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1 대한임상검사학회지 : 36 권제 2 호, , 2004 빈혈환자에서자동 ESR 기기인 Test 1 과 Westergren 법의비교 대전보건대학임상병리과 1, 충북대학병원진단검사의학과 2, 충남대학병원진단검사의학과 3 김일택 1 김종석 2 박연보 3 임재실 3 Comparative Evaluation of Erythrocyte Sedimentation Rate by the Test 1 Analyzer and Westergren method in Patients with Anemia Kim, Il Taek 1., Kim, Jong Seok 2., Park, Yeon Bo 3., Lim, Jae Sil 3 Department of Clinical Pathology, Daejeon Health College, Daejeon, Korea 1 Department of Laboratory medicine, Chungbuk Nat'l Univ. Hospital, Cheongju, Korea 2 Department of Laboratory medicine, Chungnam Nat'l Univ. Hospital, Daejeon, Korea 3 Erythrocyte sedimentation rate(esr) measurements were performed in a total of 191 blood samples from patients below a hematocrit of 35% by both the Test-1(SIRE Analytical Systems, Udine, Italy) and the Westergren method, endorsed as the reference method for ESR by the International Council for Standardization in Hematology(ICSH). The corrected Westergren ESR values were also obtained applying the formula of Fabry (corrected ESR = ESR measured x 15/55-Hct). Linear regression analysis showed a close correlation (r=0.85) between the two methods both before and after ESR correction in total samples. There was no significant correlation difference between two methods in both two groups with hemoglobin 9g/dl and <9g/dl before and after ESR correction (r=0.873, r=0.827 respectively before correction and r=0.867, r=0.830 respectively after correction). Also, for two groups with hematocrit 24% and <24%, no significant difference was observed (r=0.859, r=0.792 respectively before correction and r=0.782, r=0.842 respectively after correction). However, for samples with <60mm of Westergren ESR before correction, a better correlation coefficient was obtained than samples with 60mm(r=0.701, r=0.541 respectively). In corrected Westergren ESR, also samples that were obtained with <40mm showed better correlation than samples with 40mm (r=0.690, r=0.347 respectively). In conclusion, we found a good correlation between Test-1 and Westergren measurements in patients with anemia but an expert group discussion is required to solve discrepancy between two methods in blood samples with very high ESR. Key Words : Erythrocyte Sedimentation Rate(ESR), Test 1, Anemia, Westergren 1) 교신저자 : 김일택, ( 우 ) 대전광역시동구가양 2 동 77-3 대전보건대학임상병리과 Tel : itkim@djhealth.ac.kr 137

