were measured using antibody-based ELISA kits (Invitrogen International Inc., CA, USA, and Diagnostica Stago, France ). TF expression MPC-derived microparticles (MPC-dMPs) were detected using a Zymuphen MP-TF activity kit (Hyphen BioMed, Neuville sur Oise, France). The upper and lower normal limits (LNL and UNL) were calculated by the mean±2 SD. Results A total of 162 patients were enrolled (age 66.0±12.0 yrs; 53% male). Distribution of disease stage was as follows: 32% ISS I, 23% ISS II, 45% ISS III. Bone disease was present in 71% of patients and 19% of patients had high risk cytogenetic lesions. Patients with ongoing MM (ND, IM, PR/IM) had significantly lower Peak, ETP and MRI as compared to the CG. In contrast, patients in CR had Peak, ETP, MRI values similar to the CG. Patients with PR had lower ETP and MRI values as compared to the CR group. In ND 9% had TG &amp;gt;UNL and 22% had TG&amp;lt;LNL. In IM 10% had TG&amp;gt;UNL and 67% had TG&amp;lt;LNL. None in PR/IM had TG&amp;gt;UNL and 35% had TG&amp;lt;LNL. In CR, 23% had TG&amp;gt;UNL and 12% had TG&amp;lt;LNL. MP-TF levels and PPL were higher in untreated MM (CR) patients compared to control. MP-TF and PPL levels decreased significantly after chemotherapy in PR/IM but MP-TF remained high at CR. The plasma concentrations, PAI-1, sEPCR, and sVCAM-1 were higher in MM patients than controls. , Treatment with IMDs reduced all biomarker levels gradually from PR/IM to CR (Table 1). Conclusion Patients with active MM showed attenuated TG which was enhanced in the presence of IMiDs treatment. Complete remission was associated with normalization of TG. The plasma concentrations, TF-MP , PAI-1, sEPCR, and sVCAM-1 were increased in MM patients suggesting vascular aggression which is followed by release of these markers that could contribute to the procoagulant environment. Attention should be paid to therapy-related thrombosis indeed the effect the suggested role of IMiDs in hypercoagulability does not seem to be confirmed and requires further studies .

Using machine learning in the prediction of symptomatic venous thromboembolism following ankle fracture

BackgroundVenous thromboembolism (VTE) is a major cause of morbidity and mortality in the trauma setting, and both prediction and prevention of VTE have long been a concern for healthcare providers in orthopedic surgery. The purpose of this study was to evaluate the use of novel statistical analysis and machine-learning in predicting the risk of VTE and the usefulness of prophylaxis following ankle fractures. MethodsThe medical profiles of 16,421 patients with ankle fractures were screened retrospectively for symptomatic VTE. In total, 238 patients sustaining either surgical or nonsurgical treatment for ankle fracture with subsequently confirmed VTE within 180 days following the injury were placed in the case group. Alternatively, 937 patients who sustained ankle fractures managed similarly but had no documented evidence of VTE were randomly chosen as the control group. Individuals from both the case and control populations were also divided into those who had received VTE prophylaxis and those who had not. Over 110 variables were included. Conventional statistics and machine learning methods were used for data analysis. ResultsPatients who had a motor vehicle accident, surgical treatment, increased hospital stay, and were on warfarin were shown to have a higher incidence of VTE, whereas patients who were on statins had a lower incidence of VTE. The highest Area Under the Receiver Operating Characteristic Curves (AUROC) showing the performance of our machine learning approach was 0.88 with 0.94 sensitivity and 0.36 specificity. The most balanced performance was seen in a model that was trained using selected variables with 0.86 AUROC, 0.75 sensitivity, and 0.85 specificity. ConclusionBy using machine learning, this study successfully pinpointed several predictive factors linked to the occurrence or absence of VTE in patients who experienced an ankle fracture. Training these algorithms using larger, more granular, and multicentric data will further increase their validity and reliability and should be considered the standard for the development of such algorithms. Level of evidenceCase-Control study – 3

Arterial and Venous Thromboembolic Complications in 832 Patients with BCR-ABL-Negative Myeloproliferative Neoplasms.

Arterial (ATE) and venous (VTE) thromboembolic complications are common causes of morbidity and mortality in BCR-ABL-negative myeloproliferative neoplasms (MPNs). However, there are few studies that include all MPN subtypes and focus on both MPN-associated ATE and VTE. In our single-center retrospective study of 832 MPN patients, a total of 180 first thromboembolic events occurred during a median follow-up of 6.6 years (range: 0-37.6 years), of which 105 were VTE and 75 were ATE. The probability of a vascular event at the end of the follow-up period was 36.2%, and the incidence rate for all first ATE/VTE was 2.43% patient/year. The most frequent VTE localizations were deep vein thrombosis with or without pulmonary embolism (incidence rate: 0.59% patient/year), while strokes were the most frequent ATE with an incidence rate of 0.32% patient/year. When comparing the group of patients with ATE/VTE (n = 180) and the group without such an event (n = 652) using multivariate Cox regression analyses, patients with polycythemia vera (hazard ratio [HR]: 1.660; [95% confidence interval [CI] 1.206, 2.286]) had a significantly higher risk of a thromboembolic event than the other MPN subtypes. In contrast, patients with a CALR mutation had a significantly lower risk of thromboembolism compared with JAK2-mutated MPN patients (HR: 0.346; [95% CI: 0.172, 0.699]). In summary, a high incidence of MPN-associated VTE and ATE was observed in our retrospective study. While PV patients or generally JAK2-mutated MPN patients had a significantly increased risk of such vascular events, this risk was reduced in CALR-mutated MPN patients.

Risk of venous thromboembolism in patients undergoing gastric cancer surgery: a systematic review and meta-analysis

BackgroundVenous thromboembolism (VTE) is a common postoperative complication in patients undergoing surgery for gastric cancer (GC). Although VTE incidence may vary among cancers, guidelines rarely stratify preventive methods for postoperative VTE by cancer type. The risk of VTE in patients undergoing surgery for GC remains unclear.MethodsA systematic review and meta-analysis was undertaken to determine the risk of VTE after GC surgery and discuss the clinical value of pharmacological thromboprophylaxis in these cases. Medline, Embase, Web of Science, and Cochrane Library databases were searched for articles published from their inception to September 2022.ResultsOverall, 13 studies (111,936 patients) were included. The overall 1-month incidence of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) after GC surgery was 1.8% (95% CI, 0.8–3.1%; I²=98.5%), 1.2% (95% CI, 0.5–2.1%; I²=96.1%), and 0.4% (95% CI, 0.1–1.1%; I²=96.3%), respectively. The prevalence of postoperative VTE was comparable between Asian and Western populations (1.8% vs. 1.8%; P > 0.05). Compared with mechanical prophylaxis alone, mechanical plus pharmacological prophylaxis was associated with a significantly lower 1-month rate of postoperative VTE and DVT (0.6% vs. 2.9% and 0.6% vs. 2.8%, respectively; all P < 0.05), but not PE (P > 0.05). The 1-month postoperative incidence of VTE was not significantly different between laparoscopic and open surgery (1.8% vs. 4.3%, P > 0.05).ConclusionPatients undergoing GC surgery do not have a high risk of VTE. The incidence of VTE after GC surgery is not significantly different between Eastern and Western patients. Mechanical plus pharmacological prophylaxis is more effective than mechanical prophylaxis alone in postoperative VTE prevention. The VTE risk is comparable between open and laparoscopic surgery for GC.