Speaker: Joanna Sheldon (UK)
Moderator: Tommaso Trenti (IT)

Date: 24^th September 2019 at 18:00

The importance of standardisation is only just being realised and addressed in autoantibody measurements.  Immunoglobulins have a high degree of molecular heterogeneity, there are subclasses of IgG and IgA, and the affinity and avidity of antigen-antibody binding can vary both between and within individuals.  An immune stimulus may generate a monoclonal, oligoclonal or polyclonal response and this pattern of response will vary between individuals and even within an individual over the disease course.  There are multiple methods available for autoantibody detection which will vary in their abilities to detect different types of immunoglobulins.  Finally, the antigen to which we are trying to measure antibodies is usually a protein with its own molecular heterogeneity which may also be influenced by the source of the antigens and the preparation process.  Considering these complexities, it is unsurprising that there is marked variation in autoantibody concentrations measured with different methods.  However, the increasing reliance on automated quantitative autoantibody results has made standardisation or harmonisation of these tests vital.  The IFCC through a working group and more recently a committee have been integral to investigating and producing certified materials for IgG anti myeloperoxidase (ERM-DA476/IFCC) and IgG anti proteinase 3 (ERM-DA483/IFCC) with values assigned in mg/L, traceable to ERM Da 470k/IFCC (the certified reference materials for IgG).  Evaluation of patient samples showed that use of these materials will give a significant reduction in the spread of the numerical results over different methods.  However, there was only 30% concordance between positivity and negativity of results when interpreted with respect to each methods reference ranges.  The introduction of certified reference material (CRM) will be the essential first step in standardisation of autoantibody testing and although it does not solve every issue, it should give us a point of reference to identify the other components of the methods that need to be harmonised before we can have comparability in autoantibody results.

Speaker: Abdurrahman Coşkun
Moderator: Merve Sibel Gungoren

Date: 18^th June at 18:00 CET

Registration is open (enter the course to register).

How to enter the course?

Internal quality control (QC) is the backbone of quality system in laboratory medicine, which serves to validate patients test results. However, it monitors the system intermittently, not continuously. Classical QC monitoring system depends on periods such as weeks, days, or predetermined time intervals and therefore detects some but not all analytical defects. In this situation, we have not much information about what is going on between these periods. To overcome this problem, we need a real-time monitoring system to detect the possible errors while the instruments are running.

Autoverification programs evaluate and release test results as soon as they receive data from the instruments. Therefore, when we detect errors using classical QC monitoring system, the test results of a large number of patients might have been reported to clinicians and/or patients already. This is a major risk for patients’ safety and when we detect errors, it wouldn’t be easy to re-analyse all reported patients’ samples. 

The devil is in the detail. We should monitor the system continuously using a suitable algorithm based on patients’ data. The aim of this webinar is to raise awareness for the necessity to monitor analytical instruments continuously while reporting test results. 

Speaker: Johannes (Hans) Hoffmann (DE)
Moderator: Giuseppe Lippi (IT)

Date: 12^th Fbruary 2019 at 18:00 CET

Abstract

Modern hematology analyzers do much more than just counting blood cells. Practically all instruments currently available also perform a white blood cell (WBC) differential and they produce flags or alerts for possible morphological abnormalities. Hematology analyzers have completely replaced traditional methods of cell counting and microscopic blood smear examination for the vast majority of blood samples.

In addition to these capabilities, hematology analyzers generate an ever-increasing amount of raw data, which can be transformed into cell parameters, for which no historical equivalent exist. This trend already started in the early days when measuring and reporting mean red cell volume (MCV) became possible. MCV has evidently established its clinical significance, due to the crucial role in classifying anemia. After MCV, many other parameters have been developed, not only for red blood cells, but also for platelets and white blood cells. However, in contrast to MCV, the clinical relevance of many of the new parameters is still unclear. Hematology analyzer manufacturers are generally launching these new parameters as research tools, without the slightest clue whether they can be of clinical value. This then opens possibilities for laboratory professionals examining the potential clinical significance of such parameters. Unfortunately, this type of research is plagued by serious challenges: most of the new parameters are not internationally standardized, limiting their widespread use in clinical practice. Sometimes the parameters depend on a certain technology, meaning that only laboratories using a specific make of hematology analyzer can use the parameter. And last but not least, some parameters are even specific for one individual hematology analyzer; other analyzers of the same model may produce different results and thus require separate clinical validation. An example of the latter are the so-called cell population data that have attracted a lot of interest in recent years; some interesting and promising applications were described, but one should also be aware of the limitations of this type of parameters.

