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Background: Risk of VTE recurrence (VTEr) in patients with cancer-associated thrombosis (CAT) is high. Cancer-related risk factors for VTEr have been studied, but information about the importance of location of metastasis is scarce., Objectives: 1) Evaluate rate of VTEr in CAT patients according to location of metastasis, and 2) Identify variables associated to VTEr during long-term follow-up., Methods: A retrospective, single-center, non-interventional study of consecutives patients with CAT conducted between 2007 and 2022. Haematological neoplasms were excluded., Results: Among 1248 patients with CAT (age 64.1 ± 12.8 years; 48.2 % female) followed-up for 13.19 months (p25-75, 5.6-26.9) there were 141 VTEr. The rate of VTE recurrence in patients without and with metastasis were 4.72 per 100 patient-years (95%CI: 3.66-6) and 10.05 per 100 patient-years (95 % CI: 7.89-12.61), respectively. The metastases locations associated with VTEr, compared to those without metastasis, were lung (rate ratio [RR]: 2.21; 95 % CI: 1.42-3.43), liver (RR: 2.02; 95%CI: 1.26-3.24), pancreas (RR: 6.21; 95 % CI: 1.52-25.35), pleura (RR: 2.93; 95%CI: 1.58-5.41), bone (RR: 2.16; 95 % CI: 1.29-3.64) and adrenal (RR: 6.18; 95%CI: 2.97-12.86). Multivariate analysis of variables associated with VTEr beyond 12 months were male sex (hazard ratio [HR] 1.54, 95%CI: 1.08-2.19), ECOG performance status >1 (HR 1.74, 95%CI: 1.03-2.94), metastasis in 1-2 locations (HR 2.38, 95%CI: 1.68-3.37) and metastasis in >2 locations (HR 3.88, 95%CI: 1.68-8.98)., Conclusions: The rate of VTEr differs according to the location of metastasis. We identified variables related to VTEr during long-term follow-up which may help clinicians decide whether to continue anticoagulation., Competing Interests: Declaration of competing interest Dr. Jara-Palomares received grants from Leo Pharma and MSD, and personal fees from Daichii, Rovi, GlaxoSmithKline, and Actellion outside the submitted work. Dr. Carrier has received research funding from BMS, Pfizer, and Leo Pharma, and honoraria from Bayer, Pfizer, BMS, Servier, and Leo Pharma. No other conflicts of interest are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: There is currently no validated score capable of classifying cancer-associated pulmonary embolism (PE) in its full spectrum of severity. This study has validated the EPIPHANY Index, a new tool to predict serious complications in cancer patients with suspected or unsuspected PE., Method: The PERSEO Study prospectively recruited individuals with PE and active cancer or receiving antineoplastic therapy from 22 Spanish hospitals. The estimation of the relative frequency θ of complications based on the EPIPHANY Index categories was made using the Bayesian alternative for the binomial test., Results: A total of 900 patients, who were diagnosed with PE between October 2017 and January 2020, were enrolled. The rate of serious complications at 15 days was 11.8%, 95% highest density interval [HDI], 9.8-14.1%. Of the EPIPHANY low-risk patients, 2.4% (95% HDI, 0.8-4.6%) had serious complications, as did 5.5% (95% HDI, 2.9-8.7%) of the moderate-risk participants and 21.0% (95% HDI, 17.0-24.0%) of those with high-risk episodes. The EPIPHANY Index was associated with overall survival (OS) in patients with different risk levels: median OS was 16.5, 14.4, and 4.4 months for those at low, intermediate, and high risk, respectively. Both the EPIPHANY Index and the Hestia criteria exhibited greater negative predictive value and a lower negative likelihood ratio than the remaining models. The incidence of bleeding at 6 months was 6.2% (95% HDI, 2.9-9.5%) in low/moderate-risk vs 12.7% (95% HDI, 10.1-15.4%) in high-risk (p-value = 0.037) episodes. Of the outpatients, serious complications at 15 days were recorded in 2.1% (95% HDI, 0.7-4.0%) of the cases with EPIPHANY low/intermediate-risk vs 5.3% (95% HDI, 1.7-11.8%) in high-risk cases., Conclusion: We have validated the EPIPHANY Index in patients with incidental or symptomatic cancer-related PE. This model can contribute to standardize decision-making in a scenario lacking quality evidence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sánchez-Cánovas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Clinical guidelines indicate that in patients with cancer-associated thrombosis (CAT), anticoagulant