{"title":"Imperfect reference standards cause biased likelihood ratios.","authors":"Arne Åsberg, Ann Elisabeth Åsberg","doi":"10.1080/00365513.2025.2528214","DOIUrl":"10.1080/00365513.2025.2528214","url":null,"abstract":"<p><p>In a study of the diagnostic accuracy of a quantitative biomarker, the researcher compares the concentration of the biomarker in patients with and without the disease in question. The diagnosis must be set without knowledge of the biomarker concentration, using the best reference standard available. If the reference standard is not perfect, the estimates of the receiver operating characteristic (ROC) curves will be biased. The likelihood ratio (LR) for the biomarker concentration, the measure connecting pretest and posttest probability, will also be biased when imperfect reference standards are used. In this work, we used simulated datasets to study how much the LRs were affected in different scenarios of prevalence of disease and correlation between the biomarker and the imperfect reference standard. Using the diagnosis of iron deficiency as an example, we showed that the estimated likelihood ratios for S-transferrin saturation may be biased in a clinically significant way.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"361-367"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The impact of ABO and Rh(D) blood group on Covid-19 immune response.","authors":"Erling Englund, Anders E Henriksson","doi":"10.1080/00365513.2025.2522673","DOIUrl":"10.1080/00365513.2025.2522673","url":null,"abstract":"<p><p>Previous studies indicate that blood type O has a protective effect against Covid-19 disease. In the present study, we aimed to further explore and clarify the connection between ABO blood groups and the Covid-19 disease by examining the levels of Covid antibodies in patients with different ABO blood types. During the first pandemic year, and before the vaccine was available, SARS-CoV-2 antibody level were randomly analyzed at the regional hospital laboratory and the data was stored in the laboratory information system (LIS) Flexlab/Chemistry. The investigated cohort was created by cross-referencing the SARS-CoV-2 antibody results with the ABO Rh(D) blood group status available in the LIS Prosang. The association between antibody level and blood group was further analyzed within this cohort. There was a significantly higher odds of Covid positivity among individuals in the cohort with blood type A or AB compared to blood type O. There was no significant difference in odds of Covid positivity among between phenotypes B compared to blood type O. The quantitative levels of SARS-CoV-2 antibodies were similar in individuals with a positive Covid-19 test regardless of ABO and Rh(D) phenotype. The present cohort study supports the hypothesis that the presence of anti-A antibodies in serum should be considered as a factor more significant than the blood group itself. However, the study showed a similar immune response in individuals with a positive Covid-19 test regardless ABO phenotype.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"321-326"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abstracts from XXXIX Nordic Congress in Clinical Chemistry 2024.","authors":"Andries Blokzijl, Frida Duell","doi":"10.1080/00365513.2024.2428121","DOIUrl":"https://doi.org/10.1080/00365513.2024.2428121","url":null,"abstract":"","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":"84 sup1","pages":"S1"},"PeriodicalIF":1.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anni Mäenpää, Moona Kangastie, Päivikki Kangastupa
{"title":"Hb Tacoma by seven HbA1c methods - one with significant interference.","authors":"Anni Mäenpää, Moona Kangastie, Päivikki Kangastupa","doi":"10.1080/00365513.2024.2417383","DOIUrl":"10.1080/00365513.2024.2417383","url":null,"abstract":"<p><p>Hemoglobin Tacoma is known to potentially interfere HbA1c assays. The variant is common in Finland with prevalence of up to 2% regionally and cases are also reported in areas that have attracted Finnish immigrants, especially in Sweden and North America. Here, we investigated the effect of Hb Tacoma on seven HbA1c methods. 