Ann Lab Med.  2018 Nov;38(6):503-511. 10.3343/alm.2018.38.6.503.

Complete Blood Count Reference Intervals and Patterns of Changes Across Pediatric, Adult, and Geriatric Ages in Korea

• Nah EH
• Kim S
• Cho S
• Cho HI

• KMID: 2429114
• DOI: http://doi.org/10.3343/alm.2018.38.6.503

Abstract

BACKGROUND
Sampling a healthy reference population to generate reference intervals (RIs) for complete blood count (CBC) parameters is not common for pediatric and geriatric ages. We established age- and sex-specific RIs for CBC parameters across pediatric, adult, and geriatric ages using secondary data, evaluating patterns of changes in CBC parameters.
METHODS
The reference population comprised 804,623 health examinees (66,611 aged 3-17 years; 564,280 aged 18-59 years; 173,732 aged 60-99 years), and, we excluded 22,766 examinees after outlier testing. The CBC parameters (red blood cell [RBC], white blood cell [WBC], and platelet parameters) from 781,857 examinees were studied. We determined statistically significant partitions of age and sex, and calculated RIs according to the CLSI C28-A3 guidelines.
RESULTS
RBC parameters increased with age until adulthood and decreased with age in males, but increased before puberty and then decreased with age in females. WBC and platelet counts were the highest in early childhood and decreased with age. Sex differences in each age group were noted: WBC count was higher in males than in females during adulthood, but platelet count was higher in females than in males from puberty onwards (P < 0.001). Neutrophil count was the lowest in early childhood and increased with age. Lymphocyte count decreased with age after peaking in early childhood. Eosinophil count was the highest in childhood and higher in males than in females. Monocyte count was higher in males than in females (P < 0.001).
CONCLUSIONS
We provide comprehensive age- and sex-specific RIs for CBC parameters, which show dynamic changes with both age and sex.

Keyword

Complete blood count; Reference intervals; Secondary data; Pediatric; Geriatric; Age; Sex; Korean

MeSH Terms

Adolescent
Adult*
Blood Cell Count*
Blood Cells
Blood Platelets
Eosinophils
Female
Humans
Korea*
Leukocytes
Lymphocyte Count
Male
Monocytes
Neutrophils
Platelet Count
Puberty
Sex Characteristics

Figure

• 

  Fig. 1 Scatter plot distributions of the hematologic parameters. (A) Hemoglobin. (B) Red blood cell count. (C) White blood cell count. (D) Platelet count.

• 

  Fig. 2 Box plots of the red blood cell parameters according to age and sex. (A) Hematocrit. (B) Hemoglobin. (C) Red blood cell count. (D) Mean corpuscular volume. (E) Mean corpuscular hemoglobin. (F) Mean corpuscular hemoglobin concentration. (G) Red blood cell distribution width. Box limits and horizontal lines within boxes represent interquartile ranges and the median, respectively. The upper and lower whiskers indicate the 97.5th and 2.5th percentiles, respectively. The difference in median values between sexes in each age group was determined using the Wilcoxon rank sum test: *P<0.05; **P<0.005. The median values among age groups for each sex differed significantly (P<0.001, Kruskal-Wallis test).

• 

  Fig. 3 Box plots of the white blood cell and the platelet parameters according to age and sex. (A) White blood cell count. (B) Neutrophil count. (C) Lymphocyte count. (D) Monocyte count. (E) Eosinophil count. (F) Basophil count. (G) Platelet count. (H) Platelet distribution width. (I) Mean platelet volume. (J) Plateletcrit. Box limits and horizontal lines within boxes represent interquartile ranges and the median, respectively. The upper and lower whiskers indicate the 97.5th and 2.5th percentiles, respectively. The difference in median values between sexes in each age group was determined using the Wilcoxon rank sum test: *P<0.05; **P<0.005. The median values among age groups for each sex differed significantly (P<0.001, Kruskal-Wallis test).

Reference

1. Friedberg RC, Souers R, Wagar EA, Stankovic AK, Valenstein PN. The origin of reference intervals. Arch Pathol Lab Med. 2007; 131:348–357. PMID: 17516737.