treatment should be continued beyond 6 months as long as the cancer is active. We aimed to analyse the safety of low-molecular-weight heparin (LMWH) beyond 12 months in patients with CAT., Methods: We performed a post hoc analysis of consecutive CAT patients from October 2008 to December 2019. The primary outcome was the rate of clinically relevant bleeding (CRB), and we compared two periods (1-12 vs. 12-24 months). Hazard ratio (HR), competing risk analysis and sensitivity analyses were performed., Results: Of the 588 patients included, 30.1% (n = 177) received LMWH beyond 12 months. The rate of CRB in the first 12 months compared to the 12-24 month period was 3.2 per 100 patients/month (95% CI 2.5-4.1) vs. 0.9 per 100 patients/month (95% CI 0.4-1.5), (P < 0.0001). The competing risk analysis of CRB comparing both periods showed a lower sub-distribution hazard ratio (SHR) during the period 12-24 months (SHR: 0.5, 95% CI: 0.3-0.8, P < 0.001)., Conclusion: In patients with cancer-associated thrombosis under anticoagulant treatment with LMWH, the rate of clinically relevant bleeding and major bleeding were lower beyond 12 months., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The relationship between cancer and venous thromboembolic disease (VTD) are complex because the activated coagulation factors are not only involved in thrombosis but also in malignant processes, such as angiogenesis and metastasis., Objective: To compare phenotypes of extracellular vesicles (EVs), and levels of D-dimer, soluble P-selectin (sP-selectin) and antigenic tissue factor (TF) between unprovoked VTD patients, who did not develop cancer during one-year follow-up, and those with advanced stage of cancer but not associated with VTD., Methods: A prospective study in which we included 138 unprovoked VTD patients and 67 advanced cancer patients, who did not develop thrombosis. Levels of EVs of different cellular origin (platelet, endothelium and leukocyte), EVs positive for tissue factor (TF) and P-selectin glycoprotein ligand 1 were quantified by flow cytometry. D-dimer, soluble P-selectin (sP-selectin) and antigenic TF were determined by ELISA., Results: TF-positive EVs, D-dimer, and sP-selectin were markedly elevated in unprovoked VTD patients compared to cancer patients without association with thrombosis., Conclusions: Levels of TF-positive EVs, D-dimer and sP-selectin are able to discriminate between unprovoked VTD patients not related to cancer and cancer patients not associated with VTD. These results could lead to the application of EVs as biomarkers of both diseases. Key messages : Circulating EVs, specifically TF-positive EVs, in combination with plasmatic markers of hypercoagulable states, such as D-dimer, sP-selectin and antigen TF, are able to discriminate between cancer patients without thrombosis and patients with unprovoked VTD. Research fields could be opened. Future studies will assess if these biomarkers together serve as predicting thrombotic events in cancer populations.

Background: Optimal duration of anticoagulation for cancer-associated thrombosis (CAT) remains unclear. This study assessed D-dimer (DD) and high-sensitivity C-reactive protein (hs-CRP) levels after the withdrawal of anticoagulation treatment to predict the risk of venous thromboembolism (VTE) recurrence among patients with CAT., Methods: Prospective, multicentre study to evaluate CAT with ≥3 months of anticoagulation that was subsequently discontinued. Blood samples were taken when patients stopped the anticoagulation and 21 days later to determine the DD and hs-CRP levels. All patients were followed up for 6 months to detect VTE recurrence., Results: Between 2013 and 2015, 325 patients were evaluated and 114 patients were ultimately enrolled in the study. The mean age was 62 ± 14 years and nearly 40% had metastasis. Ten patients developed VTE recurrence within 6 months (8.8%, 95% confidence interval [CI]: 4.3-15.5%). The DD and hs-CRP levels after 21 days were associated with VTE recurrence. The subdistribution hazard ratios were 9.82 for hs-CRP (95% CI: 19-52) and 5.81 for DD (95% CI: 1.1-31.7)., Conclusions: This study identified that hs-CRP and DD were potential biomarkers of VTE recurrence after discontinuation of anticoagulation in CAT. A risk-adapted strategy could identify low-risk patients who may benefit from discontinuation of anticoagulation.