20 non-variant and 20 Hb Tacoma samples were measured with Tina-quant Gen. 3 (immunoassay, considered as reference) and the following point of care instruments: Afinion 2, HbA1c 501 (both utilizing boronate affinity), QuikRead go, cobas b 101, DCA Atellica, and Standard F (all immunoassays). Repeatability was also assessed by measuring both non-variant and Hb Tacoma samples five times each at two different levels. For non-variant samples, the mean relative bias with all methods was < ±4%, whereas for Hb Tacoma samples Standard F had 38% mean relative bias. In absolute bias, the difference was 17 mmol/mol on average and constant through the measured range. For other methods the mean relative bias for Hb Tacoma samples was < ±6%. The repeatability with all methods was similar for non-variant and Hb Tacoma samples and at highest 4.1% (mean CV% of two levels). The observed interference by Standard F is likely due to two-antibody assay design as Hb Tacoma has been shown to result in conformational change. This interference is clinically significant and highlight the need for better controlling and better understanding hemoglobin variants in HbA1c testing.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"447-451"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anders Oest, Maja Boe, Marianne Christina Harbo Mosgaard, Jeanette Elgaard, Simon Lykkeboe, Paw Jensen, Henrik Gregersen, Stine Linding Andersen, Aase Handberg, Stine Krogh Venø
{"title":"Analytical interference on measurement of immunoglobulins in monoclonal gammopathy.","authors":"Anders Oest, Maja Boe, Marianne Christina Harbo Mosgaard, Jeanette Elgaard, Simon Lykkeboe, Paw Jensen, Henrik Gregersen, Stine Linding Andersen, Aase Handberg, Stine Krogh Venø","doi":"10.1080/00365513.2024.2429081","DOIUrl":"10.1080/00365513.2024.2429081","url":null,"abstract":"<p><p>Monoclonal gammopathy has been reported to interfere with several laboratory measurement results. We investigated potential interference in monoclonal gammopathy on immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations using three different routine chemistry instruments: Alinity (Abbott Laboratories), Cobas 8000 (Roche Diagnostics) and Optilite (Binding Site) at the Department of Clinical Biochemistry, Aalborg University Hospital, Denmark. Blood samples collected from 216 patients with known monoclonal gammopathy were analyzed on Alinity, Cobas and Optilite. Diagnoses were ascertained from clinical records. Scatter plots with Passing-Bablok regression were used to investigate associations between concentrations of IgA, IgG and IgM measured with each of the different instruments. Furthermore, comparison of IgG analyses on Alinity, Optilite and Cobas according to monoclonal IgM concentration was explored with Bland-Altman plots. A total of 81 patients were identified with IgM type monoclonal gammopathy and 8 of these patients (10%) had analytical interference as reflected by more than 25% decrease in the level of IgG measured on Alinity as compared to Optilite and Cobas. All blood samples with interference on IgG measurement using Alinity were from patients with lymphoplasmacytic lymphoma/Waldenströms macroglobulinemia and all of them had monoclonal IgM concentrations above 10 g/L. This study identified a source of interference from IgM monoclonal gammopathy on IgG measurement performed using Alinity. The interferences caused falsely low results of IgG which is important to recognize to ensure proper patient management.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"502-509"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lotta Sunnersjö, Lukas Lindquist, Ulf Schött, Andreas Hillarp, Johan Undén, Thomas Kander
{"title":"Impact of direct oral anticoagulants on ROTEM® variables; a sample size-calculated experimental study.","authors":"Lotta Sunnersjö, Lukas Lindquist, Ulf Schött, Andreas Hillarp, Johan Undén, Thomas Kander","doi":"10.1080/00365513.2024.2439398","DOIUrl":"10.1080/00365513.2024.2439398","url":null,"abstract":"<p><p>Direct oral anticoagulants (DOAC) are increasingly common, with bleeding events associated with elevated plasma concentrations. Rotational thromboelastometry (ROTEM), a point-of-care tool for assessing secondary hemostasis, has demonstrated a correlation with increasing concentrations of DOAC. However, previous studies have only partially explored this relationship. The primary aim in the current study was to investigate the impact of increasing rivaroxaban concentrations on clotting time (CT) in the EXTEM assay. The secondary aims were to investigate the impact of increasing rivaroxaban concentrations on clot formation time (CFT) and α-angle (AA) and to investigate the impact of increasing concentrations of dabigatran and apixaban on CT, CFT and AA. Blood from 12 healthy volunteers was spiked to anticipated concentrations of rivaroxaban, dabigatran and apixaban at 0, 50, 100, 200, 500 and 1000 µg/L each. Blood with these varying concentrations was analyzed in four different ROTEM assays and CT, CFT and AA were extracted. CT increased linearly with increasing concentrations of all three DOACs. Rivaroxaban and dabigatran spiked blood showed an increase in CT-EXTEM for the 200-1000µg/L concentrations, compared to baseline, and apixaban for the 500-1000 µg/L concentrations. CFT and AA were affected only in supratherapeutic concentrations for all tested DOACs and primarily in the INTEM assay. Among the tested DOACs, apixaban demonstrated the least impact on CT across all assays. In conclusion, ROTEM-derived CT measurements can serve as surrogate markers for DOAC concentrations.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"540-546"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linda Østervig Henriksen, Tina Windfeld, Willemijn Jansje Comuth, Anna-Marie Bloch Münster
