Approach to the adult with unexplained neutropenia
- Nancy Berliner, MD
Nancy Berliner, MD
- Professor of Medicine
- Harvard Medical School
- Chief, Division of Hematology
- Brigham and Women's Hospital
Neutrophils are mature granulocytic white blood cells (WBC) that defend against infection. Neutropenia is an abnormally low number of circulating neutrophils, which is based on a calculated number from a complete blood count (CBC). (See 'Terminology and definition of neutropenia' below.)
The implications of neutropenia vary widely, from a risk of potentially life-threatening infections in drug-induced neutropenia to a benign finding with essentially no clinical implications in individuals with benign ethnic neutropenia. Thus, it is important to determine the cause of neutropenia, and the associated infectious (and other) risks, so that the patient can be appropriately managed and educated about his/her condition.
This topic will discuss our approach to the evaluation of the adult patient with unexplained neutropenia as a predominant feature of the CBC. The approach to the patient with neutropenia in the setting of other major cytopenias (eg, anemia, thrombocytopenia) is discussed separately. (See "Clinical manifestations and diagnosis of the myelodysplastic syndromes" and "Aplastic anemia: Pathogenesis, clinical manifestations, and diagnosis".)
The management of non-chemotherapy-induced neutropenia is presented separately. (See "Management of the adult with non-chemotherapy-induced neutropenia" and "Overview of neutropenia in children and adolescents", section on 'General aspects of treatment'.)
Fever in a patient who is neutropenic due to chemotherapy, hematopoietic cell transplant, or bone marrow suppression from any cause is a medical emergency. This issue is discussed separately. (See "Overview of neutropenic fever syndromes".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Valent P. Low blood counts: immune mediated, idiopathic, or myelodysplasia. Hematology Am Soc Hematol Educ Program 2012; 2012:485.
- Boxer LA. How to approach neutropenia. Hematology Am Soc Hematol Educ Program 2012; 2012:174.
- Andersen CL, Tesfa D, Siersma VD, et al. Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study. J Intern Med 2016; 279:566.
- Hsieh MM, Everhart JE, Byrd-Holt DD, et al. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med 2007; 146:486.
- Grann VR, Bowman N, Joseph C, et al. Neutropenia in 6 ethnic groups from the Caribbean and the U.S. Cancer 2008; 113:854.
- Rezaei N, Farhoudi A, Pourpak Z, et al. Neutropenia in patients with primary antibody deficiency disorders. Iran J Allergy Asthma Immunol 2004; 3:77.
- Akhtari M, Curtis B, Waller EK. Autoimmune neutropenia in adults. Autoimmun Rev 2009; 9:62.
- Nossent JC, Swaak AJ. Prevalence and significance of haematological abnormalities in patients with systemic lupus erythematosus. Q J Med 1991; 80:605.
- Bucknall RC, Davis P, Bacon PA, Jones JV. Neutropenia in rheumatoid arthritis: studies on possible contributing factors. Ann Rheum Dis 1982; 41:242.
- Shoenfeld Y, Alkan ML, Asaly A, et al. Benign familial leukopenia and neutropenia in different ethnic groups. Eur J Haematol 1988; 41:273.
- Shoenfeld Y, Ben-Tal O, Berliner S, Pinkhas J. The outcome of bacterial infection in subjects with benign familial leukopenia (BFL). Biomed Pharmacother 1985; 39:23.
- Hsieh MM, Tisdale JF, Rodgers GP, et al. Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy? J Clin Oncol 2010; 28:1633.
- Nalls MA, Wilson JG, Patterson NJ, et al. Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies. Am J Hum Genet 2008; 82:81.
- Paz Z, Nails M, Ziv E. The genetics of benign neutropenia. Isr Med Assoc J 2011; 13:625.
- Reich D, Nalls MA, Kao WH, et al. Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet 2009; 5:e1000360.
- Bux J, Behrens G, Jaeger G, Welte K. Diagnosis and clinical course of autoimmune neutropenia in infancy: analysis of 240 cases. Blood 1998; 91:181.
- Mariotti J, Caberlon S, Bertinato E, et al. Primary autoimmune neutropenia in adults: case report and review of the literature. Transfusion 2014; 54:2906.
- Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med 2007; 146:657.
- Klumpp TR. Antibody-mediated neutropenia following bone marrow transplantation. Int J Clin Lab Res 1993; 23:4.
- TERMINOLOGY AND DEFINITION OF NEUTROPENIA
- MAJOR CAUSES OF NEUTROPENIA
- Benign ethnic neutropenia
- Congenital neutropenias
- Acquired neutropenias
- Hospitalized patient
- DETERMINING THE CAUSE
- Overview of evaluation
- - Family and patient history
- - Medication history
- - Infection history
- Physical examination
- - Signs of an underlying disorder
- - Signs of active infection
- Laboratory testing
- - Laboratory records
- - Other cytopenias
- - Additional laboratory testing
- Distinguishing infection-induced from drug-induced neutropenia
- Trial of drug discontinuation
- FURTHER EVALUATION AND MONITORING
- Monitoring the ANC
- Determining risk of infection
- Hematologist referral
- Who needs a bone marrow evaluation?
- Indications for hospital admission
- INFORMATION FOR PATIENTS