Top-down and bottom-up approaches for the estimation of measurement uncertainty in coagulation assays.

Background: The assessment of measurement uncertainty (MU) in clinical laboratories is essential to the reliable interpretation of results in clinical laboratories. However, despite the introduction of various methods for the expression of uncertainty in measurement, the MUs of coagulation tests have not been extensively studied. The aim of this study was to quantify the MU of various coagulation assays according to international guidelines and to report an expected confidence in the quality of coagulation assays. Methods: We selected activated partial thromboplastin time, international normalized ratio (INR), protein C/S, antithrombin, fibrinogen, and Factor V/VIII/X to quantify the MUs of two coagulation testing systems: ACL TOP 750 CTS (Instrumentation Laboratory, Bedford, MA, USA) and STA Compact (Diagnostica Stago, Asnières-sur-Seine, France). We used international standards and interlaboratory comparison results in accordance with international guidelines in a top-down approach to the assessment of MU. For INR, MU was estimated in a bottom-up approach using reference thromboplastin and certified plasmas. Results: Top-down approaches resulted in MUs between 3.3% and 21.3% for each measurand. In the bottom-up approach, MUs of INR values ranged from 10.9% to 26.4% and showed an upward trend as INR increased. Conclusions: In this study, we were successful in quantifying MU of coagulation assays using practical methods. Our results demonstrated that top-down and bottom-up approaches were adequate for coagulation assays. However, some assays showed significant biases against international standards; therefore, standardization would be necessary to ensure more reliable patient results.

Post-bariatric surgery lab tests: are they excessive and redundant?

INTRODUCTION: Following bariatric surgery, ongoing postoperative testing is required to measure nutritional deficiencies; the purpose of this study was to quantify the prevalence of these nutritional deficiencies based on two-year follow-up tests at recommended time points. METHODS AND PROCEDURES: A retrospective data analysis was conducted of all laboratory tests for bariatric patients who underwent surgery between May 2016 and January 2018 with available lab data (n = 397). Results for nine different nutritional labs were categorized into six recommended postoperative time periods based on time elapsed since the procedure date. Binary variables were created for each laboratory result to calculate descriptive statistics of abnormalities for each lab test over time and used in the individual GEE logistic regression models. Grouped logistic regression examined the total nutritional deficiencies of the nine combined nutrients considering total available labs. RESULTS: Multiple lab tests indicated a very low frequency of abnormalities (e.g., Vitamin A, Vitamin B12, Copper, and Folate). Many of the nine included nutritional labs had an average deficiency of less than 10% across all time points. The grouped logistic model found preoperative nutritional deficiency to be predictive of postoperative nutritional deficiency (OR 3.70, p < 0.001). CONCLUSIONS: We found the vast majority of routine lab test results to be normal at multiple time points. Current practice can add up to significant lab expenses over time. The frequency of postoperative testing in this population may be redundant and of very little value. Unnecessary follow-up laboratory testing costs the patients and the health care system in both time and resources. Patients with preoperative deficiencies appear to be at higher risk for nutritional deficiencies when compared to bariatric surgery patients that did not have preoperative nutritional deficiencies. Future research should focus on defining cost effective postoperative lab testing guidelines for at risk bariatric patients.

Evaluation of platelet count and platelet function analyzer - 100 testing for prediction of platelet transfusion following coronary bypass surgery.

Platelet transfusions are commonly administered to treat bleeding in cardiac surgery. The aim of this study was to compare platelet (PLT) count and values of collagen adenosine diphosphate closure time (cADP-CT) measured by Platelet Function Analyzer (PFA) for prediction of PLT transfusion therapy following coronary bypass surgery. For this prospective observational study, 66 patients scheduled for coronary artery bypass grafting (CABG) who received early PLT transfusions (within 60 min after the operation) were enrolled. To assess changes in platelets, count and function, two time points were selected: 15 min before and 30 - 60 min after the end of PLT transfusion. The patients were divided into transfused and non-transfused with further PLT in the 48 h postoperatively. We used the receiver operating characteristics (ROC) curve to investigate whether the PLT count and cADP-CT values were predictors of PLT transfusion. The positive predictive values (PPV) of PLT count and cADP-CT after PLT transfusion for further PLT transfusion were 33% and 86% respectively, with a PLT count threshold of ≤200 × 109/L and cADP-CT threshold of ≥118 s. The comparison among the ROC curves showed a statistical difference (p = .0002). In multiple regression analysis, cADP-CT was the strongest predictor for the number of PLT transfusion doses in the 48 h postoperatively. In CABG patients, the results of cADP-CT after PLT transfusion have a better predictive capacity for further PLT transfusions than the PLT count.

