Matthew M. Hsieh, MD; James E. Everhart, MD, MPH; Danita D. Byrd-Holt; John F. Tisdale, MD; Griffin P. Rodgers, MD
Acknowledgments: The authors thank Drs. Geraldine Schechter and Daniel Wright for their helpful comments and Keith Rust for statistical analyses.
Potential Financial Conflicts of Interest: None disclosed.
Grant Support: By the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health.
Requests for Single Reprints: Griffin P. Rodgers, MD, Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 9000 Rockville Pike, Building 10, 9N 119, Bethesda, MD 20892; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Hsieh, Tisdale, and Rodgers: Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 9000 Rockville Pike, Building 10, 9N 119, Bethesda, MD 20892.
Dr. Everhart: Epidemiology and Clinical Trials Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, 2 Democracy Plaza, Room 655, 6707 Democracy Boulevard, MSC 5450, Bethesda, MD 20892-5450.
Ms. Byrd-Holt: Computer Systems Data Analysis Division, Social & Scientific Systems, Inc., 8757 Georgia Avenue, 12th Floor, Silver Spring, MD 20910.
Author Contributions: Conception and design: M.M. Hsieh, J.E. Everhart, J.F. Tisdale, G.P. Rodgers.
Analysis and interpretation of the data: M.M. Hsieh, J.E. Everhart, D.D. Byrd-Holt, J.F. Tisdale.
Drafting of the article: M.M. Hsieh, J.E. Everhart, D.D. Byrd-Holt, J.F. Tisdale, G.P. Rodgers.
Critical revision of the article for important intellectual content: M.M. Hsieh, J.E. Everhart, J.F. Tisdale, G.P. Rodgers.
Final approval of the article: M.M. Hsieh, J.E. Everhart, D.D. Byrd-Holt, J.F. Tisdale, G.P. Rodgers.
Statistical expertise: J.E. Everhart, D.D. Byrd-Holt.
Benign reductions in neutrophil counts may be more common at certain ages and in certain ethnic groups and may be affected by sex and smoking status.
To determine differences in neutrophil counts in the U.S. population according to ethnicity, age, sex, and smoking status.
Population-based, cross-sectional study.
Various locations in the United States.
25 222 participants in the 1999 to 2004 National Health and Nutrition Examination Survey who were 1 year of age or older.
Complete blood counts and comparison of means and the proportion of participants with neutropenia.
Relative to white participants, black participants had lower leukocyte counts (mean difference, 0.89 × 109 cells/L; P < 0.001), lower neutrophil counts (0.83 × 109 cells/L; P < 0.001), and similar lymphocyte counts (0.022 × 109 cells/L; P = 0.36), whereas Mexican-American participants had slightly higher mean leukocyte counts (0.16 × 109 cells/L; P = 0.014), higher neutrophil counts (0.11 × 109 cells/L; P = 0.026), and higher lymphocyte counts (0.095 × 109 cells/L; P < 0.001). The prevalence of neutropenia (neutrophil count <1.5 × 109 cells/L) was 4.5% among black participants, 0.79% among white participants, and 0.38% among Mexican-American participants. The prevalence of neutropenia was higher among males and children younger than 5 years of age. Neutrophil counts less than 1.0 × 109 cells/L were observed in fewer than 1% of the overall sample (0.57% in black participants, 0.11% in white participants, and 0.08% in Mexican-American participants). Smoking was associated with higher leukocyte and neutrophil counts but had a smaller effect among black and Mexican-American participants than among white participants.
Because estimates are based on single measures, fluctuations over time could not be determined.
In the United States, neutrophil counts are lower in black persons than in white persons and neutropenia is more prevalent in black persons. Neutrophil counts are slightly higher in Mexican-American persons than in white persons, and neutropenia is uncommon in both groups. The clinical implications of these findings are unclear, but they suggest that when determining the need for a diagnostic evaluation for neutropenia, clinicians should consider the patient's age, sex, ethnicity, and smoking status.
Low neutrophil counts may be more common in certain ethnic groups and ages.
When blood count data were analyzed from a national sample of presumably healthy persons, the authors found that neutrophil counts were lower and neutropenia was more prevalent in U.S. black persons compared with white persons. Smoking was associated with increased neutrophil counts, especially in white persons.
Blood counts were measured only once and could have differed in a second measurement or changed over time.
Race and smoking status influence the number of blood neutrophils and should be taken into account when considering the need to evaluate abnormal counts.
Table 1. Mean Hematologic Values, by Age, Sex, and Ethnic Group*
Appendix Table 1. Mean Hematologic Values, by Age, Sex, and Ethnic Group*
Appendix Table 2. Mean Hematologic Values in 3 Major Ethnic Groups, by Age*
Distribution of leukocyte (top) and neutrophil (bottom) counts in persons age 18 years or older from 3 ethnic groups.