The primary aim of this presentation is to discuss the technological principles used by the major hematology analyzers and to demonstrate how these technologies generate new cellular parameters. The second part will focus on understanding the potential use and limitations of new parameters, which are essential for researchers who are interested in investigating their clinical application. 

Speaker: Pieter Vermeersch (BE)
Moderator: Janne Cadamuro (AT)

Recorded on 27^th November 2018 at 18:00 CET

Abstract: The pre-analytical phase is the major source of errors in the total  testing process. The fact that many of the processes take place outside of the direct control of the laboratory and the involvement of different parties such as patients, clinicians, phlebotomists and logistics personnel make keeping the preanalytical phase under control a major challenge. The EFLM Working Group for the Preanalytical Phase has in recent years issued a number of recommendations and guidelines with the to improve standardization and harmonization of the preanalytical phase in Europe. While recommendations and guidelines are important to improve the overall quality, the devil is often in the detail. Laboratory professionals must continue to keep a careful eye (or two if they can spare them) on the preanalytical phase. The aim of this webinar is to make participants aware of the wide range of possible causes of preanalytical errors, both outside the laboratory and inside the laboratory  and illustrate these a number of mysteries from routine practice which ultimately allowed the identification of a pre-analytical problem.

Speaker: Michael Cornes (UK)
Moderator: João Tiago Guimarães (PT)

Recorded on 15^th May 2018

Abstract

National and international (WHO, CLSI) guidelines recommended that order of draw of blood during phlebotomy should be blood culture/sterile tubes, then plain tubes/gel tubes, then tubes containing additives. This prevents contamination of sample tubes with additives from previous tubes for example sodium citrate or more commonly potassium EDTA (K₃EDTA).

These recommendations are based on a case report by and a follow up study by Calam and Cooper in 1982 which reported that incorrect order of draw caused hyperkalaemia and hypocalcaemia. By measuring EDTA, it has been demonstrated that reverse order of draw of blood samples using closed loop venesection systems does not cause EDTA contamination. It is difficult to reconcile the directly conflicting results of these studies but it may be that reversed order of draw using poor technique and/or difficult venepuncture may result in sample tube cross-contamination.

It has been shown that contamination is still relatively common and may be difficult to identify. As this is not due to reversed order of draw of blood samples in a closed loop system other mechanisms must be in operation. Here I will present the evidence for and against the need to follow an order of draw.

Recorded on: 3^rd April 2018 at 18:00 CET

Speaker: Tiago Guimaraes
Moderator: Giuseppe Lippi

Abstract:

Every laboratory has to be aware of the need to validate the tubes it is using.

The importance of the pre-analytical activities is well known but sometimes not valued.

For tube validation each place has to set its own objectives according to its particular needs.

The EFLM Working Group on pre-analytics tries to help in setting some consensus on these aspects.

A EFLM Recommendation on this is being prepared.

Speaker: Aasne Karine Aarsand (NO)
Moderator: Bill Bartlett (UK)

Recorded: 06-03-2018 at h. 18.00 CET

Biological variation (BV) data has many appliances in the daily laboratory life, being used both when evaluating the diagnosis and monitoring of disease and for setting analytical performance specifications. Thus, the quality of our work directly depends on the reliability of the BV estimates used as basis for these processes. Widely varying BV estimates are available for different measurands, and it is likely that this may be caused by differences in study design and statistical handling. Addressing this issue, the EFLM established in 2014 an EFLM Task and Finish Group (TFG) for the Biological Variation Database. The TFG is made up by members from the EFLM Working Group on Biological Variation, the Analytical Quality Commission of the Spanish Society of Clinical Chemistry and experts in the area. The TFG has developed a critical appraisal list for evaluation of studies on BV and this will be used as basis for the setup of a database with measures of BV, the derived performance specifications and the evidence behind it.

