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Korean J Hematol Vol. 44, No. 4, December, 2009 Original Article 소아에있어서모세혈검사와정맥혈검사의비교평가 인하대학교의과대학소아과학교실 김명준ㆍ진지훈ㆍ권영세ㆍ전용훈ㆍ김순기 Comparison of Blood Counts in Capillary and Venous Blood in Children Myung Joon Kim, M.D., Ji Hoon Jin, M.D., Young Se Kwon, M.D., Yong Hoon Jun, M.D. and Soon Ki Kim, M.D. Department of Pediatrics, College of Medicine, Inha University, Incheon, Korea Background: Obtaining a venous blood sample from infants and children can be a painful and traumatic procedure. It has been suggested that capillary blood samples can serve as substitutes for venous blood samples to diagnose anemia. However, few data exist about the correlation between the laboratory results obtained using capillary and venous blood samples. This study was performed to determine if the results from the LC-178CRP TM are the same as the results from a conventional hematology analyzer using venous blood. Methods: After informed consent was obtained, paired venous and capillary blood sample were collected simultaneously from 104 children (M:F=50:54). The capillary blood was analyzed using the LC- 178CRP TM, and venous blood was analyzed using an automatic hematology analyzer. The following were compared from capillary and venous samples: CBC, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red cell distribution width (RDW), and platelet count. The results were analyzed by Pearson's correlation and the Bland Altman Plot method. Result: The hemoglobin values were similar between the two groups of samples and had a high coefficient correlation (r=0.877). White blood cells, hematocrit, MCV, and MCH also had a significant correlation between capillary and venous blood samples. Based on the Bland-Altman method, the agreement between the two methods was considered good. Conclusion: The hematologic results from the capillary blood had a close correlation with the conventional venous method, including white blood cell count, and hemoglobin, MCV, and MCH levels. The LC-178CRP TM should be considered as an alternative for venous blood sampling for the tested parameters in children. (Korean J Hematol 2009;44:237-243.) Key Words: Vessel, Blood, Hemoglobin, Hematocrit, Erythrocyte indices 접수 :2009 년 9 월 4 일, 수정 :2009 년 10 월 6 일승인 :2009 년 10 월 6 일교신저자 : 김순기, 인천시중구신흥동 3 가 7-206 400-711, 인하대학교의과대학소아과학교실 Tel: 032-890-2843, Fax: 032-890-2844 E-mail: pedkim@inha.ac.kr 본연구는인하대학교의지원으로이루어졌음. 237 Correspondence to:soon Ki Kim, M.D. Department of Pediatrics, College of Medicine, Inha University 7-206, Shinheung-dong, Jung-gu, Incheon 400-711, Korea Tel: +82-32-890-2843, Fax: +82-32-890-2844 E-mail: pedkim@inha.ac.kr

