ORIGINAL ARTICLE Establishing Reference Intervals for Complete Blood Cell Count in Healthy Korean Elderly

ORIGINAL ARTICLE https://doi.org/.23/jlmqa.18..1.27 Establishing Reference Intervals for Complete Blood Cell Count in Healthy Korean Elderly Individuals Eun Jin Lee, Miyoung Kim, Eunyup Lee, Kibum Jeon, Jiwon Lee, Han-Sung Kim, Hee Jung Kang, and Young Kyung Lee Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea Corresponding author: Miyoung Kim Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, 22 Gwanpyeong-ro 17beon-gil, Dongan-gu, Anyang 8, Korea Tel: +82-31-3-17 Fax: +82-31-3-178 E-mail: rabbit722@gmail.com Background: Different age groups may have different reference intervals. However, the currently used reference interval for complete blood count (CBC) in clinical laboratories is based on results from healthy adults between and years of age. In this study, we aimed to establish reference intervals for CBC parameters in Korean healthy elderly individuals. Methods: A total of 3, healthy adults were selected from 4,23 adults (aged years) who underwent regular health check-ups, based on a medical examination by interview. The reference intervals for CBC in two groups (aged < and years), and the partitioning of reference intervals between the two age groups were established. Results: Most CBC parameters showed no significant differences in reference intervals between the two age groups. Among the men, platelet distribution width (PDW) was the only parameter that required a separate reference interval between the two age groups. Among the women, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), and eosinophil % required separate reference intervals between the two age groups. Conclusions: The reference intervals for most CBC parameters were not significantly different between the two age groups. Except for PDW in men and MCV, MCHC, RDW, and eosinophil % in women, reference intervals for CBC parameters in individuals younger than years of age could also be applied to those that are years of age or older. (J Lab Med Qual Assur 18;:27-37) Key Words: Complete blood cell count, Elderlies, Reference interval pissn: 2384-248 eissn: 2288-721 Received November, 17, Revision received January, 18, Accepted February 1, 18 서론 참고구간 (reference interval) 은참고표본군의관측값이나모집단에서의예측치의간격으로하한참고치와상한참고치값간의간격으로정의되어있다 [1]. 혈액검사를통해얻은측정결과는환자의진단및치료결정을위해참고구간과의비교과정을거친다. 이와같이혈액검사결과의해석은비교를통한의사결정과정이므로모든검사항목에대하여기준이되는참고구간이필요하다. 만약적합하지않은참고구간을임상결과의해석에적용할경우잘못된진단및치료결정의위험이있다. 따라서신뢰성있는참고구간을확립하는것은임상검사실의중요한업무이다. 현대사회는급속한인구의고령화가진행되고있으며평균수명의연장과의학이발달함에따라의료기관을방문하는노인인구의비율이지속적으로상승하는추세이다 [2]. 하지만현재임상검사실에서사용하고있는참고구간은대부분 -세의건강한성인을대상으로정립한경우가많다 [3,4]. Alkaline phosphatase 등많은혈액검사항목에서연령에따른정상참고구간이달라진다는연구결과가보고되어있으며 [], 이에따라유 소아의경우성별, 연령별로국제적참고구간및한국인의참고구간이거의모든혈액검사항목에서정립되어있다 [-]. 반면에 세이상노인인구를대상으로한혈액검사참고구간에관한연구는국내 외적으로거의이루어져있지않은실정이다. Copyright 18 Korean Association of External Quality Assessment Service 27