Background and Objective: The predictive Khorana's model was developed to score the thromboembolic disease risk in cancer patients on chemotherapy and to identify which patients would benefit from thromboprophylaxis. We analized the results and applied the predictive Khorana's model in patients with cancer and who were diagnosed with deep vein thrombosis., Material and Methods: Retrospective analysis of prognostic characteristics of Khorana's model in 122 patients based on a prospective analysis., Results: Seventy-nine percent of the total were in the low and intermediate risk category and 21% had high risk according to the Khorana's predictive model. This model had a sensitivity and prognostic precision of 20.8% (95% confidence interval [95% CI]: 14.6-28.7) and a false negatives proportion of 79.2% (95% CI: 1.3-85.4)., Conclusions: Application of this model in our patients would not be enough as the unique tool to identify cancer patients who should receive tromboprophylaxis. The use of both biomarkers and clinical models seems to be the best cost-effective strategy for this purpose. Future, randomized, prospective, placebo-controlled studies are needed for find better treatment strategies in cancer patients., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Background and Objective: This is a safety and cost comparison study with an analysis of budgetary impact of ambulatory management of patients with cancer and deep vein thrombosis (DVT) compared with hospital management., Material and Methods: Prospective observational study of patients with known malignancy and diagnosed with DVT from 2003 to 2007. The outcome variables were mortality, relapse and bleeding in one month. We conducted an economic analysis to evaluate the comparative cost of ambulatory patients., Results: Three hundred and seventeen patients, 55 (17%) had cancer. The mean age of patients was 63 ± 11 years. There were 2 hemorrhagic events, 2 recurrences and 6 deaths in one month of follow-up. Of all patients, only 7 (13,7%) required hospitalization. All but one deaths were due to progression of the underlying disease. Economic analysis concluded that outpatient management is 6 times less expensive than hospital management, which would imply a cost reduction of 85%., Conclusions: Specialized outpatient treatment of cancer patients with DVT is safe and could save significant financial resources., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Introduction: An association between pulmonary embolism (PE) and a subsequent diagnosis of cancer has been repeatedly reported. Although screening and early detection might play a pivotal part in reducing mortality from cancer, there are currently no definite data to suggest that cancer screening may improve survival rates in patients with PE. We hereby present the results of a screening program and a two-year follow-up survey for detecting occult cancer in this patient population., Materials and Methods: A total of 107 patients with PE were consecutively enrolled. All subjects underwent an initial screening program followed by a two-year follow-up survey. We calculated the sensitivity of our screening program, and identified risk factors associated with occult cancer by means of logistic regression., Results: The initial screening program yielded positive results in five patients (4.7%), and four additional cases were identified during the 2-year follow-up. The overall sensitivity of our screening program in idiopathic PE was 55.5%. In the entire study cohort, the number necessary for screening was 12.1 (6.1 in idiopathic PE, and 58 in secondary PE). Logistic regression analysis revealed that a shock index >/=1 (odds ratio: 5.467; p=0.007) and idiopathic PE (odds ratio: 12.82; p=0.03) were independent risk factors for occult cancer in our PE patients., Conclusions: A simple and noninvasive screening program yields an acceptable sensitivity for detecting occult cancer in idiopathic PE patients. These results highlight the importance of screening for occult cancer in patients diagnosed with PE, especially in idiopathic forms., (Copyright 2009 Elsevier Ltd. All rights reserved.)