The
white blood cell (WBC) count is a routine laboratory test that reflects the
number of leukocytes (or WBC) distributed in the blood. The leukocytes
that make up a typical WBC count on a lab analysis include neutrophils at
60-70%, lymphocytes at 28%, monocytes at 5%, eosinophils at 2-4%, and basophils
at 0.5%.1 When a WBC count is performed, the values reflect the
leukocytes distributed within the blood and not those in the bone marrow,
tissue or attached to the endovascular lining of blood vessels. It is
evident that the neutrophils make up the greatest percentage of leukocytes and
thus can have the greatest impact on changes in the WBC count.
Neutrophils are also called polymorphonuclear leukocytes (PMN) because of the
number of stages they go through during their life cycle. They are
initially released from the bone marrow as immature neutrophils that are
characterized as having a nonsegmented, band like appearing nucleus. As
such, these immature neutrophils are called "bands". An
increase in the number of these immature neutrophils in circulation can be
indicative of a bacterial infection for which they are being generated to
fight. This is known as the "left shift" seen in a WBC
differential.2 As the immature neutrophils become activated or exposed to
bacterial pathogens, their nucleus will take on a segmented appearance due to
increases gene transcription. These and other neutrophils can be found in
several compartments in the body, but the two compartments that relate most to
this newsletter are the marginal compartment (those neutrophils attached to the
endothelium of the blood vessel) and the circulating compartment (those
circulating in the blood vessels along with other cells). Understanding
this information is critical for the proper assessment of an elevated WBC
count, especially when glucocorticoids (e.g., dexamethasone,
methylprednisolone, prednisone) have been administered to the patient.
While
glucocorticoids are used to inhibit inflammation and the immune response in
certain clinical situations, their initiation may also cause an increase in the
WBC count.2-4 A more detailed inspection of the differential will reveal
the PMNs to be the main contributors to the increase. Since increases in
PMNs can be associated with bacterial infections, the use of the WBC
differential can be helpful at determining whether or not the increase in WBC
count was from a bacterial infection or the initiation of
glucocorticoids. The initiation of glucocorticoids does not usually cause
the same degree of a "left shift" that is normally associated with
presence of a bacterial infection.3,4 In addition, glucocorticoid
induced leukocytosis generally is not associated with increases in temperature
or worsening of the condition being treated. Determining the cause of the WBC
increase is especially important, and often more difficult, in the
immunocompromised patient.
What are main causes of steroid induced increases in the WBC
count?
The answer is a multifactorial culmination of the following biological effects
of the glucocorticoids.
- The greatest effect is demargination of the
neutrophils from the endovascular lining.4 In short, this is where the
neutrophils attached to the endothelial lining of the blood vessels become
detached and are then free in circulation. As a result, when a lab
is drawn via venipuncture from a patient to determine the WBC count, there will
now be a greater number of circulating PMNs. However, it is important to
note that the total number of PMNs has not changed, just the percentage of PMNs
residing in each compartment. The demargination of neutrophils makes up
approximately 61% of the increase in WBC.4 The details of how
glucocorticoid administration causes demargination is described in this EBM Consult article ... click here
- The second contributing factor is a combination of
delayed migration from the circulation into the tissue and improved survival of
circulating neutrophils by suppressing apoptosis (programmed cell death).4-9
These two make up approximately 29% of the increase in WBC count.4 The
delayed migration into tissue is due to glucocorticoid induced down regulation
of adhesion molecules on both neutrophils (i.e., L-selectin) and endothelial
cells (i.e., ICAM-1, ECAM-1, Mac-1) lining the blood vessel; these normally
allow neutrophils to stay attached to and facilitate transmigration through the
vessel wall and into the tissue.5-7 The mechanism for delayed apoptosis
is not fully known.8,9
- The third factor is glucocorticoid induced release
of non-segmented (bands) neutrophils from the bone marrow into the general
circulation.4,10
- This last component makes up only 10% of the
increase in WBC count and thus is the reason that patients may not show as
significant a "left shift" as would be seen with bacterial
infections.
It
is common for patients to reveal a leukocytosis (increased WBC count) within 24
hours of initiation of a glucocorticoid. It is important for clinicians
to be aware of this expected side effect and to understand the rationale for
such an increase as well as appropriate interpretation of the labs given the
patient's clinical condition. Keeping all of these things in mind will
help clinicians avoid unnecessary medical work-up for other conditions and
avoid patient exposure to additional drug therapy that is not warranted, such
as intravenous antibiotics.
