Biological variations of ADAMTS13 and von Willebrand factor in human adults

Background: The ultra-large von Willebrand factor (vWF) multimers are very active and must be degraded by ADAMTS13 for optimal activity. A severe functional deficiency of ADAMTS13 has been associated with thrombotic thrombocytopenic purpura. The correct interpretation of patient vWF and ADAMTS13 plasma levels requires an understanding of the biological variation associated with these analytes. In the present paper, we aimed to determine the biological variation of ADAMTS13 and vWF in human adults. Materials and methods: Blood samples were collected weekly from 19 healthy subjects for 5 consecutive weeks. vWF activity and antigenicity were determined using aggregometric and immunoturbidimetric methods. ADAMTS13 antigenicity and activity were determined by ELISA. Results: The within-subject biological variations for vWF activity and antigenicity were 8.06% and 14.37%, respectively, while the between-subject biological variations were 18.5% and 22.59%, respectively. The index of individuality for vWF activity was 0.44, while vWF antigenicity was 0.64. Similarly, ADAMTS13 activity and antigenicity within-subject biological variations were 12.73% and 9.75%, respectively, while between-subject biological variations were 9.63% and 6.28%, respectively. The ADAMTS13 indexes of individuality were 1.32 and 1.55, respectively. Conclusion: We report high biological variation and individuality in vWF antigenicity and activity levels. However, ADAMTS13 antigenicity and activity displayed high biological variation, but low individuality. Thus, population-based reference intervals may be useful for monitoring ADAMTS13 antigenicity and activity, but not for vWF, which displays high individuality. These findings should be considered when determining the reference interval and other clinical variables associated with ADAMTS13 and vWF levels

Personalized reference intervals - Statistical approaches and considerations

Under embargo until: 2022-12-13For many measurands, physicians depend on population-based reference intervals (popRI), when assessing laboratory test results. The availability of personalized reference intervals (prRI) may provide a means to improve the interpretation of laboratory test results for an individual. prRI can be calculated using estimates of biological and analytical variation and previous test results obtained in a steady-state situation. In this study, we aim to outline statistical approaches and considerations required when establishing and implementing prRI in clinical practice. Data quality assessment, including analysis for outliers and trends, is required prior to using previous test results to estimate the homeostatic set point. To calculate the prRI limits, two different statistical models based on ‘prediction intervals’ can be applied. The first model utilizes estimates of ‘within-person biological variation’ which are based on an individual’s own data. This model requires a minimum of five previous test results to generate the prRI. The second model is based on estimates of ‘within-subject biological variation’, which represents an average estimate for a population and can be found, for most measurands, in the EFLM Biological Variation Database. This model can be applied also when there are lower numbers of previous test results available. The prRI offers physicians the opportunity to improve interpretation of individuals’ test results, though studies are required to demonstrate if using prRI leads to better clinical outcomes. We recommend that both popRIs and prRIs are included in laboratory reports to aid in evaluating laboratory test results in the follow-up of patients.publishedVersio

THE EFFECT OF RETICULOCYTE HEMOGLOBIN CONTENT ON THE DIAGNOSIS OF IRON DEFICIENCY ANEMIA: A META-ANALYSIS STUDY

Background: Iron deficiency anemia (IDA) is the most common type of anemia worldwide and has many adverse effects on life quality. This meta-analysis study aims to show that reticulocyte hemoglobin content (CHr) is more effective than routinely used parameters in the diagnosis of IDA. Methods: Comprehensive and systematic research was done using international databases including PubMed, Web of Science, Cochrane Library, Science Direct, and Google Scholar, which contain all articles published on IDA until December 29, 2020. Seventeen articles were included in the meta-analysis. Results: The analyses found the Cohens deffect size (Standardized Mean Difference) values of the parameters. Accordingly, CHr is 2.84 (95% CI 2.36 to 3.31), mean corpus volume (MCV) is 2.46 (95% CI 1.97 to 2.95), ferritin is 2.37 (95% CI 1.63 to 3.11), and transferrin saturation (TSAT) is 3.76 (95% CI 2.14 to 5.38). To diagnose IDA, the sensitivity value of the CHr concentration was found as 83.5% (95% CI 76.1 to 89.8), specificity value to be 91.8% (95% CI 85.5 to 96.4), and mean cut-off value as 28.2 pg. Conclusions: The results of our study reveal the findings that CHr is a better biomarker than MCV and ferritin used in determining IDA, and its efficacy is lower than TSAT. It is very important to use it routinely for the pre-diagnosis of IDA, which is very important for public health. The groups in the study are heterogeneous but contain bias. Therefore, meta analyses of studies with less heterogeneity of CHr are needed

