Leukocytosis

Updated: May 01, 2017
  • Author: Susumu Inoue, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Overview

Background

Leukocytosis refers to an increase in the total number of WBCs due to any cause. From a practical standpoint, leukocytosis is traditionally classified according to the component of white cells that contribute to an increase in the total number of WBCs. Therefore, leukocytosis may be caused by an increase in (1) neutrophil count (ie, neutrophilia), (2) lymphocyte count (ie, lymphocytosis), (3) monocyte count (ie, monocytosis), (4) eosinophilic granulocyte count (ie, eosinophilia), (5) basophilic granulocyte count (ie, basophilia), or (6) immature cells (eg, blasts). A combination of any of the above may be involved.

The image below is an illustration of high and low WBC counts.

WBC counts. WBC counts.

Neutrophilia also is divided into 4 categories based on the mechanism of neutrophilia: (1) increased production, (2) decreased egress from vascular space (demargination), (3) increased mobilization from the marrow storage pool, and (4) reduced margination into the tissue.

Clinically, dividing leukocytosis on the basis of its causes is more convenient. By dividing it according to causes, leukocytosis can be immediately applied for diagnostic purposes. Leukocytosis can be caused by infection, inflammation, allergic reaction, malignancy, hereditary disorders, or other miscellaneous causes.

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Pathophysiology

Leukocytosis can be a reaction to various infectious, inflammatory, and, in certain instances, physiologic processes (eg, stress, exercise). 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, and (4) the rate of consumption of the cells in the tissues (ie, cell loss). The growth factors, adhesion molecules, and cytokines control all 4 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 30,000/μL as a reaction to extrinsic factors, such as infection, it is sometimes called a leukemoid reaction.

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 in bacterial infection in patients with sickle cell disease.

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Epidemiology

Mortality/Morbidity

Clinically significant morbidity and mortality are frequently observed in patients with leukemic hyperleukocytosis. Hyperleukocytosis may result in tumor lysis syndrome and disseminated intravascular coagulopathy. In addition to well-known complications (eg, acute respiratory failure, pulmonary hemorrhage, CNS infarction, hemorrhage), splenic infarction, myocardial ischemia, renal failure due to renal vessel leukostasis, and priapism have been reported.

A study by Canaani et al indicated that in patients with newly diagnosed acute myeloid leukemia who are being treated with allogeneic stem cell transplantation, the presence of hyperleukocytosis is independently linked to an increased incidence of relapse, reduced leukemia-free survival, and decreased overall survival. [2]

A study by Martinelli et al indicated that in patients with chronic lymphocytic leukemia, disease stage and the presence of lymphocytosis predict a shorter time to first treatment. [3]

Age

Always remember age-specific reference ranges for total WBC, neutrophil, and lymphocyte counts. The total WBC and neutrophil count in neonates younger than 1 week are physiologically higher than those of older children and adults. The proportion of lymphocytes and absolute lymphocyte count in children younger than 6 years are higher than those in adults. Failure to recognize age-specific lymphocytosis may lead to unnecessary investigations (see the table below for reference ranges of age-related leukocyte counts).

Infants (usually aged < 3 mo) have small storage pools of neutrophils. In severe infections, their neutrophilic demands often exceed their supplies. Therefore, young infants may have neutropenia in response to serious infection.

Table. Normal Leukocyte Counts (Open Table in a new window)

    Total Leukocytes*   Lymphocytes   Neutrophils   Monocytes   Eosinophils
Age   Mean Range   Mean Range %   Mean Range %   Mean %   Mean %
Birth   ... ...   4.2 2-7.3 ...   4 2-6 ...   0.6 ...   0.1 ...
12 h   ... ...   4.2 2-7.3 ...   11 7.8-14.5 ...   0.6 ...   0.1 ...
24 h   ... ...   4.2 2-7.3 ...   9 7-12 ...   0.6 ...   0.1 ...
1-4 wk   ... ...   5.6 2.9-9.1 ...   3.6 1.8-5.4 ...   0.7 ...   0.2 ...
6 mo   11.9 6-17.5   7.3 4-13.5 61   3.8 1-8.5 32   0.6 5   0.3 3
1 y   11.4 6-17.5   7.0 4-10.5 61   3.5 1.5-8.5 31   0.6 5   0.3 3
2 y   10.6 6-17   6.3 3-9.5 59   3.5 1.5-8.5 33   0.5 5   0.3 3
4 y   9.1 5.5-15.5   4.5 2-8 50   3.8 1.5-8.5 42   0.5 5   0.3 3
6 y   8.5 5-14.5   3.5 1.5-7 42   4.3 1.5-8 51   0.4 5   0.2 3
8 y   8.3 4.5-13.5   3.3 1.5-6.8 39   4.4 1.5-8 53   0.4 4   0.2 2
10 y   8.1 4.5-13.5   3.1 1.5-6.5 38   4.4 1.8-8 54   0.4 4   0.2 2
16 y   7.8 4.5-13   2.8 1.2-5.2 35   4.4 1.8-8 57   0.4 5   0.2 3
21 y   7.4 4.5-11   2.5 1-4.8 34   4.4 1.8-7.7 59   0.3 4   0.2 3
 



* Numbers of leukocytes are in X 109 \L or thousands per μ L; ranges are estimates of 95% confidence limits; and percentages refer to differential counts.



Neutrophils include band cells at all ages and a small number of metamyelocytes and myelocytes in the first few days of life.



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