- Email: [email protected]
The Imperative for Race-Specific Neutrophil Count Reference Intervals in White Cell Count Evaluation
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The opinions expressed here are not necessarily the opinions of the National Medical Association. Mortality With Fracture of the Femur in African Americans in 2005-2006 To the Editor: Several recent studies have shown that higher hospital surgical volumes are associated with lower complication rates following different kinds of surgical procedures. In a recent study, SooHoo et al indicated that there are disparities in the characteristics of patients receiving care at hospitals performing a high volume or low volume of total-hip replacements.1 Hispanics/Latinos, African Americans, and Asians have been shown as more than likely to utilize a low-volume hospital, where mortality rate following procedure is more likely to be high. In an examination assessing multiple causes of death for fracture of the femur (International Classification of Diseases, Tenth Revision codes S72.0-S72.9 and T93.1) between 2005 and 2006 among African American females, it was found that the total number of deaths resulting from fracture of the femur was 733 out of 7 393 526 black females compared to 20 960 fractures out of a population of 64 434 990 Caucasian females.2 This study also indicated that the death rate increases with age, peaking at age of at least 85 years.2 The older the age, the higher the crude rate per 100 000. The crude rate per 100 000 for African American women aged 55 to 64 years was 0.9; for 65 to 74 years, 4.2; for 75 to 84 years, 17.5; and for 85 or more years, 71.1. Also, of all the deaths from fracture of the femur, 47% of such deaths occur in African American women aged less than 85 years compared to 34% in Caucasian women aged less than 85 years. When these death rates are com-
pared to a corresponding age among Caucasians, the crude death rates are much lower. The crude rate per 100 000 for African American men aged 55 to 64 years was 1.3; for 65 to 74 years, 5.4; for 75 to 84 years, 19.2; and for at least 85 years, 84.3. The total population of African American men was more than 5 000 000 and the total population of African American women was more than 7, 000 000. Even though there was a higher crude rate per 100 000 in African American males, the rate was not significant. Fracture of the femur is believed to be a female problem; however, males do also sustain hip fracture. Findings showed that there is a significant amount of mortality resulting from the fracture of the femur in African Americans at younger ages compared to their Caucasian counterparts. Though the incident rate of fracture may be lower, it is still very significant. Grace O. Akinpetide, MSN, APRN, FNP-BC, EMBA [email protected] College of Nursing University of Arizona Tucson, Ariz 1. SooHoo NF, Farng EF, Zingmond DS. Disparities in the Utilization of High-Volume Hospitals for Total Hip Replacement. J Natl Med Assoc. 2011;103:31-35. 2. Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death File 2005-2006. CDC WONDER On-line Database, compiled from Multiple Cause of Death File 2005-2006 Series 20 No. 2L, 2009. http://wonder.cdc.gov/mcd-icd10.html. Accessed March 7, 2011.