[Representation of the results when testing for syphilis.] / Оформление результатов ÑÐºÑ€Ð¸Ð½Ð¸Ð½Ð³Ð¾Ð²Ñ‹Ñ Ð¸ Ð²ÐµÑ€Ð¸Ñ„Ð¸Ñ†Ð¸Ñ€ÑƒÑŽÑ‰Ð¸Ñ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ð¹ на сифилис.

In medical organizations special forms (approved by orders of the Ministry of health and the Central statistical office) are used to present the results of laboratory examination of the population for syphilis. Currently, these forms include laboratory technologies that do not meet modern standards. In 2018-2019 the normative documents, regulating the use of accounting forms of medical documentation in the public health system, and the practice of using forms with the results of laboratory examination for syphilis were studied in 35 branches of 3 medical organizations of the Lyubertsy district of the Moscow region and in 18 branches of Moscow city was conducted. It is established that in the medical organizations of Moscow and the Moscow region are used the different forms of the registration forms approved by orders of the Ministry of health of the USSR which have now become invalid. The structure of the forms with the results of the population survey for syphilis does not correspond to the applied modern technologies and standards of the survey. On the basis of requirements of modern regulatory documents two new forms of registration forms for the presentation of results of laboratory researches have been developed, within 1,5 years tested and offered for application: one form at screening of the population for syphilis and another - for performing verification examinations for diagnostics and the subsequent clinical and serological supervision.

Therapeutic monoclonal antibodies and clinical laboratory tests: When, why, and what is expected?

BACKGROUND: We herein provide an overview of the clinical laboratory tests that should be performed before, during and after using therapeutic monoclonal antibodies (mAbs) and the clinical laboratory tests that may be affected by mAbs. METHODS: The labels of FDA-approved therapeutic mAbs were downloaded from DailyMed (the official website for drug labels) and were used as the sources of data for this review. RESULTS: It was found that most of the labels provided information relevant to the clinical laboratory tests, including the tests needed before mAbs treatment to check the patients' background status and to identify potentially sensitive patients, the tests needed during or after the treatment to evaluate the patients' response, and the mAbs that may lead to false positive or negative results for clinical laboratory tests. CONCLUSIONS: The present findings will be of interest to physicians, laboratory scientists, those involved in drug development and surveillance and individuals making health care policy.

A note from history: Landmarks in history of cancer, part 7.

In the 2 and half decades reviewed (1970-1995), research established that chromosomal translocation, deletion, and DNA amplification are prerequisites to cancerogenesis and that oncogenes, tumor-suppressor genes, growth factors, and cytokines play crucial roles in the pathomechanism of cancer. Human papillomavirus, human immunodeficiency virus, herpes virus, and hepatitis B virus were identified as cancer-causing viruses. Several laboratory tests were developed for the detection of primary and recurrent cancers, and cancer prevention by screening methods was popularized. Sonography, computerized tomography, magnetic resonance imaging, positron emission tomography, excision of sentinel lymph nodes, and immunohistochemical techniques became routine procedures. Clinicopathologic staging and classification of tumors were standardized. Limited surgery, adjuvant and neoadjuvant chemoradiation, and the therapeutic use of monoclonal antibodies, tumor vaccines, and targeted chemotherapy became routine practice. The decline in cancer incidence and mortality demonstrated that cancer prevention and advancement in oncology are pivotal to success in the crusade against cancer. Above all, it was clearly established that the care of patients with cancer can be accomplished best in a multidisciplinary setting involving surgical oncologists, radiologists, radiation therapists, medical oncologists, surgical pathologists, and laboratory scientists. In conclusion, the 25 years from 1970 and 1995 are the high-water mark in clinical oncology, and this is the period when oncology turned from art to science.

Quantification of Ions in Human Urine-A Review for Clinical Laboratories.

