Neutropenia
Neutropenia: Excerpt from The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter
Julie A. Reeves
Neutropenia is not simply a low white blood count (WBC) value. It is defined by the absolute neutrophil count (ANC). The ANC can be calculated as follows: ANC = WBC × (% bands + % neutrophils) × 0.01.
I. Approach. The many causes of neutropenia can be divided into acute and chronic (1–3).
A. Acute causes occur more frequently and produce some external effect on the body, so as to alter a normally functioning bone marrow.
1. Drug-induced. Two mechanisms have been identified—immune-mediated and direct toxicity to the bone marrow. Although theoretically recognized, the exact mechanisms are not clearly understood. Examples include antibiotics (penicillin, cephalosporins, trimethoprim-sulfamethoxazole, chloramphenicol), antithyroidals (propylthiouracil), antipsychotics (thioridazine, clozapine), angiotensin-converting enzyme inhibitors (captopril), antirheumatics (nonsteroidal antiinflammatories, gold, penicillamine), antidepressants (desipramine, imipramine), anticonvulsants (phenytoin, phenobarbital, carbamazepine), and antiarrhythmic drugs (procainamide).
2. Infection. Three mechanisms of infection-induced neutropenia are identified—increased margination of neutrophils, bone marrow suppression, and neutrophil destruction. Bacterial types include gram-positive organisms (Staphylococcus, Streptococcus, Enterococcus, Corynebacterium), gram-negative organisms (Escherichia coli, Klebsiella, Pseudomonas), and anaerobes. Tuberculosis and brucellosis are further examples. Viral sources are seen particularly in children. Respiratory syncytial virus, varicella, influenza A and B, measles, and rubella are implicated. Infection with human immunodeficiency virus (HIV), mononucleosis, or hepatitis can produce severe, protracted neutropenia. In addition, protozoal, fungal, and rickettsial infections may be culprits.
3. Others. Other less common acute or extrinsic factors include bone marrow replacement (leukemia and lymphoma), chemotherapy, radiation, and autoimmune disorders (4).
B. Chronic causes of neutropenia involve impairment of the bone marrow. Such intrinsic factors are usually genetic and, therefore, present in early childhood.
1. Chronic benign neutropenia of childhood can be either congenital or acquired (e.g., viral), and presents in patients aged less than 4 years. Antineutrophil antibodies have been linked to 80% of cases. The ANC is less than 500/mm3, seemingly placing the child in a high risk category. However, as implied in the disease name, children actually have a decreased risk of infection. Although neutrophil production can be impaired, other immunologic defense systems (e.g., lymphocytes) are functioning normally and are adequate to fight off viral invaders. Management is conservative; routinely, it consists of observation and antibiotics only with confirmed infection. The median duration is 20 months, so that by age 4, the disease has regressed (1).
2. Congenital agranulocytosis is a much more worrisome disease with the onset of life-threatening infections in the first year of life. An intrinsic stem cell defect has been implicated. The ANC is less than 500/mm3.
3. Cyclic neutropenia. The hallmark is non–life-threatening infections occurring every 21 days. The repetitive nature of this disease results from oscillations in neutrophil counts. This phenomenon can be confirmed by obtaining a complete blood count (CBC) two to three times a week for 2 months (or two cycles). There appears to be some abnormal regulation of early neutrophil precursor cells. The disease is usually benign, but unfortunately can be life-long.
II. History. The initial workup of neutropenic disease includes an extended history regarding recent or remote drug use, chemotherapy, radiation, or recent infection (5,6). With children, inquire into unexplained childhood deaths in the family. Next, thoroughly examine the skin, mouth, liver, lymph nodes, and perianal regions.
III. Physical examination. The clinical manifestations of neutropenic disease, regardless of cause, are generally the same. That is, they represent signs and symptoms of infection—fever, erythema, pain, tenderness, and increased warmth of localized tissues. All initially involve the skin and mucous membranes. The location of physical features and severity of infection are determined by the ANC. If the ANC is between 500 and 1,000/mm3, oropharyngeal problems (stomatitis, gingivitis, otitis media) and cellulitis are present. Perirectal abscess, pneumonia, and sepsis are seen with an ANC less than 500/mm3.
IV. Testing. Laboratory data should include serial CBC to check for pattern (cyclic vs. random) and evolution (transient vs. chronic). Liver function tests, electrolytes, blood urea nitrogen, creatinine, pan-cultures (blood, stool, urine, lesion), and chest x-ray study are all routine. Optional laboratory studies are a serum immunoglobulin, serum antinuclear antibody, and a bone marrow biopsy (7).
V. Diagnostic assessment. ANC values are classified as mild (1,000–1,500/mm3), moderate (500–1,000/mm3), or severe (<500/mm3). This classification helps to distinguish those patients at low or high risk for infection.
Normal values for the circulating neutrophil count are listed in many texts. In the first day of life, the neutrophil count is approximately 8,000/mm3. Thereafter, counts drop off. Between 6 and 12 months of age, neutrophil counts reach an expected nadir of 1,000/mm3 (1). Beyond 1 year to adult, values of 1,500/mm3 to 10,000/mm3 are considered normal. Interestingly, African-Americans tend to have lower values than the white population.
References
1. Bernini JC. Diagnosis and management of chronic neutropenia during childhood. Pediatr Clin North Am 1996;43:773–792.
2. Boxer LA, Blackwood RA. Leukocyte disorders: quantitative and qualitative disorders of the neutrophil, part 1. Pediatr Rev 1996;17:19–28.
3. Drug-induced agranulocytosis. Drug Ther Bull 1997;35:49–52.
4. Hathorn JW, Lyke K. Empirical treatment of febrile neutropenia: evolution of current therapeutic approaches. Clin Infect Dis 1997;24(Suppl 2):S256–S265.
5. Hughes WT, Armstrong D, Bodey GP, et al. 1997 Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Clin Infect Dis 1997;25:551–573.
6. Kim SK, Demetri GD. Chemotherapy and neutropenia. Hematol Oncol Clin North Am 1996;10:377–395.
7. Welte K, Dale D. Pathophysiology and treatment of severe chronic neutropenia. Ann Hematol 1996;72:158–165.>
Book Source Details
- Book Title: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter
- Author(s): Robert B. Taylor (editor)
- Year of Publication: 2000
- Copyright Details: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter, Copyright © 2000 Lippincott Williams & Wilkins.
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