이에본연구에서는국내최초로건강한한국노인을대상으로하여가장기본이되는 가지일반혈액검사항목에대한참고치를 Clinical and Laboratory Standards Institute (CLSI) EP28-A3 에서제시하는비모수방법 (nonparametric method) 에따라정립하고자하였다. 재료및방법 1. 연구대상건강증진센터에서 년 1월부터 년 3월까지건강검진을받은수진자중 세이상성인남녀를대상으로하였다. 건강한대상자를선별하기위하여과거병력, 복용약물, 검사소견등의기록을참조하여제외기준을다음과같이설정하였다. 1) 최근 (개월이내 ) 감염질환 (1) 염증반응이일어날수있는전신질환 ( 폐렴등 ) 을진단받았거나치료약물을복용한경우 (2) 수술력이있는경우 2) 간질환 A형간염, 활동성 B형간염, C형간염및간암, 알코올성간질환, 간경화등을진단받았거나현재치료중인간수치상승이있는경우 3) 만성질환고혈압, 당뇨, 심장병 ( 협심증, 심근경색, 부정맥 ), 신증후군을진단받았거나치료중인경우 4) 악성종양혈액종양 ( 백혈병등 ), 빈혈, 말라리아진단을받은경우 ) 약물복용피부과질환, 정신과질환, 알코올중독, 갑상선질환, 류마티스질환, 만성폐쇄성폐질환등의치료약물을복용중이거나면역억제제, 한약등을복용하는경우 ) 검사결과이상소견 (1) 심전도검사 : ST 분절의상승, 심근경색, pacemaker 삽입, 허혈성심질환의심소견을보인경우 (2) 흉부방사선 : 갑상선, 종격동종양, 활동성결핵, 폐렴, 폐암의심소견을보인경우 (3) 복부초음파 : 간경화, 만성간염, 췌장염, 알코올성간질 환소견을보인경우 (4) 내시경검사 : 위암, 대장암, 출혈성위염소견을보인경우 7) 임신중인경우 2. 측정방법진단검사의학과에서일반혈액검사에이용하고있는자동화검사기기인 Coulter LH 7 (Beckman Coulter, Brea, CA, USA) 으로측정한일반혈액검사결과를이용하였다. 적혈구 (red blood cells), 혈색소 (hemoglobin), 헤마토크리트 (hematocrit), 평균적혈구용적 (mean corpuscular volume, MCV), 평균적혈구혈색소량 (mean corpuscular hemoglobin, MCH), 평균적혈구혈색소농도 (mean corpuscular hemoglobin concentration, MCHC), 적혈구크기분포 (red cell distribution width, RDW), 백혈구 (white blood cells), 호중구 (neutrophil %), 호산구 (eosinophil %), 림프구 (lymphocyte %), 호염기구 (basophil %), 단구 (monocyte %), 혈소판 (platelet), 평균혈소판용적 (mean platelet volume, MPV), 혈소판크기분포 (platelet distribution width, PDW) 의 가지항목에대하여측정하였다. 3. 참고구간의설정및평균비교 세미만과 세이상두연령군의성별, 항목별검사결과분포를살펴보고연령군과성별에따라항목별결과에차이가있는지여부를 Mann Whitney U-test와 independent samples t-test를통해평균비교하였다. 각환자군의평균비교시에는 P<.일때통계적의의가있는것으로평가하였다. 참고구간은 CLSI EP28A-3C에서제시하는비모수방법에따라 세미만과 세이상군으로나누어설정하였다 [1,]. 비모수방법에서는하한참고한계치 (r1) 를 2.번째백분위수 {r1=.2*(n+1)} 에해당하는관측치로산출하고, 상한참고한계치 (r2) 를 7.번째백분위수 {r2=.7*(n+1)} 에해당하는관측치로산출한다. 비모수방법에서 % 신뢰도를가지는참고치를설정하기위한최소관측수를 명으로설정하고있으므로성별과연령에따라분류한각아군을 명이상으로구성하였다. 이상치 (outlier) 검출에는 Reed 등 [] 이제안한방법을사용하였다. 또한 CLSI EP28A-3C에서제시하는참고치분할방법인 Harris와 Boyd 방법에따라두연령군의참고치분할에통계적유의성이있는지평가하였다 []. 이방법에서는다음의세가지로아군의참고치분할을권장하고있다. 28 J Lab Med Qual Assur 18;:27-37 www.jlmqa.org

1) Standard normal deviation (z) 값이유의치 (z*=3 (n average /) 1/2 ) 를넘어서는경우 n average = 각각의집단의수 (n1과 n2) 의평균 2) 큰표준편차 (s 2 ) 가작은표준편차 (s 1 ) 의 1.배보다크거나같은경우 3) s 2 /(s 2 -s 1 ) 이 3보다작은경우 사용된통계프로그램은 MedCalc ver. 17..7 (MedCalc Software, Ostend, Belgium), Excel (Microsoft, Redmond, WA, USA), 및 PASW SPSS ver. 18. (SPSS Inc., Chicago, IL, USA) 였다. A WBC (x /L).. 7.. B RBC (x /L)... 4. 4. C Hemoglobin (g/dl) 18 D Hematocrit (%) 4 2. 