ABSTRACT
This quality improvement study examines the accuracy of electronic health record (EHR) documentation of aspirin use for primary prevention of atherosclerotic cardiovascular disease in adult outpatients.
Subject(s)
Aspirin , Electronic Health Records , Humans , Adult , Aspirin/therapeutic use , Outpatients , Platelet Aggregation Inhibitors/therapeutic use , Primary PreventionABSTRACT
Red blood cells (RBCs) lose plasma membrane in the spleen as they age, but the cells and molecules involved are yet to be identified. Sickle cell disease and infection by Plasmodium falciparum cause oxidative stress that induces aggregates of cross-linked proteins with N-linked high-mannose glycans (HMGs). These glycans can be recognised by mannose-binding lectins, including the mannose receptor (CD206), expressed on macrophages and specialised phagocytic endothelial cells in the spleen to mediate the extravascular haemolysis characteristic of these diseases. We postulated this system might also mediate removal of molecules and membrane in healthy individuals. Surface expression of HMGs on RBCs from patients who had previously undergone splenectomy was therefore assessed: high levels were indeed observable as large membrane aggregates. Glycomic analysis by mass spectrometry identified a mixture of Man5-9 GlcNAc2 structures. HMG levels correlated well with manual pit counts (r = 0.75-0.85). To assess further whether HMGs might act as a splenic reticuloendothelial function test, we measured levels on RBCs from patients with potential functional hyposplenism, some of whom exhibited high levels that may indicate risk of complications.
Subject(s)
Erythrocyte Membrane , Mannose , Endothelial Cells , Humans , Polysaccharides , SplenectomyABSTRACT
In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait.
Subject(s)
Anemia, Sickle Cell/metabolism , Erythrocytes/metabolism , Mannose/metabolism , Phagocytes/metabolism , Polysaccharides/metabolism , Erythrocyte Membrane/metabolism , Erythrocyte Membrane/parasitology , Erythrocytes/parasitology , Flow Cytometry/methods , Hemolysis , Humans , Ligands , Malaria, Falciparum/metabolism , Malaria, Falciparum/parasitology , Membrane Glycoproteins/metabolism , Phagocytosis , Plasmodium falciparum/physiology , Protein Binding , Receptors, Immunologic/metabolismABSTRACT
A patient receiving daptomycin developed asymptomatic transaminitis and hyperbilirubinemia without concurrent multiorgan dysfunction or elevation of his creatinine kinase level. After ruling out other etiologies, the liver injury was attributed to daptomycin and was subsequently resolved. A single-center retrospective cohort analysis of baseline and follow-up liver function panels (n = 614) from all admissions from 2008 to 2013 during which daptomycin was administered did not reveal any other cases of probable or definite drug-induced liver injury associated with daptomycin.
