Personalized Blood Count Could Lead to Early Intervention for Common Diseases

A complete blood count (CBC) screening is a routine exam requested by most physicians for healthy adults. This clinical test is a valuable tool for assessing a patient’s overall health from one blood sample. Currently, the results of CBC tests are analyzed using a one-size-fits-all reference interval, but a new study led by researchers from Mass General Brigham suggests that this approach can lead to overlooked deviations in health. In a retrospective analysis, researchers show that these reference intervals, or setpoints, are unique to each patient. The study revealed that one healthy patient’s CBC setpoints can be distinguishable from 98 percent of other healthy adults. Results are published in Nature.

“Complete blood counts are common tests, and our study suggests CBCs vary a lot from person to person even when completely healthy, and a more personalized and precision medicine approach could give more insight into a person’s health or disease,” said senior author John Higgins, MD, of the Center for Systems Biology and Department of Pathology at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham. “The long-term stability and patient-specificity of setpoints may provide new opportunities for the personalized management of healthy adults envisioned by precision medicine.”

CBC indices are known to shift due to genetics, disease history, and age. But the new study suggests that individual patients have a “setpoint”—a stable value around which measures fluctuate. By considering CBC setpoints tailored to an individual, clinicians may be able to diagnose diseases in their early stages in adults that appear otherwise healthy, including disorders such as diabetes, heart disease, and kidney failure, all of which can benefit from early intervention.

The study, with first author Brody H. Foy, a research fellow at the MGH who is now a faculty member in the Department of Laboratory Medicine & Pathology at the University of Washington, found that for multiple diseases, setpoints produce a two- to four-fold relative risk stratification which is comparable to that provided by common disease screening factors.

The researchers note that these setpoints create new opportunities to investigate the mechanisms of varying CBC thresholds and that the information from CBC setpoints could be used to create more specific treatment plans, including determining if additional screening is needed for an accurate diagnosis.

Authorship: In addition to Foy and Higgins, Mass General Brigham authors include Rachel Petherbridge, Maxwell Roth, Daniel C. De Souza, Christopher Mow, Hasmukh R Patel, Chhaya H Patel, Samantha N Ho, Evie Lam, Camille E Powe, Robert P Hasserjian, Konrad J Karczewski, and Veronica Tozzo. Additional authors include Cindy Zhang.

Disclosures: None.

Funding: National Institutes of Health (grant IDs: R01HD104756; R01DK123330).

Paper cited: Foy BH et al. “Hematologic setpoints are a stable and patient-specific deep phenotype” Nature DOI: 10.1038/s41586-024-08264-5