Click, click, click. Select. Sign and wait. Review results. Rinse and repeat. With more than 5 billion laboratory tests performed each year in the United States,1 clinical laboratories have established themselves as vital structures to the practice of medicine. For clinicians, laboratory testing is not just about detecting a problem but understanding the underlying puzzle: the right assay at the right time can unlock a world of clinical insights. Peek behind the scenes of some notable laboratory-based #ASH24 presentations to see what it takes to create and maintain the magic that happens in the space between a test order and a test result.
The Price of Hemostasis Monitoring: Who’s Paying?
In patients requiring extracorporeal membrane oxygenation (ECMO), fast and reliable hemostatic monitoring is essential, but balancing the frequency of laboratory draws, turnaround time, and testing costs is not an easy task. Scheduled for Monday evening’s Poster Session, Abstract 5018 (6:00 p.m. - 8:00 p.m., Convention Center, Exhibit Halls G-H) explores the use of these factors as motivation to eliminate the barrier of access to dilute thrombin time, an assay more reliable than activated partial thromboplastin time for the monitoring of anticoagulation with bivalirudin. The strategy of lead study author Lisa Dorn, MD, PhD, and colleagues was effective and significantly cost-saving. But a win for clinicians and the health care system’s wallet comes at the expense of significant investment from the laboratory, which must validate the assay per regulatory guidelines. The fastest and most affordable option is choosing a reagent with authorization from the U.S. Food and Drug Administration (FDA) and performing testing without modifications. The onus of proving the assay characteristics (pre-analytic conditions, precision, accuracy, analytical measuring interval, reference interval, analytical specificity, and clinical validation) is on the manufacturer, with smaller studies to verify those claims completed by the performing laboratory. (Be aware that many of the testing needs in hematology involve assays that do not have an FDA-authorized option.)
Jumping Through Hoops for Assay Modification
Not all tests are created equal, and some are labor-intensive, requiring a wealth of laboratory expertise to navigate the technical complexities that arise in the short time needed to provide an actionable result. These constraints limit the availability of testing, crushing most practicing hematologists’ dreams of having tests performed locally. Featured at tonight’s Poster Session, Abstract 2618 (6:00 p.m. - 8:00 p.m., CC, Exhibit Halls G-H) reports on the work of Maria Cristina Pascual Izquierdo, MD, PhD, and colleagues, who were determined to increase the availability and speed in ADAMTS13 testing using a rapid assay technique. With clinical sensitivity and specificity above 89%, this assay is not perfect, but its high negative predictive value fills an important gap in the care of patients with suspected thrombotic microangiopathy.
How heavy is the lift? Developing a new assay methodology or changing an existing assay is not as simple as asking for no ketchup on your burger. It is more akin to determining the breed of cow, cut and amount of meat, seasonings (which ones, how much of each), whether to grill or fry, and the length of cooking time (medium rare to well-done). When aspects of the manufacturer’s assay system are changed, the kit is labeled research use only; if the test is laboratory developed, validation is necessary. And validation is not a plug-and-play operation. It involves an extensive (and expensive) set of studies to establish and prove that the performance characteristics are safe and reliable for clinical use.
Reference Interval Is Not a Synonym for Normal
“Your bloodwork results are not abnormal; they are outside of the reference interval” is a frequent conversation starter in hematology clinics around the world. For most quantitative measurement procedures, a reference interval (RI) should accompany reported results. The Clinical and Laboratory Standards Institute (CLSI) recommends a minimum of 120 healthy individuals per population to establish the RI.2 For rare disorders and special populations, CLSI leaves room for adoption of national/international consensus on decision limits that can be used for a test with confirmed accuracy. In lieu of consensus decision limits, verification of previously established RIs (e.g., from package insert, peer-reviewed publications, etc.), with a minimum of 20 healthy individuals, is acceptable when performing the assay with the same methodology and protocol. However, this guidance, which is meant to assist in result interpretation, is far from what is needed to differentiate health and disease.
RIs are included throughout the work showcased at #ASH24. In particular, Abstract 162, presented yesterday, illustrates how robust and inclusive RIs are a necessary step toward health equity to mitigate patient harm and increased health care costs. Lauren E. Merz, MD, MSc, and colleagues employed a universal serologic testing strategy to identify Duffy null individuals, setting the stage for similar approaches that reflect honor and respect our diversity.
From genotype-phenotype correlation to using old tests for new purposes and developing the next generation of assays, the relationship between the clinical lab and direct patient care is stronger than ever, proving that great partnerships are like a well-tuned duet — each note depending on the other to create harmony, and neither shining without the support of the other.
Can’t get enough laboratory-themed science? Learn more about some of our other picks:
REFERENCES
- Koch C, Roberts K, Petruccelli C, et al. The frequency of unnecessary testing in hospitalized patients. Am J Med. 2018;131(5):500-503.
- Clinical and Laboratory Standards Institute. Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline—Third Edition (EP28-A3c). clsi.org/media/1421/ep28a3c_sample.pdf. Published 2010. Accessed November 22, 2024.
