Evaluation of Patients with Leukocytosis

1 Evaluation of Patients with Leukocytosis LYRAD K. RILEY, MD, and JEDDA RUPERT, MD, Eglin Air Force Base Family Medicine Residency, Eglin Air Force Base, Florida 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.

2 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 stor- age 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 medi- cations, asplenia, smoking, obesity, and chronic inflammatory conditions. Symptoms suggestive of a hematologic malignancy include fever, weight loss, bruising, or fatigue.

3 If malignancy cannot be excluded or another more likely cause is not suspected, referral to a hematologist/oncologist is indicated. (Am Fam Physician. 2015;92(11):1004-1011. Copyright 2015 American Academy of Family Physicians.). L. CME This clinical content eukocytosis, often defined as an ele- ( to 109 per L; 95% confidence conforms to AAFP criteria vated white blood cell (WBC) count interval) by about 21 years of There is for continuing medical education (CME). See greater than 11,000 per mm3 ( also a shift from relative lymphocyte to neu- CME Quiz Questions on 109 per L) in nonpregnant adults, trophil predominance from early childhood page 977.

4 Is a relatively common finding with a wide to the teenage years and During Author disclosure: No rel- differential. It is important for clinicians to pregnancy, there is a gradual increase in the evant financial affiliations. be able to distinguish malignant from non- normal WBC count (third trimester 95%. malignant etiologies, and to differentiate upper limit = 13,200 per mm3 [ 109. between the most common nonmalignant per L] and 99% upper limit = 15,900 per mm3. causes of Leukocytosis . [ 109 per L]), and a slight shift toward Leukocytosis in the range of approxi- an increased percentage of In mately 50,000 to 100,000 per mm3 ( to one study of afebrile postpartum Patients , 109 per L) is sometimes referred to as the mean WBC count was 12,620 per mm3.

5 A leukemoid reaction. This level of elevation ( 109 per L) for women after vaginal can occur in some severe infections, such as deliveries and 12,710 per mm3 ( 109. Clostridium difficile infection, sepsis, organ per L) after cesarean deliveries. Of note, pos- rejection, or in Patients with solid itive bacterial cultures were not associated Leukocytosis greater than 100,000 per mm3 with Leukocytosis or neutrophilia, making is almost always caused by leukemias or Leukocytosis an unreliable discriminator in myeloproliferative deciding which postpartum Patients require antibiotic Patients of black African Normal Variation descent tend to have a lower WBC count (by The normal range for WBC counts changes 1,000 per mm3 [ 109 per L]) and lower with age and pregnancy (Table 1).

6 3 Healthy absolute neutrophil newborn infants may have a WBC count from 13,000 to 38,000 per mm3 ( to Normal Leukocyte Life Cycle 109 per L) at 12 hours of life (95% and Responses confidence interval). By two weeks of age, The life cycle of leukocytes includes devel- this decreases to approximately 5,000 to opment and differentiation, storage in the 20,000 per mm3 ( to 109 per L), and bone marrow, margination within the vas- gradually declines throughout childhood to cular spaces, and migration to tissues. Stem reach adult levels of 4,500 to 11,000 per mm3 cells in the bone marrow produce cell lines 1004 American Downloaded from theFamily AmericanPhysician Family Physician website at Volume Copyright 2015 American Academy 92, Number of Family the December 1, 2015.

7 Private, noncom- . mercial use of one individual user of the website. All other rights reserved. Contact for copyright questions and/or permission requests. Leukocytosis SORT: KEY RECOMMENDATIONS FOR PRACTICE. Evidence Clinical recommendation rating References of erythroblasts, which become red blood Leukocytosis greater than 100,000 per mm3 C 2. cells; megakaryoblasts, which become plate- ( 109 per L) is almost always caused by leukemias or myeloproliferative disorders. lets; lymphoblasts; and myeloblasts. Lym- Leukocytosis is not a reliable indicator of C 6. phoblasts develop into various types of T.

8 Postpartum bacterial infection. and B cell lymphocytes. Myeloblasts further Patients with Leukocytosis and no other signs of C 19. differentiate into monocytes and granulo- systemic inflammatory response syndrome do cytes, a designation that includes neutro- not require blood cultures. phils, basophils, and eosinophils (Figure 1). Once WBCs have matured within the bone A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited- quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual marrow, 80% to 90% remain in storage in practice, expert opinion, or case series.

9 For information about the SORT evidence the bone marrow. This large reserve allows rating system, go to for a rapid increase in the circulating WBC. count within hours. A relatively small pool (2% to 3%) of leukocytes circulate freely in the peripheral blood1; the rest stay depos- Table 1. White Blood Cell Count Variation with Age ited along the margins of blood vessel walls and Pregnancy or in the spleen. Leukocytes spend most of their life span in storage. Once a leukocyte is Patient characteristic Normal total leukocyte count released into circulation and peripheral tis- Newborn infant 13,000 to 38,000 per mm3.

10 Sues, its life span ranges from two to 16 days, ( to 109 per L). depending on the type of cell. Infant two weeks of age 5,000 to 20,000 per mm3. ( to 109 per L). Differentiation by Type of White Adult 4,500 to 11,000 per mm3. Blood Cell ( to 109 per L). Changes in the normal distribution of Pregnant female (third trimester) 5,800 to 13,200 per mm3. types of WBCs can indicate specific causes ( to 109 per L). of Leukocytosis (Table 2).8 Although the Information from reference 3. differential of the major types of WBCs is important for evaluating the cause of leu- kocytosis, it is sometimes helpful to think in terms of absolute, rather than relative, leukopenias and leukocytoses.