2. Cheng CK, Chan J, Cembrowski GS, van Assendelft OW. Complete blood count reference interval diagrams derived from NHANES III: stratification by age, sex, and race. Lab Hematol. 2004; 10:42–53. PMID: 15070217.

3. Adeli K, Raizman JE, Chen Y, Higgins V, Nieuwesteeg M, Abdelhaleem M, et al. Complex biological profile of hematologic markers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey. Clin Chem. 2015; 61:1075–1086. PMID: 26044509.

4. Ambayya A, Su AT, Osman NH, Nik-Samsudin NR, Khalid K, Chang KM, et al. Haematological reference intervals in a multiethnic population. PLoS One. 2014; 9:e91968. PMID: 24642526.

5. Lee HR, Shin S, Yoon JH, Roh EY, Chang JY. Reference intervals of hematology and clinical chemistry analytes for 1-year-old Korean children. Ann Lab Med. 2016; 36:481–488. PMID: 27374715.

6. Horowitz GL, Atlaie S, Boyd JC. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline. C28-A3c. Wayne, PA: Clinical and Laboratory Standards Institute;2010.

7. Cho SM, Lee SG, Kim HS, Kim JH. Establishing pediatric reference intervals for 13 biochemical analytes derived from normal subjects in a pediatric endocrinology clinic in Korea. Clin Biochem. 2014; 47:268–271. PMID: 25241678.

8. Bachman E, Travison TG, Basaria S, Davda MN, Guo W, Li M, et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci. 2014; 69:725–735. PMID: 24158761.

9. Wakeman L, Al-Ismail S, Benton A, Beddall A, Gibbs A, Hartnell S, et al. Robust, routine haematology reference ranges for healthy adults. Int J Lab Hematol. 2007; 29:279–283. PMID: 17617078.

10. Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in the United States. JAMA. 1997; 277:973–976. PMID: 9091669.

11. Food and Agricultural Organization of the United Nations. WHO. World declaration and plan of action for nutrition: International Conference on Nutrition. Updated on Dec 1992. http://www.who.int/nutrition/publications/policies/icn_worlddeclaration_planofaction1992/en/.

12. WHO. Iron deficiency anaemia: assessment, prevention and control: a guide for programme managers. Updated on Aug 2001. http://www.who.int/nutrition/publications/micronutrients/anaemia_iron_deficiency/WHO_NHD_01.3/en/.

13. Ershler WB. Biological interactions of aging and anemia: a focus on cytokines. J Am Geriatr Soc. 2003; 51(S3):S18–S21. PMID: 12588568.

14. Balducci L. Epidemiology of anemia in the elderly: information on diagnostic evaluation. J Am Geriatr Soc. 2003; 51(S3):S2–S9. PMID: 12588565.

15. Verthelyi D. Sex hormones as immunomodulators in health and disease. Int Immunopharmacol. 2001; 1:983–993. PMID: 11407317.

16. Roshan TM, Rosline H, Ahmed SA, Rapiaah M, Wan Zaidah A, Khattak MN. Hematological reference values of healthy Malaysian population. Int J Lab Hematol. 2009; 31:505–512. PMID: 18498389.

17. Ishiguro A, Nakahata T, Matsubara K, Hayashi Y, Kato T, Suzuki Y, et al. Age-related changes in thrombopoietin in children: reference interval for serum thrombopoietin levels. Br J Haematol. 1999; 106:884–888. PMID: 10519988.

18. Daly ME. Determinants of platelet count in humans. Haematologica. 2011; 96:10–13. PMID: 21193429.

19. Kadikoylu G, Yavasoglu I, Bolaman Z, Senturk T. Platelet parameters in women with iron deficiency anemia. J Natl Med Assoc. 2006; 98:398–402. PMID: 16573304.

20. Beguin Y. Erythropoietin and platelet production. Haematologica. 1999; 84:541–547. PMID: 10366799.

21. Giles C. The platelet count and mean platelet volume. Br J Haematol. 1981; 48:31–37. PMID: 7248189.

22. Buckley MF, James JW, Brown DE, Whyte GS, Dean MG, Chesterman CN, et al. A novel approach to the assessment of variations in the human platelet count. Thromb Haemost. 2000; 83:480–484. PMID: 10744157.