Complementarity between Bayesian Internal Quality Control results management and External Quality Assessment bivariate z-score analysis: application to a concrete case study.

It is important that a clinical laboratory has implemented appropriate procedures for quality control, which includes both internal quality control (IQC) and external quality assessment (EQA) with the common goal to detect systematic errors and random errors. It is the case for both the Hemohub® Bayesian tools for IQC results interpretation and the ECAT EQA optimised bivariate z-scores analysis. On a concrete case study, we demonstrate both the higher sensitivity and specificity of optimised bivariate z-scores analysis than the univariate approach.

Assessment of accuracy of laboratory testing results, relative to peer group consensus values in external quality control, by bivariate z-score analysis: the example of D-Dimer.

Objectives: The aim of this study is to develop a practical method for bivariate z-score analysis which can be applied to the survey of an external quality assessment programme.

Methods: To develop the bivariate z-score analysis, the results of four surveys of the international D-Dimer external quality assessment programme of 2022 of the ECAT Foundation were used. The proposed methodology starts by identifying the bivariate outliers, using a Supervised Sequential Hotelling T control chart.

[Long-term automated Bayesian management of IQC results: The experience of the Lyon Hospitals Board hemostasis laboratory].

The Lyon Hospitals Board (HCL) hemostasis laboratory has shifted from a frequentist to a long-term Bayesian approach to IQC results management, using the Hemohub® software of the Werfen corporation, which hosts the requisite Bayesian tools. IQC plans based on supplier specifications proved effective in managing analytic risk in line with the ISO 15189 standard. Long-term Hemohub® control and monitoring has been validated by acceptable feedback from the EQA organization used by the hemostasis community.

Cost-effectiveness of thrombotic thrombocytopenic purpura diagnosis: a retrospective analysis in the University Hospital Center of Lyon (France).

The aim of the present study was to perform an economic evaluation of two alternative assays of ADAMTS13 activity (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats, member 13) for diagnosing thrombotic thrombocytopenic purpura (TTP) in the Hospital of Lyon (France). The study approach was more economic than clinical. We retrospectively calculated the prescription costs of ADAMST13 activity from January to December 2019 for patients depending on the assay: manual ELISA (Technozym) or automated assay (AcuStar Werfen, Instrumentation Laboratory).

Prospective evaluation of two specific IgG immunoassays (HemosIL AcuStar HIT-IgG and HAT45G ) for the diagnosis of heparin-induced thrombocytopenia: A Bayesian approach.

Introduction: The accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential to ensure adequate treatment and prevent complications. First step diagnosis test are immunoassays including enzyme-linked immunosorbent assays (ELISAs) and rapid immunoassays.

Methods: Using a Bayesian approach, we prospectively evaluated the performance of the IgG PF4/polyvinylsulfonate ELISA and a chemiluminescent immunoassay (CLIA), which are specific for IgG and use the same antigenic target to detect HIT antibodies.

[Theoretic and practical contribution of bayesian inference to statistical process control: The experience of the Lyon Hospitals Board hemostasis laboratory].

Laboratories need to set up effective overall management of their internal quality control (IQC) and external quality assessment (EQA) results as key elements in statistical process control. Quality targets need to be defined, with methods to ensure durable control with respect to the relevant specifications. The hemostasis laboratory of the Lyon Hospitals Board (HCL, Lyon, France) uses model 3 from the Milan consensus conference, which is the state of the art in terms of quality targets, and uses a common EQA provider supplying as many real patient samples as possible.

Factor VIII and IX assays for post-infusion monitoring in hemophilia patients: Guidelines from the French BIMHO group (GFHT).

Replacement therapy with plasma-derived or recombinant FVIII and FIX (pdFVIII/pdFIX or rFVIII/rFIX) concentrates is the standard of treatment in patients with haemophilia A and B, respectively. Measurement of factor VIII (FVIII:C) or factor IX (FIX:C) levels can be done by one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). The French study group on the Biology of Hemorrhagic Diseases (a collaborative group of the GFHT and MHEMO network) presents a literature review and proposals for the monitoring of FVIII:C and FIX:C levels in treated haemophilia A and B patients, respectively.

Effects of hemolysis, bilirubin, and lipemia interference on coagulation tests detected by two analytical systems.

Introduction: Interference on biological assays due to hemolysis, icterus, or lipemia (HIL) could represent a significant source of analytical errors leading to inaccurate interpretation of results. The aim of this study was to assess the HIL interference on prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen, using mechanical and optical detection methods.

Methods: Control plasmas and plasmas from patients treated with vitamin K antagonists or unfractionated heparin, with or without HIL, were performed on two analytical detection systems in order to identify potential analytical biases.

[Factor VIII assays in treated hemophilia A patients].

Replacement therapy with plasma-derived or recombinant FVIII (pdFVIII or rFVIII) concentrates is the standard of treatment in patients with hemophilia A. The reference method used for measuring factor VIII (FVIII:C) levels in patients treated by FVIII concentrates is the chromogenic substrate assay (CSA). However, the one-stage clotting assay (OSA) is predominantly used in current clinical practice, but this method depends on the activated partial thromboplastin time (APTT) reagent and the coagulation analyzer used, and wide variations in the measurements of FVIII recovery have been reported with some factor concentrates.

[Factor IX assays in treated hemophilia B patients].

