Thrombosis, Translational Medicine, and Biomarker Research: Moving the Needle.

Arterial and venous thromboembolism are leading causes of morbidity and death worldwide. Despite significant advances in the diagnosis, prognostication, and treatment of thrombotic diseases over the past 3 decades, the adoption of findings stemming from translational biomarker research in clinical practice remains limited. Biomarkers provide an opportunity to enhance our understanding of pathophysiological processes and optimize treatment strategies.

Prothrombin complex concentrate for direct factor Xa inhibitor-associated bleeding or before urgent surgery.

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.

Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH.

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.

Plants buffer some of the effects of a pair of cadmium-exposed zebrafish on the un-exposed majority.

Certain individuals have a disproportionate effect on group responses. Characteristics may include susceptibility to pollutants, such as cadmium (Cd), a potent trace metal. Here, we show how a pair of Cd-exposed individuals can impact the behavior of unexposed groups.

A Pair of Cadmium-exposed Zebrafish Affect Boldness and Landmark use in the Un-exposed Majority.

Some individuals have a disproportionate effect on group responses. These individuals may possess distinct attributes that differentiate them from others. These characteristics may include susceptibility to contaminant exposure such as cadmium, a potent trace metal present in water and food.

Periprocedural management of direct oral anticoagulants in patients with atrial fibrillation and active cancer.

Background: Cancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation.

Thrombin generation, bleeding and hemostasis in humans: Protocol for a scoping review of the literature.

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.

Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale.

 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.

Effect modification of age and hypertension on cancer and prevalence of self-reported stroke - A cross-sectional study.

The objective of this study was to examine the effect modification of age on the relationship between cancer and prevalence of self-reported stroke. We used cross-sectional data from the 2015-2016 iteration of the Canadian Community Health Survey. A multivariable logistic regression model was used to assess the association between cancer and self-reported stroke.

Assessment of Chemical Toxicity in Adult Drosophila Melanogaster.

Human industries generate hundreds of thousands of chemicals, many of which have not been adequately studied for environmental safety or effects on human health. This deficit of chemical safety information is exacerbated by current testing methods in mammals that are expensive, labor-intensive, and time-consuming. Recently, scientists and regulators have been working to develop new approach methodologies (NAMs) for chemical safety testing that are cheaper, more rapid, and reduce animal suffering.

A pair of cadmium-exposed zebrafish affect social behavior of the un-exposed majority.

To account for global contamination events, we must identify direct and indirect pollutant effects. Although pollutants can have direct effects on individuals, it is unknown how a few contaminated individuals affect groups, a widespread social organization. We show environmentally relevant levels of cadmium (Cd) can have indirect social effects revealed in the social context of a larger group.

DOAC-associated bleeding, hemostatic strategies, and thrombin generation assays - a review of the literature.

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.

Thrombotic and bleeding outcomes following the perioperative interruption of anticoagulation among patients with nonvalvular atrial fibrillation and active cancer.

Background: Patients with cancer are at an increased risk of developing atrial fibrillation (AF) and often need to undergo procedures or surgery that requires periprocedural interruption of anticoagulation. Anticoagulated patients with cancer might be at increased risk of postprocedural thromboembolic and bleeding complications. Data on postprocedural outcomes among patients with concurrent active cancer and AF are sparse.

Coagulation assays and direct oral anticoagulant levels among patients having an elective surgery or procedure.

Background: The Perioperative Anticoagulation Use for Surgery Evaluation study prospectively evaluated a prespecified periprocedural interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Coagulation testing is widely available and frequently requested prior to invasive procedures. Coagulation assays display poor sensitivity to clinically relevant DOAC concentrations.

Toxicity by descent: A comparative approach for chemical hazard assessment.

Toxicology is traditionally divided between human and eco-toxicology. In the shared pursuit of environmental health, this separation does not account for discoveries made in the comparative studies of animal genomes. Here, we provide evidence on the feasibility of understanding the health impact of chemicals on all animals, including ecological keystone species and humans, based on a significant number of conserved genes and their functional associations to health-related outcomes across much of animal diversity.

