The preanalytical phase – a field for improvement

Demand management

Considering the principle of the five rights, we always should aim to order the right test at the right time in the right patient [1]. However, ordering laboratory tests has become quite easy, especially when electronic order-entry systems are being used, often leading to the phenomena of overutilization of laboratory tests. The consequence hereof is not only an increased financial burden, but also increased risk of patient safety. Additionally, the underuse of tests as well as misinterpretation of laboratory test results is an issue laboratory specialists have become increasingly concerned about. Cadamuro et al. address the issue of demand management and optimal utilization showing ways to improve it [2].

One way of overcoming these issues is educating health care professionals on the appropriate use of laboratory tests [3]. An impressive project, following this aim is the “choosing wisely initiative”, a guideline approach for matching correct laboratory orders to the corresponding clinical question. Starting in the US and spreading to many other countries within the last few years, the main difference to regular guidelines is that this initiative focuses also on “don’ts”, helping to minimize inappropriate tests and follow-up diagnostics or treatment. Baird shows the advantages of working with these new information [4].

Venous blood collection

One of the most important steps concerning sample quality and patient safety is the sampling itself. The most used sample matrix in laboratory medicine is venous blood. Issues in the preanalytical phase are often mentioned alongside the term “blood sample quality”. For many health care workers involved in the preanalytical phase this is a relative abstract term. To be able to improve the quality of blood samples, one needs to understand the underlying causes affecting it. In their overview on this topic, Lippi et al. discuss causes and consequences of unsuitable blood samples. Aiming to improve preanalytical processes, the authors also provide recommendations on how to manage and prevent respective errors [5].

Knowing of the difficulties of correct sampling, many single or national guidelines, partially with conflicting content and recommendations, exist. In an effort to combine all these guidelines with current evidence, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group “Preanalytical Phase” (WG-PRE) recently published the first joint EFLM-COLABIOCLI (Latin America Confederation of Clinical Biochemistry) recommendation for venous blood sampling [6]. Cornes et al. review the key errors of the sampling process and summarize the evidence of the different steps [7].

Sample transportation

After patient samples have been collected, they need to be transported to the laboratory. This task may seem easy, but is often the source of impaired sample quality and delays in turn-around times. Many preanalytical aspects need to be noticed in organizing sample transport. The crucial role of sample transportation has been widely acknowledged and adopted into respective regulations such as the International Organization for Standardization (ISO) standards 15189 and 20658 [8]. Nybo et al. reflect on the relevant pitfalls and outline possible ways of handling this task [9].

Interference testing (hemolysis, icterus, lipemia)

Sample quality is usually checked before or during routine laboratory testing using special automated serum index measurements for hemolysis, icteria and lipemia (HIL). Changing the HIL assessment from a visual inspection of the centrifuged sample to an automated technique brought great advantages in reliability and precision. As a state-of-the-art principle, the majority of laboratories already use this technique. The cut-off levels for defining a sample as hemolytic, lipemic or icteric are mainly derived from the manufacturer’s information. This information, however, mostly does not distinguish between the matrix of serum or heparin plasma. Lippi et al. illustrate the respective matrix effects and discuss whether or not it affects routine laboratory testing [10].

Besides the clinical aspects of sample quality, the financial impact of low sample quality is becoming increasingly important in today’s health care settings. Lippi et al. outline the economic effect of hemolyzed samples in special clinical settings and calculate a “willingness-to-pay-threshold” for its prevention, thereby making it evident that investments in improving the preanalytical phase are inevitable when aiming to provide sustainable high-quality laboratory tests [11].

Sample storage

Before and after the analysis itself, the sample is usually stored either at room temperature, refrigerated or frozen, potentially influencing its quality. In routine situations, reordering tests from a stored sample is common practice and needs well-established information on the stability of ordered tests, especially in samples being stored for longer time periods (e.g. biobanking). Grankvist et al. review these different facets of this important topic [12].

Sample matrix

Compared to venous blood samples, the use of dried blood spots for laboratory testing may have advantages especially in sampling and transportation processes. As not all preanalytical requirements may be transferred from venous samples to dried blood spots, these have to be reevaluated separately. Vermeersch et al. focus on the preanalytical considerations of dried blood spots as established matrix in therapeutic drug monitoring and emphasize the effects of preanalytical deviation [13].

Clinical information in test ordering

Correct interpretation of laboratory results may be biased by preanalytical issues. Drug laboratory test interactions (DLTI) are a substantial cause of diagnostic error. van Balveren et al. explain the importance of having more information about DLTI and depicture future ways on how to secure correct test interpretation and patient safety [14].

Preanalytics in genetic testing

Future advances in medicine will require further improvements in laboratory medicine. Genetic testing is one of these growing areas. As in all other fields of laboratory medicine, the preanalytical phase needs to be meticulously controlled also in genetic testing. Lippi and Simundic illustrate the relevance of the preanalytical phase in future high-throughput genetic testing [15].

All preanalytical aspects have one thing in common: To improve it, laboratory professionals need to focus far more on processes outside of laboratory, reinforcing interactions and collaborations with clinicians and the nursing staff. Only when all involved parties are aiming in the same direction, improvements in providing high quality laboratory diagnostics and subsequent patient outcome may be achieved.

All authors have reviewed current evidence of many different aspects of the preanalytical phase. We appreciate their high expertise and contribution to this special issue. With this special issue, we hope to provide relevant information to all health care professionals looking forward to future improvements.