Who dies from venous thromboembolism after hospitalisation for other reasons in England?: a national retrospective cohort study.

OBJECTIVES: Venous thromboembolism (VTE) is a major cause of morbidity and mortality globally, with hospital-associated thrombosis (HAT) accounting for at least half of VTE. We set out to understand more about deaths from HAT in England, to focus improvement efforts where they are needed most. DESIGN: A retrospective cohort combining death certification and hospital activity data to identify people with an inpatient or day case hospitalisation where no VTE diagnosis was recorded, and who died from VTE in a hospital or within 90 days of discharge, between April 2017 and March 2020. SETTING: All deaths occurring in England and all National Health Service-funded hospital care in England. PARTICIPANTS: After 0.1% of cases were excluded due to duplicate but conflicting records, a cohort of 13 995 deaths remained; 54% were women, and 26% were aged under 70 years. OUTCOME MEASURES: Analysis of age, gender, primary diagnosis, type of admission, specialties and (for day cases) procedure types were preplanned. RESULTS: Only 5% of these deaths followed planned inpatient admissions. Day case admissions preceded 7% of VTE deaths. Emergency inpatient admissions, medical specialties and infection-related primary diagnoses predominated in people who died from VTE after hospitalisation where no VTE diagnosis was recorded. Most deaths occurred in a hospital or within 30 days of discharge. CONCLUSIONS: International efforts to reduce HAT historically focused on planned inpatient admissions. Further initiatives and research to prevent deaths from VTE after hospitalisation should focus on the emergency care pathway where most deaths occurred, with people undergoing day case procedures an important additional focus.

Association of scrub typhus with the risk of venous thromboembolism and long-term mortality: a population-based cohort study.

BACKGROUND: The existing literature lacks studies examining the epidemiological link between scrub typhus and deep vein thrombosis (DVT) or pulmonary embolism (PE), and the long-term outcomes. The objective of this study is to explore the potential association between scrub typhus and the subsequent risk of venous thromboembolism, and long-term mortality. METHOD: This nationwide cohort study identified 10,121 patients who were newly diagnosed with scrub typhus. Patients with a prior DVT or PE diagnosis before the scrub typhus infection were excluded. A comparison cohort of 101,210 patients was established from the general population using a propensity score matching technique. The cumulative survival HRs for the two cohorts were calculated by the Cox proportional hazards model. RESULT: After adjusting for sex, age, and comorbidities, the scrub typhus group had an adjusted HR (95% CI) of 1.02 (0.80-1.30) for DVT, 1.11 (0.63-1.93) for PE, and 1.16 (1.08-1.25) for mortality compared to the control group. The post hoc subgroup analysis revealed that individuals younger than 55 years with a prior scrub typhus infection had a significantly higher risk of DVT (HR: 1.59; 95% CI: 1.12-2.25) and long-term mortality (HR: 1.75; 95% CI, 1.54-1.99). CONCLUSION: The scrub typhus patients showed a 16% higher risk of long-term mortality. For those in scrub typhus cohort below 55 years of age, the risk of developing DVT was 1.59 times higher, and the risk of mortality was 1.75 times higher. Age acted as an effect modifier influencing the relationship between scrub typhus and risk of new-onset DVT and death.

Extending venous thromboembolism secondary prevention with apixaban in cancer patients. The EVE trial.

BACKGROUND: Cancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment. OBJECTIVES: The study's purpose was to determine whether this dose reduction is advisable for cancer-associated VTE. METHODS: A randomized, double-blind trial compared apixaban 2.5 mg with 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 to 12 months of anticoagulation therapy. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding. RESULTS: Of 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus clinically relevant nonmajor bleeding occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared with 22 of 181 patients (12.2%) in the 5 mg group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P = .39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and in 2.2% of the 5 mg group (HR, 1.26; 95% CI, 0.34-4.66; P = .73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR, 1.0; 95% CI, 0.40-2.53; P = 1.00). All-cause mortality rates were similar between groups, 13% vs 12% (HR, 1.14; 95% CI, 0.63-2.04; P = .67). CONCLUSION: For secondary prevention of cancer-associated VTE, apixaban 2.5 mg compared with 5 mg twice daily did not lower combined bleeding events (EVE trial NCT03080883).