238 Korean J Hematol Vol. 44, No. 4, December, 2009 서 론 대상및방법 경제성장과더불어전반전인영양상태가개선되어있음에도불구하고, 빈혈은여전히전세계적으로흔히볼수있으며, 특히영유아기및사춘기여아에많이발생하는것으로알려져있다. 1-4) 빈혈이가장많은연령층인 6개월에서 24개월사이의영유아들에서빈혈의원인은대부분철분공급의부족에기인하며, 이경우소적혈구 (microcytic) 빈혈로진행하기쉽다. 두뇌를포함한급속한성장이이루어지는영유아기에철분이부족하면빈혈뿐아니라인지및행동장애및성장과발달지연이생길수있으며, 5,6) 이러한손상은비가역적일수있다. 7,8) 그러므로철결핍빈혈 (iron deficiency anemia, IDA) 을신속히발견하여치료하는것이중요하고, 그러기위해서는적어도빈혈이의심되는영유아를대상으로혈액검사를하여확인하는것이필요한데, 혈액검사가쉽지않기때문에실제로검사가많이기피되고있는실정이다. 이러한어려움때문에정맥혈대신모세혈 (capillary blood) 에서채혈하여, 헤모큐 (HemoCue) 라는기계로혈색소 (hemoglobin, HGB) 를측정하기도한다. 9,10) 그러나이검사는 HGB만측정하기때문에다른혈액수치를알수없다는한계가있다. 또한몸의수분함량에따라 HGB 수치가변동할수있기때문에탈수등에의하여실제보다증가하거나감소할수있다. 빈혈환자의선별검사로서 HGB, 적혈구, 백혈구, 적혈구지수 [erythrocyte indices, 즉 mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) 및 mean corpuscular hemoglobin (MCHC)], 혈소판, 망상적혈구및말초혈도말검사가일반적이다. 이러한검사를모세혈로대신할수있다면용이하게여러가지정보를얻을수있다. 특히 MCV는탈수나수화등에의해서변동하지않고, IDA가심해짐에따라 MCV가감소하기때문에소구성빈혈을감별하는데유용하게사용될수있다. 그러나아직이에대한연구가많지않고, 11-17) 국내에서의연구는거의없는실정이다. 18) LC-178CRP TM 의료장비는모세혈채혈만으로도말초혈도말을제외하고는위에언급한모든검사가가능하다 (Horiba Ltd., Kyoto, Japan, LC-178CRP). 문제는이것이기존검사실장비의검사와어느정도로일치하는가일것이다. 본연구는 LC-178CRP TM 장비를이용한모세혈검사결과가기존정맥혈의검사결과와같은지를알아보기위해서시행하였다. 인하대학병원에입원하거나외래진료를받은 15세까지의환자를대상으로, 인하대병원임상시험심사위원회 (Institutional Review Board) 를통과한동의서를보호자로부터받았는데, 총 104명 ( 남 50명, 여 54명 ) 이었다. 이들에서의모세혈검사는다음과같았다. 신생아는발뒤꿈치에서그리고영유아는중지또는약지끝에서알코올로소독한후, needle lanset으로 puncture 하여한방울은버린다음, 2 3방울채취하여 microtainer에받아서, LC-178CRP TM 장비로측정하였다. 한편, 거의동시에정맥혈을뽑았다. 소아의경우좌측혹은우측의 median cubital vein에서신생아의경우는경정맥에서알코올로소독후에 3 ml 이상채혈하여자동혈구분석기 (Automated Cell Counting, ADVIA 2120, SIEMENS 사, GERMAN) 로측정하였고, 백혈구 (WBC), 적혈구 (RBC), HGB, 적혈구용적치 (HCT), MCV, 평균적혈구혈색소량 (mean corpuscular hemoglobin, MCH), 적혈구분포폭 (red cell distribution width, RDW), 혈소판 (PLT) 을측정하여모세혈및정맥혈검사의두결과를비교분석하였다. 통계처리는 Microsoft excel 2003 및 SAS 9.1 (SAS Institute Inc., Cary, NC, USA) 프로그램을이용하였고, HGB, HCT, MCV, MCH 등각변수의값은평균 ± 표준편차로표기하였고, 모세혈및정맥혈두군사이의각각의변수값에대한 paired t-test를실시하여 P<0.05 일때유의하다고판정하였다. 각변수마다, 모세혈및정맥혈결과의상관관계를 Pearson's correlation test 로구하였고, 한편 Bland Altman Plot 방법 19) 으로분석하였고 95% 신뢰구간을일치한계선으로정의하였다. 결과 1. 모세혈및정맥혈의혈액수치 Table 1에서보이는것처럼, 모세혈및정맥혈의평균 WBC는각각 10,000/mm 3 및 10,800/mm 3 으로모세혈에서통계적으로유의하게높았다. 모세혈및정맥혈의적혈구의평균치는모세혈에서유의하게높았다 (Table 1). HGB 각각 12.2 g/dl 및 12.1 g/dl로서두혈액간에통계적인차이가없었다. HCT는모세혈에서유의하게높았다. 평균 MCV 및 MCH는모세혈에서유의하게높은값을보였다. 혈소

