Publications by authors named "Lana A Castellucci"
Introduction: Factor Xa inhibitor (FXaI)-associated bleeding events are common and associated with substantial morbidity. Systematic evaluation of widely available, effective, and affordable FXaI bleed management strategies is needed.
Materials And Methods: We conducted a single-center retrospective cohort study of FXaI-treated patients presenting to a tertiary academic medical center from January 2018 to May 2019 who received 25-50 IU/kg 4F-PCC for either FXaI-associated major bleeding or urgent surgery.
The currently approved direct oral anticoagulants (DOACs) are increasingly used in clinical practice. Although serious bleeding risks are lower with DOACs than with vitamin K antagonists, bleeding remains the most frequent side effect. Andexanet alfa and idarucizumab are the currently approved specific reversal agents for oral factor (F)Xa inhibitors and dabigatran, respectively.
View Article and Find Full Text PDFBackground: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation.
Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin.
Methods: Patients who received initial anticoagulation dosed consistently with randomization were included.
Article Synopsis
- There are currently no direct comparisons of the effectiveness and safety of the two most common oral anticoagulants, apixaban and rivaroxaban, for older patients with atrial fibrillation (AF), creating uncertainty regarding which drug is better.
- This study examined older adults (66 and older) in Ontario, Canada, comparing the incidence of major bleeding and thromboembolic events in patients treated with either apixaban or rivaroxaban from 2011 to 2020.
- The findings revealed that apixaban was associated with a significantly lower risk of major and any bleeding compared to rivaroxaban, while both drugs had similar risks for thromboembolic events.
Article Synopsis
- Clinical trials are increasingly adopting Bayesian methods for design and analysis, using simulation-based approaches like Markov Chain Monte Carlo (MCMC), which can be computationally expensive and complex.
- The Integrated Nested Laplace Approximations (INLA) algorithm offers a more efficient alternative to MCMC for approximate Bayesian inference without heavy simulation costs.
- Research using data from a COVID-19 trial will compare INLA and MCMC to assess INLA's feasibility and accuracy for Bayesian trial design, providing insights for trialists.
Article Synopsis
- Venous thromboembolism (VTE) significantly impacts cancer patients' health but education and awareness about it are severely lacking, with 63.5% of surveyed patients receiving inadequate information.
- A study of 2262 cancer patients from 42 countries revealed that many felt unprepared to recognize VTE risks, with only 67.8% receiving guidance on seeking medical help when needed.
- The research highlights critical gaps in VTE education and support, emphasizing the need for improved patient-centered care in managing cancer-associated VTE risks.
Article Synopsis
- Balancing the safety and effectiveness of antithrombotic drugs in patients with gastrointestinal disorders is complex due to issues with drug absorption and increased bleeding risks.
- The review focuses on enteral antithrombotic therapy for patients with cardiovascular conditions and gastrointestinal issues, outlining risk assessment and methods to reduce gastrointestinal bleeding (GIB).
- It emphasizes the importance of teamwork in customizing antithrombotic therapy, based on medical society guidelines and the unique needs of patients with both cardiovascular and gastrointestinal conditions.
Introduction: Hemostasis and bleeding are difficult to measure. Thrombin generation assays (TGAs) can measure both procoagulant and anticoagulant contributions to coagulation. TGAs might prove useful for the study of bleeding disorders.
View Article and Find Full Text PDFBackground: Patients hospitalized for COVID-19 are at high risk of thrombotic complications and organ failure, and often exhibit severe inflammation, which may contribute to hypercoagulability.
Objectives: To determine whether patients hospitalized for COVID-19 experience differing frequencies of thrombotic and organ failure complications and derive variable benefits from therapeutic-dose heparin dependent on the extent of systemic inflammation and whether observed benefit from therapeutic-dose anticoagulation varies depending on the degree of systemic inflammation.
Methods: We analyzed data from 1346 patients hospitalized for COVID-19 enrolled in the ATTACC and ACTIV-4a platforms who were randomized to therapeutic-dose heparin or usual care for whom levels of C-reactive protein (CRP) were reported at baseline.
