Single-cell modeling of routine clinical blood tests reveals transient dynamics of human response to blood loss

Low blood count is a fundamental disease state and is often an early sign of illnesses including infection, cancer, and malnutrition, but our understanding of the homeostatic response to blood loss is limited, in part by coarse interpretation of blood measurements. Many common clinical blood tests actually include thousands of single-cell measurements. We present an approach for modeling the unsteady-state population dynamics of the human response to controlled blood loss using these clinical measurements of single-red blood cell (RBC) volume and hemoglobin. We find that the response entails (1) increased production of new RBCs earlier than is currently detectable clinically and (2) a previously unrecognized decreased RBC turnover. Both component responses offset the loss of blood. The model provides a personalized dimensionless ratio that quantifies the balance between increased production and delayed clearance for each individual and may enable earlier detection of both blood loss and the response it elicits.