A New Take on Antenatal Immunohematology Testing

Hemolytic disease of the fetus and newborn (HDFN) is caused by red blood cell (RBC) alloimmunization, most commonly when a mother with a D-negative blood type develops antibodies against her D-positive baby during her first pregnancy. This immune response may lead to a range of morbidities in subsequent pregnancies, such as severe fetal anemia and hydrops fetalis, and in extreme cases, fetal death.

Fortunately, the incidence of HDFN is presently as low as 0.1 percent in developed countries due to advances in antibody screening and the administration of prophylactic anti-D immunoglobulins to D-negative mothers at key stages in pregnancy and postpartum.

Quantitating the maternal antibodies during gestation is, therefore, critical for preventing HDFN, as it identifies the need to involve a fetal medicine specialist and guides further investigation and intervention during the pregnancy. This quantification also helps categorize the nature and clinical significance of any anti-D detected—whether it is immune or passive—from the anti-D prophylaxis treatment. 

Identifying bottlenecks in antenatal antibody testing

The UK antenatal testing guidelines state that when an anti-D or an anti-c antibody is present in an antenatal sample, it must be quantified using continuous flow analysis (CFA)—the current standard technique. Though expensive and time-consuming, anti-D quantification using CFA can help determine if the antibody is of immune origin or not.

However, HDFN may be caused by antibodies that are not quantified by CFA, including anti-C, anti-e, anti-E, and anti-K, as well as those developed against antigens of the Kidd and Duffy blood group systems. In these cases, the results of antibody titration can give clinicians an insight into the risk and clinical management of fetal health. 

Immunohematology labs in healthcare settings may have to perform time-consuming manual testing protocols, such as the tube method of antibody titration, to quantitate these antibody specificities. Antibody titration methods are critical for providing meaningful results to clinicians but are inherently inaccurate when performed manually. Sources of inaccuracy include variations in dilution preparation, the dilution medium being used, RBC selection, and reaction analysis—a step that is difficult to standardize, particularly when performing the tube method. In addition, this method can be labor-intensive, requires a high degree of skill and experience, and may yield results that are difficult to interpret.

Moreover, staffing shortages, worsening financial constraints, and increasing workload are placing additional pressures on healthcare systems around the world to up their testing throughput while keeping costs to a minimum. Therefore, laboratories based in hospitals are struggling to provide crucial results quickly and support timely and appropriate treatment. 

As a result, antibody titration is often outsourced to reference laboratories that have the skill and experience needed to carry out this critical test. Outsourcing can slow down the testing process, leading to longer turnaround times. A shrinking workforce limits the reference labs, so manually processing samples from multiple healthcare institutions can be a burden. 

Decentralizing testing with automation 

Automated immunohematology platforms and systems can help solve this crisis, as: They can not only handle the routine workload of antenatal blood typing and antibody screening but also bring antibody identification and titration of alloimmunized cases back into local labs. 

Several immunohematology labs across Europe have already adopted automation to perform testing and streamline processes. This has reduced hands-on time and improved lab productivity, freeing up staff to perform other vital tasks. 

Automation has also reduced waiting time for many labs—sometimes down to just a few hours after sample collection—helping clinicians make quicker clinical decisions and reducing stress and anxiety in patients. 

Some automated immunohematology platforms possess superior random-access capabilities for both STAT and batch testing with 24/7 availability. They eliminate postanalytical processing through automatic reflex testing, on-board titration, and eluted sample testing. 

Automation also carries the benefit of higher precision and standardization. Integrating additional software with automated platforms can help interpret results, preventing technical and manual errors. These features alleviate the need for extensive training and experience, enabling more staff members to carry out analyses and reducing the workload on skilled specialists. 

Addressing future healthcare challenges 

There is a growing understanding among immunohematology laboratories of the need to automate antenatal antibody testing. A drop in the new recruits entering the immunohematology field and mounting workload are key drivers of this transition. 

Adopting automation can shorten the turnaround times and the costs associated with outsourcing, conserving precious financial resources and empowering healthcare providers to deliver world-class patient care.