Perioperative risk factors of acute kidney injury after non-cardiac surgery: A multicenter, prospective, observational study in patients with low grade American Society of Anesthesiologists physical status

Background: The aim of this study was to determine the incidence and the perioperative risk factors of acute kidney injury (AKI) using "Kidney Disease: Improving Global Outcomes" (KDIGO) guidelines, in patients with low grade American Society of Anesthesiologists physical status (ASA-PS) undergoing noncardiac surgery

Comparative Effects of Blood and Crystalloid Cardioplegia on Cellular Injury and Oxidative Stress in Cardiovascular Surgery

Purpose: The purpose of this study was to evaluate the effect of different cardioplegic solutions on endothelial integrity and oxidative stress in cardiovascular surgery

Untargeted urinary metabolomic profiling in post-kidney transplant with different levels of kidney function

The ability to monitor patients plays a major role in the success of kidney transplants. However, transplant monitoring still depends on relatively outdated, inadequate technologies. The aim of this study was to reveal the metabolomic profile of the kidney allograft using the metabolomic screening technique and to identify specific eGFR-based biomarkers to monitor individuals with different levels of post-transplantation graft dysfunction. In the current study, urine samples from 131 unique kidney transplant recipients were collected and analyzed by ultra-high performance liquid chromatography and benchtop QTof mass spectrometer (Xevo G2 XS QTof). Acquired data were first pre-processed by Progenesis QI 2.3 (Nonlinear Dynamics, Waters, UK). Putative annotation was performed against the HMDB database following multivariate statistical analysis. Post-transplant biomarker panels that can distinguish stages of renal dysfunction were created by combining the significant markers and taking their ratios. Overall, 8 metabolites were significantly altered within three groups of kidney transplant recipients:4,5-Dihydroorotic acid, N2-Succinyl-L-glutamic acid 5-semialdehyde, Valyl-Arginine, Pantothenic acid, L-phenylalanyl-L-hydroxyproline, MG(0:0/24:0/0:0), QYNAD and 12-Hydroxy-13-O-D-glucuronoside-octadec-9Z-enoate as biomarker candidates (p0.05). The ratio of 4,5-Dihydroorotic acid to Pantothenic acid (panel-1) can be used to monitor kidney function. Specifically, these metabolite ratios were found to be more sensitive to changes in kidney function than panel-2, which consisted of 7 metabolites, excluding QYNAD, of the 8 major metabolites. Our results may contribute to the monitoring of kidney transplant patients based on post-transplant eGFR-based kidney function stages, thus providing a method for the early evaluation and monitoring of the kidney transplant recipient after transplantation for kidney transplant patient management.We thank all the participants who participated in this study. This research was funded by Acibadem Labmed Laboratories in Turkey and supported by 2244 Industrial Ph.D. program provided by The Scientific and Technological Research Council of Turkey (TUBITAK-Grant# 118C082). All procedures involving human participants have been approved according to the ethical standards of the institutional research committee, including the 1964 Helsinki Declaration and its later amendments of comparable ethical standards. The Ethics Committee approved the study of Acibadem Mehmet Ali Aydinlar University (Turkey). Informed written consent was obtained from all participants (Approval ID: 2020-08/14). Written informed consent was obtained from all participants in this study.Acibadem Labmed Laboratories in Turkey; 2244 Industrial Ph.D. program by The Scientific and Technological Research Council of Turkey (TUBITAK) [118C082

dilutional anemia induces renal dysfunction in diabetic patients undergoing coronary artery bypass grafting: a consequence of microcirculatory alterations?

Background In this study we aimed to evaluate the effects of dilutional anemia resulting from cardiopulmonary bypass (CPB) and its correction with red blood cell (RBC) transfusion on tissue oxygenation and renal function in diabetic patients undergoing coronary artery bypass grafting (CABG)