Introduction Some local protocols suggest using intermediate or therapeutic doses of anticoagulants for thromboprophylaxis in hospitalized patients with coronavirus disease 2019 (COVID‐19). However, the incidence of bleeding, predictors of major bleeding, or the association between bleeding and mortality remain largely unknown. Methods We performed a cohort study of patients hospitalized for COVID‐19 that received intermediate or therapeutic doses of anticoagulants from March 25 to July 22, 2020, to identify those at increased risk for major bleeding. We used bivariate and multivariable logistic regression to explore the risk factors associated with major bleeding. Results During the study period, 1965 patients were enrolled. Of them, 1347 (69%) received intermediate‐ and 618 (31%) therapeutic‐dose anticoagulation, with a median duration of 12 days in both groups. During the hospital stay, 112 patients (5.7%) developed major bleeding and 132 (6.7%) had non‐major bleeding. The 30‐day all‐cause mortality rate for major bleeding was 45% (95% confidence interval [CI]: 36%‐54%) and for non‐major bleeding 32% (95% CI: 24%‐40%). Multivariable analysis showed increased risk for in‐hospital major bleeding associated with D‐dimer levels >10 times the upper normal range (hazard ratio [HR], 2.23; 95% CI, 1.38–3.59), ferritin levels >500 ng/ml (HR, 2.01; 95% CI, 1.02–3.95), critical illness (HR, 1.91; 95% CI, 1.14–3.18), and therapeutic‐intensity anticoagulation (HR, 1.43; 95% CI, 1.01–1.97). Conclusions Among patients hospitalized with COVID‐19 receiving intermediate‐ or therapeutic‐intensity anticoagulation, a major bleeding event occurred in 5.7%. Use of therapeutic‐intensity anticoagulation, critical illness, and elevated D‐dimer or ferritin levels at admission were associated with increased risk for major bleeding.

Significant differences in the clinical profile of venous thromboembolic-related outcomes were observed according to the site of cancer. These findings suggest the development of cancer-specific anticoagulant strategies as an area for further research.

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Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55–74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84–91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3–15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6–4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1–13%) among patients in hospital wards and 19% (95% CI: 13–26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated.

BackgroundPatients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE. As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients.MethodsCOPD patients included in the on-going world-wide RIETE Registry were studied. The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)).ResultsOf the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE. PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death). Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7).ConclusionsCOPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone. More efficient therapy is needed in this subtype of patients.

During the first week of treatment, the risk of fatal bleeding and fatal PE were similar. Then, particularly in patients who were aged ≥ 60 years, the risk of dying from bleeding exceeded the risk of dying from PE.

Summary Background Information on recurrent venous thromboembolic events (VTEs) and major bleeding risks during anticoagulant treatment in patients with cancer‐associated VTEs and chronic kidney disease (CKD) is scarce, although it is of relevance in establishing better tailored management strategies in these patients. Objectives We compared risks of recurrent VTEs and major bleeds in cancer‐associated VTE patients with and without CKD. Methods A total of 1684 patients diagnosed with a cancer‐associated VTE between 2001 and 2011 were followed for 180 days after VTE diagnosis. Patients were treated mainly with low‐molecular‐weight heparin (LMWH) or vitamin‐K antagonists (VKA). Primary outcomes were recurrent VTE and major bleeding. Secondary outcome was fatal bleeding. Results Recurrent VTEs occurred in 15.9/100 patient years (py) in patients without CKD (eGFR > 60 mL min−1), 19.5/100 py in those with CKD stage 3A (eGFR 45–60 mL min−1), 14.9/100 py in those with CKD 3B (eGFR 30–45 mL min−1), and 6.8/100 py in patients with CKD 4–5 (eGFR < 30 mL min−1). Major bleeding occurred in 11.4/100 py in patients without CKD, 18.5/100 py in those with CKD stage 3A, 16.0/100 py in those with CKD 3B, and 40.8/100 py in patients with CKD 4–5. Fatal bleeding occurred in 1.1/100 py, 3.4/100 py, 6.3/100 py and 15.7/100 py, respectively. These increased bleeding risks in CKD patients were mainly observed in those on LMWH treatment, not VKA. Conclusions The risk of major bleeding was increased in CKD patients with VTE and cancer, and was most prominent in those treated with LMWH and an eGFR < 30 mL min−1. These results indicate that LMWH should be used with caution in this specific population.

BackgroundIn cancer patients with symptomatic venous thromboembolism (VTE) (deep-vein thrombosis (DVT) and/or pulmonary embolism (PE)), clinical factors that influence the benefit-risk balance of anticoagulation need to be identified so treatment intensity and duration can be optimally adjusted for the individual patient.MethodsUsing clinical data for cancer patients with VTE obtained from the RIETE registry, we compared how rates of fatal PE and fatal bleeding during and after anticoagulation vary depending on patients‘ clinical characteristics.ResultsData were analysed from the 10,962 cancer patients with VTE (5,740 with PE with or without DVT; 5,222 with DVT alone) in RIETE registry as of March 2016. Fatal PE occurred in 2.18% of patients, while fatal bleedings occurred in 1.55%. During the 12 months from initial VTE, fatal PE was the most common cause of death, after disseminating cancer, and bleeding the fourth most common. In patients initially presenting with PE, fatal PE during anticoagulation was 4-fold more frequent than fatal bleeding (204 vs 51 deaths) and occurred mostly during the first month of treatment (196/223, 88%). In patients initially presenting with DVT, fatal PE was 3-fold lower than fatal bleeding during (25 vs 85 deaths) and after anticoagulation treatment (8 vs 37 deaths). During the 12-month follow-up, other characteristics of cancer patients with VTE were identified as more common in fatal cases of PE and/or bleeding than in surviving cases.InterpretationBaseline clinical characteristics may determine anticoagulation outcomes in cancer patients with VTE and should be further investigated as possible factors for guiding changes in current practices of anticoagulation, such as adjusting anticoagulation intensity and duration in selected patients.