Comparison of Thrombophilia Assay Results for the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Plasma Standard from Different External Quality Assessment Providers-for the External Quality Assurance in Thrombosis and Haemostasis Group.

External quality assessment (EQA) is used to evaluate laboratory performance in tests of hemostasis; however, some esoteric tests are performed by too few centers in any one EQA program to allow valid statistical assessment. To explore the feasibility of pooling data from several EQA providers, an exercise was carried out by the External Quality Assurance in Thrombosis and Haemostasis group, using the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee (SSC) plasma standard for thrombophilia screening assays. Six EQA providers took part in this exercise, distributing the SSC plasma standard as a "blinded" sample to participants for thrombophilia tests between November 2020 and December 2021. Data were collected by each provider, anonymized, and pooled for analysis. Results were analyzed as overall results from each EQA provider, and by kit/method-specific comparisons of data from all providers pooled together. For each parameter, median results and range were determined. Over 1,250 sets of data were returned in the six EQA programs. The overall medians (all data pooled) were <4% of the assigned values for each parameter with the exception of protein C activity by clot-based assay. Method-related differences in median results were observed for free protein S antigen and protein S activity-a pattern seen across data from the different EQA providers. Antithrombin antigen results reported in mg/dL provided an example where small numbers of results for a single EQA provider may be supplemented by pooling data from multiple providers with good agreement seen among results reported by the different EQA providers. This study demonstrated that a multicenter EQA provider collaboration can be carried out and demonstrated benefit for assays with smaller number of participants. In addition, results showed good agreement with the assigned values of the SSC plasma standard. Further exercises for tests performed by only small numbers of laboratories can be planned.

Lack of grading agreement among international hemostasis external quality assessment programs.

: Laboratory quality programs rely on internal quality control and external quality assessment (EQA). EQA programs provide unknown specimens for the laboratory to test. The laboratory's result is compared with other (peer) laboratories performing the same test. EQA programs assign target values using a variety of methods statistical tools and performance assessment of 'pass' or 'fail' is made. EQA provider members of the international organization, external quality assurance in thrombosis and hemostasis, took part in a study to compare outcome of performance analysis using the same data set of laboratory results. Eleven EQA organizations using eight different analytical approaches participated. Data for a normal and prolonged activated partial thromboplastin time (aPTT) and a normal and reduced factor VIII (FVIII) from 218 laboratories were sent to the EQA providers who analyzed the data set using their method of evaluation for aPTT and FVIII, determining the performance for each laboratory record in the data set. Providers also summarized their statistical approach to assignment of target values and laboratory performance. Each laboratory record in the data set was graded pass/fail by all EQA providers for each of the four analytes. There was a lack of agreement of pass/fail grading among EQA programs. Discordance in the grading was 17.9 and 11% of normal and prolonged aPTT results, respectively, and 20.2 and 17.4% of normal and reduced FVIII results, respectively. All EQA programs in this study employed statistical methods compliant with the International Standardization Organization (ISO), ISO 13528, yet the evaluation of laboratory results for all four analytes showed remarkable grading discordance.

Cystatin C-Creatinine Based Glomerular Filtration Rate Equation in Obese Chronic Kidney Disease Patients: Impact of Deindexation and Gender.

BACKGROUND: Cystatin C is considered an alternative to creatinine to estimate glomerular filtration rate (GFR). However, studies have reported that increased adiposity is associated with a higher level of circulating cystatin C questioning the performance of estimation of GFR using cystatin C in obese subjects. METHODS: We prospectively included 166 obese stages 1-5 chronic kidney disease (CKD) patients between 2013 and 2015. GFR was measured with a reference method without (measured GFR [mGFR]) and with adjustment to body surface area (mGFRr) and estimated (eGFR) or de-indexed eGFR using the Chronic Kidney Disease and Epidemiology (CKD-EPI) equation using creatinine (CKD-EPIcreat), cystatin (CKD-EPIcyst) and the combination of cystatin and creatinine (CKD-EPIcyst-creat). RESULTS: The biases between mGFR and de-indexed CKD-EPIcyst-creat were significantly lower than de-indexed CKD-EPIcreat (p = 0.001). Accuracies were significantly better with de-indexed CKD-EPIcyst-creat compared to CKD-EPIcreat and CKD-EPIcyst, respectively (p = 0.04 and 0.03). Bland and Altman plot showed a great dispersion of all formulae when patients had a GFR >60 ml/min. Interestingly, there is a gender difference; biases, precisions and accuracies of de-indexed CKD-EPIcyst-creat were significantly lower in obese women. These results may be related to a difference in the change of body composition during obesity in men versus women and in fact only waist circumference (WC) was positively and significantly correlated with cystatin C (p < 0.0001) whereas body mass index (BMI; p = 0.3) was not; bias for CKD-EPIcyst-creat was related with WC. CONCLUSION: Cystatin C-creatinine-based GFR equations outperform creatinine-based formula in obese CKD patients especially those with BMI ≥35 and in obese women.