3. E RDW (%) 18 F Platelet (x /L) G MCV (fl) 1 7 H MCH (pg) 37 31 2 27 2 I 3 J K L MCHC (g/dl) 32 31 PDW (fl) 18 MPV (fl) 8 7 Neutrophil (%) 7 M Eosinophil (%) N Basophil (%) 2. 1. 1.. O Lymphocyte (%) P Monocyte (%).. 7.. 2. Fig. 1. Distributions for complete blood cell count in male healthy geriatric population ( years old). The solid lines represent the median values, and the dotted lines denote lower and upper reference limit, respectively. (A) WBC, (B) RBC, (C) hemoglobin, (D) hematocrit, (E) RDW, (F) platelet, (G) MCV, (H) MCH, (I) MCHC, (J) PDW, (K) MPV, (L) neutrophil, (M) eosinophil (N) basophil, (O) lymphocyte, and (P) monocyte. Abbreviations: WBC, white blood cells; RBC, red blood cells; RDW, red cell distribution width; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; PDW, platelet distribution width; MPV, mean platelet volume. www.jlmqa.org J Lab Med Qual Assur 18;:27-37 2

결과 1. 연구대상군의선정건강증진센터에서 년 1월부터 년 3월까지건강검진을받은 세이상수진자중 Coulter LH 7으로측정한일반혈액검사결과가있는수진자는총 4,23명이었다. 이중에서제외기준에의해 84명이제외되었으며총 3,명의수 진자가건강한대상자에포함되었다. 이중 세이상은 374 명이었으며평균연령은.±.88세였다. 남성의경우 22 명으로평균연령은.±.31세였으며, 여성은 8명으로평균연령은 7.2±.42였다. 세미만대상자는 2,명이었으며평균연령은 4.4±7.세였다. 남성은 1,81명이었으며평균연령은 47.3±.77세였고, 여성은 1,4명으로평균연령은 4.1±7.32세였다. A B C D WBC (x /L) E F G H I M MCHC (g/dl) RDW (%).. 8.. 4. 2. Eosinophil (%) RBC (x /L) Platelet (x /L) J K L N.. 4. 4. 3. 3. 3 13 2 1 18 32 8 4 2 PDW (fl) Basophil (%) 3. 2. 2. 1. 1.. Hemoglobin (g/dl) MCV (fl) MPV (fl) O Lymphocyte (%) 13 8 7 Hematocrit (%) MCH (pg) Neutrophil (%) P Monocyte (%) 4 32 28 7 8 4 Fig. 2. Distributions for complete blood cell count in female healthy geriatric population ( years old). The solid lines represent the median values, and the dotted lines denote lower and upper reference limit, respectively. (A) WBC, (B) RBC, (C) hemoglobin, (D) hematocrit, (E) RDW, (F) platelet, (G) MCV, (H) MCH, (I) MCHC, (J) PDW, (K) MPV, (L) neutrophil, (M) eosinophil (N) basophil, (O) lymphocyte, and (P) monocyte. Abbreviations: WBC, white blood cells; RBC, red blood cells; RDW, red cell distribution width; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; PDW, platelet distribution width; MPV, mean platelet volume. J Lab Med Qual Assur 18;:27-37 www.jlmqa.org

2. 항목별일반혈액검사결과의분포 세이상연령군의일반혈액검사항목별분포는 Figs. 1, 2 와같았다. 많은검사항목에서연령증가에따른뚜렷한방향성을관찰할수는없었다. 세이상연령군의평균을 Mann Whitney U-test 를통해 세미만군과비교하였을때다수 의항목에서연령군별평균에유의한차이를보였다 (Table 1). 유의한차이를보이지않은항목은남성의백혈구, 호산구, 호염기구, 단구와여성의백혈구, 적혈구, PDW, 호염기구, 단구였다. 세이상연령군에서남성과여성의아군으로나누어 independent samples t-test로평균을비교하였을때역시성 Table 1. The comparison of the median between age groups and < years using Mann Whitney U-test Variable Number Median (range) P-value* Number Median (range) P-value* White blood cells ( /L) 22.1 (3.3.). 