Disorders of White Blood Cells

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51 Disorders of White Blood Cells

Daniel A. Weiser

White blood cells (WBCs), or leukocytes, are an integral part of the host immune system. Their microscopic appearance after Wright-staining categorizes them as either granulocytes (neutrophils, eosinophils, and basophils) or agranulocytes (monocytes, macrophages, and lymphocytes). Each WBC has a specific function within the immune system (Figure 51-1).

Figure 51-1 Features of white blood cells in Wright-stained blood smears.

A complete blood count (CBC) and manual differential notes the total number of WBCs per microliter of sample as well as the percentages of each subset of WBC. Absolute counts for each WBC are more clinically meaningful than percentages. Reference ranges for the WBC differential vary by age. In general, newborns have high total WBC counts (≤30,000/µL). At about 1 week of age, an infant’s total WBC decreases into the range of 5000 to 21,000/µL. Through the toddler and childhood years, the mean WBC count decreases slowly to an adult average of 7500/µL. Lymphocyte predominance is seen from 2 weeks to about 5 years of age. Then neutrophils are predominant, making up more than 50% of the differential. Monocytes, eosinophils, and basophils make up a very small percentage of the total WBC from the neonatal period through adulthood.

Etiology and Pathogenesis

WBCs derive from hematopoietic progenitor cells in the bone marrow (Figure 51-2). Their maturation is induced by colony-stimulating factors.

Figure 51-2 Stages of hematopoiesis.

This chapter focuses on congenital and acquired neutrophil disorders with a brief discussion regarding disorders of eosinophils, basophils, and monocytes. Disorders of lymphocytes, part of the body’s acquired (adaptive) immunity, are discussed in the immunology section (see Chapter 21).

Neutrophils are part of the innate (natural) immune system. After they are released by the bone marrow, they remain in the circulation for 6 to 12 hours. They migrate to sites of infection and engulf, digest, and destroy microorganisms. A large portion of mature neutrophils reside in the bone marrow and along blood vessels in endothelial cells.

Neutropenia is defined as a decrease in the absolute neutrophil count (ANC) to less than 1500/µL. Neutropenia is considered severe if the ANC is less than 500/µL, moderate between 500/µL and 1000/µL, and mild between 1000/µL and 1500/µL. The risk of serious infection is inversely proportional to the ANC. Of note, the ANC is usually about 200 to 600/µL lower in African Americans compared with other races likely secondary to decreased neutrophil release from the bone marrow. This does not lead to a greater predisposition for infection.

Clinical Presentation and Differential Diagnosis

Congenital Disorders of Neutrophils

Because neutrophils play a key role in host defense, the primary signs and symptoms of neutropenia are related to an increased susceptibility to infection, particularly bacterial and fungal. Children with chronic neutropenia can develop cellulitis, perirectal or other deep tissue abscesses, oral ulcers, periodontal disease, pneumonia, and septicemia. Endogenous Staphylococcus aureus or gram negative organisms are frequently isolated. Clinical signs of infection, such as erythema and warmth, may be diminished secondary to a decreased neutrophil response.

There are multiple congenital neutropenias that are being further categorized as knowledge of the genetic basis of disease improves (Tables 51-1 and 51-2). These congenital disorders are exceedingly rare.

Table 51-1 Congenital Disorders of Neutrophil Development

Table 51-2 Additional Congenital Disorders Associated with Neutropenia

Disorder	Clinical Manifestations
Cartilage-hair hypoplasia	Short limbs, dwarfism, abnormally fine hair
Myelokathexis with dysmyelopoiesis	Marrow retention of neutrophils, recurrent bronchopulmonary infections
Dyskeratosis congenita	Bone marrow failure syndrome; dystrophic changes in nails, skin (hyperpigmentation), and mucous membranes (leukoplakia)
Fanconi anemia	Bone marrow failure syndrome; GU and skeletal abnormalities, increased chromosome fragility
Organic acidemias (propionic, methylmalonic)	Initially well at birth, then toxic encephalopathy
Osteopetrosis	Defective bone turnover with resultant hematopoietic insufficiency and bone fragility
Reticular dysgenesis (congenital aleukocytosis)	Absent WBC, hypogammaglobulinemia, thymic hypoplasia, severe infection and death in infancy
Immunodeficiencies (severe combined immunodeficiency, common variable immunodeficiency, hyper-IgM)	Frequent infections, failure to thrive, hepatosplenomegaly
Glycogen storage disease type 1b (von Gierke disease) and other inborn errors of metabolism	Neutropenia and functional neutrophil defect, hepatosplenomegaly

GU, genitourinary; WBC, white blood cell.

Neutrophil Function Defects

Complex physiologic processes are involved in neutrophil phagocytosis of microbes. An abnormality in any of the steps—adhesion, chemotaxis, opsonization, ingestion/phagocytosis, degranulation, and oxidative metabolism (bacterial killing)—results in inadequate neutrophil functioning. Susceptibility is to bacteria and fungi, with intact resistance to viral infections.

Although very rare in general, some neutrophil function defects are relatively more common (Table 51-3). Acquired defects of chemotaxis can also occur secondary to diabetes mellitus, metabolic storage diseases, malnutrition, immaturity, and burns.

Table 51-3 Congenital Disorders of Neutrophil Function

Acquired Disorders of Neutrophils

Acquired neutropenia, which is much more common than congenital neutropenia, is the result of decreased WBC production secondary to suppression of bone marrow synthesis or antibodies directed against neutrophils.

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