Age-Related Differences in the Presentation, Management, and Clinical Outcomes of 100,000 Patients With Venous Thromboembolism in the RIETE Registry / Diferencias relacionadas con la edad en la presentación, el tratamiento y los resultados clínicos de 100.000 pacientes con tromboembolismo venoso en el registro RIETE

Introduction: Although older adults represent a significant proportion of patients with venous thromboembolism (VTE), the data on the impact of age-related differences in the clinical presentation, management, and outcomes of VTE are scarce. Methods: We analyzed data from the RIETE registry database, an ongoing global observational registry of patients with objectively confirmed VTE, to compare patient characteristics, clinical presentation, treatments, and outcomes between elderly (≥70 years) vs. non-elderly (<70 years) patients. Results: From January 2001 to March 2021, 100,000 adult patients were enrolled in RIETE. Elderly patients (47.9%) were more frequently women (58.2% vs. 43.5%), more likely had unprovoked VTE (50.5% vs. 45.1%) and most often presented with severe renal failure (10.2% vs. 1.2%) and acute pulmonary embolism (PE) (vs. deep vein thrombosis) (54.3% vs. 44.5%) compared to non-elderly patients (p<0.001 for all comparisons). For the PE subgroup, elderly patients more frequently had non-low risk PE (78.9% vs. 50.7%; p<0.001), respiratory failure (33.9% vs. 21.8%; p<0.001) and myocardial injury (40.0% vs. 26.2%; p<0.001) compared to non-elderly patients. Thrombolysis (0.9% vs. 1.7%; p<0.001) and direct oral anticoagulants (8.8% vs. 11.8%; p<0.001) were less frequently administered to elderly patients. Elderly patients showed a significantly higher 30-day all-cause mortality (adjusted odds ratio [OR] 1.36, 95%CI: 1.22–1.52) and major bleeding (OR, 2.08; 95%CI, 1.85–2.33), but a lower risk of 30-day VTE recurrences (OR, 0.62, 95%CI, 0.54–0.71). Conclusions: Compared with non-elderly patients, elderly patients had a different VTE clinical profile. Advanced therapies were less frequently used in older patients. Age was an independent predictor of mortality.(AU)

Early Chemoprophylaxis Against Venous Thromboembolism in Patients With Traumatic Brain Injury.

INTRODUCTION: Timing to start of chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) remains controversial. We hypothesize that early administration is not associated with increased intracranial hemorrhage. METHODS: A retrospective study of adult patients with TBI following blunt injury was performed. Patients with penetrating brain injury, any moderate/severe organ injury other than the brain, need for craniotomy/craniectomy, death within 24 hours of admission, or progression of bleed on 6 hour follow-up head computed tomography scan were excluded. Patients were divided into early (≤24 hours) and late (>24 hours) cohorts based on time to initiation of chemoprophylaxis. Progression of bleed was the primary outcome. RESULTS: 264 patients were enrolled, 40% of whom were in the early cohort. The average time to VTE prophylaxis initiation was 17 hours and 47 hours in the early and late groups, respectively (P < .0001). There was no difference in progression of bleed (5.6% vs. 7%, P = .67), craniectomy/-craniotomy rate (1.9% vs. 2.5%, P = .81), or VTE rate (0% vs. 2.5%, P = .1). CONCLUSION: Early chemoprophylaxis is not associated with progression of hemorrhage or need for neurosurgical intervention in patients with TBI and a stable head CT 7 hours following injury.

Efficacy and Safety of Low Molecular Weight Heparin Versus Unfractionated Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-analysis.

