How Glucocorticoids Affect the Complete Blood Count

What are the effects of glucocorticoids on the results of a hemogram (complete blood count)?

I know that glucocorticoids may cause a neutrophilia. But my main question is —if a dog or cat is on prednisone or another glucocorticoid, how would one know that a neutrophilia was due to a glucocorticoid effect vs. an infectious agent? I've read that if there is no left shift, toxic changes or clinical signs of fever that one could assume it was due to the glucocorticoids. But, is there a number cut-off at which it is too high to be attributable to glucocorticoid administration?

I also remember that glucocorticoids lower lymphocyte numbers (hence it is used to treat leukemia potentially). But what is the mechanism by which it does that?

And finally, what effect do glucocorticoids have on platelet number? How about the effects on red blood cell (RBC) count and hematocrit?

My Response:

Stress leukogram of glucocorticoid excess
The hematological response to glucocorticoid effect is a bit variable between species, but the classic glucocorticoid response in dogs is a mature neutrophilia (without a left shift), lymphopenia, eosinopenia and monocytosis (1-4). In cats, we would more likely see just a neutrophilia with lymphopenia and eosinopenia (without the monocytosis).

This hemogram response associated with glucocorticoid excess is sometimes referred to as a "stress leukogram," since it is also a common and nonspecific finding in many sick or stressed dogs (1).

The major acute effect of steroids on WBCs is to cause "washout" of marginated neutrophils and monocytes from periphery into circulation. Decreased amounts of lymphocytes (peripheral) and eosinophils are seen as glucocorticoids can sequester these cells into the lungs and spleen and prompt decreased release from the bone marrow. When administered chronically at high enough doses, glucocorticoids can cause involution of lymphoid tissue (1,2).

Steroid effect versus a response to infection?
Infectious responses will often be associated with toxic change in the neutrophils or a significant left shift, which is unusual with steroids. The magnitude of the neutrophilia is also helpful to distinguish between a steroid effect and a response to infection. With glucocorticoids, we can see up to 2-fold increase in dogs and up to 3-fold increase in cats (they have different proportions of neutrophils in circulating versus marginated pools). If the magnitude of the patient's neutrophilia is more severe, then infection is more likely.

Increased platelet numbers
Finally, glucocorticoids inhibit platelet aggregation and can also increase platelet numbers.

Erythrocytosis
With chronic administration (or spontaneous Cushing's syndrome), glucocorticoid excess can increase red cell production and diminish removal of old RBCs, resulting in mild erythocytosis.

References:

1. Feldman BF, Zinkl JG, Jain NC (eds): Schalm's Veterinary Hematology (Fifth edition). New York, Wiley-Blackwell, New York, 2000.
2. Behrend EN, Kemppainen RJ. Glucocorticoid therapy. Pharmacology, indications, and complications. Veterinary Clinics of North America: Small Animal Practice 1997;27:187-213. 
3. Melián C, M. Pérez-Alenza, D, Peterson ME. Hyperadrenocorticism in dogs, In: Ettinger SJ (ed): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Seventh Edition). Philadelphia, Saunders Elsevier, 2010;1816-1840.
4. Herrtage ME, Ramsey IK. Canine hyperadrenocorticism. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association; 2012:167-189.