There will be blood...

But what kind? Today’s clinical chemistry laboratories play a critical role in the provision of patient care: fast and accurate pathology testing is vital. But which type of blood samples should laboratories use to obtain quick and high-quality results? 

In an emergency situation, rapid and accurate diagnosis is critical. Faster intervention is associated with better patient outcomes and can even be life-saving in some cases. It is estimated that 70-80% of all healthcare decisions affecting diagnosis or treatment involve a pathology investigation. Individual treatment decisions and the monitoring of an individual’s response to treatment are often dependent on a range of pathology based tests and investigations¹. Consequently, there is a high demand among clinicians for fast delivery of test results from clinical chemistry laboratories².

There’s an ongoing debate on what types of blood sample chemistry laboratories should be using

In order to meet demands, clinical chemistry laboratories need to consider two factors when deciding which type of samples to process: providing both fast and accurate results from a high-quality sample. There’s an ongoing debate on what types of blood sample chemistry laboratories should be using. For instance, plasma samples can be processed faster than serum samples, enabling analytical results to be made available in less time. So should we be making a proactive move towards the processing of more plasma samples in clinical chemistry laboratories?

Turnaround time is critical

Turnaround time (TAT) is the time taken between the request for analysis and the clinician receiving the result. A short TAT delivers quick results, meaning that a diagnosis can be made and the most appropriate treatment implemented in the shortest possible timeframe. Fast, informed decisions can be critical in particular types of patients – including those being admitted to a hospital as an emergency, in patients with cardiac symptoms, diabetics, and patients on dialysis.

TAT can have a direct effect on the request-to-diagnosis time, consequently having an impact on:

• Request-to-therapy time – the faster the clinical team get the results to provide the most appropriate treatment, the better the patient outcomes.
• Emergency department discharge delays – the faster patients can be treated, the sooner they can be discharged and hence new patients treated.
• Hospital length-of-stay – as soon as the patients receive appropriate treatment the faster they recover and be discharged. This can have economic consequences and impact on hospital bed availability.
• Patient outcome – accurate test results enable appropriate treatment, which leads to better patient outcomes.

However, while there is a requirement for TAT in a clinical chemistry laboratory to be as short as possible – according to a survey from 2009² – it ranks low in satisfaction of actual delivery. A retrospective analysis – using data on emergency department visits during 2012 from 486 hospitals and health systems in the US – suggested that a longer TAT in clinical chemistry laboratories is associated with a longer length of stay by patients in the emergency department³. Other studies – including one conducted in Australia – have derived similar results, confirming that the number of tests requested and the TAT from the clinical chemistry laboratory will have an impact on the patients’ length of stay⁴.

At least one laboratory test was requested for almost 1 million of the 4.5 million visitors (aged 18 or over) to the emergency department in the data set from 486 US institutions³. A number of variables can impact on patient length-of-stay across any medical department, but this analysis suggests that the TAT of clinical chemistry laboratories might affect the length of stay of at least 25% of patients visiting emergency departments. Further studies need to be conducted – and data analysis of specific patient types might be enlightening – but, nevertheless, the implication is that initiatives to reduce TAT in clinical laboratories would have a significant impact on the patient burden in emergency departments.

More, more, more

Data analyses suggest that serum samples are still the most widely used blood sample across Europe

The separation of blood samples with a barrier to create stable supernatant is a key step in modern clinical chemistry laboratories – but the process has remained almost unchanged for 40 years. Today, the majority of laboratories utilise a gel-based separation media to obtain a stabilised sample. Data analyses suggest that serum samples are still the most widely used blood sample across Europe. In some countries – including Italy, Spain and the UK – less than 10% of patient blood samples tested are plasma. However, in a few regions – including the Nordic and Benelux – as many as 70% of the samples are plasma-based (based on sales data). Traditionally serum samples have been considered easier to process, but they do not provide the accuracy of results that plasma samples offer.

Both serum and plasma samples are commonly collected in evacuated tubes with a gel barrier to separate the sample from the cellular elements that could impact analytical values. When centrifuged, the gels migrate into place based on a density gradient between the supernatant and the red blood cells. During centrifugation of a serum sample, the gel moves up the sidewall of the tube around the fibrin meshwork of the clot to settle into position. In a plasma sample, the free cellular elements move downwards between the gel as it migrates up. Both serum and plasma sampling have innate challenges requiring specific laboratory procedures.

