Bio-Rad - Preparing for a Stress-free QC Audit

Advances in point-of-care hematology analysis

Point-of-care hematology analysis can help to generate the data needed to make decisions about patient care quickly, both of which can improve patient outcomes in emergency situations and also help hospitals to meet waiting time targets safely. CLI asked Cleve Wright, Director of Medical HORIBA UK Ltd, about recent developments in this field.

Blood is an incredibly useful sample for diagnostic/prognostic purposes. What are some of the components that are measured and why?

The full blood count (FBC) is one of the most common ‘routine’ tests in clinical pathology because of the valuable information it provides in diagnosing and monitoring disease and in controlling patient treatments, such as pre- and post-operative checks and determining if chemotherapy or other medications can be given.

The FBC is not a single test but a profile which examines the numbers, volumes, and other physical attributes of the cellular components of blood. In a FBC analyser, whole blood is aspirated automatically before being split into several smaller aliquots. The different measurements take place simultaneously in dedicated chambers with corresponding dedicated reagents which are connected directly to the analyser. The raw measurements are then used to generate the primary results of the FBC and to calculate additional parameters. The time taken from aspiration to results varies slightly from instrument to instrument; in general this is around 60 seconds.

The cells under scrutiny are red blood cells (RBC), white blood cells (WBC) and platelets plus a colorimetric measurement of hemoglobin, the protein responsible for transporting oxygen around the body.

RBCs are the cells which contain hemoglobin. In addition to counting their overall number, the FBC analyser also produces values for mean cell volume and mean cell hemoglobin content plus a parameter called the hematocrit which is a measure of the proportion of the blood made up of red cells. These values can help in the diagnosis of anemia, the potential cause of anemia and aid in the decision for treatment and/or blood transfusion.

WBCs help to protect the body against infection. There are five different types of normal WBC which all have different functions. The two most common types are neutrophils (a sub-type of granulocyte or granule-containing WBC) and lymphocytes. Granulocytes are involved in inflammatory responses and in fighting bacterial infections. In the latter case, they engulf bacteria and destroy them with substances contained within their granules. They then ‘present’ some molecules of the bacteria to the immune system so that it can develop antibodies. Lymphocytes play a part in this immune response, recognizing infection and generating antibodies.

In additional to an overall count of WBCs, the FBC analyser also sub-divides the different types of WBC and detects and flags abnormal or immature WBCs. The numbers of these different types of WBC and the total count provides invaluable information about various disease processes. For example, a raised WBC may indicate an infection and a raised neutrophil or granulocyte count suggests that this is bacterial in origin. A raised lymphocyte count, on the other hand, more commonly occurs in viral infections.

Platelets are small fragments of cells which play a crucial role in blood coagulation pathways. They are activated when a blood vessel is damaged, stick together to plug the vessel wall and then stimulate the pathways to form a clot and stop bleeding. Detecting low levels of platelets is important for surgical operations, treating patients following trauma and detecting those who may be at risk of bleeds. Low platelets counts are used as a trigger for transfusion decisions and there is much debate regarding optical versus impedance platelet counts; however, in truth the functionality of platelets should be considered. These values are inter-related and it is the combination of these results provided by the FBC that provides a useful insight into many medical conditions.

What are some of the challenges with analysing blood?

One of the biggest challenges of analysing blood is time. Because the FBC examines cells as opposed to a chemical component, they can potentially start to change as soon as the blood sample is taken. For example, the coagulation process begins immediately and, if this is not prevented, then the blood would clot, and the individual cells would be impossible to count. Blood is taken into sample tubes containing an anticoagulant, EDTA, which prevents it from clotting. It is still important that the blood sample is taken relatively quicky and well mixed with the EDTA or the platelets will clump. As cells will also begin to deteriorate once the blood is taken, samples should ideally be analysed as soon as possible for the best results.

It is also important to make sure that samples are mixed prior to analysis to make sure that the cells are in homogenous suspension to prevent inaccuracies. The cells in a sample tube can separate out relatively quickly if left standing. Large FBC analysers in laboratories have automatic mixing but small analysers, such as point-of-care (POC) devices, process single samples and the operator needs to ensure they are mixed.

Unlike a panel of biochemical tests that are measured individually, the parameters of a FBC analyser are inter-related so FBC results should be interpreted as a whole, because one parameter can influence another. For this reason, it is also important that an analyser has clear flags, alarms, and interpretive messaging to assist the operator.

The availability and use of POC blood testing has increased in recent decades – what are some of the advantages and limitations of POC blood testing compared with lab analysis?

The availability and use of POC blood testing has increased in recent decades – what are some of the advantages and limitations of POC blood testing compared with lab analysis?

The use of POC testing brings the results closer to the patient and reduces turnaround time; however, there are considerations that should be weighed up when deciding to implement POC testing.

Biomedical staff within the laboratory are skilled in the operation and maintenance of analysers and the interpretation of results. POC instruments are normally operated by other healthcare professionals whose primary focus is not the analyser.