Urine is an organic fluid produced by the kidney, and its analysis is one of the most requested laboratory tests by clinicians. The ionic composition of urine has been shown to be a good health indicator: it is useful for the diagnosis of several diseases, as well as monitoring therapeutics. This review considers laboratorial techniques that have been used throughout time for the quantification of ions in urine, and also considers some methodologies that can potentially be used in clinical laboratories for this kind of analysis. Those methods include gravimetry, titration, flame emission spectrophotometry (flame photometry), fluorimetry, potentiometry (ion selective electrodes), ion chromatography, electrophoresis, kinetic colorimetric tests, enzymatic colorimetric tests, flow cytometry, atomic absorption, plasma atomic emission spectrometry, and paper-based devices. Sodium, potassium, chloride, calcium, and magnesium are among the most important physiological ions, and their determination is frequently requested in hospitals. There have been many advances regarding the analysis of these ions in 24 h urine. However, there is still some way to go concerning the importance of intracellular ions in this type of sample as well as the use of occasional urine for monitoring these parameters.

Evaluation of Cardiovascular Disease Risk in Patients with Type 2 Diabetes Mellitus Using Clinical Laboratory Markers.

Background: Cardiovascular diseases (CVD) are the main cause of death in the population with diabetes mellitus. This study purposed to determine clinical laboratory markers that might be correlated with the risk of CVD in individuals with type 2 diabetes mellitus (T2DM). Methods: Using data from the Clinical Center of the University of Debrecen from 2016 to 2020, we assessed cardiovascular risk in 5593 individuals with T2DM over a five-year follow-up period. There were 347 new cases of acute myocardial infarction (AMI) and stroke during the period. Following the stratification of these individuals into two groups according to the diagnosis of these CVDs until 2020, the risk of these CVDs was assessed through the utilization of the Chi-square test and Cox proportional hazards regression. Results: The findings of the Cox proportional hazards regression model showed that the number of HbA1C measurements per year (HR = 0.46, 95% CI 0.31-0.7), decreased levels of estimated glomerular filtration rate (eGFR) (HR = 1.6, 95% CI 1.04-2.47), and elevated triglyceride levels (HR = 1.56, 95% CI 1.06-2.29) were correlated with CVD in patients with T2DM. The area under the curve (AUC) was increased from 0.557 (95% CI 0.531-0.582) to 0.628 (95% CI 0.584-0.671) after the inclusion of the laboratory variables into the model showing improved discrimination for AMI and stroke. Conclusions: These findings indicated that eGFR, triglyceride, and the number of HbA1C per year are correlated with AMI and stroke in patients with T2DM.

Concordance and generalization of an AI algorithm with real-world clinical data in the pre-omicron and omicron era.

All viruses, including SARS-CoV-2, the virus responsible for COVID-19, continue to evolve, which can lead to new variants. The objective of this study is to assess the agreement between real-world clinical data and an algorithm that utilizes laboratory markers and age to predict the progression of disease severity in COVID-19 patients during the pre-Omicron and Omicron variant periods. The study evaluated the performance of a deep learning (DL) algorithm in predicting disease severity scores for COVID-19 patients using data from the USA, Spain, and Turkey (Ankara City Hospital (ACH) data set). The algorithm was developed and validated using pre-Omicron era data and was tested on both pre-Omicron and Omicron-era data. The predictions were compared to the actual clinical outcomes using a multidisciplinary approach. The concordance index values for all datasets ranged from 0.71 to 0.81. In the ACH cohort, a negative predictive value (NPV) of 0.78 or higher was observed for severe patients in both the pre-Omicron and Omicron eras, which is consistent with the algorithm's performance in the development cohort.

Validity of Lognormal Distribution in Analyzing Laboratory Test Values.

We compared the distribution of laboratory test values with several parametric statistical distributions to show that a lognormal distribution can represent the distribution of laboratory test values. Then, we estimated the distributions of laboratory test values of four datasets including only three published values: two endpoints of reference interval (RI) and one median.

Ristocetin dependent cofactor activity in von Willebrand disease diagnosis: Limitations of relying on a single measure.