In either case, the goal is to obtain a specimen fit for analysis and to report accurate and reliable results in the shortest possible time. In order to deliver such a service, there is a need to keep abreast of innovative developments in the clinical chemistry laboratory arena – and integrate appropriate ones into the laboratory processes. One such development is the broader acceptability, and applicability, of plasma for chemistry testing – which could play an important role in meeting these demands for accuracy and speed.

Advantages of plasma

Serum is most often used in laboratories as it is considered a ‘cleaner’ sample, free of cells and platelets; these are trapped in the fibrin meshwork of the clot. Plasma is produced from an anticoagulated whole blood sample and so, unlike serum, contains no fibrin. Hence plasma samples have an immediate positive impact on TAT in the laboratory as they avoid the time required for clot formation, which can take up to 60 minutes (and even longer if a patient is on anticoagulant therapy). If a serum sample is centrifuged prior to the completion of the clotting process, fibrin formation within the serum can create significant quality and analytical issues. Analyte values in plasma are more reflective of in vivo patient levels and, as a result can be a more accurate measure for the healthcare team to make appropriate clinical decisions.

Analyte methods have previously been validated on serum as the predominant sample type

Plasma chemistry tubes can be used for the majority of analytes that a clinical chemistry laboratory may process, enabling testing to be conducted using a single sample type. As a result of sample tube consolidation, and the fact that laboratory personnel are less likely to have to conduct unscheduled maintenance on instruments, the laboratory becomes more efficient. Analyte methods have previously been validated on serum as the predominant sample type. However, today most methodologies are suitable for both plasma and serum sample types⁵.

Clinical chemistry laboratories can now easily introduce plasma sample processing into the service that they provide to clinical care teams. As described above, plasma sample separation using gel barriers can lead to higher levels of platelets and blood cells in the supernatant – when compared to a non-gel sample, reducing its stability over time. In addition, gel artifacts such as gel globules (small particles of gel that separate from the barrier) may be seen in the sample. If any gel is aspirated by the sampling probe, either as a result of these artifacts or by direct contact with the gel layer, it can lead to unscheduled instrument maintenance. This can cause a delay in TAT and consequently a potential delay in patient treatment. Another possible challenge is that for certain therapeutic drugs gel adsorption has been reported and could, therefore, have an impact on analyte results⁶.

It’s clear blood collection needs to be quick, accurate, efficient, and provide a high-quality sample in order to facilitate fast and correct diagnosis and prompt treatment. To provide this high standard of service to patients and the healthcare community, clinical laboratories have a critical role to play and should be at the forefront of keeping abreast of all industry developments and implementing new innovations – aiding physicians in the provision of the very best patient care.

Author: Stephen Church is Associate Medical Affairs Director at BD Life Sciences, Preanalytical Systems

http://barricor.bd.com/

References: 1. Report of the Review of NHS Pathology Services in England. Lord Carter of Coles. Department of Health. 2006. 2. Jones BA, et al. Physician satisfaction with clinical laboratory services: a College of American Pathologists Q-probes study of 138 institutions. Arch Pathol Lab Med. 2009;133:38-43. 3. Mitral D, Erdal E, Khangulov V, Tuttle R. Association between laboratory test turnaround time and emergency department length of stay: a retrospective electronic health record database study. Poster presented at the American Academy for Clinical Chemistry Annual Meeting & Clinical Lab Expo, July 26-30, 2015, Atlanta, GA, USA. 4. Li L, Georgiou A, Vecellio E, et al. Acad Emerg Med. 2015;22(1):38-46. The effect of laboratory testing on emergency department length of stay: a multihospital longitudinal study applying a cross-classified random-effect modeling approach 5. Dubrowny N. Raising awareness of assay compatibility with heparinized plasma. Clin Chem Lab Med. 2016 Ahead of print. 6. Dasgupta A, Dean R, Saldana S, et al. Absorption of therapeutic drugs by barrier gels in serum separator blood collection tubes: volume- and time-dependent reductions in total and free drug concentrations. Am J Clin Pathol 1994;101:456–61.