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Complete blood count indices and their ratios are associated with adverse clinical outcomes for many acute illnesses, but the mechanisms generating these associations are not fully understood. Recent identification of a consistent pattern of white blood cell and platelet count co-regulation during acute inflammatory recovery provides a potentially unifying explanation. Here we show that the platelet-to-white-cell ratio, which was selected based on this conserved recovery pattern, is more strongly associated with mortality than other blood count markers and ratios in four important illnesses involving acute inflammation: COVID-19, acute heart failure, myocardial infarction, and stroke. Patients recovering well from these acute illnesses tend to follow a joint white cell and platelet trajectory that can be reduced to this one-dimensional ratio. The platelet-to-white-cell ratio's association with prognosis is consistent with recently identified inflammatory dynamics and may provide a convenient and interpretable summary of patient inflammatory state., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The complete blood count (CBC) is an important screening tool for healthy adults and a common test at periodic exams. However, results are usually interpreted relative to one-size-fits-all reference intervals 1,2 , undermining the precision medicine goal to tailor care for patients on the basis of their unique characteristics 3,4 . Here we study thousands of diverse patients at an academic medical centre and show that routine CBC indices fluctuate around stable values or setpoints 5 , and setpoints are patient-specific, with the typical healthy adult's nine CBC setpoints distinguishable as a group from those of 98% of other healthy adults, and setpoint differences persist for at least 20 years. Haematological setpoints reflect a deep physiologic phenotype enabling investigation of acquired and genetic determinants of haematological regulation and its variation among healthy adults. Setpoints in apparently healthy adults were associated with significant variation in clinical risk: absolute risk of some common diseases and morbidities varied by more than 2% (heart attack and stroke, diabetes, kidney disease, osteoporosis), and absolute risk of all-cause 10 year mortality varied by more than 5%. Setpoints also define patient-specific reference intervals and personalize the interpretation of subsequent test results. In retrospective analysis, setpoints improved sensitivity and specificity for evaluation of some common conditions including diabetes, kidney disease, thyroid dysfunction, iron deficiency and myeloproliferative neoplasms. This study shows CBC setpoints are sufficiently stable and patient-specific to help realize the promise of precision medicine for healthy adults., Competing Interests: Competing interests: Mass General Brigham submitted a provisional patent application (63/695,679) on 17 September 2024, related to diagnostic and prognostic applications of haematological setpoints that includes B.H.F., M.T.R., V.T. and J.M.H. as inventors., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)