Leukopenia
David T. Teachey
INTRODUCTION
Leukopenia is defined as a decrease in the total white blood cell (WBC) count, usually to >4,000/mm3. Neutropenia is defined as a decrease in the number of circulating neutrophils (both segmented and band forms). An absolute neutrophil count (ANC) of 1,500/mm3 or less is typically considered neutropenia. Severe neutropenia refers to an ANC of >500/mm3. The ANC is calculated by multiplying the total WBC count by the sum of the percentage of segmented neutrophils plus the percentage of band forms in the differential count. For example, if the WBC count is 4,000/mm3, with 12% segmented neutrophils/polymorphonuclear leukocytes, 10% bands, 60% lymphocytes, and 18% monocytes, the ANC will be 880 [4000 × (0.12 + 0.10)]. The differential diagnoses of isolated leukopenia and neutropenia are similar; the two conditions are, therefore, considered one entity for the purpose of this chapter.
HINT: In 3% to 5% of African-American children, the total WBC count normally may be as low as 3,600/mm3, and the ANC may be as low as 1,000/mm3.
DIFFERENTIAL DIAGNOSIS LISTInfectious Causes
Bacterial Infection
Sepsis syndrome, bacteremia (especially group B streptococcal disease in neonates)
Tuberculosis
Brucellosis
Tularemia
Typhoid
Paratyphoid
Viral Infection
Hepatitis A or B
Parvovirus B19
Respiratory syncytial virus
Influenza A or B
Rubeola
Varicella
Rubella
Infectious mononucleosis (Epstein-Barr virus)
HIV
Cytomegalovirus
Protozoal Infection
Malaria
Kala-azar (visceral leishmaniasis)
Rickettsial Infection
Scrub typhus
Sandfly fever
Congenital Causes
Kostmann syndrome
Cyclic neutropenia
Shwachman-Diamond syndrome (neutropenia and exocrine pancreatic insufficiency)
Reticular dysgenesis
Barth syndrome (neutropenia, cardiomyopathy, myopathy)
Neutropenia associated with X-linked agammaglobulinemia
Neutropenia associated with dysgammaglobulinemia type I (neutropenia, absent immunoglobulin A [IgA] and IgG, and increase in IgM)
Neutropenia associated with metabolic disease (hyperglycemia, isovaleric acidemia, propionic acidemia, methylmalonic acidemia)
Neutropenia as part of bone marrow failure syndrome (Fanconi anemia, dyskeratosis congenital, Blackfan-Diamond syndrome)
Immune-Mediated Causes
Autoimmune neutropenia (owing to IgG-mediated destruction of neutrophils)
Felty syndrome (triad of neutropenia, splenomegaly, and rheumatoid arthritis)
Secondary to collagen vascular disease—juvenile rheumatoid arthritis or systemic lupus erythematosus (SLE) (lymphopenic common in SLE)
Neonatal alloimmune neutropenia (antibody derived from mother)
Miscellaneous Causes
Aplastic anemia
Splenic sequestration
Nutritional deficiency (B12 or folate deficiency)
Copper deficiency
Familial benign neutropenia
Leukemia
Bone marrow infiltration (with tumor, osteopetrosis, Gaucher disease)
Chronic idiopathic neutropenia
DIFFERENTIAL DIAGNOSIS DISCUSSION
Neutropenia Associated with Infection
Infection, usually viral, is the most common cause of neutropenia in childhood. Typically, neutropenia develops during the first few days of infection and persists for 3 to 8 days. Neonates are at especially high risk for developing neutropenia because they have only a small neutrophil reserve in their bone marrow, and they release neutrophils too quickly into the circulation when stressed. The mechanism by which an infection causes neutropenia is most often caused by direct marrow suppression or viral-induced immune neutropenia. Leukopenia is common in patients with HIV. Management of neutropenia in patients with infections consists of treating the underlying infection.
TABLE 49-1 Drugs That Can Induce Neutropenia or Leukopenia Cytotoxic Chemotherapeutics | |||||||||||||||||||
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Drug-Induced Neutropenia
Etiology
Drug-induced neutropenia may be caused by a cytotoxic effect, an immunologic effect, or may be an idiosyncratic reaction. Neutropenia can be a result of the following:
Increased sensitivity of myeloid precursors to appropriate drug concentrations.
Altered drug metabolism resulting in toxic levels of the drug in the bone marrow.
An immunologic response that occurs after exposure to the drug, resulting in neutrophil destruction. In some cases, the drug serves as a hapten in promoting antibodies that can destroy neutrophils. In other cases, the drug causes the formation of circulating immune complexes that attach to the surface of the neutrophil and lead to its destruction.
