Much of the time, when a patient has a neutrophilia, it is due to infection. But are there any clues on the blood smear that would make that diagnosis more definitive?

Well, yes, as a matter of fact, there are. These clues are called toxic changes and they encompass three main findings: toxic granulation (as seen above), Döhle bodies (also present above – look closely), and cytoplasmic vacuolization. If you see any of these changes, you can be quite certain that the patient has an infection.

Toxic granulation is the accumulation of big, dark granules in segmented neutrophils (or, sometimes, in earlier neutrophil precursors). It is likely due to the demand placed on the marrow to get those neutrophils out in the circulation as soon as possible in order to fight the infection. Under those conditions, the promyelocytes (the last cell of the neutrophil lineage which has the capability to divide) say, “Okay, fine. You want segmented neutrophils out in the circulation immediately? I’ll quit spending my time dividing so much, and I’ll just mature!”

This is a good strategy for getting mature neutrophils out of the marrow as quickly as possible. But in this process a weird thing happens: you wind up with segmented neutrophils that have tons of primary (dark purple) granules in their cytoplasm. Why would this happen? It has to do with promyelocytes and their ability to either divide or mature.

Under normal conditions, promyelocytes divide a few times before they undergo maturation. This means that their primary granules get spread out among many generations of cells. When there’s a rush demand on the marrow, though, the promyelocytes skip the dividing part and move on to maturation – which means that all their primary granules are retained as the cell matures. So instead of neutrophils with just a few primary granules, you get neutrophils with tons of primary granules.

Cool, huh?

The two other changes are Döhle bodies (pretty sky-blue cytoplasmic inclusions in neutrophils; look closely at the above image – you can just barely make one out at 6 o’clock) and cytoplasmic vacuolization (an ominous change, by the way – if you see a lot of cytoplasmic vacuolization, and particularly if it is increasing over time, watch out.). These changes, too, are quite specific for infection.