Background: Von Willebrand disease (VWD) is a common inherited bleeding disorder, however the diagnosis can be complicated by a subjective bleeding history and issues with some current von Willebrand factor (VWF) laboratory assays. Objectives: In the Zimmerman Program, we sought to determine how often a type 1 diagnosis was based on a single low VWF ristocetin cofactor (VWF:RCo) level resulting from the common genetic variant p.D1472H or an isolated assay issue, if that low value was corroborated by the VWF glycoprotein-IbM (VWF:GPIbM) assay, and if retesting confirmed original levels. Methods: New patients being evaluated for bleeding were consented. Analysis included VWF sequencing, bleeding scores, and comparisons of local VWF antigen (VWF:Ag) and VWF:RCo to central VWF:Ag and VWF:GPIbM. Results: A total of 18% of VWD subjects had a low local VWF:RCo, but normal VWF:Ag and normal central testing including VWF:GPIbM. Seventy percent of the low VWF:RCo cohort had no pathogenic VWF variants; however, 33% carried p.D1472H. Low VWF:RCo subjects with follow-up local testing within 2 years showed those with p.D1472H continued to have low VWF:RCo and VWF:RCo/VWF:Ag ratio with normal VWF:GPIbM. Subjects without p.D1472H had an increase mean VWF:RCo, resulting in 59% with normal levels on repeat testing. Conclusions: The diagnosis of VWD based on a single low VWF:RCo but normal VWF:Ag, was often attributed to p.D1472H or variability in VWF:RCo that was eliminated with VWF:GPIbM. Our study suggests that using VWF:RCo alone for diagnostic purposes may be insufficient while repeat VWF:RCo or VWF:GPIbM testing can be valuable in establishing a VWD diagnosis.

Exposing and Overcoming Limitations of Clinical Laboratory Tests in COVID-19 by Adding Immunological Parameters; A Retrospective Cohort Analysis and Pilot Study.

Background: Two years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited. Objectives: To measure the predictive performance of currently used clinical laboratory tests alone or combined with clinical variables and explore the predictive power of immunological tests adequate for clinical laboratories. Methods: Data from 2,600 COVID-19 patients of the first wave of the pandemic in the Barcelona area (exploratory cohort of 1,579, validation cohorts of 598 and 423 patients) including clinical parameters and laboratory tests were retrospectively collected. 28-day survival and maximal severity were the main outcomes considered in the multiparametric classical and machine learning statistical analysis. A pilot study was conducted in two subgroups (n=74 and n=41) measuring 17 cytokines and 27 lymphocyte phenotypes respectively. Findings: 1) Despite a strong association of clinical and laboratory variables with the outcomes in classical pairwise analysis, the contribution of laboratory tests to the combined prediction power was limited by redundancy. Laboratory variables reflected only two types of processes: inflammation and organ damage but none reflected the immune response, one major determinant of prognosis. 2) Eight of the thirty variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the combined statistical predictive power. 3) The interpretation of clinical and laboratory variables was moderately improved by grouping them in two categories i.e., inflammation related biomarkers and organ damage related biomarkers; Age and organ damage-related biomarker tests were the best predictors of survival, and inflammatory-related ones were the best predictors of severity. 4) The pilot study identified immunological tests (CXCL10, IL-6, IL-1RA and CCL2), that performed better than most currently used laboratory tests. Conclusions: Laboratory tests for clinical management of COVID 19 patients are valuable but limited predictors due to redundancy; this limitation could be overcome by adding immunological tests with independent predictive power. Understanding the limitations of tests in use would improve their interpretation and simplify clinical management but a systematic search for better immunological biomarkers is urgent and feasible.

Recommendations for the measurement of thrombin generation: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

Thrombin generation (TG) assay is an overall assay to assess the functionality of the hemostatic system and may be a useful tool in diagnosing patients with hyper- and hypocoagulability. Lack of standardization in performing the assays contributes largely to poor correlation between assays and study results. The current lack of standardization remains a major issue in the setting of TG, as illustrated in a recent survey of the ISTH/SSC indicating differences in pre-, analytical, and post-analytical factors among users. These factors may considerably affect the between-laboratory reproducibility of results. Based on the results of the survey and a current review of the literature, along with insights and strong consensus of key investigators in the field, we present guidance for measurement of TG in a clinical setting. Recommendations on blood drawing, handling, processing, and sample storage; reagent concentration and source; analytical conditions on dilution of samples and temperature; calibration and replicate testing; calculation and interpretation of results; and reference values are addressed to help in reducing interlaboratory variation. These recommendations aim at harmonization between methods and laboratories to support the application of TG in patient diagnosis and management.

Isaric 4c Mortality Score As A Predictor Of In-Hospital Mortality In Covid-19 Patients Admitted In Ayub Teaching Hospital During First Wave Of The Pandemic.

