Chromogenic and Clot-Based Bivalirudin Assays for Monitoring Anticoagulation.

BACKGROUND: Direct thrombin inhibitors (DTIs) are usually monitored with the activated partial thromboplastin time (aPTT) or activated clotting time (ACT). Both are complex assays with multiple enzymatic steps, and performance may be influenced by physiologic and pathologic factors unrelated to the DTI. Simpler systems, such as clot-based dilute thrombin time (dTT) and chromogenic anti-factor IIa assays, have been developed for monitoring DTIs, but there is limited data on their performance in clinical settings. METHODS: Medical records of patients who received bivalirudin between March 2020 and April 2022 at a single institution were reviewed for demographic data and adverse outcomes. Plasma samples drawn for aPTT testing were analyzed with chromogenic anti-IIa and dTT bivalirudin assays. Results were compared to bivalirudin dosing. RESULTS: Results of aPTT assays from 32 patients were compared with the chromogenic (n = 136) and dTT (n = 120) bivalirudin assays. Correlations between the aPTT and the chromogenic and dTT assays were poor (Spearman coefficients 0.55 and 0.62, respectively). There was a stronger correlation when results of the chromogenic and dTT assays were compared to each other (Spearman coefficient 0.92). When assay results were compared to bivalirudin dose, there were stronger correlations with the chromogenic and dTT assays than with the aPTT (Spearman coefficients 0.51, 0.63 and 0.22, respectively). CONCLUSIONS: There was considerable variation between results of specific bivalirudin assays and the aPTT. While bivalirudin assay results correlated better with administered drug dose, suggesting improving reliability, more studies are needed to determine if there is correlation between testing and clinical outcomes.

Clinical Response to PI3K-α Inhibition in a Cohort of Children and Adults With PIK3CA-Related Overgrowth Spectrum Disorders.

Objective: The goal of this report is to describe, through a series of 5 cases, the clinical response and safety of alpelisib (BYL719) use in children and adults with PIK3CA-related overgrowth spectrum (PROS) disorders at our center. Methods: We reviewed clinical records of 5 patients from October 2019 through September 2021 followed by the pediatric hematology and multidisciplinary vascular anomalies teams at the Monroe Carell Jr. Children's Hospital at Vanderbilt (MCJCHV). All patients carried a clinical or genetic diagnosis of PROS and were treated with alpelisib provided by a Novartis managed access program. Results: We highlight improvement in reported symptoms, objective overgrowth measurements, and quality of life to varying degrees in all patients. We note dose-dependent hyperglycemia and gastrointestinal side effects in 2 of the 5 patients. No patients experienced any serious side effects. Conclusion: This case series reports on the real-world use of PI3K-α inhibition in the management of PROS. Ongoing clinical trials will provide efficacy and safety data as these drugs become more widely used in patients with vascular anomalies and syndromes secondary to somatic PIK3CA mutations.

Transitions of Care for Healthy Young Adults: Promoting Primary Care and Preventive Health.

The transition of care between pediatric and adult medicine is a challenging time for patients and physicians. This longitudinal process encompasses much more than the physical transfer of a patient between providers. Established transition of care processes and literature exist for many chronic disease populations, but little focus has been directed toward the transition of care and the delivery of preventive medicine for healthy young adult patients. The 18- to 30-year-old age group is a heterogenous population that often engages in high-risk behaviors and has high rates of preventable morbidity and mortality. A significant number of these patients do not receive routine primary care and are high users of costly emergency services. Without a continuous source of care, many young adults do not receive age-appropriate screening or preventive health guidance. Structured transition practices improve outcomes in the chronic disease population, and anticipatory guidance has a positive effect on patient lifestyle modification. Adult providers should use these practices to ensure the successful integration of healthy young adult patients into an adult medical home. By establishing an ongoing source of preventive care, providers could reduce morbidity and mortality in this vulnerable population.

Outcomes of Using IVC Filters in Patients with Malignancy at an Academic Medical Center.

Systemic anticoagulation is regarded as optimal treatment and prophylaxis of venous thromboembolism (VTE). In malignancy, bleeding risk is increased while the patients remain hypercoagulable, making anticoagulation management troublesome. Inferior vena cava (IVC) filters have emerged as an option in the management of VTE, especially when anticoagulant agents are contraindicated. There is limited data on the overall outcomes of patients with malignancy and IVC filter placement. This descriptive study identifies individuals with filters placed and reviews outcomes to guide appropriate care of patients with malignancy and VTE. We performed a retrospective chart review of 115 patients with malignancy who had a filter placed between July 2014 and December 2016. Eighty-seven patients were tracked until December 2017 for significant events (VTE and/or death). In total, 61% ( n = 70) had metastatic solid tumor malignancy and 77% ( n = 88) were receiving anticoagulation therapy prior to IVC filter placement. Fifty-three percent ( n = 61) had bleeding events and 25% ( n = 29) had thrombocytopenia. Patients with isolated solid tumors receiving frequent surgery were also common recipients of filters. Sixty-six percent (57/87) of patients had a significant event; 85% of them were anticoagulated. Eighty-two percent of events occurred within 6 months of filter placement, with death occurring on average within 5 months of placement. Overall, use of IVC filters was more common in cancer patients who developed bleeding complications on anticoagulation and with metastatic malignancy. However, in patients with metastatic or hematologic disease, filter placement did not prevent all-cause mortality. Individualized risk-benefit consideration is needed before IVC filters are placed.