PURPOSE: Trauma patients are at high risk of VTE. We summarize the efficacy and safety of LMWH versus UFH for the prevention of VTE in trauma patients. METHODS: We searched 6 databases from inception through March 12, 2021. We included randomized controlled trials (RCTs) or observational studies comparing LMWH versus UFH for thromboprophylaxis in adult trauma patients. We pooled effect estimates across RCTs and observational studies separately, using random-effects model and inverse variance weighting. We assessed risk of bias using the Cochrane tool for RCTs and the Risk of Bias in Non-Randomized Studies (ROBINS)-I tool for observational studies and assessed certainty of findings using Grading of Recommendations, Assessment, Development and Evaluations methodology. RESULTS: We included 4 RCTs (879 patients) and 8 observational studies (306,747 patients). Based on pooled RCT data, compared to UFH, LMWH reduces deep vein thrombosis (RR 0.67, 95% CI 0.50 to 0.88, moderate certainty) and VTE (RR 0.68, 95% CI 0.51 to 0.90, moderate certainty). As compared to UFH, LMWH may reduce pulmonary embolism [adjusted odds ratio from pooled observational studies 0.56 (95% CI 0.50 to 0.62)] and mortality (adjusted odds ratio from pooled observational studies 0.54, 95% CI 0.45 to 0.65), though based on low certainty evidence. There was an uncertain effect on adverse events (RR from pooled RCTs 0.80, 95% CI 0.48 to 1.33, very low certainty) and heparin induced thrombocytopenia [RR from pooled RCTs 0.26 (95% CI 0.03 to 2.38, very low certainty)]. CONCLUSIONS: Among adult trauma patients, LMWH is superior to UFH for deep vein thrombosis and VTE prevention and may additionally reduce pulmonary embolism and mortality. The impact on adverse events and heparin induced thrombocytopenia is uncertain.

Time is of the Essence: Impact of a More Aggressive Chemical Venous Thromboembolism Prophylaxis Regimen on Trauma Patients.

BACKGROUND: Trauma patients are at high risk for venous thromboembolism (VTE). Opportunity for chemical VTE prophylaxis improvement was identified and practice was altered to start chemoprophylaxis on admission in most patients. The purpose of this study was to determine if early VTE prophylaxis is safe and reduces VTE. METHODS: The trauma registry was queried over a 12-month period for patients admitted greater than 1 day for traumatic injury. The study spanned 6 months on either side of instituting aggressive chemoprophylaxis. Patients were risk adjusted on demographics, Injury Severity Score, transfusions, procedure type, length of stay, and mortality. Pre-intervention patients were then compared to patients in the aggressive cohort with the primary outcome of VTE. Secondary outcomes included transfusions, mortality, and length of stay (LOS). RESULTS: 1597 patients were identified over the study period with 754 (47%) patients in the aggressive period. There were no differences in age, sex, Injury Severity Score, transfusions, procedures, or LOS between cohorts. Pre-algorithm patients were more likely to have penetrating mechanism (9.3% vs 6.6%; P = .009) and longer time to VTE prophylaxis (23.3 vs 13.9 hours; P < .001). No differences were noted in anticoagulant, VTE rate (2.0% vs 1.2%; P = .195), or mortality. Linear regression analysis identified time to chemical prophylaxis as significant predictor of VTE (ß = 43.9, P < .001). CONCLUSIONS: Early aggressive chemical VTE prophylaxis is safe without increasing transfusions. Venous thromboembolism rates were decreased, but did not reach statistical significance.

Efficacy of Rivaroxaban Use in Solid Tumour Malignancy: Experience from a Tertiary Care Cancer Centre.

OBJECTIVE: Cancer-associated venous thromboembolism (CAT) is a common disease or complication which is associated with reduced survival and incurring a substantial health-care cost. Low molecular weight heparin (LMWH) remained the gold standard treatment option available. Direct oral anticoagulants (DOACs) have recently become more popular in the guidelines, they are still few and inconsistent across the current literature. The aim of this study was to evaluate rivaroxaban in treatment of CAT. METHODS: In this prospective real-world study, we recruited and followed up patients diagnosed with CAT treated with rivaroxaban or standard of care as a control for 12 months or until death. Baseline characteristics were collected at the study entry. The primary outcomes were recurrent DVT or PE and death within 12 months after treatment initiation. Safety outcomes were composite outcomes of major and minor bleeding.    Results: A total of 80 patients confirm CAT with radiological imaging were recruited; 39 patients were evaluated in the control arm and 41 patients in the rivaroxaban arm. The 12 months cumulative CAT recurrence rate was 46.2% in control and 39% in rivaroxaban (p=0.519). The 12-month death was not a statistically significant difference between both arms (20.5% vs. 31.7%, p=0.255). The cumulative rate of composite safety outcomes was similar in both groups (17.9% vs. 12.2%, p=0.471). CONCLUSION: The result of this small but important real-world evidence proofs that rivaroxaban is an effective and safe alternative to the standard of care for CAT in Malaysia's cancer population.

