Piet Meijer

External quality assessment of point-of-care International Normalized Ratio (INR) testing in Europe

Abstract Background: Point-of-care testing (POCT) of prothrombin time, expressed as International Normalized Ratio (INR), is widely used to monitor patients in oral anticoagulation treatment. Guidelines recommend that POCT users should participate in an external quality assessment (EQA) scheme whenever available. The aim of this study was to investigate which European countries provide EQA for POCT INR and to compare how these schemes are organized. Methods: Thirty European countries were invited to participate in this study. Those who reported that they provide EQA for POCT INR filled in a questionnaire dealing with different aspects of their schemes. Results: Nineteen countries reported that they do not provide EQA for POCT INR, while 12 organizations from nine countries reported that they provide this service. Most of these countries circulate lyophilized samples with for the participants unknown target values. Samples with certified INR values and procedures using split samples with fresh patient samples are also used. The acceptability limits vary from 15% to 30%, and the total number of samples circulated per year varies from 1 to 12. Most of the countries organize educational activities together with their schemes. Conclusions: This study demonstrates that there is a wide variation in the way EQA for POCT INR is performed in Europe and that there are many European countries that do not provide this service. Even though our findings indicate that EQA for POCT INR draws some challenges, especially in providing suitable control materials, participation in such schemes is considered useful.

Interpretation and management of INR results: A case history based survey in 13 countries

INTRODUCTIONnStandardisation of treatment with vitamin K antagonists (VKAs) is still an issue after 60 years of use. The study aimed to explore aspects of VKA monitoring in primary and secondary care.nnnMETHODSnTwo case histories were distributed to physicians in 13 countries. Case history A focused on a patient with atrial fibrillation on stable anticoagulation (latest INR 2.3). Physicians were asked about frequency of INR measurement, when to change the VKA dose, and the patients annual risk of ischemic stroke and bleeding. Case history B focused on a patient with an unexpected INR of 4.8, asking for the patients 48-hour bleeding risk, the immediate dose reduction and time until a repeat INR.nnnRESULTSnAltogether, 3016 physicians responded (response rate 8 - 38%), of which 82% were from primary care and 18% from secondary care. Answers varied substantially within and between countries regardless of level of care and VKA used. Median number of weeks between INR measurements was 4 - 6 weeks. Median threshold INR for increasing or decreasing the VKA dose was 1.9 and 3.1, respectively. Risk of ischemic stroke and bleeding were overestimated 2 - 3 times. In case history B, the median dose reduction the two first days was 75% for GPs and 55% for specialists, irrespective of estimates of bleeding risk; with one week to a repeat INR.nnnCONCLUSIONnVariation in VKA monitoring is substantial implying clinical consequences. Guidelines seem either unknown or may be considered impracticable. Further efforts towards standardisation of VKA management are needed.

Is D-dimer used according to clinical algorithms in the diagnostic work-up of patients with suspicion of venous thromboembolism? A study in six European countries

INTRODUCTIONnClinical algorithms consisting of pre-test probability estimation and D-dimer testing are recommended in diagnostic work-up for suspected venous thromboembolism (VTE). The aim of this study was to explore how physicians working in emergency departments investigated patients suspected to have VTE.nnnMATERIALS AND METHODSnA questionnaire with two case histories related to the diagnosis of suspected pulmonary embolism (PE) (Case A) and deep venous thrombosis (DVT) (Case B) were sent to physicians in six European countries. The physicians were asked to estimate pre-test probability of VTE, and indicate their clinical actions.nnnRESULTSnIn total, 487 physicians were included. Sixty percent assessed pre-test probability of PE to be high in Case A, but 7% would still request only D-dimer and 11% would exclude PE if D-dimer was negative, which could be hazardous. Besides imaging, a D-dimer test was requested by 41%, which is a waste of resources (extra costs and efforts, no clinical benefit). For Case B, 92% assessed pre-test probability of DVT to be low. Correctly, only D-dimer was requested by 66% of the physicians, while 26% requested imaging, alone or in addition to D-dimer, which is a waste of resources.nnnCONCLUSIONSnThese results should encourage scientific societies to improve the dissemination and knowledge of the current recommendations for the diagnosis of VTE.