2 I. 서론 적혈구침강속도 (erythrocyte sedimentation rate ; ESR) 는비특이적이고예민도가낮은검사이긴하지만 (Kallner, 1991), 급성기염증성반응의신뢰할만한직접적인지표로서인식되고있으며 (Van Leeuwen와 van Rijswijk, 1994), 검사비용이저렴하고신속하게직접적으로결과를알수있기때문에현재도널리이용되고있다 (Hertzman, 1993). ESR의측정법은 1921년 Westergren에의해구연산소다항응고제에채혈한희석혈액을이용한 Westergren 측정법이고안되었으며 (Westergren, 1921), ICSH는이방법을약간변형시켜 K3-EDTA 항응고제에채혈한혈액을이용하는방법을참고방법으로권장하고있다 (ICSH, 1993). 그러나이참고방법은수기법으로손이많이가며번거롭고무엇보다검사자에게감염의위험성이있다는것이문제점으로지적되고있다 (Caswell와 Stuart, 1991; Patton 등, 1989). 이러한문제점을해소하기위해밀폐된채혈시험관을이용하여자동판독할수있는 Sediplast ESR system (Polymedco, Cortland Manor, NY, USA) 이나, Diesse Ves-Matic System(Diesse Diagnostica Senese, Milano, Italy) 등이개발되어유럽이나미국의검사현장에도입되고있으며 (Zlonis. 1993) 우리나라에도상당수가보급되어있다. 최근들어서는완전자동화 ESR 기기인 TEST 1(SIRE Analytical Systems, Udine, Italy) 이국내시장에도소개되어상당수의종합병원에설치되어사용되고있다. Test 1 기기는 150μl의미량혈액을 20g의원심력이걸려있는모세관으로흐르게한다음, 37 조건이유지되고있는판독지점에서 950nm의적외선을투과하여흡광도를측정하는전혀새로운방식의 ESR 측정법으로서 (Plebani, 1998) 재현성이좋을뿐만아니라 ICSH 표준법인 Westergren 방법과비교했을때상관성이매우좋은것으로보고되고있다 (Giavarina 등, 2002 ; Romero 등, 2003). 그러나저자들의실무경험을통해서볼때, 혈색소값이매우낮은빈혈환자의경우에는두방법간에상당한차이를확인할수있었으므로이러한결과가통계적으로유의한의미가있는지를알아보기위해본연구를수행하게되었다. II. 재료및방법 1. 실험대상 2004년 7월 12일부터 8월 22일까지충남대학병원과충북대학병원의진단검사의학과에의뢰된 ESR 검체중 ICSH(1988) 기준에따라 Hematocrit 수치가 35% 이하인 191명의환자 ( 남자 97명, 여자 94명 ) 를대상으로자동 ESR기기인 TEST-1과 ICSH의표준법인 Westergren 결과를비교평가하였다. 2. 실험방법환자로부터 K3-EDTA 진공시험관에채혈한혈액을먼저 SE-9000(TOA Medical Electronics Co., Kobe, Japan) 자동혈구계산기로혈색소 (Hemoglobin ; Hb) 와적혈구용적률 (Hematocrit ; Hct) 을측정하였다. ESR의측정은모든혈액가검물을 TEST-1 자동 ESR 기기에서먼저측정한다음, 4시간이내에 Westergren 법의원리를이용한 VACUETTE Manual ESR System (Greiner Bio-One Co., Kremsmünster, Austria) 을이용하여수기법으로 ESR을측정하였다. Westergren 법에서적혈구용적이 ESR에미치는영향을교정하기위하여 Fabry(1987) 의교정공식을이용하였다. Fabry 교정공식 : Corrected ESR = ESR x (15/55-피검자의 Hct) 3. 통계처리실험결과는 SPSS/PC package(version 10.0) 를이용하여적혈구용적률 24% 이하군과이상군의평균비교를위하여 Group t-test를하였으며, Test 1과 Westergren 방법의상관관계를알아보기위하여단순선형회귀분석법 (simple linear regression analysis) 에의해통계적인유의성을분석하였다. p<0.05일경우에통계적으로유의성이있는것으로판정하였다. 138

3 III. 결과 1. 적혈구용적률에따른평균치의비교적혈구용적률 35% 이하인총 191명의혈액가검물을 24% 이하군 (26명) 과이상군 (165명) 및전체대상군 (191 명 ) 으로나누어평균값을분석한결과는 Table 1과같다. 모든비교대상군에서 Test-1 ESR 값이교정전 Westergren ESR보다는낮게나왔고, 교정후의 Fabry ESR 값보다는높게나왔다. 적혈구용적률이 24% 이상군에서는 Westergren ESR이교정후보다 27.63mm 높은반면에, 24% 이하군에서는교정후보다 41.42mm나높은수치를보여 Westergren ESR이적혈구용적률의영향을많이받는것으로나타났다. 