{"title":"Acid-base parameters in venous blood - agreement between values from safePICO syringes and lithium-heparin vacutainer tubes.","authors":"Linda Østervig Henriksen, Tina Windfeld, Willemijn Jansje Comuth, Anna-Marie Bloch Münster","doi":"10.1080/00365513.2024.2420317","DOIUrl":"10.1080/00365513.2024.2420317","url":null,"abstract":"<p><p>Venous blood is considered an acceptable alternative to arterial blood for assessment of metabolic acid-base disorders. Also, venous sampling using lithium-heparin (Li-Hep) tubes is advantageous to arterial sampling using PICO syringes, the risk of complications being lower. Usage of partly filled tubes without firm knowledge about the clinical consequences is, however, a pre-analytic consideration. The study evaluated primary acid-base parameters (pH, standardized hydrogen carbonate (HCO<sub>3</sub>), standardized base excess (SBE), lactate) and co-determined parameters in venous blood stored at room temperature up to 60 min in Li-Hep tubes vs. venous blood in PICO syringes analyzed immediately. Also, 50% filled tubes stored up to 30 min were compared to filled tubes analyzed immediately. Significant differences were generally observed. Stability was parameter and time dependent (filled tubes: 30 min: pH, (preferably 15 min for optimal stability), SBE, potassium and lactate, 60 min: HCO<sub>3</sub>, hemoglobin, methemoglobin (MetHb), carbon monoxide hemoglobin (COHb), sodium, chloride, glucose and creatinine; 50% filled tubes: 15 min: lactate, 30 min: HCO<sub>3</sub>, hemoglobin, MetHb, COHb, potassium, sodium, chloride, glucose and creatinine). In conclusion, storage in filled Li-Hep tubes for 30 min generates comparable results to blood in PICO syringes for all parameters, except pCO<sub>2</sub>, pO<sub>2</sub> and sO<sub>2</sub>. Storage in 50% filled Li-Hep tubes is not acceptable for pH, pCO<sub>2</sub>, pO<sub>2</sub>, sO<sub>2</sub> and SBE, and lactate is only stable for 15 min.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"459-469"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A bivariate reference interval for TSH and free thyroxine.","authors":"Arne Åsberg, Gustav Mikkelsen","doi":"10.1080/00365513.2024.2437613","DOIUrl":"10.1080/00365513.2024.2437613","url":null,"abstract":"<p><p>Frequently, the serum concentrations of TSH (s-TSH) and free thyroxine (s-FT4) are interpreted together when a physician considers the patient's thyroid status. Then, each measurement is compared with its univariate reference interval. However, a pair of s-TSH and s-FT4 may be more appropriately assessed if compared with a <i>bivariate</i> reference interval. We constructed a bivariate reference interval for s-TSH and s-FT4 from their measurements in 495 healthy blood donors. After Box-Cox transformation, we estimated the Mahalanobis distances from each pair of s-TSH and s-FT4 to the center of the bivariate distribution. The 95 percentile in the distribution of the Mahalanobis distances was defined as the limit of the bivariate reference interval. Univariate reference intervals comprising the central 95% (2.5-97.5 percentile) and 97.5% (1.25-98.75 percentile) of reference values were estimated from the same data. Normal thyroid function was defined as both s-TSH and s-FT4 within their respective univariate reference intervals, or as a Mahalanobis distance within the 95% bivariate reference interval. In 177,514 specimens from adult individuals in out-patient care, 76.6% were classified as bivariate normal. The corresponding figures for the 95% and 97.5% univariate reference intervals were 68.9% and 76.2%, respectively. The kappa statistics for classification agreement between the bivariate 95% reference interval and the 95% and 97.5% univariate reference intervals were 0.790 and 0.881, respectively. We thought the bivariate reference interval to be clinically most accurate but were unable to prove it.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"521-526"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sevil Oskay Halacli, Deniz Cagdas, Saliha Esenboga, Dilan Inan, Ismail Yaz, Begum Cicek, Hacer Neslihan Bildik, Ilhan Tezcan
