EBM Consult

Average Increases in White Blood Cell (WBC) Counts with Glucocorticoids (e.g., Dexamethasone, Methylprednisolone, and Prednisone)

Summary:

  • Glucocorticoids (e.g., dexamethasone, methylprednisolone, prednisone) are known to increase the white blood cell (WBC) count upon their initiation.  The increase in WBC count is primarily contributed from neutrophils (polymorphonuclear leukocytes; PMN).
  • The biologic effects that contribute to the increase in PMNs in the circulation are multifactorial with demargination of neutrophils contributing the most, as well as delayed migration of PMNs into tissue, delayed rate of apoptosis and the release of immature (bands) neutrophils from the bone marrow into the circulation.
  • Increases in the WBC count have been reported to be approximately 4,000/mm3 with the use of glucocorticoids although with a high degree of variability with some patients reaching levels greater than 20,000/mm3.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA

Last Reviewed: October 2017

Explanation

  • The white blood cell (WBC) count normally drawn from a patient is made up of a number of different leukocytes which include neutrophils at 60-70%, lymphocytes at 28%, monocytes at 5%, eosinophils at 2-4%, and basophils at 0.5% of the total.1  When a WBC count is done on a patient, the lab value reflects 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 amount of leukocytes in the total WBC count 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 in their appearance.  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 called to fight against.  This is normally seen or called a "left shift" in a WBC differential.2  As the immature neutrophils become activated or exposed to bacterial pathogens, their nucleus will take on a segmented appearance.  These and other neutrophils can be found in several compartments within the body, but the two compartments that relate to the importance of 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).  All of this information is important for the proper interpretation for the reasons that the WBC count has increased, especially when glucocorticoids (e.g., dexamethasone, methylprednisolone, and prednisone) are being given.  

    It is well known that glucocorticoids (e.g., dexamethasone, methylprednisolone, prednisone) cause increases in the WBC counts.2-4  Upon further evaluation of the increased WBC count, it is the PMNs that contribute the most to the increase.  The causes for glucocorticoid induced increases in WBC counts include demargination of neutrophils from the endothelial surface of blood vessels, delayed transmigration of neutrophils into the tissue, delayed apoptosis, and an increase in the release of neutrophils from the bone marrow.4-10  While all of these contribute to the increases in circulating neutrophils seen on a WBC count, they do so at different degrees with demargination being the predominate effect.4  Some studies have shown increases in WBC counts greater than 20,000/mm3 that started as early as the first day and reached maximum levels at approximately two weeks.3,6,11  The average increases in WBC count have been reported to be approximately 4,000/mm3 in patients taking 40-80 mg of oral prednisone, however there is a high degree of variability that may, in part, be related to the dose of glucocorticoid.3,12

    While it is important to know the degree of increases in WBC counts, it is just as important to be able to appropriately assess the WBC differential, so as to avoid missing a treatable condition.  The above increases in neutrophils are made up by a small portion of immature (bands) WBC that predominately came from the bone marrow.  However, this contribution of bands does not usually cause the same degree of a "left shift" that is normally associated with presence of a bacterial infection.3  In addition, glucocorticoid induced leukocytosis is generally not associated with increases in temperature or worsening in the condition that is being appropriately treated.  Therefore, it is important for the clinician to put all of these factors in context when assessing, monitoring and treating the patient's medical condition.

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References

    1. Junqueira LC, Carneiro J.  Blood cells.  In: Basic Histology.  11th ed.  Junqueira LC, Caneiro J eds.  McGraw-Hill Medical Publishing Division.  New York, NY. 2005; 223-237.
    2. Abramson N, Melton B.  Leukocytosis: basic of clinical assessment.  Am Fam Physician  2000;62:2053-60.  
    3. Shoenfeld Y, Gurewich Y, Gallant LA, et al.  Prednisone-induced leukocytosis. Influenced of dosage, method and duration of administration on the degree of leukocytosis.  Am J Med  1981;71:773-8.  
    4. Nakagawa M, Terashima T, D'yachkova Y et al.  Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes.  Circulation  1998;98:2307-13.  
    5. Burton JL, Kehrli ME Jr, Kapil S et al.  Regulation of L-selectin and CD18 on bovine neutrophils by glucocorticoids: effects of cortisol and dexamethasone.  J Leukoc Biol  1995;57:317-25.  
    6. Waisman D, Van Eeden SF, Hogg JC et al.  L-selectin expression on polymorphonuclear leukocytes and monocytes in premature infants: reduced expression after dexamethasone treatment for bronchopulmonary dysplasia.  J Pediatr  1998;132:53-6.  
    7. Weber PS, Toelboell T, Chang LC et al.  Mechanisms of glucocorticoid-induced down-regulation of neutrophil L-selectin in cattle: evidence for effects at the gene-expression level and primarily on blood neutrophils.  J Leukoc Biol  2004;75:815-27.     
    8. Liles WC, Dale DC, Klebanoff SJ.  Glucocorticoids inhibit apoptosis of human neutrophils.  Blood  1995;86:3181-8.  
    9. Cox G.  Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes.  J Immunol  1995;154:4719-25.  
    10. Bishop CR, Athens JW, Boggs DR et al.  Leukokinetic studies. 13. A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis.  J Clin Invest  1968;47:249-60.  
    11. Fauci AS, Dale DC, Balow JE.  Glucocorticoid therapy: mechanisms of action and clinical considerations.  Ann Intern Med  1976;84:304-15.  
    12. Dale DC, Fauci AS, Guerry D IV et al.  Comparison of agents producing a neutrophilic leukocytosis in man.  Hydrocortisone, prednisone, endotoxin, and etiocholanolone.  J Clin Invest  1975;56:808-13.

Keywords

  • Steroids, Glucocorticoids, Dexamethasone, Methylprednisolone, Prednisone, White Blood Cell, WBC, Neutrophils, Leukocytes, PMN, Polymorphonuclear Neutrophils