Speaker: Giuseppe Lippi (IT)

Recorded on 19^th December 2017 at h. 18.00 CET

Hemostasis is a complicated mechanism finalized to preventing unjustified bleeding during vascular injury, or unwarranted thrombosis when the vessels are substantially intact. Hemostasis is typically classified in two essential steps. The first event is an endothelial injury, which activates primary hemostasis and is then followed by activation of secondary hemostasis. Specifically, primary hemostasis develops with recruitment of a many platelets being at site of vascular injury. Platelets are subjected to a sequential process of activation, adhesion and aggregation. This initial hemostatic plug is however unstable, since it is vulnerable to fast dissolution within in the local blood, especially in arteries. To prevent dissolution, additional fundamental mechanisms of secondary hemostasis (also known as blood coagulation) are activated, with the aim to stabilize the initial plot by large fibrin deposition.

The diagnostics of bleeding disorders of primary and secondary hemostasis remains a challenge for laboratory professionals, especially those lacking experience background, experience and skill on this topic. Bleeding is essentially due to many acquired or congenital conditions, impairing either primary or secondary hemostasis. A universal consensus on the diagnostics of bleeding diseases remains an unmet target, so that the aim of this Webinar is providing practical guidance for laboratory professionals who are less familiar with this important area of in vitro diagnostic testing. A practical strategy for diagnosing bleeding disorders of primary and secondary hemostasis is necessarily based on a multifaceted and multistep strategy, entailing accurate personal and family history collection, interpretation results of the so-called first-line hemostasis tests, then followed by interpretation (when necessary) of second- and third-line test to identify the both nature and severity of bleeding disease.

The observation of profound hemorrhages rather than muco-cutaneous bleeding suggests a disorder of secondary hemostasis. Although positive family history can be frequently seen in patients with congenital disorders, the absence of clinically significant symptoms in relatives cannot be considered always suggestive of acquired disorders. The next phase is based on performance of the so-called first-line coagulation tests, mainly represented by activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen, especially when the family history is not indicative of specific factor deficiencies. The observation of abnormal results of these tests and the combination of results can help driving performance of the so-called second-line tests, which especially entail clotting factor assays. The so-called third-line tests (especially entailing immunologic tests of coagulation factors and molecular biology) are then useful to make a final diagnosis and/or for detecting the specific nature of the protein deficiency.

Speaker: Anna Merino (ES)
Moderator: Ciriaco Carru (IT)

Recorded at  7^th November 2017 18:00 CET

With the advance of the technology of hematology analyzers, the indications for peripheral blood film (PBF) review by an expert have declined, but still remain essential. PBF review contributes to the following: 1) Complements/validates the findings of automated hematology analyzers, 2) Provides information on hematologic abnormalities that cannot be assessed by the current hematology analyzers, 3) Abnormal red cell morphology detection, 4) Identification of blasts, lymphoma or other abnormal cells, 4) Platelet clumping or abnormal platelet morphology inspection and 5) Dyshematopoiesis detection. Some examples are provided in the presentation. It also discusses on some issues related to who performs the PBF review.

 The PBF review by laboratory technologists validates hematology analyzer flags and identifies specific cells or qualitative abnormalities that cannot be identified by hematology analyzers. In addition, technologists triage blood films that require expert morphology review. The contribution of the pathologists is relevant since they are able to make a specific diagnosis, provide differential diagnosis, and/or recommend further testing based on all hematologic quantitative and qualitative values. In addition, they can summarize the findings in a narrative interpretation that becomes part of patient’s medical chart.

 The International Council of Standardization in Hematology (ICSH) is developing standards, guidelines and recommendations in peripheral blood film review internationally, which can provide the following benefits for pathologists: 1) Define the role and standardize the expectations of laboratory physicians, 2) Narrow the indications for PBF review by pathologists to those that contribute to patient care, 3) Provide a framework for reporting and 4) Opportunity for national and international collaboration & advancement of the field. Some of the ICSH recommendations are discussed in the presentation.

A 66-year-old woman was admitted to our hospital with shock and multiorgan failure. She was resident in the United States, in a rural area of New Jersey. She had been on vacation in Europe for 3 weeks and had suffered fever and chills for 1 week, and nausea, vomiting and abdominal pain for 2 days.On admission she showed respiratory, hepatic and renal failure, anemia, lymphopenia, thrombocytopenia, high lactate dehydrogenase (3500 IU/L; normal: 250–450) and negative direct and indirect Coombs test.The peripheral blood (PB) film revealed the diagnosis of the patient. Some interesting images of the morphological findings in blood cells will be discussed during the presentation. It will be useful for the participants to learn about the differential diagnosis in this special case, since the abnormalities that we found in blood cells can be easily confused with those of other more frequent disease. Diagnosis can be challenging and therefore knowledge of the distinguishing clinical features and epidemiology of these diseases is important. In addition to morphology, an adequate clinical history is important for speedy and accurate diagnosis.