The Imperative for RaceSpecific Neutrophil Count Reference Intervals in White Cell Count Evaluation To the Editor: The white blood cell (WBC) count is a valuable
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
indicator of immunocompetence, infection, and inflammation.1,2 WBC monitoring therefore has implications for patient management across all clinical disciplines. Several decades of studies and analysis have consistently demonstrated an appreciable difference in the WBC count of a large proportion of healthy African Americans compared to subjects of European ancestry.1-3 This difference is due to the reduction in the absolute neutrophil count in people of African descent; a condition referred to as benign ethnic neutropenia. This condition can have significant impact on clinical decision making as a result of the central role of neutrophils in immune response. For example, the US Food and Drug Administration requires absolute neutrophil count monitoring of patients on clozapine (an important antipsychotic drug) for the commencement of treatment and also monitoring for signs of toxicity which would lead to discontinuation of treatment. An important concern, therefore, in the use of clozapine in African American patients is having a rational basis for “intervention” with the use of Caucasian WBC count cutoff values in the absence of an appropriate lower threshold. The decision to stop the drug in such patients would therefore be difficult when only Caucasian reference intervals are used.3 The widely accepted concept of evidenced-based medicine as an important cornerstone of modernday medical practice makes it all the more challenging. With reference to clinical trials, use of “whitecentric” reference values for neutrophil counts inadvertently leads to unnecessary exclusion of a large number of African Americans. In a recent clinical trial of a lipid-lowerVOL. 103, NO. 8, AUGUST 2011 771
Letters to the Editor
ing agent in Philadelphia, in which patients were selected for participation conditional on normal white counts, too many patients of African descent were excluded, necessitating the investigators to rewrite their research proposal using race-appropriate reference intervals for WBC.3 An analysis of the US National Health and Nutrition Examination Survey data shows that the differences between the lower reference limits of WBC counts for non-Hispanic black and non-Hispanic white individuals can vary as much as 1 to 1.5 × 109/L (for both males and females). This difference is of high clinical significance given that absolute neutrophil counts below 1.5 × 109/L are empirically regarded inadequate in persons of all ethnic groups who are aged more than 1 year, although there is no scientific basis for this.1 Early studies carried out to understand the basis of this important laboratory parameter were inconclusive, with hypotheses ranging from environmental, socioeconomic, and dietary to racial factors. Recent analysis of population genetics, including single-nucleotide polymorphism analysis, has convincingly demonstrated a genetic
basis for this significant laboratory finding. Polymorphism of the Duffy antigen receptor for chemokines gene, with a locus on chromosome 1, is now known to be the single most important factor responsible for the differences in neutrophils counts between Caucasians and African Americans.5 As early as 1970, the necessity for race-specific reference intervals for leucocytes was raised by Orfanakis et al.6 In 1999, Haddy et al suggested that the lower limit now considered acceptable for absolute neutrophil count should be readjusted downward for all ethnic groups.1 In light of overwhelming scientific evidence for the intrinsically lower neutrophil counts in African Americans, it is inappropriate to continue with the universal use of Caucasian reference limits for evaluating neutropenia. The implementation of separate reference intervals poses practical issues in reporting proper reference limits by both laboratory information systems and medical information systems. Therefore, an important first step requires that pathologists and clinicians work with their laboratory information systems and medical information systems sections across North
America to reappraise the existing reference limits. Dr Oladimeji Arewa MBBS(Ib), FMCPath [email protected] Department of Laboratory Medicine and Pathology University of Alberta Hospital Edmonton, Alberta, Canada
George S. Cembrowski, MD, PhD O.P. Arewa, MBBS, FMCPath 1. Haddy TB, Rana SR, Castro O. Benign ethnic neutropenia; what is an normal absolute netrophil count? J Lab Clin Med. 1999;133:15-22 2. Arewa O, Kalamawei I. Benign ethnic neutropenia; A pilot study of the Ijaws in the Niger Delta of Nigeria. International Society for Laboratory Hematology (ISLH) 2010. Abstracts; 71. http:// www.flip-programs.com/ISLH/2010_Abstracts/. Accessed 02/04/11. 3. Lim EM, Cembrowski G, Cembrowski M, Clarke G. Race specific WBC and neutrophils count reference intervals. Int J Lab Hematol. 2010;32:590-597. 4. Whiskey E, Taylor D. Restarting clozapine after neutropenia: evaluating the possibilities and practicalities. CNS Drugs. 2007;21:25-35. 5. Reich D, Nalls MA, Kao Linda 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. 5(1):e1000360.doi:10.1371/journal. pgen.1000360. Accessed 04/03/11. 6. Orfanakis NG, Ostlund RE, Bishop CR, Athens JW. Normal blood leukocyte concentration values. Am J Clin Path. 1970;53:647-751.
We Welcome Your Comments The Journal of the National Medical Association welcomes your Letters to the Editor about articles that appear in the JNMA or issues relevant to minority healthcare. Address correspondence to [email protected].