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main Outcomes and Measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Hemostatic Biomarkers and Venous Thromboembolism Are Associated With Mortality and Response to Chemotherapy in Patients With Pancreatic Cancer.

Objective: Pancreatic cancer activates coagulation and increases risk of venous thromboembolism (VTE). We aimed at characterizing the association of hemostatic biomarkers and VTE with mortality and chemotherapy response. Approach and Results: Pancreatic cancer patients (N=145) were included in a prospective, observational cohort study (CATS [Vienna Cancer and Thrombosis Study]). Hemostatic biomarkers (D-dimer, extracellular vesicle-tissue factor activity, prothrombin fragment 1+2, fibrinogen, factor VIII, PAI-1 [plasminogen activator inhibitor 1], sP-selectin [soluble P-selectin], thrombin generation assay) were measured at inclusion. The impact of VTE on overall survival/progression-free survival (OS/PFS) was evaluated by multistate modeling. The association of biomarkers with OS was analyzed by Cox-regression and with PFS and disease control rate in patients initiating palliative chemotherapy (n=95) by Cox-regression and logistic regression. Multivariable analysis included stage, grade, sex, age, performance status, VTE (time-dependent), vascular infiltration/compression, and tumor marker levels (carbohydrate-antigen 19-9, carcinoembryonic antigen). VTE occurrence was associated with shorter OS (transition hazard ratio, 3.40 [95% CI, 2.05-5.64]) and shorter PFS (transition hazard ratio, 2.10 [1.16-3.79]). Median post-VTE OS/PFS in months was 5.5 [2.2-6.5] and 3.0 [1.5-3.9], compared with 13.4 [9.7-16.6] and 7.5 [5.9-9.8] in patients without VTE (both P<0.001). D-dimer, extracellular vesicle-tissue factor activity, PAI-1, and sP-selectin were associated with increased mortality (hazard ratio per doubling, 1.27 [1.00-1.61]; 1.63 [1.14-2.36]; 1.25 [1.06-1.47]; 1.52 [1.05-2.20]). In patients initiating palliative chemotherapy, higher D-dimer predicted shorter PFS (hazard ratio per doubling, 1.27 [1.01-1.60]) and lower disease control rate (odds ratio per doubling, 0.59 [0.36-0.98]). Conclusions: VTE diagnosis is associated with shorter OS and PFS. Higher baseline levels of D-dimer, extracellular vesicle-tissue factor activity, PAI-1, and sP-selectin were independently prognostic for increased mortality, and D-dimer predicted response to palliative chemotherapy.

Meta-regression of randomized control trials with antithrombotics: weak correlation between net clinical benefit and all cause-mortality.

This study aimed to explore the validity of the use of the net clinical benefit (NCB), i.e. the sum of major bleeding and thrombotic events, as a potential surrogate for all-cause mortality in clinical trials assessing antithrombotics. Published randomized controlled trials testing anticoagulants in the prevention or treatment of venous thromboembolism (VTE) and non-valvular atrial fibrillation (NVAF) were systematically reviewed. The validity of NCB as a surrogate endpoint was estimated by calculating the strength of correlation of determination (R2) and its 95% confidence interval (CI) between the relative risks of NCB and all-cause mortality. Amongst the 125 trials retrieved, the highest R2trial values were estimated for NVAF (R2trial = 0.41, 95% CI [0.03; 0.48]), and acute VTE (R2trial = 0.30, 95% CI [0.04; 0.84]). Conversely, the NCB did not correlate with all-cause mortality in prevention studies with medical (R2trial = 0.12, 95% CI [0.00; 0.36]), surgical (R2trial = 0.05, 95% CI [0.00; 0.23]), and cancer patients (R2trial = 0.006, 95% CI [0.00; 1.00]). A weak correlation between NCB and all cause-mortality was found in NVAF and acute VTE, whereas no correlation was observed in clinical situations where the mortality rate was low. Consequently, NCB should not be considered a surrogate outcome for all cause-mortality in anticoagulation trials.

