The role of automated gel column testing technology in enhancing transfusion safety

Transfusion services in the United States are currently undergoing dynamic changes in an effort to optimize patient blood management and ensure rapid availability of the safest, most compatible blood products possible. Providing precisely matched blood to transfusion patients to reduce the risk of adverse events and improve transfusion outcomes remains the ultimate goal of immunohematology practice. This is particularly important when managing patients who receive chronic transfusions, including those with sickle cell disease, thalassemia, or chronic anemia, who are more likely to produce alloantibodies. 

Increasing workloads and demands for cost-containment have driven many blood transfusion centers still using manual procedures to adopt automated or semi-automated systems to improve flexibility, efficiency, and reliability of compatibility testing in high-volume settings. 

Historically, red blood cell agglutination testing has been conducted using conventional tube techniques due in large part to their simplicity. Although suitable for individual testing, the tube method presents some limitations, including low reproducibility, the potential for human error, and inefficient personnel management. For example, tube shaking methods may differ by user and affect the grading and interpretation of the results. Other challenges include repeated washing steps, resulting in loss of red blood cells (RBCs) and weakly bound antibody; difficulty detecting mixed-field populations; and providing accurate RBC typing in recently transfused individuals. Additionally, the limited capacity for automation inherent with tube testing results in increased frequency of transcription errors.¹ Tube testing also is considered fairly labor-intensive, resulting in high costs and inadequacy for large-scale implementation.²

Benefits of automated technology 

New automated and semi-automated agglutination methods have emerged in the last two decades, and are quickly replacing manual tube methods due in large part to their flexibility, efficiency, and reliability. There are three major techniques used in immunohematology testing automation: column agglutination technique (CAT), solid phase red cell adherence assay (SPRCA), and erythrocyte-magnetized technique (EMT). 

The CAT test consists of a plastic card with six to eight inbuilt individual columns. The upper part of the column is the reaction chamber, and the lower part contains a gel with specific reagents (e.g., antihuman globulin (AHG) antisera) for a particular test. For SPRCA, one of the immuno-reactive components, either antigen or antibody, is immobilized on a solid carrier prior to testing. EMT testing is based on paramagnetic particles adsorbed onto the surface of RBCs. 

Although there are differences in sensitivity and specificity between these automated methods, all commercially available gel column agglutination systems have proven to be highly accurate with a sensitivity >97.58% and a specificity >99.93%.^3,4 Similarly, automated testing methods are superior to standard tube low-ionic-strength solution (LISS) indirect antiglobulin test (IAT) (tube LISS-IAT) in detecting antibodies of known clinical significance, therefore increasing blood safety for transfused patients.^4,5  

In addition to these clinical advantages, automated systems allow transfusion services to customize their system based on workload. Workflow can be prioritized, and the system’s software versatility allows seamless interface with laboratory information systems (LIS), thus eliminating transcriptional errors inherent with tube testing. ^1,6 In addition, the high-throughput capacity allowed with automation delivers quicker, more reliable turnaround times. Walkaway operation improves personnel management by allowing staff to focus on other tasks. 

Gel column agglutination, which has gained popularity in recent years, also has the unique advantage of detecting mixed-field agglutination patterns, because the high-density media allows a clear separation between agglutinated and non-agglutinated cells, thus indicating the presence of a dual population of red blood cells. A study of D negative combat trauma patients massively transfused with D positive RBCs⁷ confirmed that gel column agglutination is superior to other commonly used serology methods, including SPRCA, in the detection and monitoring of mixed-field reaction patterns. 

Also, in certain situations with antibody and/or complement attached to RBCs, the gel column method appears to be more accurate in estimating the degree of RBC sensitization in direct antiglobulin testing.⁸ On a practical level, the stability of the gel-based agglutination method’s endpoint is another important advantage of the test. The results can be read and reviewed at a later time, whereas the endpoint of the manual tube method is stable for less than an hour. This stability allows the less-experienced laboratorian to review ambiguous results with a supervisor and enables documentation in the patient’s chart with photographs of the gel card. Finally, CAT offers several technical benefits including pre-dispensed reagents, omission of the washing step in the antiglobulin phase, and stability of the reaction in the column. 

Considerations for implementation 

The decision to automate a laboratory is complex and involves several factors, including clinical demand, technical considerations, prioritization of resources, and the capacity to interface the new operating platform with already-existing LIS. The selection process begins with the transfusion service defining its needs for testing and identifying any limiting factors such as space or financial constraints. The path of the workflow needs to be considered. There may be significant costs to renovate the laboratory to accommodate the new instrument, and these facility renovations need to be included in the budget. 

The cost of automation can be broken down into three areas: 1) acquisition of the instrument; 2) training and validation; and 3) ongoing operation and maintenance. The capital outlay for a new instrument ranges from $50,000 to $250,000, depending on the instrument’s capabilities and features. The benefits of automation include better compliance with regulatory requirements through standardization of testing procedures and increased safety resulting from positive sample identification and error reduction. Transfusion services also are faced with increased demands for after-hours work and increased cross coverage by other laboratory disciplines with less experience in transfusion medicine. Therefore, system validation and operator training remain critically important. 

Although the reagent costs for automation tend to be higher than the cost of manual testing, the operational costs may be reduced by efficiencies such as bulk purchases, reduced waste disposal, and reduced personnel costs. Undoubtedly, automation reduces the need for extensive hands-on time for specimen processing, and a single individual may be able to operate multiple instruments, or be relocated to other projects. 

In one study comparing staff performance using different serological methods when processing large batches of samples, automation of pre-transfusion testing reduced staff hands-on intervention and simplified performance and interpretation of results, resulting in decreased mean technologist time required to process samples as compared to the conventional tube method.⁹ An additional area of focus on the operator includes innovations to minimize the risk of error from operator manual manipulations, reduce operator exposure to hazardous biological material, and eliminate operator injuries.

Factors to be considered when selecting a particular instrument include available test menus, on-board reagent storage, bi-directional connectivity with the existing LIS, turnaround and throughput times, time to first ABO/Rh result, stat processing, minimum sample volume and test tube size requirements, operator hands-on time, instrument-operator interface complexity, instrument reliability, and maintenance requirements. Fully automated systems would also be expected to have security systems that track users and limit access to unauthorized personnel, store and archive data, monitor reagent levels and expiration, ensure that quality control procedures have been successfully completed, detect clots in samples, use barcoded samples, and allow customization. 

Increasingly, transfusion services are dealing with high workloads and demands for cost-containment, making provision of high quality blood products a constant challenge. The development of gel column agglutination methods in parallel with advances in automation over the last 20 years has allowed immunohematologists to meet the needs of these competing forces. Test standardization, minimizing manual steps, enhanced traceability, and improved accuracy have led to greater patient safety while increasing throughput and minimizing costs. Continued innovation in automation and test performance are critical to meet the increasing demands of the future.