Evaluation of Patients with Leukocytosis

 


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An elevated white blood cell count has many potential etiologies, including malignant and nonmalignant causes. It is important to use age- and pregnancy-specific normal ranges for the white blood cell count. A repeat complete blood count with peripheral smear may provide helpful information, such as types and maturity of white blood cells, uniformity of white blood cells, and toxic granulations. The leukocyte differential may show eosinophilia in parasitic or allergic conditions, or it may reveal lymphocytosis in childhood viral illnesses. Leukocytosis is a common sign of infection, particularly bacterial, and should prompt physicians to identify other signs and symptoms of infection. The peripheral white blood cell count can double within hours after certain stimuli because of the large bone marrow storage and intravascularly marginated pools of neutrophils. Stressors capable of causing an acute leukocytosis include surgery, exercise, trauma, and emotional stress. Other nonmalignant etiologies of leukocytosis include certain medications, asplenia, smoking, obesity, and chronic inflammatory conditions. Symptoms suggestive of a hematologic malignancy include fever, weight loss, bruising, or fatigue. If malignancy cannot be excluded or another more likely cause is not suspected, referral to a hematologist/oncologist is indicated.

Leukocytosis, often defined as an elevated white blood cell (WBC) count greater than 11,000 per mm3 (11.0 × 109 per L) in nonpregnant adults, is a relatively common finding with a wide differential. It is important for clinicians to be able to distinguish malignant from non-malignant etiologies, and to differentiate between the most common nonmalignant causes of leukocytosis.

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Leukocytosis greater than 100,000 per mm3 (100.0 × 109 per L) is almost always caused by leukemias or myeloproliferative disorders.

C

2

Leukocytosis is not a reliable indicator of postpartum bacterial infection.

C

6

Patients with leukocytosis and no other signs of systemic inflammatory response syndrome do not require blood cultures.

C

19


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Leukocytosis greater than 100,000 per mm3 (100.0 × 109 per L) is almost always caused by leukemias or myeloproliferative disorders.

C

2

Leukocytosis is not a reliable indicator of postpartum bacterial infection.

C

6

Patients with leukocytosis and no other signs of systemic inflammatory response syndrome do not require blood cultures.

C

19


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

Leukocytosis in the range of approximately 50,000 to 100,000 per mm3 (50.0 to 100.0 × 109 per L) is sometimes referred to as a leukemoid reaction. This level of elevation can occur in some severe infections, such as Clostridium difficile infection, sepsis, organ rejection, or in patients with solid tumors.1 Leukocytosis greater than 100,000 per mm3 is almost always caused by leukemias or myeloproliferative disorders.2

Normal Variation

The normal range for WBC counts changes with age and pregnancy (Table 1).3 Healthy newborn infants may have a WBC count from 13,000 to 38,000 per mm3 (13.0 to 38.0 × 109 per L) at 12 hours of life (95% confidence interval). By two weeks of age, this decreases to approximately 5,000 to 20,000 per mm3 (5.0 to 20.0 × 109 per L), and gradually declines throughout childhood to reach adult levels of 4,500 to 11,000 per mm3 (4.5 to 11.0 × 109 per L; 95% confidence interval) by about 21 years of age.3 There is also a shift from relative lymphocyte to neutrophil predominance from early childhood to the teenage years and adulthood.4 During pregnancy, there is a gradual increase in the normal WBC count (third trimester 95% upper limit = 13,200 per mm3 [13.2 × 109 per L] and 99% upper limit = 15,900 per mm3 [15.9 × 109 per L]), and a slight shift toward an increased percentage of neutrophils.5 In one study of afebrile postpartum patients, the mean WBC count was 12,620 per mm3 (12.62 × 109 per L) for women after vaginal deliveries and 12,710 per mm3 (12.71 × 109 per L) after cesarean deliveries. Of note, positive bacterial

The Authors

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LYRAD K. RILEY, MD, is a faculty member at the U.S. Air Force Eglin Family Medicine Residency Program, Eglin Air Force Base, Fla., and an assistant professor in the Department of Family Medicine at the Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Md....

JEDDA RUPERT, MD, is a second-year resident at the U.S. Air Force Eglin Family Medicine Residency Program

Author disclosure: No relevant financial affiliations.

Address correspondence to Lyrad K. Riley, MD, Eglin AFB Family Medicine Residency, 307 Boatner Rd., Eglin Air Force Base, FL 32542 (e-mail: lyrad.riley@us.af.mil). Reprints are not available from the authors.

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