Thromboprophylaxis strategies to improve the prognosis of COVID-19.

The outbreak of 2019 novel coronavirus disease (Covid-19) has deeply challenged the world population, but also our medical knowledge. Special attention has been paid early to an activation of coagulation, then to an elevated rate of venous thromboembolism (VTE) in patients hospitalized with severe COVID-19. These data suggested that anticoagulant drugs should be evaluated in the treatment of patients with COVID-19. The publication of unexpected high rates of VTE in patients hospitalized with COVID-19, despite receiving thromboprophylaxis, open the way to dedicated trials, evaluating modified regimens of thromboprophylaxis. Moreover, the further improvement in our comprehension of the disease, particularly the pulmonary endothelial dysfunction increased the hope that anticoagulant drugs may also protect patients from pulmonary thrombosis. In this comprehensive review, we cover the different situations where thromboprophylaxis standard may be modified (medically-ill inpatients, ICU inpatients, outpatients), and describe some of the current randomized controls trials evaluating new regimens of thromboprophylaxis in patients with COVID-19, including the preliminary available results. We also discuss the potential of anticoagulant drugs to target the thromboinflammation described in patients with severe COVID-19.

Clinical Features of COVID-19 Patients With Venous Thromboembolism.

This study aimed to assess the clinical features of coronavirus disease 2019 (COVID-19) patients with VTE, to help develop preventive measures for venous thromboembolism (VTE in COVID-19) cases. COVID-19 patients admitted to Henan Provincial People's Hospital were retrospectively analyzed, including 23, 4 and 8 cases with mild to moderate, severe and critical symptoms, respectively. VTE incidence, age at onset, relevant laboratory parameters and prognosis were analyzed. Overall, VTE incidence in the 35 patients was 20.0%, occurring in severe (n = 1) and critical (n = 6) cases. D-dimer showed statistical significance in laboratory examination, representing except a diagnostic index and especial can be a prognostic factor in VTE among COVID-19 patients. Severe and critical COVID-19 cases had significantly reduced platelet counts, with a risk of hemorrhage. During treatment, the risk of both hemorrhage and thrombosis should be considered. VTE occurs in COVID-19 cases, affecting individuals with severe and critical symptoms. Significant D-dimer increase is of great significance in the risk assessment of death in critical cases of COVID-19. Appropriate measures should be taken to prevent VTE during treatment.

High Mortality and Venous Thromboembolism Risk Following Major Penetrating Abdominal Venous Injuries.

BACKGROUND: Penetrating injuries to the inferior vena cava and/or iliac veins are a source of hemorrhage but may also predispose patients to venous thromboembolism (VTE). We sought to determine the relationship between iliocaval injury, VTE and mortality. METHODS: The National Trauma Data Bank was queried for penetrating abdominal trauma from 2015-2017. Univariate analyses compared baseline characteristics and outcomes based on presence of iliocaval injury. Multivariable analyses determined the effect of iliocaval injury on VTE and mortality. RESULTS: Of 9,974 patients with penetrating abdominal trauma, 329 had iliocaval injury (3.3%). Iliocaval injury patients were more likely to have a firearm mechanism (83% vs. 43%, P < 0.001), concurrent head (P = 0.036), spinal cord (P < 0.001), and pelvic injuries (P < 0.001), and higher total injury severity score (median 20 vs. 8.0, P < 0.001). They were more likely to undergo 24-hr hemorrhage control surgery (69% vs. 17%, P < 0.001), but less likely to receive VTE chemoprophylaxis during admission (64% vs. 68%, P = 0.04). Of patients undergoing iliocaval surgery, 64% underwent repair, 26% ligation, and 10% unknown. Iliocaval injury patients had higher rates of VTE (12% vs. 2%), 24-hr mortality (23% vs. 2.0%) and in-hospital mortality (33% vs. 3.4%) (P < 0.001 for all). VTE rates were similar following repair (14%) and ligation (17%). Iliocaval injury patients also had higher rates of cardiac complications (10.3% vs. 1.4%), acute kidney injury (8.2% vs. 1.3%), extremity compartment syndrome (4.0 vs. 0.2%), and unplanned return to OR (7.9% vs. 2.5%) (P < 0.001 for all). In multivariable analyses, iliocaval injury was independently associated with risk of VTE (OR 2.12; 95% CI, 1.29-3.48; P = 0.003), and in-hospital mortality (OR = 9.61; 95% CI, 4.96-18.64; P < 0.001). CONCLUSION: Iliocaval injuries occur in <5% of penetrating abdominal trauma but are associated with more severe injury patterns and high mortality rates. Regardless of repair type, survivors should be considered high risk for developing VTE.

