ABSTRACT
Laboratory test overutilization increases health care costs, leads to unwarranted investigations, and may have a negative impact on health outcomes. The American Society of Clinical Pathology, in its Choosing Wisely Campaign, advocates that inflammation be investigated with C-reactive protein (CRP) instead of Erythrocyte Sedimentation Rate (ESR). London Health Sciences Centre (LHSC), a tertiary care hospital organization in Ontario, Canada, set a goal to reduce inappropriate ESR orders by 50%. After developing appropriateness criteria for ESR, we used a series of PDSA cycles to reduce inappropriate ESR ordering and analyzed our results with an interrupted time series design. Our intervention began with an educational bulletin and moved to city-wide implementation of computerized Clinical Decision Support (CDS). After implementation, ESR orders decreased by 40% from 386 orders per week to 241 orders per week. Our results are supported by previous literature on the effectiveness of CDS in reducing overutilization and suggest that provider habit is a significant contributor to inappropriate ordering.
ABSTRACT
BACKGROUND: Patients may present with an antibody against a blood group antigen, a negative direct antiglobulin test (DAT), and a null phenotype. Typically, this represents an alloantibody in a null individual. However, on occasion, the antibody disappears coincident with conversion to a positive red blood cell (RBC) phenotype. This has been called antigen loss, antigen suppression, or weakened antigenicity. Herein, a unique serologic profile that mimics this pattern, when in fact antigen loss did not occur, is described. STUDY DESIGN AND METHODS: RBCs and serum were analyzed using a gel microtyping system and flow cytometry. Genomic DNA was amplified by polymerase chain reaction and sequenced. RESULTS: Initially, an anti-Kp(b) was detected in MTS gel, RBCs typed K-k-Kp(b-), and the DAT was negative for immunoglobulin G (IgG). Later, the anti-Kp(b) disappeared and RBCs phenotyped as K-k+Kp(b+). Analysis of initial specimens by flow cytometry identified an immunoglobulin M (IgM) anti-Kp(b) with a positive IgM-specific DAT; eluates contained an anti-Kp(b) at immediate spin. Supporting the presence of the Kell glycoprotein, RBCs agglutinated with anti-Js(b). Sequencing showed homozygosity for Kp(b) with no mutations surrounding the Kp(b) polymorphism. CONCLUSION: In antigen loss, antibody masking is excluded by a negative DAT. However, because typical DAT reagent does not detect IgM, such reasoning was inaccurate in the current case. In addition, an anti-Kp(b) resulted in RBCs typing k-, even though no anti-k was detected. Overall, this case suggests that an IgM may mask adjacent epitopes and illustrates the potential to mistake a non-IgG autoantibody as antigen loss.
Subject(s)
Autoantibodies/physiology , Immune Tolerance/immunology , Immunoglobulin M/physiology , Kell Blood-Group System/immunology , Agglutination Tests , Antigens/immunology , Autoantibodies/analysis , Autoantibodies/blood , DNA Mutational Analysis , Erythrocytes/immunology , Humans , Kell Blood-Group System/genetics , Male , Middle AgedABSTRACT
BACKGROUND: The Cromer blood group system consists of nine high-prevalence and three low-prevalence antigens carried on decay-accelerating factor (DAF). This report describes three new Cromer high-prevalence antigens, named ZENA, CROV, and CRAM. STUDY DESIGN AND METHODS: Sequence analyses were performed on DNA from three probands whose serum samples each contained an alloantibody to a high-prevalence antigen in the Cromer blood group system. Polymerase chain reaction-restriction fragment length polymorphism analysis to detect the mutation encoding the CROV- phenotype was performed on 100 Croatian donors. To map the respective epitopes, DAF deletion mutants were tested by immunoblotting with eluates containing the antibodies. RESULTS: In each proband, sequence analysis revealed a single-nucleotide substitution in DAF: ZENA, 726T>G mutation, predicted change His242Gln; CROV, 466G>A mutation, predicted change Glu156Lys; and CRAM, 740A>G mutation, predicted change Gln247Arg. By analysis of DAF deletion mutants, the CROV antigenic determinant mapped to the complement control protein (CCP) domain 2, which is encoded by exon 3, whereas ZENA and CRAM mapped to CCP4, which is encoded by exon 6. CONCLUSION: This study describes three novel high-prevalence antigens in the Cromer blood group system each characterized by a predicted single-amino-acid substitution. The antigens have been assigned the following International Society of Blood Transfusion (ISBT) numbers: ZENA is CROM13, CROV is CROM14, and CRAM is CROM15.
Subject(s)
Blood Group Antigens/classification , Blood Group Antigens/genetics , Animals , Base Sequence , Blood Group Antigens/analysis , Blood Group Antigens/immunology , CD55 Antigens/genetics , CHO Cells , Cricetinae , Cricetulus , DNA, Complementary/genetics , Exons/genetics , Humans , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Sequence Analysis, DNA , Sequence Deletion/geneticsABSTRACT
Galanin is a 29-amino-acid peptide expressed in dorsal root ganglion (DRG) neurones and spinal dorsal horn neurones. It affects pain threshold and has developmental and trophic effects. Galanin acts at three G-protein-coupled receptors, galanin receptors (GalR1-3), each expressed in the DRGs as suggested by in situ hybridization and/or reverse transcriptase-polymerase chain reaction. The GalR2 knockout (-/-) mice permit studies on the contributions of this receptor subtype to the role of galanin at the spinal level. At 1 week after sciatic nerve transection (axotomy), there were 16-20% fewer neurones in intact and contralateral DRGs of -/- mice as compared with wild-type (WT) mice. In addition, a significant neurone loss (26% reduction) was found in the ipsilateral DRGs of WT mice, whereas no further neurone loss was seen in -/- mice. Expression of several peptides has been examined after axotomy, including galanin, neuropeptide Y and two of its receptors as well as substance P, and no significant differences were found between -/- and WT mice in either ipsi- or contralateral DRGs, respectively. After thermal injury and spinal nerve ligation, onset and duration of hyperalgesia in the injured paw were similar in GalR2-/- and WT animals. Recovery from spinal nerve ligation-caused allodynia had the same kinetics in -/- and WT animals. These data are in line with earlier observations from the peripheral and central nervous system, suggesting that galanin actions mediated by GalR2 subtype are of importance in neurodevelopment and neuroprotection.