WBC population dynamics differ in response to acute ischemic and infectious insults and can discriminate clinically maladaptive responses to myocardial infarction.

Leukocytosis, or elevated white blood cell count (WBC), is a clinical hallmark of the systemic inflammatory response following acute ischemia or infection. However, WBC population dynamics during the initial inflammatory response are poorly understood. It is unknown whether early WBC dynamics differ by etiology or impact clinical risk. We fit mathematical models to WBC trajectories for patients hospitalized following acute ischemia or infection. We found differences between responses to strong ischemic insult (acute myocardial infarction, AMI) and strong infectious insult (sepsis). Among patients who recovered and survived hospitalization, net WBC growth following ischemia was [~]1.8x faster than following infection. Response kinetics and dynamics were correlated with short-term mortality in AMI. Increased immature neutrophil production over 24h preceding WBC peak was associated with [~]2x increased odds of short-term AMI mortality, suggesting that dysregulated responses to ischemia may involve bone marrow overactivation towards increased proliferation. Our work provides novel insight into fundamental etiology-specific differences in acute inflammatory responses from routine clinical data and is consistent with recent evidence of a maladaptive role for emergency granulopoiesis in AMI. One Sentence SummaryWBC dynamics differ between ischemia and infection in the early response to acute inflammatory insult, and can discriminate clinically maladaptive responses to myocardial infarction.