A biomarker of hypoxic exposure would be useful in clinical diagnosis and prognosis. Acute hypoxia stimulates large increases in serum erythropoietin (EPO), and EPO induces formation of characteristic enlarged red blood cells (RBCs). The presence of large RBCs perturbs red cell distribution width (RDW).

Using a > 2 M patient medical claims database, the human pathome was scanned for diseases where RDW rose 0–50 days following a new diagnosis. The course of RDW after selected diagnoses was visualized by registering RDW measurements by diagnosis date.

Acute hemorrhage, which provokes EPO-driven erythropoiesis, is followed by increases in RDW but not mean cell volume (MCV). Similar RDW increases follow many acute diseases with risk of hypoxia, including heart failure, pneumonia, atelectasis, pulmonary embolism, pneumothorax, and sepsis. Elevations reach maximum within 1 month after onset and subside to pre-disease levels about 6 months later. Unlike the case with iron-deficiency anemia (IDA), RDW elevations after hypoxia-associated diseases are unaccompanied by discernible change in average RBC size.

As predicted by a model risk pathway linking hypoxia to formation of enlarged RBCs via EPO, acute hypoxemia-related disease episodes induce change in RBC size distribution. Further study is needed to explore whether a more sensitive and specific signal can be extracted from the fine structure of the RBC size distribution routinely measured in automated hemocytometers.