Blood count stability reveals new path to personalized care

See how stable blood count setpoints are reshaping decades of risk assessment and disease prediction, unlocking the future of personalized diagnostics.

study: Hematological setpoints are stable patient-specific deep phenotypes. Image credits: A faction / Shutterstock

In a recent study published in the journal natureresearchers investigated the stability and clinical utility of complete blood count (CBC) settings in advancing personalized risk assessment and diagnosis in precision medicine.

background

CBC is a widely used clinical test that evaluates a patient's hematological and immunological status by measuring parameters such as red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). It serves as a non-specific diagnostic tool for various medical conditions. However, current interpretations rely on broad reference intervals across populations and are often insensitive to subtle variations in individual physiology. Studies have shown that within-patient CBC variation is narrow over short periods of time, but its stability over long periods of time, particularly over decades, remains unclear.

This study provides a deeper understanding of long-term hematologic regulation, a critical step toward accurate diagnosis. Further research is needed to understand the mechanisms of hematological regulation and improve personalized diagnostic and prognostic capabilities.

About research

This study focuses on adult outpatient clinics across three cohorts (A, B, and C) drawn from Mass General Brigham (MGB) facilities during overlapping time periods (2002-2021, 2002-2006, and 2017-2021). Patients' CBC data were analyzed. Patients were eligible for inclusion if they had at least five CBC measurements taken at least 90 days apart and had no hospitalization for more than 48 hours during the study period.

To strengthen the validity of their findings, the researchers excluded duplicate patients from multiple cohorts and ensured rigorous quality control measures. The final cohort consisted of 12,407 patients in Cohort A, 14,371 patients in Cohort B, and 20,062 patients in Cohort C.

Data on patient demographics, CBC index, medical procedures, prescribed medications, and clinical diagnoses were collected from the MGB Research patient data registry and electronic data warehouse. Mortality data were obtained from the United States (US) National Death Index and Social Security Death Master File, considering deaths that occurred outside the hospital system.

The CBC indices analyzed included RBC count, WBC count, PLT count, hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), avg. Platelet volume (MPV), and red blood cell distribution width (RDW). In particular, we used advanced computational techniques, such as Gaussian mixture modeling, to calculate patient-specific setpoints and distinguish between temporary deviations from the physiological baseline.

Research results

Analysis of CBC data from three cohorts provided clear evidence of stability and individuality of hematological settings. CBC indices, including RBC, WBC, PLT, HGB, HCT, MCV, MCH, MCHC, MPV, and RDW, showed narrow intrapatient variation over a 20-year period.

The long-term intra-patient coefficient of variation (CV) was significantly lower than the inter-patient coefficient of variation (CV), confirming the existence of stable patient-specific setpoints. These set points persist despite demographic variations such as age, sex, race, and ethnicity, suggesting that their regulation is a fundamental physiological property.

This study demonstrated that the CBC index of a typical patient is distinguishable from the CBC index of 98% of other healthy individuals when all settings are considered together. Importantly, these findings were replicated in an independent cohort, improving their reliability.

The patient-specificity of this hematological setting highlights its potential in precision medicine. Furthermore, the stability of these settings over decades allows us to identify subtle deviations that may indicate early pathological changes.

An association between setpoints and clinical outcomes was also evident. Differences in settings were associated with variations in the risk of several diseases, including cardiovascular disease, diabetes, kidney disease, and osteoporosis. Importantly, variation in set point was also correlated with increased risk of all-cause mortality, highlighting its prognostic relevance.

Retrospective analysis revealed that the use of setpoints improved sensitivity and specificity in diagnosing conditions such as diabetes, thyroid dysfunction, and iron deficiency compared with traditional reference intervals.

The study also identified 397 loci associated with CBC setpoints, some of which were novel discoveries. These findings highlight the interplay between hereditary genetic factors and acquired influences in the formation of hematological regulation.

conclusion

This study concludes that the hematological setpoints derived from the CBC index are stable, patient-specific, and persist for decades in healthy individuals. These settings reflect deep physiological phenotypes, allowing for increased sensitivity and specificity in diagnosing and predicting clinical outcomes. The association with disease risk and mortality highlights its potential as a valuable tool in precision medicine. By incorporating these settings into routine clinical practice, healthcare providers may be able to personalize diagnostic thresholds and improve risk stratification for major diseases.

Furthermore, this study highlights the need for additional research to investigate the mechanisms underlying set point regulation and its application in diverse clinical settings. The findings of this study will improve risk stratification, personalize diagnosis, and improve interpretation of CBC results by incorporating patient-specific settings into daily clinical practice to improve personalized medicine for healthy adults. This suggests that we can advance this goal.