Acquired Functional Coagulation Inhibitors: Review on Epidemiology, Results of a Wet-Workshop on Laboratory Detection, and Implications for Quality of Inhibitor Diagnosis

The accurate detection and quantification of coagulation inhibitors remains a challenging problem for most diagnostic laboratories. Prolonged screening assays and abnormal results of mixing tests with normal plasma may indicate the presence of such inhibitors. Yet, the presence of lupus anticoagulant, heparin, and potential contamination of plasma with therapeutically active antithrombotic drugs has to also be ruled out. This review covers the epidemiology of acquired functional coagulation inhibitors, and reports the results of a wet-workshop, organized by the External Quality Control for Assays and Test (ECAT) Foundation, on laboratory detection of such inhibitors. The aim of the workshop was to investigate, within groups of experts from dispersed professional laboratories, the quality of inhibitor detection and the difficulties encountered during the analytical process. In this workshop 8 samples representing varying milieu were tested by 10 groups of participants from 20 different countries. Workshop participants were asked to report the results of all investigations performed and to provide a likely diagnosis and/or a conclusion of the hemostasis abnormality represented by the test samples. Generally, the sensitivity of inhibitor detection was high but the differential diagnosis of the type of inhibitors identified was unsatisfactory, as many false-positive and false-negative results were observed. The most remarkable observation was the lack of a clear step-by-step analysis of the nature of an inhibitor once a positive mixing test had been detected. The possible consequences of these observations for the appropriate diagnosis and clinical management of patients are outlined. A diagnostic algorithm for the differential diagnosis and confirmation of acquired coagulation inhibitors is presented.

An international study of how laboratories handle and evaluate patient samples after detecting an unexpected APTT prolongation

Abstract Background: An unexpectedly detected prolonged activated partial thromboplastin time (APTT) can be a harmless laboratory finding, but can also reflect a thrombotic tendency or a bleeding disorder. The assistance of laboratory professionals in the interpretation of an unexpectedly detected prolonged APTT (uAPTT) is often required. The way in which uAPTTs are evaluated in laboratories was assessed in this international study with the aim of determining whether laboratory professionals are able to fulfill this need. Methods: Postanalytical practices after uAPTT were investigated and the mixing study methodology (if used) was studied by circulating a case report with a questionnaire to staff in the invited laboratories. In addition, the interpretations of those staff regarding the presence or absence of inhibitors in three APTT mixing study scenarios were examined. Results: Large within- and between-country variations were detected in both postanalytical practices and mixing study methodologies among the 990 responding laboratories, 90% of which were in 13 countries. Shortcomings regarding the investigation of uAPTTs leading to potentially incorrect or delayed clinical diagnoses were found in 88% of the laboratories. Of the laboratories to which the interpretative questions were sent, 49% interpreted all mixing study scenarios correctly. uAPTTs were investigated appropriately and all mixing study scenarios interpreted correctly in parallel in only 9.6% of the participating laboratories. Conclusions: The clinical requirement for the assistance of laboratory professionals in the interpretation of uAPTTs cannot be met at most of the participating laboratories. Laboratory professionals should be trained in the evaluation of ordinary laboratory tests, such as that for uAPTTs.

An overview of the European Organization for External Quality Assurance Providers in Laboratory Medicine (EQALM)

The European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM) was founded in 1996 and currently has members from 29 European countries and 6 countries from outside Europe. EQALM provides a forum for co-operation and exchange of knowledge on quality-related matters in laboratory medicine, especially with regard to external quality assessment (EQA) programs in Europe. In addition, EQALM represent the EQA providers in laboratory medicine at European level vis-ŕ-vis political, professional, scientific and other bodies, including patients’ organisations. To this end EQALM promotes activities such as organizing meetings with scientific and practical themes for members and other interested parties, issuing scientific publications, developing EQA projects and representing laboratory medicine EQA activities within other organisations and networks. EQALM is active in scientific and educational activity in different fields such as survey frequency, haematology, haemostasis, microbiology, nomenclature, virtual microscopy, traceability, accreditation, and quality assurance of the total testing process. The aim of this paper is to give an overview of the EQALM organisation.

Special issue on External Quality Assessment in Laboratory Medicine – current challenges and future trends

Quality assurance in the modern clinical laboratory is evidenced through the complementary processes of internal quality control and external quality assessment, also known as proficiency testing. By these processes and the achievement of accreditation to international (e.g. ISO) standards, the laboratory is able to demonstrate its competence to the users of its services, i.e. the clinicians and the patients they care for, who have an expectation that the results of diagnostic testing and monitoring of treatment are correct, comparable and fit-for- purpose within the scope of the service, wherever they are performed. External quality assessment (EQA) was first introduced in the 1950s and 1960s in response to the growing role of laboratory testing as an essential part of disease diagnosis and management and an awareness of the extent of variability in results from one laboratory to another, for example as described by Mitchell Lewis following his initial interlaboratory trials in the UK (1). The earliest EQA services were developed by committed and enthusiastic individual pathologists and laboratory scientists, often with limited resources and alongside their day-to-day clinical services ; at the time, it was thought that harmonisation of performance would be achieved by the operation of a short-term programme of inter-laboratory testing rounds. The aim of this Special issue of Biochemia Medica is to provide a comprehensive overview of the latest developments in EQA and keep our readers up-to-date with the role and significance of EQA in laboratory medicine and its future directions taking into account the changing demands of the profession and the evolution of analytical technology. In this issue we provide a number of outstanding contributions by internationally recognised experts in the field, who have been invited to address various issues and different aspects of EQA in the modern time, almost seven decades after its very origins.