What is the pathophysiology of leukocytosis?

Updated: May 19, 2020
  • Author: Susumu Inoue, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Leukocytosis can be a reaction to various infectious, inflammatory, and, in certain instances, physiologic processes (eg, stress, exercise, a surgical procedure [as described below]). This reaction is mediated by several molecules, which are released or upregulated in response to stimulatory events that include growth or survival factors (eg, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, c-kit ligand), adhesion molecules (eg, CD11b/CD18), and various cytokines (eg, interleukin-1, interleukin-3, interleukin-6, interleukin-8, tumor necrosis factor).

The peripheral leukocyte count is determined by several mechanisms, including (1) the size of precursor and storage pool of myeloid and lymphoid cells, (2) the rate of release of the cells from the storage pool in the bone marrow, (3) the rate of marginating cells out of blood vessels into the tissues, (4) the rate of consumption of the cells in the tissues (ie, cell loss), and (5) elimination by the spleen. The growth factors, adhesion molecules, and cytokines control the first four mechanisms listed above. For a detailed discussion, see Robbins Pathologic Basis of Disease. [1]

Hyperleukocytosis (WBC count >100 X 109/L, or >100 X 103/µL) occurs in leukemia and myeloproliferative disorders. Hyperleukocytosis often causes vascular occlusion, resulting in ischemia, hemorrhage, and edema of the involved organs. The problem is most commonly observed in acute myelogenous leukemia with high WBC counts. Individuals often clinically present with mental status changes, stroke, and renal or pulmonary insufficiency. If the neutrophil count exceeds 3 x 105/μL as a reaction to extrinsic factors, such as infection, it is sometimes called a leukemoid reaction.

Below are several causes of leukocytosis not related to infection.

In a person with sickle cell disease, the baseline WBC count is elevated with a mean of 12-15 X 109/L (12-15 X 103/µL). This change mainly is due to a shift of granulocytes from the marginated pool to the circulating compartment. The segmented neutrophil count increases in both vaso-occlusive crisis and bacterial infection, in patients with sickle cell disease.

Postoperative leukocytosis is common. A clinical study in patients who had orthognathic (maxillofacial) surgery, which is clean-contaminated surgery, found that postoperative leukocytosis was associated with the preoperative white count and the duration of surgery. Though this study included adult patients, a large percentage were aged 20 years or younger. [37]

Leukocytosis and neutrophilia are very common in Sweet syndrome, or acute febrile neutrophilic dermatosis, with the syndrome being more common in adults. In a retrospective review, the age range of patients with Sweet syndrome was 7-84 years, with the disorder occurring more often in women. The etiology is unknown, but the syndrome is associated with a variety of conditions such as drug intake, autoimmune disease, malignancy, and infection, among others.{ref a }

A retrospective study to look for predictor variables for pulmonary embolism in children found leukocytosis (WBC>11,000) to be one of nine significant variables (odds ratio = 2.1). [38]

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