{"title":"Comparative analysis of protein expression profiles with genotypes in the diagnosis of Inborn Errors of Immunity.","authors":"Sevil Oskay Halacli, Deniz Cagdas, Saliha Esenboga, Dilan Inan, Ismail Yaz, Begum Cicek, Hacer Neslihan Bildik, Ilhan Tezcan","doi":"10.1080/00365513.2024.2439401","DOIUrl":"10.1080/00365513.2024.2439401","url":null,"abstract":"<p><strong>Background: </strong>Inborn Errors of Immunity (IEIs) are genetic diseases resulting from harmful genetic variations that hinder the proper functioning of the immune system. The broad range of IEIs involves multiple systems, presenting characteristics similar to allergies, autoimmune or inflammatory diseases, and malignancies. Given this complexity, there is an urgent need for a precise multi-parametric molecular diagnostic approach.</p><p><strong>Objective: </strong>In this work, we demonstrated the effectiveness of accurate diagnosis by flow cytometry in patients with IEI by comparing genotype analysis with the expression levels of particular proteins and signaling activities.</p><p><strong>Methods: </strong>We examined the expression levels or signaling activities of 28 cell surface and intracellular proteins using flow cytometry in a cohort of 352 patients and 189 healthy controls, in conjunction with genotype analysis for comparison. Results: We identified alterations in protein expression in 60 individuals, among them, 55 exhibited the presence of an underlying pathogenic mutation. Complete loss of protein expression was observed in seven patients, constituting 2% of the total, while reduced protein expression was noted in 35 patients (9%). Notably, despite mutations in the relevant genes, protein expression levels were normal in five patients (2%), in all investigated patients. 37% of patients had elevated signaling activity, and 17% were suggestive of a particular IEI diagnosis following protein expression analysis.</p><p><strong>Conclusion: </strong>The correspondence between flow cytometry-based protein analyses and genotype facilitates a prompt diagnosis, providing patients with swift access to therapeutic options.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"547-556"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joris Godelaine, Toon Schiemsky, Ben Persy, Joris Penders
{"title":"Prevalence of monoclonal proteins in patients with isolated hypogammaglobulinemia on serum protein electrophoresis.","authors":"Joris Godelaine, Toon Schiemsky, Ben Persy, Joris Penders","doi":"10.1080/00365513.2024.2429090","DOIUrl":"10.1080/00365513.2024.2429090","url":null,"abstract":"<p><p>Isolated hypogammaglobulinemia (IH) is an electrophoretic pattern that can be encountered on serum protein electrophoresis (SPEP) and is defined as a decreased but morphologically normal γ-globulin fraction with normal α- and β-globulin fractions. SPEP is mainly used to detect monoclonal proteins which are usually observed as additional peaks in the electropherogram. However, they may also be more discretely present in a significant proportion of patients presenting with IH. Therefore, we aimed to evaluate i) via both retrospective and prospective analysis to what extent paraproteins as identified by immunofixation are present in patients demonstrating IH on SPEP and ii) whether other parameters may predict their presence in IH-patients. For this purpose, we first reviewed historic SPEP- and immunofixation results in our tertiary hospital and determined paraprotein prevalence in this retrospective cohort. This analysis showed immunofixation was requested in only 519/3938 (13.2%) historic IH-results with 52/519 (10%) patients demonstrating paraproteins. Next, various laboratory parameters were compared between paraprotein-positive and -negative patients and subjected to logistic regression models but regrettably, no parameter could be retained as promising predictor of paraproteins. Lastly, to confirm paraprotein prevalence seen in the historical query, we conducted a six-month prospective analysis during which immunofixation was requested more frequently in IH-cases during routine diagnostics and which showed paraproteins to be present in 20/83 (24.1%) of IH-patients. Hence, as up to 24% of patients with IH may harbour paraproteins, one should consider performing follow-up analyses (e.g. immunofixation, urine electrophoresis and/or free light chain analysis) for all IH-cases identified via SPEP.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"510-514"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}