8. (2.8.2).17 < 1,81. (2.7.1) 1,4.3 (2. 17.) Red blood cell ( /L) 22 4. (3.1.) <.1 8 4. (3.4.3). < 1,81 4. (3.1.) 1,4 4.21 (2..4) Hemoglobin (g/dl) 22. (. 18.) <.1 8 13.2 (.3.) <.1 < 1,81.3 (8. 1.) 1,4 13. (8.2.) Hematocrit (%) 22 44.7 (32.2 3.2) <.1 8 3.3 (..2).1 < 1,81 4.2 (27..7) 1,4 38.8 (24.8 48.) Red cell distribution width (%) 22 13.1 (. 1.) <.1 8. (.7.). < 1,81. (.4.7) 1,4 13. (.1 22.4) Platelet ( /L) 22 2. (. 441.) <.1 8 223. (. 37.). < 181 228. (8. 4.) 1,4 2. (. 1.) Mean corpuscular volume (fl) 22.7 (. 1.8) <.1 8 4.2 (. 1.) <.1 < 1,81 3.4 (.8 3.3) 1,4 2.2 (2..8) MCH (pg) 22 32.1 (.1 37.) <.1 8 31. (28..) <.1 < 1,81 31. (17.3 3.) 1,4 31. (18.7 3.) MCH concentration (g/dl) 22. (.7.2) <.1 8.7 (31..3).3 < 1,8.7 (2.8 3.1) 1,4. (2. 3.2) Platelet distribution width (fl) 22.4 (.1 18.1).3 8.1 (8. 17.8).7 < 1,81.3 (. 18.) 1,4.2 (8.4 1.) Mean platelet volume (fl) 22 8.4 (.3.7).13 8 8.4 (.2.).3 < 1,81 8.4 (.7 13.1) 1,4 8.7 (.3 13.2) Neutrophil (%) 22.1 (.3 8.4).1 8 3.4 (2.2 77.) <.1 < 1,81 4.1 (2.2 87.) 1,4.8 (27.7 8.4) Eosinophil (%) 22 2. ( 18.).7 8 1.8 (.3 7.2).18 < 1,81 2. ( 21.8) 1,4 1.8 ( 18.4) Basophil (%) 22. ( 1.).4 8. (.1 2.8).1 < 1,81. ( 2.) 1,4. ( 2.) Lymphocyte (%) 22 32.4 (4. 7.1).3 8 3. (.7 1.8) <.1 < 1,81.7 (8.4.3) 1,4. (. 7.) Monocyte (%) 22 7.2 (3..). 8.7 (4. 13.).1 < 1,81 7. (2.1 1.1) 1,4. (2..) Values are presented as number or median (range). Abbreviation: MCH, mean corpuscular hemoglobin. *For each variable, two age groups were compared using the Mann Whitney U-test. P-values. were considered statistically significant. www.jlmqa.org J Lab Med Qual Assur 18;:27-37 31

별에따른평균에유의한차이를보였다. 유의한차이를보이지않은항목은혈소판, MCHC, MPV, 호염기구였다 (Fig. 3). 3. 참고구간의설정비모수방법에따라성별, 연령별로설정된참고구간은 Tables 2, 3에나타내었다. 남성의일반혈액검사의경우거의모든일반혈액검사항목에서 세이상건강노인과 세 미만군과의참고구간을분할하는것은통계적의의가없었다 (Table 4). PDW에서만큰표준편차 (s 2 ) 가작은표준편차 (s 1 ) 의 1.배보다커서참고구간의통계적차이를보였다. 여성에서 z>z* 의결과를보였거나, s 2 /(s 2 -s 1 ) 이 3보다작은결과를보여참고구간의통계적차이가관찰된항목은 MCV와 MCH, RDW 및호산구였다. 이외의일반혈액검사항목에서 세이상건강노인과 세미만군과의참고구간은통계적차이가 A B C D WBC (x /L) E F G H I J K L M RDW (%) MCHC (g/dl) Eosinophil (%) 18 3 32 31 327 7 24 17 2 27 313 41 47 3 7 213 2 17 1 237 83 18 P<.1.3.27 P<.1 217 1 2 3 372 7 3 1 27 RBC (x /L) Platelet (x /L) N PDW (fl) Basophil (%) 4 3 2 18.. 13.. 3. 2. 1. 8. 3 213 22 2 1 131 1 242 3 17 2 1 7 327 P<.1..1 272 2 374 32 J Lab Med Qual Assur 18;:27-37 www.jlmqa.org Hemoglobin (g/dl) MCV (fl) MPV (fl) O Lymphocyte (%) 1 17 13 7 1 7 8 7 1 1 23 2 174 13 27 2 23 3 1 4 P<.1.1.4 P<.1. 