Background: Data on availability, affordability, and accessibility is key for the planning of global strategies to reduce the burden of venous thromboembolism (VTE).
Objectives: A survey was conducted for the 10th anniversary of World Thrombosis Day to assess the availability of VTE therapies worldwide and challenges in uniform implementation.
Methods: We gathered information on the approval status, availability, utilization, occurrence of shortages, and spread of medical and interventional therapies for VTE.
Background: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support.
Objectives: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19.
Direct factor Xa inhibitors (FXaIs) account for most oral anticoagulant use and FXaI-associated bleeding events are common. Clinicians have variable national and regional access to specific FXaI reversal agents such as andexanet alfa. Many centers have adopted the use of prothrombin complex concentrates (PCCs) as hemostatic therapy for FXaI-associated major bleeding events.
View Article and Find Full Text PDFImportance: Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making.
Objective: To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE.
Article Synopsis
- Oral anticoagulation therapy has advanced from traditional vitamin K antagonists to newer options like direct thrombin inhibitors and factor Xa inhibitors, collectively known as direct oral anticoagulants (DOACs), which are now standard for treating conditions such as atrial fibrillation and venous thromboembolism.
- New medications targeting factors XI/XIa and XII/XIIa are being researched for various thrombotic and nonthrombotic conditions, potentially offering different benefits and risks compared to current DOACs.
- The International Society on Thrombosis and Haemostasis has suggested a new naming system for anticoagulants based on their administration route and target, aiding clarity in their clinical use.
Direct oral anticoagulants (DOACs) account for most oral anticoagulant use. DOAC-associated bleeding events are commonly encountered in clinical practice and are associated with substantial morbidity and mortality. Both specific reversal agents and nonspecific hemostatic therapies, such as prothrombin complex concentrates, are used in the management of DOAC-associated bleeding.
View Article and Find Full Text PDFBackground: It is uncertain if medical masks offer similar protection against COVID-19 compared with N95 respirators.
Objective: To determine whether medical masks are noninferior to N95 respirators to prevent COVID-19 in health care workers providing routine care.
Design: Multicenter, randomized, noninferiority trial.
Article Synopsis
- - The study aims to assess the case-fatality rate (CFR) of major bleeding in patients on dual antiplatelet therapy (DAPT) after undergoing percutaneous coronary intervention (PCI) and to analyze how this rate varies based on the duration of DAPT.
- - From a search of 2777 potential studies, 16 studies were included, revealing 823 major bleeding events with 91 being fatal among nearly 49,000 patients on DAPT, resulting in an overall CFR of 10.8%.
- - The findings indicate that while fatal bleeding is often not reported in DAPT studies, the CFR is significant, particularly higher within the first 12 months, suggesting that shorter DAPT durations may
No clinical prediction model has been specifically developed or validated to identify patients with unprovoked venous thromboembolism (VTE) who are at high risk of major bleeding during extended anticoagulation. In a prospective multinational cohort study of patients with unprovoked VTE receiving extended anticoagulation after completing ≥3 months of initial treatment, we derived a new clinical prediction model using a multivariable Cox regression model based on 22 prespecified candidate predictors for the primary outcome of major bleeding. This model was then compared with modified versions of 5 existing clinical scores.
View Article and Find Full Text PDFObjectives: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19.
Design: Multicentre pragmatic randomised clinical trial.
Setting: 15 hospitals in Canada and the United States from May 2020 until May 2021.
Introduction: Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality. The majority of VTE events are hospital-associated. In 2008, the Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) multinational cross-sectional study reported that only approximately 40% of medical patients at risk of VTE received adequate thromboprophylaxis.
View Article and Find Full Text PDFBackground: Apixaban has been shown to significantly decrease the rate of VTE among intermediate-to-high risk patients starting chemotherapy compared to placebo. This investigation sought to determine the impact of apixaban among different subgroups of patients with cancer.
Methods: This is a pre-planned post-hoc analysis of the AVERT randomized controlled trial which compared apixaban to placebo for the primary prevention of VTE in ambulatory patients initiating chemotherapy.
Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial.
BMJ
October 2021
Objective: To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards.
Design: Randomised controlled, adaptive, open label clinical trial.
Setting: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US.