Modern POC analysers are designed to be easy to use with clear assistance for the operator and offer comparable results; however, if the turnaround time from the laboratory does not impede patient care, then a laboratory processed test will always be preferable.

That said, there are many instances where very rapid access to results can make a tangible difference to patient care and diagnosis. The Microsemi CRP LC-767G (HORIBA), for instance, combines the FBC with a C-reactive protein level (CRP) which is a marker for acute inflammation and infection. This suite of results helps the clinician quickly assess the patient and make decisions about the next steps such as whether to admit or whether to prescribe antibiotics. This is an important weapon in the fight against anti-microbial resistance. If deployed in the community, POC testing can help to avoid costly and unnecessary admissions to hospital which is a benefit to the patient, particularly with children and the elderly, and can also save valuable hospital resources.

Other POC FBC instrumentation, such as the Yumizen H500 (HORIBA), may be used to assess patient medication. By placing an analyser in a chemotherapy unit, cancer patients can have blood taken to determine if it is safe for them to receive their treatment. As the results are available immediately, these vulnerable patients do not have to spend any longer than necessary in a hospital or clinic and can avoid additional visits. This has been invaluable during the pandemic to keep chemotherapy patients away from areas where there was a high-risk of exposure to COVID-19.

A similar solution, where an instrument is deployed in mental health clinics and used to manage the prescription of the anti-psychotic drug, clozapine. Access to POC FBC testing means that patients can be treated in the community. The ability to test and prescribe in a single visit helps patient compliance with the medication.

Thus, with well established procedures, the right equipment and excellent operator training, a POC solution has the capacity to transform the patient pathway

How is appropriate quality control assessment and results interpretation ensured with POC testing?

Laboratory quality is ensured by quality control procedures and adherence to good practice as outlined in the ISO15189 Standard ( It is important that the use of POC testing does not compromise that quality. When selecting and validating POC analysers, the laboratory should be involved to ensure that it is the optimal solution and to assist in ongoing operations. The routine running procedures of the analyser should conform to the required standards and the design of the analyser should contribute to this by having automatic checks, quality control files, password protection, reagent logs, result files and other auditable functions.

It is important that the company providing the POC device also supplies control materials for all parameters and that instruments will flag any values outside the expected ranges to the operator so that the appropriate action can be taken. We also recommend that all instruments are enrolled in external quality control schemes plus we offer our own quality control programme where the day-to-day control results can be uploaded online and compared with peer groups in real time, locally, nationally, and internationally.

Instrument software should provide a clear interface with the user and provide flags, alarms and interpretive messaging to assist the operator. This is an important area of development, as detailed below, and of particular interest in POC, where additional interpretive information is provided from instrument raw data or by assessing results in combination. The interrelation of FBC results, lends itself to this development.

Analyser, reagent and software development need to be backed up by support from the supplier. The importance of good and ongoing training and support cannot be over-emphasized, both for the optimal operation of the instrument and for quality control and results interpretation.

How has the technology for POC blood analysis developed in recent years and what did you want to accomplish with your new analyser, the Microsemi CRP LC-767G?

POC testing is expanding in many areas of the world where it provides real benefits in managing patients’ needs quickly and efficiently. There have been several important areas in the development of POC FBC testing analysers.

They have become easier to use and more reliable. This is accomplished by robust design and user-friendly software development which means that they can be safely operated by non-laboratory personnel and inspire confidence in the results.

Instruments such as the Microsemi CRP LC-767G (HORIBA) provide acute inflammatory parameters from both hematology (FBC) and clinical chemistry (CRP) from a single small blood sample on one instrument. It thus simplifies the process for the operator and saves time and bench space.

The instrument has a new parameter, the granulocyte-to-lymphocyte ratio. This factor, combined with other white blood cell parameters and the CRP result, has a strong predictive value in assessing the severity of patients with COVID-19 and the necessity for admission and intensive care.

It is an example of where the interpretive power of the POC instrument can be extended to meet specific needs.

The results provided by this and other HORIBA instruments, are derived from multiple points of ‘raw’ data produced from the different channels of the instrument. This data can be explored by a process called data mining to look for patterns generated by certain pathologies. For example, further work has been carried out by HORIBA to assess flags for diseases such as malaria (including recognition of sub-species) and dengue fever. These, derived from a routine analyser, can potentially provide powerful interpretive indicators without the need for extra time, equipment or expense. This area of development has some exciting prospects for the near future.

Another area of development is in instrument connectivity to allow results to be easily transmitted and viewed. This has benefits in terms of patient data management but also allows POC instruments to be managed remotely by pathology staff to assist the implementation of a POC solution and ensure quality.

Ultimately, the future of POC analysers should be shaped by the needs of the clinicians and the patient. HORIBA is committed to uncovering those requirements, being responsive to change and developing future instrumentation in partnership with our customers.

The interviewee

Cleve Wright, Director of Medical HORIBA UK Ltd,
Moulton Park, Northampton, Northamptonshire, UK