2 2 272 21 272 3 371 7 374 2 1 1 1 4 1 372 2 2 8 27 18 Hematocrit (%) MCH (pg) Neutrophil (%) P Monocyte (%) 2 171 323 2 23 2 4 13 8 1 2 218 13 13 Fig. 3. Comparison of complete blood cell count between males and females in healthy geriatric population ( years old). For each variable, the two gender groups were compared using Student t-test. P-values. were considered statistically significant. (A) WBC, (B) RBC, (C) hemoglobin, (D) hematocrit, (E) RDW, (F) platelet, (G) MCV, (H) MCH, (I) MCHC, (J) PDW, (K) MPV, (L) neutrophil, (M) eosinophil (N) basophil, (O) lymphocyte, and (P) monocyte. Abbreviations: WBC, white blood cells; RBC, red blood cells; RDW, red cell distribution width; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; PDW, platelet distribution width; MPV, mean platelet volume. 4222 2 372 1 7 7 213 P<.1.3.1.1 372 2 273 1

Table 2. The RIs in healthy geriatric population ( years old) Variable RI Lower % CI Higher % CI RI Lower % CI Higher % CI White blood cells ( /L) 3..8 3. 4..3.7 3.3 8. 2.8 3.7 7..2 Red blood cells ( /L) 3.1.4 3.8 3...1 3.4 4.8 3.42 3.7 4.72. Hemoglobin (g/dl). 17.2.8 13.1. 17..8.1.3.1.8. Hematocrit (%) 38.2 1.2 32. 3.2.1 2.2 4.2.. 44.1.2 Red cell distribution width (%).1...2. 17.3...7.1.1. Platelet ( /L).4 32.8 1 1.. 31. 7. 322. 3 37 Mean corpuscular volume (fl) 8.2 3.7 83.8 88.8 2.3 7.8 87.8.. 88.7 1. MCH (pg) 28.1 27.1 2.7. 3. 2.2.3 28. 2..8. MCH concentration (g/dl) 32..7 32 32.8..1 32. 31. 32.7.7.3 Platelet distribution width (fl) 13 17..2.7 17.3 18..7 17 8. 13.7. 17.8 Mean platelet volume (fl).8.7. 7.1.2.3.8.3.2 7.1.. Neutrophil (%) 3. 74.7.8.3 72..1. 73.4 2.2 37.8 7. 77. Eosinophil (%).4.3.7...4..3. 4. 7.2 Basophil (%).2 1.4.3 1.1 1..2 1.4.1.3 1.3 2.8 Lymphocyte (%)... 18. 47. 3. 1.1 3..7 23..3 1.8 Monocyte (%) 4.2. 3.1... 4.2. 4. 4..8 13. All RIs were established according to the Clinical and Laboratory Standards Institute guideline EP28-A3c and 2.th 7.th percentile. The % CI was calculated according to the following formula: mean±1.4 standard deviation number. Abbreviations: RI, reference interval; CI, confidence interval; MCH, mean corpuscular hemoglobin. Table 3. The RIs in healthy adult population ( and < years old) Variable RI Lower % CI Higher % CI RI Lower % CI Higher % CI White blood cells ( /L) 3.8.2 3.7 3... 3.3 8.8 3.1 3.3 8..2 Red blood cells ( /L) 4.2. 4. 4.23.3.1 3.7 4. 3. 3.73 4.77 4.88 Hemoglobin (g/dl) 13.4 17.2 13.3 13. 17.1 17.3...3..7 Hematocrit (%) 3. 1 3.3.2. 1.3 31.3 43.4.1 31. 43.1 43. Red cell distribution width (%)..1.8.1.1.3.8 17..8. 17.2 18.7 Platelet ( /L). 3 3 7.1 3.4. 1. 2. 383. Mean corpuscular volume (fl) 8. 1.8 8..4 1.7 7..8 73.1 77.2.1.2 MCH (pg) 2.3 28.8 2.2.1.4 24 23.4 24.8.7.1 MCH concentration (g/dl) 32.7 32. 32.8..1 31..8 31.3 31.8.7. Platelet distribution width (fl).7 17.4.. 17.3 17.. 17.3.3. 17.1 17.4 Mean platelet volume (fl).8.8..8.1 7.2. 7.1..3 Neutrophil (%) 3.1 71.7 37.8.1. 73.2 3.8 72.2 38.2 41.2 7. 