BACKGROUND: Many factors have been identified which can predict severe outcomes and mortality in hospitalized patients of COVID-19. This study was conducted with the objective of finding out the association of various clinical and laboratory parameters as used by International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO)- ISARIC/WHO 4C Mortality score in predicting high risk patients of COVID-19. Ascertaining the parameters would help in triage of patients of severe disease at the outset, and shall prove beneficial in improving the standard of care. METHODS: This cross-sectional study was carried out in COVID-19 Department of Ayub Teaching Hospital, Abbottabad. All COVID-19 patients admitted from 15th April to 15th July 2020 were included. RESULTS: A total of 347 patients were included in the study. The mean age was 56.46±15.44 years. Male patients were 225 (65%) and female 122 (35%). Diabetes (36%) was the most common co-morbidity, followed by hypertension (30.8%). Two hundred & six (63.8%) patients recovered and 117 (36.2%) patients died. Shortness of breath (80%), fever (79%) and cough (65%) were the most common presenting symptoms. Patients admitted with a 4C Mortality score of 0-3 (Low Risk Category), the patients who recovered were 36 (90%) and those who died were 4 (10.0%). In patients admitted with a 4C Mortality score of more than 14 (Very High-Risk Category), the number of patients who recovered was 1 (20%), and those who died were 4 (80%). The difference in mortality among the categories was statistically significant (p<0.001). Hypertension was a risk factor for death in patients of COVID-19 (Odds ratio=1.24, 95% CI [0.76-2.01]). Lymphopenia was not associated with statistically significant increased risk for mortality. CONCLUSIONS: The ISARIC 4C mortality score can be used for stratifying and predicting mortality in COVID-19 patients on arrival in hospital. We propose that it should be used in every patient of COVID-19 presenting to the hospital. Those falling in Low and Intermediate Risk Category should be managed in ward level. Those falling in High and Very High Category should be admitted in HDU/ICU with aggressive treatment from the start.

Hospitalization budget impact during the COVID-19 pandemic in Spain.

OBJECTIVES: The aim was to determine the direct impact of the COVID-19 pandemic on Spain's health budget. METHODS: Budget impact analyses based on retrospective data from patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) admitted to a Spanish hospital between February 26 and May 21, 2020. Direct medical costs from the perspective of the hospital were calculated. We analyzed diagnostic tests, drugs, medical and nursing care, and isolation ward and ICU stays for three cohorts: patients seen in the emergency room only, hospitalized patients who tested positive for SARS-CoV-2, and patients who tested negative. RESULTS: The impact on the hospital's budget for the 3 months was calculated at €15,633,180, 97.4% of which was related to health care and hospitalization. ICU stays accounted for 5.3% of the total costs. The mean cost per patient was €10,744. The main costs were staffing costs (10,131 to 11,357 €/patient for physicians and 10,274 to 11,215 €/patient for nurses). Scenario analysis showed that the range of hospital expenditure was between €14,693,256 and €16,524,924. The median impact of the pandemic on the Spanish health budget in the sensitivity analysis using bootstrapped individual data was €9357 million (interquartile range [IQR], 9071 to 9689) for the conservative scenario (113,588 hospital admissions and 11,664 ICU admissions) and €10,385 million (IQR, 110,030 to 10,758) for the worst-case scenario (including suspected cases). CONCLUSION: The impact of COVID-19 on the Spanish public health budget (12.3% of total public health expenditure) is greater than multiple sclerosis, cancer and diabetes cost.

Dataset of clinical laboratory tests according to ordering variance among family physicians in Calgary, Alberta, Canada.

This data incorporates 2016 testing volumes ordered by family physicians and performed at Calgary Laboratory Services (CLS), the sole supplier of clinical laboratory services for the catchment area of the City of Calgary, Alberta, Canada. For each test, the mean number of tests ordered per patient was calculated over ordering Calgary physicians, along with arithmetic coefficients of variation (CV's). The latter parameter is reflective of variance in ordering practice among family physicians practicing in Calgary and is proposed as a benchmark measure for laboratory utilization in our accompanying research article [1]. The data table encompasses 358 tests ordered by at least 3 family physicians at a minimum total frequency of 100 within the 2016 study period and is presented in ascending order of rank in CV.

A New Insight Into Missing Data in Intensive Care Unit Patient Profiles: Observational Study.

