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August 2012

Editor:
Deborah Sesok-Pizzini, MD, MBA

Tandem mass spectrometry findings at infant autopsy to detect metabolic disease Tandem mass spectrometry findings at infant autopsy to detect metabolic disease

Autopsy protocols for sudden unexpected death in infancy (SUDI or, in the first week of life, SUEND) include recommendations for acylcarnitine profile analysis using tandem mass spectrometry (MS/MS). Blood and bile spots for MS/MS acylcarnitine profiling identify inborn errors of metabolism, including fatty acid oxidation defects (FAOD), as a cause of infant death. It is necessary to collect blood and bile for analysis because some specific fatty and oxidation disorders may be undiagnosed with single-sample analysis. The authors conducted a study in the United Kingdom, where limited newborn screening is performed, to examine acylcarnitine profiles in a large cohort of infant deaths to determine variables that affect postmortem MS/MS analysis. They studied autopsy findings over a 14-year period in which 744 MS/MS results were available. Seventy-nine of these were excluded from the study due to incomplete results or lack of demographic data or because samples were taken antemortem or were duplicates. Of the remaining 665 samples, 397 were blood and 268 were bile, of which 82 percent of the blood samples and 89 percent of the bile samples were classified as normal. These samples reflected 410 autopsies, where 255 had results with blood and bile, 142 with blood only, and 13 with bile only. Family history was not provided for 52 percent of the cases. Statistical analysis included regression analysis to determine the relationship between demographic and biochemical parameters. Blood and bile profiles were also compared and differences examined between groups using the Mann-Whitney U test. The authors showed that two percent of the infant autopsies for SUDI/SUEND demonstrated abnormal blood or bile MS/MS profiles consistent with an underlying metabolic disease. They found that blood and bile samples were required for detecting some metabolic diseases, such as very long chain acyl-CoA dehydrogenase deficiency. The authors also demonstrated that blood and bile postmortem MS/MS profiles were affected by different variables. The blood samples were influenced more by age, body mass index, liver weight, and postmortem interval. The authors suggested that this may aid in the postmortem interpretation and quantitative diagnosis of specific patterns of disease. They concluded that the significant differences between blood and bile findings in some cases, including changes suggestive of low carnitine status or deficiency or ketone body metabolism defects, underscore the importance of interpretation by a specialist in the field.

Pryce JW, Weber MA, Heales S, et al. Tandem mass spectrometry findings at autopsy for detection of metabolic disease in infant deaths: postmortem changes and confounding factors. J Clin Pathol. 2011;64:1005–1009.

Correspondence: N. J. Sebire at sebirn@gosh.nhs.uk

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Value of a well-designed online transfusion reaction reporting system Value of a well-designed online transfusion reaction reporting system

Reporting of transfusion reactions is an important aspect of the medical care of patients receiving blood transfusions. Blood transfusions are not risk-free, but with modern infectious disease testing, risk of transfusion-transmitted viral disease is much lower. However, noninfectious complications reported during transfusions have become much more common. It is the responsibility of the clinical provider to stop a transfusion for a patient experiencing a reaction and to submit information, including vital signs, symptoms, and a sample of blood, to the laboratory for evaluation. In some centers, a urine sample is also submitted. The timing of the report of the reaction is critical to ensure that hemolytic reactions are excluded and no special modified or red blood cell antigen-selected products are required for future safe transfusions. The authors described a new system implemented in their hospital for electronic reporting of transfusion reactions. They compared the new online system with the older paper method for reporting transfusion reactions. The authors sent an anonymous questionnaire to 40 nurses with experience in reporting in both systems. The questionnaires were returned by 32 nurses for a response rate of 80 percent. The authors reported that 78 percent of the nurses noted that they had not reported a transfusion reaction in the past. The new reporting system was considered to be user-friendly, with 94 percent of the nurses educated on the system within one week and the majority of the nurses claiming that their workload was the same or decreased. Of interest, the authors noted that 88 percent considered the new system to be helpful in improving the quality of clinical transfusion care. The new system allowed for easy calculation of the incidence of transfusion reactions and type of each reaction. With the system, the hospital’s documented incidence of transfusion reaction increased from 0.21 percent to 0.61 percent per unit of blood. The authors cited as a limitation of the new system the potential for underreporting delayed transfusion reactions. They asserted that this limitation requires additional educational efforts on behalf of the transfusion service. The authors concluded that a well-designed online reporting system may improve the ability to estimate the incidence of transfusion reactions and the quality of transfusion care.

Yeh SP, Chang CW, Chen JC, et al. A well-designed online transfusion reaction reporting system improves the estimation of transfusion reaction incidence and quality of care in transfusion practice. Am J Clin Pathol. 2011;136(6):842–847.

Correspondence: Dr. Su-Peng Yeh, Division of Hematology and Oncology, Dept. of Medicine, China Medical University Hospital, 2 Yuh Der Road, Taichung 404, Taiwan

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Usefulness of repeat testing practices in a large hospital clinical chemistry lab Usefulness of repeat testing practices in a large hospital clinical chemistry lab

A long-standing practice in clinical laboratories has been to automatically repeat tests when values trigger automated “repeat rules” in the laboratory information system. The practical utility of repeating these tests, in terms of turnaround times and reporting delays for critical values, becomes an important question if repeat testing results are not adding value to clinical care. When lab instruments were less reliable, repeat testing formulae were more critical. However, with newer analyzers, accuracy and reliability may be less of a concern and repeat testing may result in unnecessary reporting delays. The authors performed a study in a large tertiary care hospital in which they examined 855,009 results from 30 different clinical chemistry tests to determine if it may be possible to reduce repeat testing and improve efficiency and turnaround time for reporting lab values. A report was created to retrieve only tests that initiated the automated repeat testing response. The flags that resulted in the automatic testing rules were linear high (values above the analytic measurement range), linear low (values below the analytic measurement range), repeat for clinically significant values, critical alert values that require call backs to the health care provider, and delta check values. Of the 855,009 test results examined, 25,553 (three percent) were repeated due to an automated result repeat flag. While initial values outside the analytic measurement range accounted for only 19.9 percent of all automated repeat testing, these values accounted for 84.7 percent of the 668 testing errors. These errors were defined in accordance with CAP/CLIA standards where the difference between the initial and verified values exceeded the allowable error limit. The authors suggested that when values are outside the analytic measurement range, repeat testing will continue to be necessary. However, for initial results within that range for many chemistry tests, repeats may be unnecessary and result in a delay in reporting critical results. Exceptions to this may be for sodium and pO2, for which the authors’ findings suggested that repeat testing is needed to detect large errors in the initial result. In addition, the delta check flag will also need to be investigated to determine mislabeled samples and sample integrity problems.

Deetz CO, Nolan DK, Scott MG. An examination of the usefulness of repeat testing practices in a large hospital clinical chemistry laboratory. Am J Clin Pathol. 2012;137(1):20–25.

Correspondence: Dr. Mitchell G. Scott, Division of Laboratory and Genomic Medicine, Box 8118, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110

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Clinical pathology abstracts editor: Deborah Sesok-Pizzini, MD, MBA, associate professor, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and medical director, Blood Bank and Transfusion Medicine, Children’s Hospital of Philadelphia.