73.7 Eosinophil (%)..4.. 8..2.3 8.8.3.4 8.. Basophil (%).2 1.3.2.2 1.2 1.3.2 1..2.2 1.4 1. Lymphocyte (%) 1.1 4.2 18.3.4 48..2 48.1 1..8 47.4 4.4 Monocyte (%) 4.4. 4.3 4..7.2 4.1. 3.8 4.2.2. All reference ranges were established according to Clinical and Laboratory Standards Institute guideline EP28-A3c and 2.th 7.th percentile. The % CI was calculated according to the following formula: mean±1.4 standard deviation number. Abbreviations: RI, reference interval; CI, confidence interval; MCH, mean corpuscular hemoglobin. www.jlmqa.org J Lab Med Qual Assur 18;:27-37

Table 4. Partitioning of RI for age groups ( and < years old) according to Harris and Boyd method Variable z z* s 1 s 2 1.s 1 s 2 /(s 2 -s 1 ) z z* s 1 s 2 1.s 1 s 2 /(s 2 -s 1 ) White blood cells ( /L) 1. 8.84 1.1 1. 2.42 41.2 1..1 1.4 1.4 2.1 24. Red blood cells ( /L).7 8..3.38.4 1..1.2.3.44 Hemoglobin (g/dl) 4.23 8..8 1. 1.47 8.27.1. 1. 1.28 4.48 Hematocrit (%) 3. 8. 2.1 3.3 4.3 7.42 4.1.1 2. 2.8 3.8.3 Red cell distribution width (%).7 8...8. 4.3.42.1.1 1.4.2 1.72 Platelet ( /L) 3.3 8. 48. 4. 73.44 1.7 2.43.1 48.4.4 72.81 7. Mean corpuscular volume (fl).3 8. 3.87 4.7.81.3.4.1 3.. 4.8 2.21 MCH (pg) 4. 8. 1.44 1.74 2..8 8..1 1.2 2.2 1.8 2.22 MCH concentration (g/dl) 3.72 8.84.7..8 2. 3..1..77. 4.3 Platelet distribution width (fl).3 8..1 1.48 1.37 2. 1.4.1 1.1 1. 1. 3.24 Mean platelet volume (fl) 2.7 8..2 1.4 1.38 8.7 2.71.1 1. 1. 1.8.27 Neutrophil (%) 2.23 8. 8.32.1.48 7.4 3.4.1 8.38..7.3 Eosinophil (%). 8. 2.38 2.2 3.7.73 3.22.1 1.44 2.2 2. 2.78 Basophil (%). 8..28.2.42 3.44 1..1.31.3.47 7.2 Lymphocyte (%) 2.77 8. 7.8 8.7.37 7.77 4.7.1 7.4 8.2.1.31 Monocyte (%) 1.42 8. 1.4 1. 2.31 1.2.1 1. 1. 2.4. Abbreviations: RI, reference interval; MCH, mean corpuscular hemoglobin. *We used the method of Harris and Boyd to decide whether it was necessary to separate the RIs for age groups. The standard normal deviation (z) and critical value {z*=3(n average /) 1/2 } were calculated. If the calculated z exceeds z*, or the larger standard deviation (s 2 ) exceeds 1. smaller standard deviation (s 1 ), or s 2 /(s 2 -s 1 ) is less than 3, it is recommended partitioning the RIs for age groups. J Lab Med Qual Assur 18;:27-37 www.jlmqa.org

없었다. 고찰 평균수명의증가에따른노인인구는계속증가추세에있으며 년통계청의조사에따르면한국의 세이상노인인구는약 1,13만명으로전체인구의약 % 에달한다 [13]. 의료기관을방문하는노인의비중은인구구성비율보다더높아서, 건강보험심사평가원의 년조사에따르면노인인구 (세이상 ) 의진료비가건강보험전체진료비의 37.% 를차지했다 [2]. 이처럼병원에서노인의참고구간에대한임상적필요성은증가하고있지만현재임상검사실에서사용하고있는참고구간은대부분 -세의건강한성인을대상으로정립한경우가많다 [3,4]. 전세계적으로도노인인구의참고구간에관한연구는미미한상태로, 본연구에서정립한건강한한국노인인구의일반혈액검사참고구간은실제임상검사실에서유용하게이용될수있을것으로보인다. 본연구에서정립한한국노인의일반혈액검사참고구간은대부분의일반혈액검사항목에서 세이상건강노인과 세미만군간에통계적차이가관찰되지않았다. 남성의경우 PDW를제외한검사항목에서참고구간의통계적차이가보이지않아기존에정립된성인의혈액검사참고치를대부분그대로이용할수있을것으로생각된다. 