772 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
VOL. 103, NO. 8, AUGUST 2011
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t
t
e
r
s
t
o
t
h
e
e
d
i
t
o
r
The opinions expressed here are not necessarily the opinions of the National Medical Association. Mortality With Fracture of the Femur in African Americans in 2005-2006 To the Editor: Several recent studies have shown that higher hospital surgical volumes are associated with lower complication rates following different kinds of surgical procedures. In a recent study, SooHoo et al indicated that there are disparities in the characteristics of patients receiving care at hospitals performing a high volume or low volume of total-hip replacements.1 Hispanics/Latinos, African Americans, and Asians have been shown as more than likely to utilize a low-volume hospital, where mortality rate following procedure is more likely to be high. In an examination assessing multiple causes of death for fracture of the femur (International Classification of Diseases, Tenth Revision codes S72.0-S72.9 and T93.1) between 2005 and 2006 among African American females, it was found that the total number of deaths resulting from fracture of the femur was 733 out of 7 393 526 black females compared to 20 960 fractures out of a population of 64 434 990 Caucasian females.2 This study also indicated that the death rate increases with age, peaking at age of at least 85 years.2 The older the age, the higher the crude rate per 100 000. The crude rate per 100 000 for African American women aged 55 to 64 years was 0.9; for 65 to 74 years, 4.2; for 75 to 84 years, 17.5; and for 85 or more years, 71.1. Also, of all the deaths from fracture of the femur, 47% of such deaths occur in African American women aged less than 85 years compared to 34% in Caucasian women aged less than 85 years. When these death rates are com-
pared to a corresponding age among Caucasians, the crude death rates are much lower. The crude rate per 100 000 for African American men aged 55 to 64 years was 1.3; for 65 to 74 years, 5.4; for 75 to 84 years, 19.2; and for at least 85 years, 84.3. The total population of African American men was more than 5 000 000 and the total population of African American women was more than 7, 000 000. Even though there was a higher crude rate per 100 000 in African American males, the rate was not significant. Fracture of the femur is believed to be a female problem; however, males do also sustain hip fracture. Findings showed that there is a significant amount of mortality resulting from the fracture of the femur in African Americans at younger ages compared to their Caucasian counterparts. Though the incident rate of fracture may be lower, it is still very significant. Grace O. Akinpetide, MSN, APRN, FNP-BC, EMBA [email protected] College of Nursing University of Arizona Tucson, Ariz 1. SooHoo NF, Farng EF, Zingmond DS. Disparities in the Utilization of High-Volume Hospitals for Total Hip Replacement. J Natl Med Assoc. 2011;103:31-35. 2. Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death File 2005-2006. CDC WONDER On-line Database, compiled from Multiple Cause of Death File 2005-2006 Series 20 No. 2L, 2009. http://wonder.cdc.gov/mcd-icd10.html. Accessed March 7, 2011.