김명준외 : 소아에있어서모세혈검사와정맥혈검사의비교평가 239 판은모세혈에서 247,500/mm 3 정맥혈에서 329,000/ mm 3 으로서모세혈에서더낮았다. 신생아, 영아및그이상연령의소아로구분하였을때모세혈및정맥혈사이에 HGB은차이가없었다 (Table 2). 평균 MCV는신생아에서는차이가없었고, 영아의경우통계적차이를보였으나, 각각 82.9 및 82.0으로서큰차이를보이지않았고, 1세이상소아의경우모세혈에서 83.2 fl, 정맥혈에서 80.7 fl으로유의한차이를보였다. MCH는신생아의경우유의한차이를보이지않았고, 영아에서각각 27.1 및 27.4 pg이 Table 1. Hematologic values*of capillary and venous blood in 104 children Table 2. Hematologic values of capillary and venous blood according to the age distribution HGB (g/dl) HCT (%) MCV (fl) MCH (pg) Capillary Venous P-value WBC 10 3 /mm 3 10.0±4.7 10.8±4.8 0.003 RBC 10 6 /mm 3 4.42±0.67 4.31±0.60 0.004 HGB (g/dl) 12.2±2.0 12.1±1.9 0.137 HCT (%) 37.5±6.2 35.6±5.4 <.001 MCV (fl) 85.2±8.4 83.2±8.8 <.001 MCH (pg) 27.8±2.9 28.2±2.9 <.001 MCHC (g/dl) 32.6±0.9 33.9±1.4 <.001 RDW (%) 14.8±1.4 13.7±2.1 <.001 PLT 10 3 /mm 3 247.5±129.1 329.0±146.6 <.001 *Hematologic values are indicated as the mean±standard deviation. Abbreviations: WBC, white blood cell; RBC, red blood cell; HGB, hemoglobin; HCT, hematocrit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; RDW, red cell distribution width; PLT, platelet. Capillary Venous P-value Neonates (n=10) 13.3±4.1 13.2±4.2 0.715 Infants (n=26) 11.4±1.3 11.1±1.2 0.177 1 yr (n=68) 12.4±1.6 12.3±1.4 0.476 Neonates 40.6±12.6 39.4±12.2 0.351 Infants 35.1±4.5 33.0±3.3 0.007 1 yr 38.0±5.1 36.1±4.0 <.001 Neonates 104.2±8.1 103.3±10.7 0.384 Infants 83.0±5.80 82.0±6.4 0.048 1 yr 83.2±5.1 80.7±4.4 <.001 Neonates 34.1±2.6 34.1±2.6 0.899 Infants 27.1±2.5 27.4±2.4 0.008 1 yr 27.2±1.9 27.5±2.0 <.001 Abbreviations: HGB, hemoglobin; HCT, hematocrit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin. 었고, 1 세이상에서각각 27.2 pg 및 27.5 pg 을보였다. 2. 직선성 (Linearity) 및상관관계 모세혈및정맥혈검사사이의상관관계를보면, 적혈구의상관계수 (correlation coefficient) 는 0.829이었고, HGB 0.877, HCT 0.835로높은상관계수를보였다 (Table 3, Fig. 1 3). MCV와 MCH는각각 0.968 및 0.970로매우높은양 ( 陽 ) 의상관관계를보였다. 백혈구의경우상관계수 (correlation coefficient) 는 0.835, 반면 MCHC는낮은상관관계를보였고, RDW는상관관계가없었다 (Table 3). 3. Bland Altman 방법에의한모세혈및정맥혈결과의일치도 모세혈및정맥혈에서백혈구수의일치도를보면 Table 3. Correlation between variables capillary versus venous blood Hematologic variables Correlation coefficient P-value WBC 0.835 <.001 RBC 0.829 <.001 HGB 0.877 <.001 HCT 0.835 <.001 MCV 0.968 <.001 MCH 0.970 <.001 MCHC 0.421 <.001 RDW -0.057 0.572 PLT 0.688 <.001 Abbreviations: WBC, white blood cell; RBC, red blood cell; HGB, hemoglobin; HCT, hematocrit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; RDW, red cell distribution width; PLT, platelet. Fig. 1. Correlation and linearity in HGB.