여성에서도많은검사항목에서참고구간이통계적차이를보이지않아기존의정립된성인의혈액검사참고치를이용할수있을것으로생각된다. 다만여성의경우 세미만군에비해 세이상군에서 MCV 와 MCH가증가하는경향을보였다. 또한 RDW의참고구간은좁아지고호산구는감소하는경향을보였다. 노인인구에서 MCV 증가의경우기존의문헌에서보고한결과들과일치하는결과를보였으며 [,], 이는연령의증가에따른적혈구의수명변화가원인인것으로추측되고있다 []. 그밖에통계적의의가있는차이가관찰된항목의경우현재까지그의의가연구된경우는거의없으며노인인구의다른특징적인요소와의관련성및임상적인유용성등의분석이추가적으로필요할것으로생각된다. 노인의일반혈액검사참고구간에대해기존에보고된연구는미국과중국등몇몇소수의국가에서만존재하였으며 [- 18], 이결과들은대부분의항목에서본연구에서정립한결과와큰차이를보이지않았다. 혈색소를예시로살펴보면, 본연구에서는 세이상군에서남성은.-17.2, 여성은.8-.1의참고구간을보였는데, 미국의 세이상인구를대상으로연구한결과에의하면남성의경우.-17.4, 여성의경 우.7-.1의참고구간을보였다 []. 반면본연구결과보다다소낮은혈색소참고구간을보이는경우도있었는데, 중국의 세이상인구를대상으로연구한결과에의하면남성은.1-., 여성은.7-.의참고구간을보였다 [17]. 이처럼다른국가의구성원간의일반혈액검사참고구간은인종이나경제수준등에따라다를수있으므로한국인을대상으로한노인인구의참고구간을정립하여이용하는것이필요하며, 본연구결과는실제한국인을대상으로한진료에유용하게이용될수있을것으로보인다. 참고구간의설정에서가장중요한부분은건강군의참고치를설정하는것이다. 건강은보편적정의가없는상대적인상태로, 건강하다는것을어떻게정의하는지가참고치설정의기본이된다 [1]. 그러나노인의경우젊은성인에비해기저질병을가지고있는경우가많으며, 약물을복용하고있는경우가많아그필요성에비해참고구간설정에관한연구에어려움이있었다. 본연구에서는장기간의건강검진환자데이터를바탕으로건강검진시작성한문진결과에따라제외기준을설정하여참고치설정에필요한비교적많은수의건강노인의데이터를수집할수있었다. 요약하면, 본연구에서정립한건강한한국노인의일반혈액검사참고구간은남성의경우대부분의일반혈액검사항목에서 세이상건강노인과미만군사이에통계적차이를보이지않았다. 다만여성에서는 세이상건강노인과미만군사이에통계적차이를보이는구간이다소존재하였다. 따라서임상검사실에서는특히여성노인의혈액검사해석시기준이되는참고치를검사실의사정에맞추어재설정하는과정이필요할것으로생각된다. 감사의글 이논문은대한임상검사정도관리협회 년학술연구비지원에의해이루어졌다 (-). REFERENCES 1. Clinical and Laboratory Standards Institute. Defining, establishing, and verifying reference intervals in the clinical laboratory: approved guideline: EP28-A3c. 3rd ed. Wayne (PA): Clinical and Laboratory Standards Institute,. 2. National Health Insurance Service, Health Insurance Review and Assessment Service. Korea health insurance statistics. http://www.nhis.or.kr/menu/retrivemenu- www.jlmqa.org J Lab Med Qual Assur 18;:27-37

Set.xx?menuId=F23 (Accessed November 18, 17). 3. Wu X, Zhao M, Pan B, Zhang J, Peng M, Wang L, et al. Complete blood count reference intervals for healthy Han Chinese adults. PLoS One ;:e1. 4. Park SH, Park CJ, Lee BR, Kim MJ, Han MY, Cho YU, et al. Establishment of age- and gender-specific reference ranges for 3 routine and 7 cell population data items in a new automated blood cell analyzer, Sysmex XN-. Ann Lab Med ;3:244-.. Turan S, Topcu B, Gokce I, Guran T, Atay Z, Omar A, et al. Serum alkaline phosphatase levels in healthy children and evaluation of alkaline phosphatase z-scores in different types of rickets. J Clin Res Pediatr Endocrinol ;3:7-.. Colantonio DA, Kyriakopoulou L, Chan MK, Daly CH, Brinc D, Venner AA, et al. Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of biochemical markers in a healthy and multiethnic population of children. Clin Chem ;8:4-8. 7. Ridefelt P, Hellberg D, Aldrimer M, Gustafsson J. Estimating reliable paediatric reference intervals in clinical chemistry and haematology. Acta Paediatr ;3:-. 