Search

Introduction Instituto do Câncer do Estado de Sao Paulo (ICESP-HCFMUSP) is a public universitaryoncological hospital, with currently 43 thousand active patients. As an exception in Brazil, it deliversanticoagulants to outpatients to assure the continuation of treatment after hospital discharge.Anticoagulants are considered high vigilance medicines due to their potential to significantly jeopardizepatients health if misused. They are specially identified and stored to differentiate them from otherproducts, exhibit a special alert when prescribed and are delivered to patients with a folder containinginformation on them. In October 2018, a recommendation on the treatment of venous thromboembolism incancer patients was launched at ICESP-HCFMUSP aiming to optimize local resources, improve theanticoagulation management, overcome the irregular supply of enoxaparin and reduce the burden ofparenteral anticoagulation whenever possible. It's available at the intranet. Concomitantly, rivaroxabanbecame available and a 6-month period of dedicated pharmaceutical vigilance was started. Aim This report aims to show the relevance of pharmaceutical vigilance, how it can be carried out and itscontribution to refine the management of a new anticoagulant. Materials and methods 48 pharmacists and 2 hematologists (Thrombosis and Hemostasis team)handled the pharmaceutical vigilance process from October 2018 to April 2019. All professionals weretrained on the recommendation regarding the eligibility and exclusion criteria for prescribing rivaroxaban,its dosage, interactions and management details. The process comprised: evaluation of inpatients andoutpatients rivaroxaban prescriptions, investigation of adverse events, longitudinal evaluation of clinicalrecords of patients on rivaroxaban and medical support to anticoagulation management as requested. Anydiscrepancy between the recommendation and a prescription was considered a non conformity. Specialmaterials to identify the new anticoagulant and educate professionals and patients were developed. Allclinical documents were electronic (TASY) accessible only by authorized professionals by password.Results are described as frequencies. Results 762 evaluations were performed by the pharmacists in the 6-month period: 490 inpatients (100%)and 199 outpatients (44.6%) prescriptions, 69 recordings and 4 notified (100%) adverse events, resultingin 126, 13, 9 and 8 non conformities, respectively. Besides supporting the pharmacists, the hematologistsreplied to additional 22 requests, finding out 15 non conformities. Seven bleeding episodes and 7thrombosis recurrences were detected, none resulting in death. All except 1 recurrence were associated tosome non conformity. Clarification and/or educational actions were carried out whenever a non conformitywas found. Around 500 outpatients received the folder on rivaroxaban. Conclusions The comprehensive analysis of prescriptions and records with prompt interaction withprescribers facing non conformities could contribute to improve the management of a new anticoagulant ata cancer institution.

The integrity of the endothelial layer, which lines the entire cavity of the vascular system, depends on tight adhesion of the cells to the underlying basement membrane as well as to each other. It has been previously shown that such interactions occur via membrane receptors that determine the specificity, topology, and mechanical properties of the surface adhesion. Cell-cell junctions between endothelial cells, in culture and in situ, involve both Ca(2+)-dependent and -independent mechanisms that are mediated by distinct adhesion molecules. Ca(2+)-dependent cell-cell adhesion occurs mostly via members of the cadherin family, which locally anchor the microfilament system to the plasma membrane, in adherens junctions. Ca(2+)-independent adhesions were reported to mainly involve members of the Ig superfamily. In this study, we performed three-dimensional microscopic analysis of the relative subcellular distributions of these two endothelial intercellular adhesion systems. We show that cadherins are located at adjacent (usually more apical), yet clearly distinct domains of the lateral plasma membrane, compared to PECAM-1. Moreover, cadherins were first organized in adherens junctions within 2 h after seeding of endothelial cells, forming multiple lateral patches which developed into an extensive belt-like structure over a period of 24 h. PECAM-1 became associated with surface adhesions significantly later and became progressively associated with the cadherin-containing adhesions. Cadherins and PECAM-1 also differed in their detergent extractability, reflecting differences in their mode of association with the cytoskeleton. Moreover, the two adhesion systems could be differentially modulated since short treatment with the Ca2+ chelator EGTA, disrupted the cadherin junctions leaving PECAM-1 apparently intact. These results confirm that endothelial cells possess distinct intercellular contact mechanisms that differ in their spatial and temporal organization as well as in their functional properties.