White blood cell population dynamics for risk stratification of acute coronary syndrome

The complete blood count (CBC) provides a high-level assessment of a patient's immunologic state and guides the diagnosis and treatment of almost all diseases. Hematology analyzers evaluate CBCs by making high-dimensional single-cell measurements of size and cytoplasmic and nuclear morphology in high throughput, but only the final cell counts are commonly used for clinical decisions. Here, we utilize the underlying single-cell measurements from conventional clinical instruments to develop a mathematical model guided by cellular mechanisms that quantifies the population dynamics of neutrophil, lymphocyte, and monocyte characteristics. The dynamic model tracks the evolution of the morphology of WBC subpopulations as a patient transitions from a healthy to a diseased state. We show how healthy individuals and hospitalized patients with similar WBC counts can be robustly classified based on their WBC population dynamics. We combine the model with supervised learning techniques to risk-stratify patients under evaluation for acute coronary syndrome. In particular, the model can identify more than 70% of patients in our study population with initially negative screening tests who will be diagnosed with acute coronary syndrome in the subsequent 48 hours. More generally, our study shows how mechanistic modeling of existing clinical data can help realize the vision of precision medicine.