Cardiovascular events in cancer patients with bone metastases-A Danish population-based cohort study of 23,113 patients.

INTRODUCTION: The incidence of cardiovascular events among cancer patients with bone metastases is poorly understood. We examined rates of cardiovascular events among cancer patients with bone metastases and mortality following such events. METHODS: Using Danish health registries, we identified all Danish cancer patients diagnosed with bone metastases (1994-2013) and followed them from bone metastasis diagnosis. We computed incidence rates (IR) per 100 person-years and cumulative incidence for first-time inpatient hospitalization or outpatient clinic visit for cardiovascular events, defined as myocardial infarction, ischemic stroke, or venous thromboembolism (VTE). We also analyzed all-cause mortality rates including cardiovascular events as time-varying exposure with adjustment for age, sex, and Charlson Comorbidity Index score. All analyses were performed overall and stratified by cancer type (prostate, breast, lung, and other). RESULTS: We included 23,113 cancer patients with bone metastases. The cumulative incidence of cardiovascular events was 1.3% at 30 days, 3.7% at 1 year, and 5.2% at 5 years of follow-up. The highest IR was observed for VTE, followed by ischemic stroke and myocardial infarction, both overall and by cancer types. Lung cancer patients with bone metastases had the highest incidence of cardiovascular events followed by prostate and breast cancer. Occurrence of any cardiovascular event was a strong predictor of death (5 years following the event, the adjusted hazard ratio was 1.8 [95% confidence interval: 1.7-1.9]). CONCLUSION: Cancer patients with bone metastases had a substantial risk of developing cardiovascular events, and these events were associated with a subsequent increased mortality. Our findings underscore the importance of continuous optimized prevention of and care for cardiovascular disease among cancer patients with bone metastases.

Acute Hospital Mortality of Venous Thromboembolism in Patients With Cancer From Registry Data.

Background The prognosis of patients with cancer-venous thromboembolism (VTE) is not well known because of a lack of registry data. Moreover, there is also no knowledge on how specific types are related to prognosis. We sought to evaluate the clinical characteristics and outcomes of patients with cancer-associated VTE, compared with a matched cohort without cancer using real-world registry data of VTE. Methods and Results This study was based on the Diagnosis Procedure Combination database in the JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination). Of 5 106 151 total patients included in JROAD-DPC, we identified 49 580 patients who were first hospitalized with VTE from April 2012 to March 2017. Propensity score was estimated with a logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates. After propensity matching, there were 25 148 patients with VTE with or without cancer. On propensity score-matched analysis with 25 148 patients with VTE, patients with cancer had higher total in-hospital mortality within 7 days (1.3% versus 1.1%, odds ratio [OR], 1.66; 95% CI, 1.31-2.11; P<0.0001), 14 days (2.5% versus 1.5%, OR, 2.07; 95% CI, 1.72-2.49; P<0.0001), and 30 days (4.8% versus 2.0%, OR, 2.85; 95% CI, 2.45-3.31; P<0.0001). On analysis for each type of cancer, in-hospital mortality in 11 types of cancer was significantly high, especially pancreas (OR, 12.96; 95% CI, 6.41-26.20), biliary tract (OR, 8.67; 95% CI, 3.00-25.03), and liver (OR, 7.31; 95% CI, 3.05-17.50). Conclusions Patients with cancer had a higher in-hospital acute mortality for VTE than those without cancer, especially in pancreatic, biliary tract, and liver cancers.

