Pediatric Fever And Neutropenia: An Evidence-Based Approach
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Pediatric Fever And Neutropenia: An Evidence-Based Approach

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Table of Contents
Table of Contents
  1. Abstract
  2. Practice Recommendations (key points from the issue)
  3. Case Presentations
  4. Pathophysiology
  5. Epidemiology And Etiology
  6. Causes Of Neutropenia
    1. Acute Transient Neutropenia Of Childhood
    2. Chronic Benign Neutropenia Of Childhood
    3. Cyclic Neutropenia
    4. Aplastic Anemia
    5. Congenital Neutropenia
  7. Prehospital Treatment
  8. Emergency Department Evaluation
  9. Diagnostic Studies
  10. Emergency Department Management
  11. Special Circumstances: Neutropenia In Patients Undergoing Chemotherapy
  12. Controversies And Cutting Edge
  13. Disposition
  14. Risk Management Pitfalls For Pediatric Fever And Neutropenia
  15. Summary
  16. Case Conclusion
  17. Clinical Pathway 1: Patient With ANC < 500 Or Chemotherapy-Induced Neutropenia
  18. Clinical Pathway 2: Patient With Mild To Moderate Neutropenia
  19. References


A complete blood cell count (CBC) is often ordered by emergency department (ED) staff in an effort to better define a disease process or assign risk to a patient's illness. The ED clinician must be prepared to manage the CBC results even when they are abnormal or not easily explained. One of the most worrisome abnormal findings in children is pediatric neutropenia, defined as an absolute neutrophil count (ANC) less than 1500/μL. Neutropenia can represent an increased risk for invasive disease and have an etiology that is not always readily apparent, especially when accompanied by a fever. This issue of Pediatric Emergency Medicine Practice focuses on the challenge of evaluating and treating the pediatric patient who presents with a fever and neutropenia. A discussion of chemotherapy- induced neutropenia is included in the Special Circumstances section at the end of the article.

Practice Recommendations (key points from the issue)

Click here to download a PDF of the Evidence-Based Practice Recommendations for this issue.

Case Presentations

A resident asks you to review a patient at the end of your shift. The patient, a 4-year-old Caucasian female, has a 2-day history of fever (temperature up to 39.4°C [102.9ºF]), a 3-day history of cough, and symptoms suggestive of a URI. Her triage sheet notes BP, 120/45 mm Hg; HR, 135 bpm; R, 20 bpm; temperature, 38.9°C (102.2ºF); and oxygen saturation of 99% on room air. Upon entering the room, you notice that the girl appears well. The results of her physical examination are normal, with the exception of mildly dry mucous membranes and mild tachycardia. The resident had previously ordered a complete blood cell count that reveals the following values: WBC, 3000/μL; Hb, 13g/dL; Hct, 39%; and Plt, 150,000/μL. The patient's differential count shows 33% neutrophils, 62% lymphocytes, and 5% monocytes. The resident asks if an absolute neutrophil count of 990 μ/L is normal for a patient of this age. How do you respond?

Risk Management Pitfalls For Pediatric Fever And Neutropenia

1. "The total white blood cell count was normal, so I didn't think the patient was neutropenic." Too often CBCs are ordered, but the differential count is not fully examined. Focusing on the total WBC might lead the emergency clinician to miss a potentially important diagnosis. To evaluate for neutropenia, the clinician must always calculate the ANC.

2. "I've diagnosed this patient with neutropenia, but my colleagues tell me the ANC might be normal for this patient." Normal values for ANC vary not only with age, but also with race. An emergency clinician should consult a reference manual for normal values.

3. "My neutropenic patient is irritable and febrile and is refusing oral medications. I have ordered rectal acetaminophen to treat the fever." Obtaining rectal temperatures or administering medications by the rectal route may disrupt the mucosa and introduce bacteria. These seemingly minor occurrences can cause a potentially life-threatening infection.

4. "I did a quick examination of a patient who is neutropenic, but I didn't find the source of any infection." The practitioner must ensure that a thorough examination is completed on every patient who is febrile and neutropenic. This examination must include an inspection of mucosal surfaces such as the oral mucosa and perirectal area.

5. "A CBC shows that my patient has an ANC of 1200/μL. I've initiated broad-spectrum antibiotics and admitted this patient to the hospital." Although fever and neutropenia can represent a potentially life-threatening infection, a previously healthy patient who is well appearing with normal vital signs may be discharged to home if adequate follow-up can be obtained. Please note this does not include any patient with chemotherapy-induced fever and neutropenia.

6. "A patient who is neutropenic needs an immediate

referral to a specialist." Although some episodes of neutropenia may represent severe underlying illnesses, a thorough history with careful attention to recurrent infections, cyclic fevers, or current medications may help to elucidate a diagnosis requiring follow-up with a general pediatrician.

7. "My patient has a fever, neutropenia, and a cough. However, results of the chest radiograph are normal, so the patient cannot have pneumonia."A patient with neutropenia may not have the same radiographic findings as a child with a healthy immune system. Neutropenia may affect the patient's ability to mount an inflammatory response, resulting in an infiltrate visible on radiograph.

8. "A patient who has chemotherapy-induced neutropenia and is well appearing can be admitted to the hospital for observation, but he or she doesn't need to have antibiotics initiated." Infection in chemotherapy-induced neutropenia is a significant cause of morbidity and mortality. Prompt initiation of broad-spectrum antimicrobials can significantly improve the outcome in these patients. Empiric parenteral antibiotic therapy (eg, ceftazidime, cefepime, or meropenem with or without vancomycin) should be initiated to cover S aureusP aeruginosaE coli, and Klebsiella organisms.

9. "My patient has cancer and received chemotherapy 2 weeks ago. I should wait for the laboratory results to make sure she is neutropenic before starting antibiotics." Early initiation of antibiotics has drastically reduced the mortality rates related to infectious complications in patients with chemotherapy-induced fever and neutropenia. Prompt institution of broad-spectrum antibiotics such as cefepime or meropenem is recommended and should not be delayed while awaiting laboratory results for patients with suspected neutropenia.


Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report. To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study, will be included in bold type following the reference,where available.

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Jennifer Sundberg; Cristina Estrada; Thomas J. Abramo

Publication Date

July 1, 2009

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