240 Korean J Hematol Vol. 44, No. 4, December, 2009 Bland Altman 방법에서두방법사이를비교한결과, 대부분 95% 신뢰구간인일치한계선사이에들어있었다 (Fig. 4). 모세혈및정맥혈에서 RBC 수의일치도역시대부분이 95% 의신뢰구간의일치한계선내에서측정되었다 (Fig. 5). HGB 및 HCT 역시높은일치도를보였다 (Fig. 6, 7). 모세혈및정맥혈에서 MCV 및 MCH 각각에대한 Bland Altman 방법에의한일치도에서, 대부분이 95% 의신뢰구간의일치한계선내에서측정되었다 (Fig. 8, 9). 모세혈및정맥혈에서의 Plt 역시대부분이 95% 의신뢰구간의일치한계선내에서측정되었다 (Fig. 10). MCV, MCH, WBC, PLT, 망상적혈구및말초혈도말검사를포함한다. 이러한혈액검사를위한채혈은대 고 찰 빈혈환자의 1 차적선별검사에는보통 HGB, HCT, Fig. 4. Differences against mean for white blood cells by Bland Fig. 2. Correlation and linearity in MCV. Fig. 5. Differences against mean for RBC data by Bland Fig. 3. Correlation and linearity in MCH. Fig. 6. Differences against mean for HGB data by Bland

김명준외 : 소아에있어서모세혈검사와정맥혈검사의비교평가 241 Fig. 7. Differences against mean for HCT data by Bland Fig. 9. Differences against mean for MCH data by Bland Fig. 8. Differences against mean for MCV data by Bland Fig. 10. Differences against mean for PLT data by Bland 체로정맥혈에서하고있지만, 그간편성때문에모세혈에서시도되어왔고, 이두검사간의차이에대해서는많은보고가있었다. 11,15,16) 정맥혈의채혈부위로는두피정맥, 주전정맥, 대퇴정맥이흔히사용되며 1회에충분한양을채혈할수있으며채혈부위가다르더라도결과의변화가없다는장점이있다. 그러나비만, 탈수환자의경우채혈이어려울수있고혈관파열에의한혈종을일으킬수있으며, 특히신생아및영유아에서채혈이더욱어려운경우가있다. 모세혈관에서의채혈은정맥채혈보다용이한데, 소량의혈액이필요할때적합하며채혈부위는수지, 발뒤꿈치, 귓불이흔히사용되며신생아의경우는발뒤꿈치측면이안전하고쉬운채혈부위이다. 정맥혈대신모세혈로검사를대신할수만있다면, 매우간편하고편리할것이다. 문제는모세혈의결과가정맥혈만 큼정확한가일것이다. 정맥혈백혈구수가모세혈의백혈구수보다적다는기존의연구결과 11) 와달리본연구에서는모세혈과정맥혈에서의백혈구수의평균값이각각 10,000/mm 3 대 10,800/mm 3 으로측정되었으나차이가크지는않았다. 본연구에서는백혈구수가전체적으로평균값의차이가크지않고, 또한상관계수가 0.835이며 Bland Atman 방법에서일치도가높은점에서두방법은서로큰차이가없다고볼수있다. 본연구에서 HGB 결과는두방법사이에차이가없었다. 따라서정맥채혈이어려울경우, 모세혈검사로대치할수있을것이다. HGB와 HCT는생후 1개월이전까지는모세혈에서의미있게높다가, 1개월이후에는점차감소되어생후 3개월이후에는거의차이가없어진다는보고가많다. 11,23,24) 2세이상에서오히려

242 Korean J Hematol Vol. 44, No. 4, December, 2009 정맥혈의 HGB가더높았다는보고도있다. 20) 본연구에서신생아의경우모세혈에서약간높았으나통계적으로유의한차이를보이진않았는데, 이는검사숫자가 10명에불과한때문인지도모른다. 차제에숫자를늘려검사하는것이필요할것으로사료된다. HCT의경우기존의연구를보면결과가정립되어있지는않으나, 국내연구결과에서는 23,24) 모세혈에서더높다는결과가보고되어있고본연구에서도모세혈에서더높게측정되었으며통계적으로유의한차이를보였다. MCV 역시두방법간에차이가있었지만, 실제임상에서 MCV의정상최저치는성인에서 80 fl, 5세이상의소아에서 75 fl이므로, 25) MCV 2 fl 정도의차이가빈혈의접근방향에큰영향을줄정도는아닐것으로판단된다. 