Timing of pharmacologic venous thromboembolism prophylaxis initiation for trauma patients with nonoperatively managed blunt abdominal solid organ injury: a systematic review and meta-analysis.

Background: Blunt abdominal solid organ injury is common and is often managed nonoperatively. Clinicians must balance risk of both hemorrhage and thrombosis. The optimal timing of pharmacologic venous thromboembolism prophylaxis (VTEp) initiation in this population is unclear.

Genome-Wide Analysis of Cadmium-Induced, Germline Mutations in a Long-Term Mutation-Accumulation Experiment.

Background: Germline mutations provide the raw material for all evolutionary processes and contribute to the occurrence of spontaneous human diseases and disorders. Yet despite the daily interaction of humans and other organisms with an increasing number of chemicals that are potentially mutagenic, precise measurements of chemically induced changes to the genome-wide rate and spectrum of germline mutation are lacking.

Objectives: A large-scale mutation-accumulation experiment was propagated in the presence and absence of an environmentally relevant cadmium concentration to quantify the influence of cadmium on germline mutation rates and spectra.

Extensive standing genetic variation from a small number of founders enables rapid adaptation in Daphnia.

We lack a thorough understanding of the origin and maintenance of standing genetic variation that enables rapid evolutionary responses of natural populations. Whole genome sequencing of a resurrected Daphnia population shows that standing genetic variation in over 500 genes follows an evolutionary trajectory that parallels the pronounced and rapid adaptive evolution of multiple traits in response to predator-driven natural selection and its subsequent relaxation. Genetic variation carried by only five founding individuals from the regional genotype pool is shown to suffice at enabling the observed evolution.

Arsenic exposure induces a bimodal toxicity response in zebrafish.

In toxicology, standard sigmoidal concentration-response curves are used to predict effects concentrations and set chemical regulations. However, current literature also establishes the existence of complex, bimodal concentration-response curves, as is the case for arsenic toxicity. This bimodal response has been observed at the molecular level, but not characterized at the whole organism level.

Biomarker-enhanced VTE risk stratification in ambulatory patients with cancer.

Introduction: Risk assessment models are used to stratify cancer patients according to their underlying risk of VTE. The CATS score has been shown to enhance VTE risk stratification as compared to the modified Khorana score by incorporating d-dimer and soluble p-selectin measurements. Our aim was to evaluate the performance of the CATS score with respect to VTE risk stratification.

D-Dimer Enhances Risk-Targeted Thromboprophylaxis in Ambulatory Patients with Cancer.

Background: Thromboprophylaxis for ambulatory patients with cancer is effective, although uncertainties remain on who should be targeted. Using D-dimer values from individuals enrolled to the AVERT trial, we sought to identify and validate a more efficient venous thromboembolism (VTE) risk threshold for thromboprophylaxis.

Materials And Methods: The AVERT trial compared thromboprophylaxis with apixaban with placebo among patients with cancer with a Khorana Risk Score ≥2.

Predictors of preprocedural direct oral anticoagulant levels in patients having an elective surgery or procedure.

The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) study prospectively evaluated a prespecified periprocedural-interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Logistic regression analyses were performed to identify clinical parameters associated with residual DOAC levels ≥30 ng/mL or ≥50 ng/mL. Patients undergoing low-bleed-risk procedures were more likely to have residual levels of ≥30 ng/mL and ≥50 ng/mL.

Activated prothrombin complex concentrates for direct oral anticoagulant-associated bleeding or urgent surgery: Hemostatic and thrombotic outcomes.

Introduction: Studies evaluating the use of activated prothrombin complex concentrates (aPCCs) for DOAC-associated bleeding are sparse.

Materials And Methods: We conducted a retrospective study of patients receiving aPCC for DOAC-associated bleeding or for pre-operative optimization of hemostasis prior to urgent surgery. The primary efficacy outcome was hemostatic efficacy, the primary safety outcome was the 30-day thromboembolic complication rate.