Purpose: We evaluated the role of residual vein thrombosis (RVT) to assess the optimal duration of anticoagulants in patients with cancer who have deep vein thrombosis (DVT) of the lower limbs. Patients and Methods: Patients with active cancer and a first episode of DVT treated with low molecular weight heparin (LMWH) for 6 months were eligible. Patients were managed according to RVT findings: those with RVT were randomly assigned to continue LMWH for an additional 6 months (group A1) or to discontinue it (group A2), and patients without RVT stopped LMWH (group B). The primary end point was recurrent venous thromboembolism (VTE) during the 1 year after disconinuation of LMWH, and the secondary end point was major bleeding. Analyses are from the time of random assignment. Results: Between October 2005 and April 2010, 347 patients were enrolled. RVT was detected in 242 patients (69.7%); recurrence occurred in 22 of the 119 patients in group A1compared with 27 of 123 patients in group A2. The adjusted hazard ratio (HR) for group A2 versus A1 was 1.37 (95% CI, 0.7 to 2.5; P = .311). Three of the 105 patients in group B developed recurrent VTE; adjusted HR for group A1 versus B was 6.0 (95% CI, 1.7 to 21.2; P = .005). Three major bleeding events occurred in group A1, and two events each occurred in groups A2 and B. The HR for major bleeding in group A1 versus group A2 was 3.78 (95% CI, 0.77 to 18.58; P = .102). Overall, 42 patients (12.1%) died during follow-up as a result of cancer progression. Conclusion: In patients with cancer with a first DVT, treated for 6 months with LMWH, absence of RVT identifies a population at low risk for recurrent thrombotic events. Continuation of LMWH in patients with RVT up to 1 year did not reduce recurrent VTE.

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

In cancer patients, hypercoagulability is a common finding and it has been associated to an increased risk of venous thromboembolisms, but also to tumor proliferation and progression. In this prospective study, in a large cohort of patients with breast cancer, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: 1. are associated with breast cancer-specific clinicopathological features; and 2. can predict for disease recurrence. D-dimer, fibrinogen, prothrombin fragment 1+2, and FVIIa/antithrombin levels were measured in 701 early-stage resected breast cancer patients, candidate to adjuvant chemotherapy and prospectively enrolled in the HYPERCAN study. Significant prognostic parameters for disease recurrence were identified by Cox-regression multivariate analysis and used for generating a risk assessment model. Pre-chemotherapy D-dimer, fibrinogen, and prothrombin fragment 1+2 levels were significantly associated with tumor size and lymph node metastasis. After 3.4 years follow-up, 71 patients experienced a recurrence. Cox-multivariate analysis identified prothrombin fragment 1+2, tumor size, and Luminal B HER2-neg or triple negative molecular subtypes as independent risk factors for disease recurrence. Based on these variables, we generated a risk assessment model that significantly differentiated patients at low- and high-risk of recurrence (cumulative incidence: 6.2 vs 20.7%; HR=3.5; p<0.001). Our prospective clinical and laboratory data from the HYPERCAN study were crucial for generating a scoring model for disease recurrence risk assessment in resected breast cancer patients, candidate to systemic chemotherapy. This finding stimulates future investigations addressing the role of plasma prothrombin fragment 1+2 in breast cancer patients9 management, and in providing the rationale for new therapeutic strategies.

Introduction Endothelial damage and hypercoagulability are major players behind the hemostatic derangement of SARS-CoV-2 infection.Aim In this prospective study we assessed endothelial and inflammatory biomarkers in a cohort of COVID-19 patients, aiming to identify predictive factors of in-hospital mortality.Methods COVID-19 patients hospitalized in intensive care (ICU) and non-ICU units at 2 Bergamo (Italy) hospitals from March 23 to May 30, 2020, were enrolled. Markers of endothelium activation including von-Willebrand factor (vWF), soluble thrombomodulin (sTM), and fibrinolytic proteins (t-PA and PAI-1) were measured. Additionally, D-dimer, Fibrinogen, FVIII, nucleosomes, C reactive protein (CRP) and procalcitonin were assessed.Results Sixty-three (45 ICU, and 18 non-ICU) patients, with a median age of 62 years were analyzed. Increased plasma levels of D-dimer, FVIII, fibrinogen, nucleosomes, CRP, and procalcitonin were observed in the whole cohort. Extremely elevated vWF levels characterized all patients (highest values in ICU-subjects). After a median time of 30 days, death occurred in 13 (21%) patients. By multivariable analysis, vWF-activity, neutrophil-count and PaO2/FiO2 were significantly associated with death. Using these variables, a linear score with 3-risk groups was generated that provided a cumulative incidence of death of 0% in the low-, 32% in the intermediate-, and 78% in the high-risk group.Conclusions COVID-19-induced hemostatic abnormalities are exacerbated by the severity of the disease and strongly correlate with the inflammatory status, underlying the link between coagulation, endothelial activation, and inflammation. Our study provides evidence for a role of vWF, together with neutrophils and PaO2/FiO2, as a significant predictor of in-hospital mortality by SARSCoV-2 infection.