Replacement therapy with plasma-derived or recombinant FIX (pdFIX or rFIX) concentrates is the standard of treatment in patients with hemophilia B. The method predominantly used for measuring factor IX (FIX:C) levels is the one-stage clotting assay (OSA) but this method depends on the activated partial thromboplastin time (APTT) reagent and the coagulation analyzer used, and wide variations in the measurements of FIX recovery have been reported with some factor concentrates. The French study group on the biology of hemorrhagic diseases (a collaborative group of the GFHT and MHEMO network), presents a review of the literature and proposals for the monitoring of FIX:C levels in treated hemophilia B patients.

Pre-analytical effects of pneumatic tube system transport on routine haematology and coagulation tests, global coagulation assays and platelet function assays.

Introduction: Pneumatic tube system (PTS) in hospitals is commonly used for the transport of blood samples to clinical laboratories, as it is rapid and cost-effective. The aim was to compare the effects on haematology samples of a newly acquired ~2km-long PTS that links 2 hospitals with usual transport (non-pneumatic tube system, NPTS).

Methods: Complete blood cell count, routine coagulation assays, platelet function tests (PFT) with light-transmission aggregometry and global coagulation assays including ROTEM® and thrombin generation assay (TGA) were performed on blood samples from 30 healthy volunteers and 9 healthy volunteers who agreed to take aspirin prior to blood sampling.

Use of prior manufacturer specifications with Bayesian logic eludes preliminary phase issues in quality control: an example in a hemostasis laboratory.

The present study seeks to demonstrate the feasibility of avoiding the preliminary phase, which is mandatory in all conventional approaches for internal quality control (IQC) management. Apart from savings on the resources consumed by the preliminary phase, the alternative approach described here is able to detect any analytic problems during the startup and provide a foundation for subsequent conventional assessment. A new dynamically updated predictive control chart (PCC) is used.

A comparison of the 12s rule and Bayesian approach for quality control: application to one-stage clotting factor VIII assay.

An ideal medical biology internal quality control (IQC) plan should both monitor the laboratory methods efficiently and implement the relevant clinical-biological specifications. However, many laboratories continue to use the 12s quality control rule without considering the high risk of false rejection and without considering the relationship of analytical performance to quality requirements. Alternatively, one can move to the Bayesian arena, enabling probabilistic quantification of the information coming in, on a daily basis from the laboratory's IQC tests, and taking into account the laboratory's medical and economic contexts.

Analytic variability due to change of deficient plasma vials: application to one-stage clotting factor VIII assay.

The statistical process control required under International Organization for Standardization 15189 as well as economic considerations necessitates having robust methods that do not need systematic recalibration for each series of analyses. Using the concrete example of one-stage clotting factor VIII assay, we assessed the analytic variability specifically linked to changing factor VIII deficient plasma vials. The study used freeze-dried (Instrumentation Laboratory, Siemens, Stago and T-Coag) and frozen (Affinity Biologicals and Precision Biologic) factor VIII deficient plasmas.

Impact of quality control matrix effect: application to the calculation of uncertainty of measurement in one-stage clotting factor VIII assay.

In Europe, the ISO 15 189 standard requires uncertainty of measurement to be calculated for all measurands. We calculated the analytical imprecision and bias of our factor VIII coagulometric assay method between 5 and 80 U/dl, using plasmas expected to be at 5, 30 and 80 U/dl of factor VIII. We implemented Meijer et al.

Bayesian logic in statistical test control: application to coagulation factor VIII assay.

Coagulation factor VIII was assayed around the critical concentration of 80 U/dl, which is optimal for postoperative haemostasis in haemophiliac patients, in order to assess the use of Bayesian logic in interpreting internal quality control results during a change of reagent or control batch. A mathematical model based on Bayesian inference, requiring no preliminary control-plan phase, was compared with a classical approach, which necessarily involves performing a preliminary phase. Tsiamyrtzis and Hawkins' Bayesian model proved applicable to rapid statistical control of factor VIII assay, detecting shift at least as efficiently as classical approaches, which depend on running the kind of costly and controversial preliminary control phase recommended by Shewhart.

Determining the adequate number of internal quality control levels: the example of coagulation factor VIII assay.

Taking the specific case of coagulation factor VIII assay, we determined the characteristics of an internal quality control panel assuring control of the assay method for all of the critical factor VIII concentrations. The precision of the assay method was determined on six control materials C1-C6, with expected factor VIII levels of 1, 5, 30, 50, 80 and 150 U/dl, respectively. Given that, when two control levels correlate statistically, the information provided by one of them is redundant, we used correlation and principal components analysis to define a priori adequate and inadequate control panels.

Activated partial thromboplastin time waveform analysis: a new tool to detect infection?

Objective: An abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time (aPTT) has been described to identify a high-risk intensive care unit population consisting of patients with sepsis or with higher mortality rates than patients with normal aPTT waveforms. We investigated the abnormal aPTT biphasic waveform as a diagnostic and prognostic marker of infection.

Design: Prospective, observational study investigating the predictive value of aPTT waveform analysis for the diagnosis and prognosis of sepsis.

In vitro tests for assessing heparin-induced thrombocytopenia in patients after elective hip replacement. A medico-economical evaluation.

Objectives: Considering the previously published incidences of heparin-induced thrombocytopenia (HIT) in patients receiving a thromboprophylactic therapy, the role of the hemostasis laboratory is essential in making a clinical decision. The purpose of this project was to compare the strategies of diagnosis and associated care of patients with suspected HIT after elective hip replacement using platelet aggregation assay, carbon 14-serotonin release, and "doing nothing."

Methods: The authors used an incremental cost-effectiveness analysis based on data extracted from the literature.