Appendix Table 3 shows the actual percentages and number of participants.
Appendix Table 3. Number and Proportion of Participants, by Distribution of Leukocyte and Neutrophil Count
Table 2. Comparative Mean Leukocyte and Neutrophil Counts in Smokers and Nonsmokers Age 20 Years or Older
Percentage of females (top) and males (bottom) with neutrophil counts less than 1.5 × 109 cells/L.
The error bars refer to the standard errors. Appendix Table 4 shows the actual percentages and number of participants.
Appendix Table 4. Percentage of Male and Female Participants with Neutrophil Counts Less than 1.5 × 109 Cells/L
Table 3. Prevalence of a Neutrophil Count Less than 1.5 × 109 Cells/L
Table 4. Overall Prevalence of Black Participants with Neutrophil Counts of 1.0 to 1.5 × 109 Cells/L and Less than 1.0 × 109 Cells/L
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Mukaila A Raji
University of Texas Medical Branch
May 20, 2007
Idiopathic neutropenia: a potential source of ethnic disparity in health care
Hsieh and colleagues concluded that benign neutropenia in US blacks (benign ethnic neutropenia) had implications for diagnostic evaluation of neutropenia in blacks (1). Benign neutropenia in US blacks also carries important therapeutic implications, especially as a potential source of ethnic disparity in treatment (and prognosis) for black patients with cancer and mental health conditions. Initiation, optimal dosing and duration of cancer chemotherapy depend, at least in part, on neutrophil count being within the normal range i.e. >1500/mm3 . In the face of benign ethnic neutropenia, there is a high likelihood that blacks with cancer (e.g. breast cancer) may not get optimal adjuvant chemotherapy (2). For example, Hershman and colleagues found that among women (43 blacks and 93 whites) with early stage breast cancer, black women had lower white blood cell count (wbc) cont, lower dose intensity of adjuvant chemotherapy and longer duration of cancer treatment (2). Another implication of benign neutropenia in blacks relates to under-use and increased discontinuation rate of clozapine in blacks with treatment-resistant schizophrenia (3-5). Clozapine has been shown to be effective for treatment-resistant schizophrenia (3-5). The use of clozapine is contraindicated in patients with wbc below 3500/mm3 or absolute neutrophil count <2000/mm3. Such contraindications based on the current wbc range may explain, in part, the lower use and high discontinuation rate of clozapine in blacks with treatment resistant schizophrenia (3). In a study of 1287 Caucasian and 588 African American patients on clozapine for treatment-resistant schizophrenia or schizoaffective disorder, blacks were about 2 times as likely as whites to have their clozapine discontinued as a result of leucopenia (4). In that study, all the patients (n=8) who developed agranulocytosis were white (4). A recent review by Mallinger and Lamberti emphasized the need for a US guideline that recognizes benign ethnic neutropenia and considers alternative normal wbc range for those with this condition, as has been done in Canada and the United Kingdom (3,5). I agree with Hsie et al. that clinicians should consider the possibility of benign ethnic neutropenia in their diagnostic evaluations. Such consideration should also extend to decision-making regarding optimal use of recommended therapies for cancer and schizophrenia. Such consideration may contribute to a reduction of health disparity in blacks.
1)Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146:486-92.
2)Hershman D, Weinberg M, Rosner Z, Alexis K, Tiersten A, Grann VR, et al. Ethnic neutropenia and treatment delay in African American women undergoing chemotherapy for early-stage breast cancer. J Natl Cancer Inst. 2003;95:1545-8.
3)Mallinger JB, Lamberti JS. Clozapine--should race affect prescribing guidelines? Schizophr Res. 2006 ;83:107-8..
4)Kelly DL, Kreyenbuhl J, Dixon L, Love RC, Medoff D, Conley RR. Clozapine Underutilization and Discontinuation in African Americans Due to Leucopenia. Schizophr Bull, 2006;doi:10.1093/schbul/sbl068v1. PMID: 17170061
5)Rajagopal S. Clozapine, agranulocytosis, and benign ethnic neutropenia, Postgrad. Med. J. 2005;81:545"“46
Matthew M. Hsieh, James E. Everhart, Danita D. Byrd-Holt, John F. Tisdale, Griffin P. Rodgers. Prevalence of Neutropenia in the U.S. Population: Age, Sex, Smoking Status, and Ethnic Differences. Ann Intern Med. 2007;146:486–492. doi: 10.7326/0003-4819-146-7-200704030-00004
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Published: Ann Intern Med. 2007;146(7):486-492.
Cardiology, Coronary Risk Factors, Smoking, Tobacco, Alcohol, and Other Substance Abuse.
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