The Imperative for RaceSpecific Neutrophil Count Reference Intervals in White Cell Count Evaluation To the Editor: The white blood cell (WBC) count is a valuable
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
indicator of immunocompetence, infection, and inflammation.1,2 WBC monitoring therefore has implications for patient management across all clinical disciplines. Several decades of studies and analysis have consistently demonstrated an appreciable difference in the WBC count of a large proportion of healthy African Americans compared to subjects of European ancestry.1-3 This difference is due to the reduction in the absolute neutrophil count in people of African descent; a condition referred to as benign ethnic neutropenia. This condition can have significant impact on clinical decision making as a result of the central role of neutrophils in immune response. For example, the US Food and Drug Administration requires absolute neutrophil count monitoring of patients on clozapine (an important antipsychotic drug) for the commencement of treatment and also monitoring for signs of toxicity which would lead to discontinuation of treatment. An important concern, therefore, in the use of clozapine in African American patients is having a rational basis for “intervention” with the use of Caucasian WBC count cutoff values in the absence of an appropriate lower threshold. The decision to stop the drug in such patients would therefore be difficult when only Caucasian reference intervals are used.3 The widely accepted concept of evidenced-based medicine as an important cornerstone of modernday medical practice makes it all the more challenging. With reference to clinical trials, use of “whitecentric” reference values for neutrophil counts inadvertently leads to unnecessary exclusion of a large number of African Americans. In a recent clinical trial of a lipid-lowerVOL. 103, NO. 8, AUGUST 2011 771
Letters to the Editor
ing agent in Philadelphia, in which patients were selected for participation conditional on normal white counts, too many patients of African descent were excluded, necessitating the investigators to rewrite their research proposal using race-appropriate reference intervals for WBC.3 An analysis of the US National Health and Nutrition Examination Survey data shows that the differences between the lower reference limits of WBC counts for non-Hispanic black and non-Hispanic white individuals can vary as much as 1 to 1.5 × 109/L (for both males and females). This difference is of high clinical significance given that absolute neutrophil counts below 1.5 × 109/L are empirically regarded inadequate in persons of all ethnic groups who are aged more than 1 year, although there is no scientific basis for this.1 Early studies carried out to understand the basis of this important laboratory parameter were inconclusive, with hypotheses ranging from environmental, socioeconomic, and dietary to racial factors. Recent analysis of population genetics, including single-nucleotide polymorphism analysis, has convincingly demonstrated a genetic
basis for this significant laboratory finding. Polymorphism of the Duffy antigen receptor for chemokines gene, with a locus on chromosome 1, is now known to be the single most important factor responsible for the differences in neutrophils counts between Caucasians and African Americans.5 As early as 1970, the necessity for race-specific reference intervals for leucocytes was raised by Orfanakis et al.6 In 1999, Haddy et al suggested that the lower limit now considered acceptable for absolute neutrophil count should be readjusted downward for all ethnic groups.1 In light of overwhelming scientific evidence for the intrinsically lower neutrophil counts in African Americans, it is inappropriate to continue with the universal use of Caucasian reference limits for evaluating neutropenia. The implementation of separate reference intervals poses practical issues in reporting proper reference limits by both laboratory information systems and medical information systems. Therefore, an important first step requires that pathologists and clinicians work with their laboratory information systems and medical information systems sections across North
America to reappraise the existing reference limits. Dr Oladimeji Arewa MBBS(Ib), FMCPath [email protected] Department of Laboratory Medicine and Pathology University of Alberta Hospital Edmonton, Alberta, Canada
George S. Cembrowski, MD, PhD O.P. Arewa, MBBS, FMCPath 1. Haddy TB, Rana SR, Castro O. Benign ethnic neutropenia; what is an normal absolute netrophil count? J Lab Clin Med. 1999;133:15-22 2. Arewa O, Kalamawei I. Benign ethnic neutropenia; A pilot study of the Ijaws in the Niger Delta of Nigeria. International Society for Laboratory Hematology (ISLH) 2010. Abstracts; 71. http:// www.flip-programs.com/ISLH/2010_Abstracts/. Accessed 02/04/11. 3. Lim EM, Cembrowski G, Cembrowski M, Clarke G. Race specific WBC and neutrophils count reference intervals. Int J Lab Hematol. 2010;32:590-597. 4. Whiskey E, Taylor D. Restarting clozapine after neutropenia: evaluating the possibilities and practicalities. CNS Drugs. 2007;21:25-35. 5. Reich D, Nalls MA, Kao Linda 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. 5(1):e1000360.doi:10.1371/journal. pgen.1000360. Accessed 04/03/11. 6. Orfanakis NG, Ostlund RE, Bishop CR, Athens JW. Normal blood leukocyte concentration values. Am J Clin Path. 1970;53:647-751.
We Welcome Your Comments The Journal of the National Medical Association welcomes your Letters to the Editor about articles that appear in the JNMA or issues relevant to minority healthcare. Address correspondence to [email protected].
772 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
VOL. 103, NO. 8, AUGUST 2011