Predictors of direct oral anticoagulant concentrations in the trauma population.

Introduction: Direct oral anticoagulant (DOAC) use is becoming more prevalent in patients presenting after trauma. We sought to identify the prevalence and predictors of subtherapeutic and therapeutic DOAC concentrations and hypothesized that increased anti-Xa levels would correlate with increased risk of bleeding and other poor outcomes. Methods: A retrospective cohort study of all trauma patients on apixaban or rivaroxaban admitted to a level 1 trauma center between January 2015 and July 2021 was performed. Patients were excluded if they did not have a DOAC-specific anti-Xa level at presentation. Therapeutic levels were defined as an anti-Xa of 50 ng/mL to 250 ng/mL for rivaroxaban and 75 ng/mL to 250 ng/mL for apixaban. Linear regression was used to identify correlations between study variables and anti-Xa level, and binomial logistic regression was used to test the association of anti-Xa level with outcomes. Results: There were 364 trauma patients admitted during the study period who were documented to be on apixaban or rivaroxaban. Of these, 245 patients had anti-Xa levels measured at admission. The population was 53% woman, with median age of 78 years, and median Injury Severity Score of 5. In total, 39% of patients had therapeutic and 20% had supratherapeutic anti-Xa levels. Female sex, increased age, decreased height and weight, and lower estimated creatinine clearance were associated with higher anti-Xa levels at admission. There was no correlation between anti-Xa level and the need for transfusion or reversal agent administration, admission diagnosis of intracranial hemorrhage (ICH), progression of ICH, hospital length of stay, or mortality. Conclusions: Anti-Xa levels in trauma patients on DOACs vary widely; female patients who are older, smaller, and have decreased kidney function present with higher DOAC-specific anti-Xa levels after trauma. We were unable to detect an association between anti-Xa levels and clinical outcomes. Level of evidence: III-Prognostic and Epidemiological.

Impact of Protocolized Pharmacist Intervention on Critical Activated Partial Thromboplastin Time Values With Heparin Infusions.

Background: Unfractionated heparin (UFH) infusions are commonly managed with nurse-driven nomograms titrated to activated partial thromboplastin time (aPTT). In some patients, anti-Xa values may be more appropriate measures of anticoagulation. At the present institution, an update to the nurse-driven aPTT nomogram requires pharmacist notification and clinical assessment for critically supratherapeutic aPTT results. Objective: The purpose of this study was to evaluate the efficacy and safety of the nomogram update. Methods: A single-center, retrospective, pre-post analysis was conducted in patients treated with UFH who experienced a critical aPTT during the 6 months preceding and following the nomogram update. Patients with erroneous critical aPTT results were excluded. The primary endpoint was the time in therapeutic range (Rosendaal method) from the first critical aPTT until UFH discontinuation. Secondary endpoints included the proportion of patients transitioned to anti-Xa monitoring and the incidence of Bleeding Academic Research Consortium (BARC) 2, 3, 5 bleeding. Data were analyzed by the χ2 test. The study was institutional review board approved. Results: Of 277 UFH infusions, 142 belonged to the pre-implementation group and 135 to the post-implementation group. Baseline aPTTs were similar between the 2 groups. Time in therapeutic range was 58.1% versus 62.4% of between groups (P = .467). UFH was transitioned to pharmacist-driven anti-Xa monitoring in 16.2% versus 40.3% of patients (P < .001). BARC 2, 3, 5 bleeding occurred in 23.2% versus 13.4% of patients (P < .001). Conclusions: Application of these data suggest improved safety and efficacy outcomes with directed pharmacist management of UFH in patients with critically elevated aPTTs.

Comparison of the changes in global gene expression of Escherichia coli induced by four bactericidal agents.

DNA microarrays provide a global view of the physiological state of the cell by parallel analysis of the expression levels of all the genes in an organism. The effects of four bactericidal agents on the expression pattern of Escherichia coli MG1655 were assessed. Compounds were chosen on the basis of their different mechanisms of action and included inhibitors of DNA replication and recombination, translation, transcription and cell wall biosynthesis. The addition of rifampin resulted in increased expression of the target, rpoB, as well as several genes involved in nucleotide salvage and purine biosynthesis. The addition of ampicillin resulted in overall changes in gene expression that showed some similarity to changes induced by rifampin. The addition of the antibiotics kanamycin or norfloxacin resulted in the induction of unique gene expression signatures: a heat shock response to kanamycin and an SOS response to norfloxacin. Several genes of unknown function showed expression profiles similar to the genes associated with the SOS or the heat shock response. Thus, these profiles define families of genes with similar expression phenotypes that can be tested for related function.