또한상관관계및 Bland Atman 방법에서의일치도가높았다는점에서정맥채혈을대치할수있는방법으로사료된다. 본연구에서혈소판은정맥혈에서더높은값을보였는데, 이는다른많은보고와유사한결과로서, 12,13,21,22) 천자시에조직에서야기되는혈소판의활성화및조직에가해지는압력에의한것으로설명되고있다. 그러나보고자에따라서증가한경우도있었고, 14) 별차이가없었다는보고도있었다. 11) 이미알려진것처럼혈소판수는측정시의수치가잘변하기때문에충분히추론할수있는결과로생각된다. 본연구에서도일치율이높지않았는데, 정확한혈소판수를알기위해서는정맥혈이선호될수있을것으로생각된다. 본연구에서모세혈채취전충분한가온 (warming) 을시행하는등, 혈액이잘나오도록천자하는경험이요구된다. 그리고같은환자에서모세혈과정맥혈두가지의혈액채취를해야되기때문에보호자의동의를얻기가쉽지않았는데, 향후신생아의경우좀더많은표본수를얻어통계를내는것이필요할것이다. 영유아에서철결핍에의한소구성빈혈이여전히발견되고있는바, 이를쉽게발견한다면매우유용할것이다. 기존의 HemoCue, STAT-Site R MHgb (Stanbio Laboratory, Boerne, TX, USA), CompoLab HB Sytem (Fresenius Kabi AG, Bad Homburg, Germany) 같은기계의의한 HGB 검사만으로는다른혈액수치를알수없기때문에정보의제한이따른다. 그러므로 HGB 뿐만아니라 RBC, MCV, MCH, WBC, PLT 등의결과를같이얻는다면매우유용한정보를얻는것이다. 특히 MCV는철결핍이진행됨에따라감소하고, 탈수나수화등에의해서변동하지않기때문에소구성빈혈을감별하는데유용하다. 결론적으로, 본연구에서모세혈의 HGB, MCV, MCH는정맥혈과매우상관관계가높았으므로, LC- 178CRP TM 검사는임상적으로사용하기에큰문제가없을것으로사료된다. 여러가지검사를하는데있어정맥혈검사가더좋겠지만, 채혈이어려운경우에나대규모선별검사시에는모세혈채혈검사로대신하는것도고려할수있을것이다. 요 배경 : 영ㆍ유아에서는채혈의어려움때문에혈액검사를하기가쉽지않으므로, 모세혈채혈만으로전혈구계산값 (CBC), 적혈구지수 (erythrocyte indices) 를알수있다면매우요긴하고유용한정보를얻을수있을것이다. 본연구는 LC-178CRP TM 장비에의한검사결과가기존검사실의자동혈구분석기와같은지를알아보기위해서시행하였다. 방법 : 인하대학병원에입원하거나외래진료를받은 104명 (0 15세, 남녀 50:54) 을대상으로정맥혈은 Bayer Advia 2120 (Bayer Diagnostics, USA), 모세혈은 LC- 178CRP TM 장비를사용해검사하였다. 비교검사항목은백혈구 (WBC), 적혈구 (RBC), 혈색소 (HGB), 적혈구용적치 (HCT), 평균적혈구용적 (MCV), 평균적혈구혈색소량 (MCH), 혈소판 (Plt), 적혈구분포폭 (RDW) 이다. 각변수에따른모세혈및정맥혈결과의상관관계는 Pearson's correlation test 및 Bland Altman Plot 방법으로분석하였다. 결과 : 모세혈및정맥혈검사사이의상관관계를보면, 대부분의항목이매우높은높은양 ( 陽 ) 의상관관계를보인반면 MCHC는낮은상관관계를보였고, RDW는상관관계가없었다. Paired t-test로분석한결과혈색소는모세혈과정맥혈에서의유의한차이를보이지않았다. Bland Altman Plot으로분석한결과혈색소, 적혈구수, 평균적혈구용적등대부분의항목에서 95% 신뢰구간의일치한계선내에서측정되었다. 결론 : 모세혈의 HGB, MCV, MCH는정맥혈과의상관관계및일치도가높았다. 여러혈액검사를하는데있어정맥혈검사가더좋겠지만, 채혈이어려운경우에 LC-178CRP TM 를이용한모세혈에서의채혈은정맥혈검사를대신할수있는간편한방법으로사료된다. 약 참고문헌 1) Dallman PR, Yip R. Changing characteristics of child-

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