Homoarginine and methylarginines independently predict long-term outcome in patients presenting with suspicion of venous thromboembolism.

Endogenous arginine derivatives homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethyarginine (SDMA) are independent mortality predictors in atherosclerotic cardiovascular disease (CVD). Our study reports the first analysis, whether homoarginine, ADMA and SDMA predict venous thromboembolism (VTE) recurrence and overall mortality in patients with suspected acute VTE. We assessed serum levels of homoarginine, ADMA and SDMA by LC-MS/MS in 865 individuals from a prospective consecutive cohort of patients with clinical suspicion of VTE. The median follow-up time for mortality was 1196 days. VTE was confirmed by imaging in 418 patients and excluded in 447 patients. Low levels of homoarginine and high levels of ADMA or SDMA independently predicted all-cause mortality after adjustment for sex, age, oral anticoagulants, body mass index, arterial hypertension, diabetes mellitus, smoking, dyslipidemia, chronic heart failure, history of stroke, creatinine and cancer both in patients with VTE and without VTE. Interestingly, none of those parameters was predictive for VTE recurrence. We provide the first report that low circulating levels of homoarginine and high circulating levels of ADMA and SDMA independently predict all-cause mortality in patients with suspected VTE. These parameters might serve as markers of "frailty" and should be considered for future risk stratification approaches in this clinical population. Taking into account that homoarginine supplementation is protective in animal models of CVD and safe in healthy human volunteers, our study provides the basis for future homoarginine supplementation studies in patients with suspected VTE to investigate possible direct protective effects of homoarginine in this population.

Thromboembolic Complications in the First Year After Acute Pancreatitis Diagnosis.

OBJECTIVES: This study aimed to quantify the prevalence of venous thromboembolic (VTE) events in patients with pancreatitis requiring hospitalization and its impact on outcomes. METHODS: Adult patients admitted from 2011 to 2018 for pancreatitis were identified. Every admission for pancreatitis in the first year after diagnosis was evaluated for a VTE (pulmonary embolism, deep vein thrombosis, or mesenteric vessel thrombosis) within 30 days of discharge. Characteristics of patients who developed a thromboembolic event were compared with those who did not. RESULTS: There were 4613 patients with pancreatitis identified, 301 of whom developed a VTE (6.5%). Patients who developed a VTE were more likely to be male (P < 0.01), older (P = 0.03), and have an underlying coagulopathy (P < 0.01). Those with VTEs were more likely to die (27% vs 13%, P < 0.01), have more readmissions for pancreatitis (1.7 vs 1.3, P < 0.01), longer length of stay (16 vs 5.5 days, P < 0.01), and be discharged to acute or long-term rehabilitation rather than home (P < 0.01). CONCLUSIONS: Acute pancreatitis requiring hospitalization is associated with high risk of VTE in the first year after diagnosis. Thromboembolic disease is associated with worse morbidity and mortality.

Inflammatory Biomarkers in the Short-Term Prognosis of Venous Thromboembolism: A Narrative Review.

The relationship between inflammation and venous thrombosis is not well understood. An inflammatory response may be both the cause and consequence of venous thromboembolism (VTE). In fact, several risk factors of VTE modulate thrombosis through inflammatory markers. Acute pulmonary embolism (PE) is burdened by a remarkable mortality rate, up to 34% in severely ill patients presenting with hemodynamic instability. Initial mortality risk stratification is based on hemodynamic instability. Patients with a situation of hemodynamic stability require immediate further risk assessment based on clinical, imaging, and circulating biomarkers, as well as the presence of comorbidities. Some inflammatory biomarkers have shown potential usefulness in the risk stratification of patients with VTE, especially acute PE. C-reactive protein on admission is associated with 30-day mortality and bleeding in VTE patients. P-selectin is associated with right ventricle dysfunction in PE patients and might be associated with VTE recurrences and the extension of thrombosis. Tissue factor microparticles are associated with VTE recurrence in cancer-associated thrombosis. Other inflammatory biomarkers present scarce evidence (inflammatory cytokines, erythrocyte sedimentation rate, fibrinogen, leukocyte count). In this manuscript, we will review the prognostic role of different inflammatory biomarkers available both for clinical practice and research in VTE patients.