8. 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 ;3:481-8.. Zierk J, Arzideh F, Rechenauer T, Haeckel R, Rascher W, Metzler M, et al. Age- and sex-specific dynamics in 22 hematologic and biochemical analytes from birth to adolescence. Clin Chem ;1:4-73.. Solberg HE. Approved recommendations (187) on the theory of reference values: part. statistical treatment of collected reference values: determination of reference limits. J Clin Chem Clin Biochem 187;2:4-.. Reed AH, Henry RJ, Mason WB. Influence of statistical method used on the resulting estimate of normal range. Clin Chem 171;17:27-84.. Harris EK, Boyd JC. On dividing reference data into subgroups to produce separate reference ranges. Clin Chem ;3:2-7. 13. Korean Statistical Information Service. http://kostat.go.kr/ portal/korea/kor_nw/2/1/index.board?bmode=read& aseq=32 (Accessed November 18, 17).. Gamaldo AA, Ferrucci L, Rifkind JM, Zonderman AB. Age-related changes in mean corpuscular volume in adult whites and African Americans. J Am Geriatr Soc ;:173-4.. Danon D, Bologna NB, Gavendo S. Memory performance of young and old subjects related to their erythrocyte characteristics. Exp Gerontol ;27:27-.. Yip R, Johnson C, Dallman PR. Age-related changes in laboratory values used in the diagnosis of anemia and iron deficiency. Am J Clin Nutr 184;3:427-3. 17. Woo J, Arumanayagam M, Ho SC, Swaminathan R. Hematological indices and the prevalence of anemia in an elderly Chinese population. Pathology 18;21:31-4. 18. Tsang CW, Lazarus R, Smith W, Mitchell P, Koutts J, Burnett L. Hematological indices in an older population sample: derivation of healthy reference values. Clin Chem 18;44:-1. 3 J Lab Med Qual Assur 18;:27-37 www.jlmqa.org

건강노인에서의일반혈액검사참고구간의설정이은진 김미영 이은엽 전기범 이지원 김한성 강희정 이영경한림대학교성심병원진단검사의학과 배경 : 많은혈액검사항목에서연령에따른정상참고구간이달라진다는연구결과가보고되어있다. 그러나현재사용하고있는참고구간은대부분 - 세의건강한성인을대상으로정립한경우가많다. 이에본연구에서는건강한한국노인을대상으로하여 가지일반혈액검사항목에대한참고치를정립하고자하였다. 방법 : 건강검진을받은 세이상수진자 4,23 명중문진결과를바탕으로 3, 명의건강한성인을선정하였다. 일반혈액검사항목별로 Clinical and Laboratory Standards Institute EP28-A3 에서제시하는비모수방법에따라 세미만연령군과 세이상연령군의참고구간을설정하였다. 또한남성과여성에서각각 Harris 와 Boyd 방법에따라두연령군의참고치분할에통계적유의성이있는지평가하였다. 결과 : 다수의일반혈액검사항목에서 세이상건강노인군과 세미만연령군의참고구간은통계적차이가없었다. 남성의경우 platelet distribution width 을제외한거의모든일반혈액검사항목에서 세이상건강노인과 세미만군과의참고구간을분할하는것은통계적의의가없었다. 여성의경우에는 mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width 및호산구에서연령군별통계적차이가관찰되었다. 결론 : 건강한한국노인의일반혈액검사참고구간은대부분 세미만군의참고구간과유사하였으나, 여성에서는두연령군의참고구간에통계적차이를보이는구간이존재하였다. 따라서특히여성노인에서일반혈액검사참고구간을재설정하는과정이필요할것으로생각된다. (J Lab Med Qual Assur 18;:27-37) 교신저자 : 김미영우 )8 안양시동안구관평로 17 번길 22, 한림대학교성심병원진단검사의학과 Tel: 31)3-17, Fax: 31)3-178, E-mail: rabbit722@gmail.com www.jlmqa.org J Lab Med Qual Assur 18;:27-37 37