Uncertainty in measurement for 43 biochemistry, immunoassay, and hemostasis routine analytes evaluated by a method using only external quality assessment data.

BACKGROUND: International organizations require from medical laboratories a quantitative statement of the uncertainty in measurement (UM) to help interpret patient results. The French accreditation body (COFRAC) recommends an approach (SH GTA 14 IQC/EQA method) using both internal quality control (IQC) and external quality assessment (EQA) data. The aim of this work was to validate an alternative way to quantify UM using only EQA results without any need for IQC data. This simple and practical method, which has already been described as the long-term evaluation of the UM (LTUM), is based on linear regression between data obtained by participants in EQA schemes and target values. We used it for 43 routine analytes covering biochemistry, immunoassay, and hemostasis fields. METHODS: Data from 50 laboratories participating in ProBioQual (PBQ) EQA schemes over 25 months were used to obtain estimates of the median and 90th percentile LTUM and to compare them to the usual analytical goals. Then, the two UM estimation methods were compared using data from 20 laboratories participating in both IQC and EQA schemes. RESULTS: Median LTUMs ranged from 2.9% (sodium) to 16.3% (bicarbonates) for biochemistry analytes, from 12.6% (prothrombin time) to 18.4% (factor V) for hemostasis analytes when using the mean of all participants, and were around 10% for immunoassays when using the peer-group mean. Median LTUMs were, in most cases, slightly lower than those obtained with the SH GTA 14 method, whatever the concentration level. CONCLUSIONS: LTUM is a simple and convenient method that gives UM estimates that are reliable and comparable to those of recommended methods. Therefore, proficiency testing (PT) organizers are allowed to provide participants with an additional UM estimate using only EQA data and which could be updated at the end of each survey.

Creatinine- versus cystatine C-based equations in assessing the renal function of candidates for liver transplantation with cirrhosis.

UNLABELLED: Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFR-predicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI-CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4- and 6-variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR-predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score ≤ or >15 and KDOQI stages, respectively). In the whole population, CystC-based equations showed a better performance than Pcr-based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR <60 mL/min/1.73 m(2)). CONCLUSION: Pcr-based GFR predicting equations are not reliable in pre-OLT patients even when an IDMS-traceable enzymatic Pcr assay is used. Whenever a CystC-assay traceable to primary reference materials is performed and when a true measurement of GFR is not possible, CystC-based equations, especially CKD-EPI-CystC, may be recommended to evaluate renal function and for KDOQI staging.

Clinical performance of the carbohydrate-deficient transferrin (CDT) assay by the Sebia Capillarys2 system in case of cirrhosis. Interest of the Bio-Rad %CDT by HPLC test and Siemens N-Latex CDT kit as putative confirmatory methods.

BACKGROUND: The CDT assay used to detect chronic alcohol abuse is difficult with cirrhotic patients. This article describes the performances of several CDT assays in case of cirrhosis. The CDT-Capillarys assay by capillary zone electrophoresis was used for initial testing. Two additional methods were tested as putative confirmatory methods. METHODS: 110 patients with known hepatic status had their CDT measured by the Capillarys2 or alternative methods. Self-reported alcohol intake was used to assess the performances of CDT assays. RESULTS: Capillarys2 performance was lower in case of cirrhosis, many electropherograms displaying various abnormalities. We used the proper separation of the di- and tri-sialotransferrin peaks to select reliable profiles. This selection led to the classification of cirrhotic and non-cirrhotic patients in abusers and abstainers with similar performances. However, no interpretation was available for 54% of the cirrhotic patients and neither the BioRad %CDT by HPLC test, nor the Siemens N-Latex CDT kit was suitable as confirmatory methods for these samples. CONCLUSIONS: An attentive profile examination is required for the validation of Capillarys CDT results of cirrhotic patients. Reliability is significantly improved when samples with an improper separation are excluded. To date, no commercial test can confirm the excluded samples.