Fasting blood samples have been the standard for measurement of triglycerides and cholesterol, despite the fact that we spend the vast majority of our time in non-fasting conditions. However, when recent studies suggest that postprandial effects do not substantially alter lipid concentrations and do not weaken, and even may strengthen, their association with cardiovascular risk, then a non-fasting blood draw has many practical advantages. Non-fasting cholesterol measurements include the ‘remnant cholesterol’ fraction, a strong risk factor for developing atherosclerosis independent of LDL cholesterol. Remnant cholesterol reflects the cholesterol in chylomicron- and VLDL-remnant particles and it is included in the ‘non-HDL cholesterol’ calculation.
Until recently, most guidelines focused on targeting primarily LDL cholesterol for the prevention of cardiovascular disease, but they now recognize that non-HDL cholesterol (or apolipoprotein B, the molecule carried by all non-HDL particles) is a more accurate and comprehensive predictor of atherogenic lipoprotein-related risk.
In 2016, the European Atherosclerosis Society (EAS) and EFLM Joint Consensus Panel recommended using non-fasting lipid testing for routine clinical practice and provided specific cutpoints for desirable fasting and non-fasting lipid concentrations to be reported by the laboratories uniformly.

At the beginning of 2015 the monograph “Rational Ordering of Laboratory Parameters” in Slovak language has been issued. The monograph with 185 pages from 4 editors and 18 authors represents an attempt to create a common denominator contributing to the consensus between clinicians, laboratory specialists and healthcare providers. This webinar discusses common problems in rational ordering of laboratory test.

The preanalytical phase is the main contributor to diagnostic errors. Modifying staff behaviour to conform to venous specimen collection practice guidelines and other recommended practices has proved to be a difficult task.

Recordings of lectures

2nd EFLM Strategic Conference in Mannheim

Handling disruption of Laboratory Medicine in digital health

• the impact that the on-going digitalization of technologies and a digitalized society on the medical laboratory in future health care
  
• changing our capabilities to compile, integrate and visualize complex diagnostic data
• providing the opportunity for radical changes to diagnostic health strategies.
  

With the digital revolution spreading into every realm of modern medicine, we will experience a democratisation of health care, i.e. a comprehensive data usage not just being in the hands of health care professionals, but also in the patients´. Indeed, a central concept of digital health medicine is patient empowerment as demonstrated by key words like “electronic health record”, “patient access”, “health apps”, “wearable health tech” etc. In this rapidly changing health care environment, Laboratory Medicine must redefi ne its positions, not only acting in its classical role as provider of laboratory results, but also adopting new roles and responsibilities in the clinical dialogue.

Recorded on 18-19 June 2018.

The course will provide an overview of different models to set performance specifications in laboratory medicine; 1) based on clinical outcome, on 2) biological variation, and 3) state of the art. In addition, it will address the total error concept, and performance specifications in external quality assessment schemes and in the extra-analytical phases.

A recording of a plenary presentation by professor Mauro Panteghini, recorded at 4^th Joint EFLM-UEMS Congress: Warsaw, Poland, 21–24 September, 2016

Harmonization in laboratory testing is more than merely analytical harmonization. Although the focus was mainly on the standardization and harmonization of measurement procedures and their results, the scope of harmonization goes beyond method and analytical results. It includes all aspects of the total examination process from the “pre-pre-analytical” phase through analysis to the “post-post-analytical” phase. Rapidly available and precise results can indeed be of very limited value if they cannot be compared with each other, are produced on a wrong material or within an inappropriate diagnostic workflow. In particular, as evidence collected in last decades demonstrates that pre-pre- and post-post-analytical steps are more vulnerable to errors, harmonization initiatives should be performed to improve procedures and processes at the laboratory–clinical interface. Managing upstream demand, down-stream interpretation of laboratory results, and subsequent appropriate action through close relationships between laboratorians and clinicians remains a crucial issue of the laboratory testing process. Therefore, initiatives to improve test demand management from one hand and to harmonize procedures to improve physicians’ acknowledgment of laboratory data and their interpretation from the other hand are needed in order to assure quality and safety in the total examination process. A harmonized context will increase the value of laboratory results facilitating their interpretation and thus improving the patient’s outcome.

Tutorials serving for WG-DE activities.