BACKGROUND: The data missing from patient profiles in intensive care units (ICUs) are substantial and unavoidable. However, this incompleteness is not always random or because of imperfections in the data collection process. OBJECTIVE: This study aimed to investigate the potential hidden information in data missing from electronic health records (EHRs) in an ICU and examine whether the presence or missingness of a variable itself can convey information about the patient health status. METHODS: Daily retrieval of laboratory test (LT) measurements from the Medical Information Mart for Intensive Care III database was set as our reference for defining complete patient profiles. Missingness indicators were introduced as a way of representing presence or absence of the LTs in a patient profile. Thereafter, various feature selection methods (filter and embedded feature selection methods) were used to examine the predictive power of missingness indicators. Finally, a set of well-known prediction models (logistic regression [LR], decision tree, and random forest) were used to evaluate whether the absence status itself of a variable recording can provide predictive power. We also examined the utility of missingness indicators in improving predictive performance when used with observed laboratory measurements as model input. The outcome of interest was in-hospital mortality and mortality at 30 days after ICU discharge. RESULTS: Regardless of mortality type or ICU day, more than 40% of the predictors selected by feature selection methods were missingness indicators. Notably, employing missingness indicators as the only predictors achieved reasonable mortality prediction on all days and for all mortality types (for instance, in 30-day mortality prediction with LR, we achieved area under the curve of the receiver operating characteristic [AUROC] of 0.6836±0.012). Including indicators with observed measurements in the prediction models also improved the AUROC; the maximum improvement was 0.0426. Indicators also improved the AUROC for Simplified Acute Physiology Score II model-a well-known ICU severity of illness score-confirming the additive information of the indicators (AUROC of 0.8045±0.0109 for 30-day mortality prediction for LR). CONCLUSIONS: Our study demonstrated that the presence or absence of LT measurements is informative and can be considered a potential predictor of in-hospital and 30-day mortality. The comparative analysis of prediction models also showed statistically significant prediction improvement when indicators were included. Moreover, missing data might reflect the opinions of examining clinicians. Therefore, the absence of measurements can be informative in ICUs and has predictive power beyond the measured data themselves. This initial case study shows promise for more in-depth analysis of missing data and its informativeness in ICUs. Future studies are needed to generalize these results.

Thrombin generation measurement using the ST Genesia Thrombin Generation System in a cohort of healthy adults: Normal values and variability.

BACKGROUND: Thrombin generation (TG) assays evaluate the balance between pro- and anticoagulant forces, to better assess bleeding and thrombotic risks. Although TG readouts obtained with the calibrated automated TG have been investigated in multiple clinical conditions, TG still needs standardization and clinical validation. The automated TG instrument ST Genesia® (STG, Stago, Asnières-sur-Seine, France) provides a normalization of TG parameters based on a reference plasma aiming to reduce the interlaboratory variability and the variability between different measurement runs. OBJECTIVES: To evaluate STG in a group of healthy adults. METHODS: Reference intervals in healthy adults and variability of the new standardized reagents for bleeding (BleedScreen) and thrombophilic (ThromboScreen) conditions were determined using STG. RESULTS: TG was measured in platelet-free plasma (PFP) samples of 123 healthy adults. Reference intervals were determined for TG parameters. Intra- and interassay coefficients of variation were calculated on quality controls and PFP samples from healthy adults. Oral contraception (OC) possibly influenced TG parameters, resulting in a higher median and a broader reference interval for peak height and endogenous thrombin potential (ETP) in women aged 20 to 49 years than in all other sex and age categories. Therefore, we propose the following reference interval categories: men, women aged <50 years not using OC, women aged <50 years using OC, and women aged ≥50 years. Normalization was effective to reduce the interassay variability of quality controls for ETP (BleedScreen assay), and peak height and ETP (ThromboScreen assay without thrombomodulin), but had little impact on PFP sample variability. CONCLUSION: STG appears suitable for accurate measurement of TG in healthy adults.

Current Flow Cytometric Assays for the Screening and Diagnosis of Primary HLH.

Advances in flow cytometry have led to greatly improved primary immunodeficiency (PID) diagnostics. This is due to the fact that patient blood cells in suspension do not require further processing for analysis by flow cytometry, and many PIDs lead to alterations in leukocyte numbers, phenotype, and function. A large portion of current PID assays can be classified as "phenotyping" assays, where absolute numbers, frequencies, and markers are investigated using specific antibodies. Inherent drawbacks of antibody technology are the main limitation to this type of testing. On the other hand, "functional" assays measure cellular responses to certain stimuli. While these latter assays are powerful tools that can be used to detect defects in entire pathways and distinguish variants of significance, it requires samples with robust viability and also skilled processing. In this review, we concentrate on hemophagocytic lymphohistiocytosis (HLH), describing the principles and accuracies of flow cytometric assays that have been proven to assist in the screening diagnosis of primary HLH.