그러나 24% 이하군과이상군의평균차이는 Group t-test를하여본결과, Test-1 ESR 이나 Westergren ESR의교정전과교정후모두유의한차이가없는것으로나타났다 (p>0.05). Westergren ESR을 Fabry 공식에의해교정한결과를보면, 전체대상군과 24% 이하군및 24% 이상군에서거의동일한결과 ( 각각 36.74mm, 36.70mm, 36.75mm) 를보여주고있어 Fabry 공식이적혈구용적률이 ESR에미치는영향을잘보정해주고있다는것을알수있었다. Table 1. Mean value of ESR(mm/hr) by Hematocrit level (Mean ±SD) Method Test-1 Westergren Fabry <24% (n=26)* 51.00± ± ± % (n=165) 44.38± ± ±21.33 Total (n=191) 45.28± ± ±1.53 *There is no significant difference in the mean value of ESR between <24% and 24% group (p>0.05) 상관성을단순선형회귀분석법에의해분석해본결과교정전 (r=0.876) 이나교정후 (r=0.857) 모두비슷하게상관성이매우높은것으로나타났다 (Fig. 1). 혈색소값을 9.0g/dL 이상군과 9.0g/dL 이하군으로나누어두방법간의상관성을분석해보면교정전 ( 9.0g/dL : r=0.827, <9.0g/dL : r=0.873) 이나교정후 ( 9,0g/dL : r=0.867, <9.0g/dL : r=0.830) 모두상관성이매우높은것으로나타났다 (Fig. 2). 적혈구용적률값을 24% 이상군과 24% 이하군으로나누어비교하였을때에도, 교정전 ( 24% : r=0.859, <24% : r=0.792) 이나교정후 ( 24% : r=0.782, <24% : r=0.842) 모두상관성이매우높은것으로나타났다 (Fig. 3). 2. 혈색소와적혈구용적률에따른상관관계분석 3. ESR 에따른상관관계분석 전체대상군에대해 Test-1 과 Westergren 방법사이의 빈혈의지표가되는혈색소와적혈구용적률과는별도 Fig. 1. Comparison of two methods for ESR measurements in total samples: Test 1 vs. Westergren method. A. Linear regression graph showing the correlation between the Westergren ESR test results(x-axis) and those of the Test 1(y-axis) before Fabry correction. B. The correlation between two methods after Fabry correction. 139

4 Fig. 2. Comparison of two methods for ESR measurements between <Hb 9.0g/dl and Hb 9.0g/dl group : Test 1 vs. Westergren method. A. Linear regression graph showing the correlation between the Westergren ESR test results(x-axis) and those of the Test 1(y-axis) before Fabry correction. B. The correlation between two methods in the low(<9.0g/dl) and high( 9.0g/dl) hemoglobin groups after Fabry correction. Fig. 3. Comparison of two methods for ESR measurements between <Ht 24% and Ht 24% group : Test 1 vs. Westergren method. A, Linear regression graph showing the correlation between the Westergren ESR test results(x-axis) and those of the Test 1(y-axis) before Fabry correction. B, The correlation between two methods in the low(<24%) and high( 24%) hematocrit groups after Fabry correction. 로 ESR이낮은군과높은군을비교하여두방법간의상관관계를분석하여보았다. 교정전 Westergren ESR은 60mm를기준으로, 그리고교정후 Fabry ESR은 40mm를기준으로두방법간의상관관계를분석해본결과, 교정전 (<60mm : r=0.701, 60mm : r=0.542) 이나교정후 (<40mm : r=0.690, 40mm : r=0.347) 모두 ESR이낮은군보다높은군에서상대적으로상관관계가낮은것으로나타났다 (Fig. 4). 교정했을때의상관계수차이가 으로교정전의 0.159보다큰값을보여, 교정후가교정전보다더상관성이떨어짐을알수있었다. IV. 고찰 ICSH에서는새로운 ESR 측정법을임상검사현장에적용할때에는, 적혈구용적률이 35% 이하인검체군을대상으로 Westergren법과비교하여그상관성을평가하도록권장하고있다 (ICSH, 1988). 이러한 ICSH의기준을적용하여적혈구용적률이 35% 이하인 191명의입원및외래환자를대상으로, 자동 ESR 기기인 Test-1 과 Westergren법의원리를이용한 VACUETTE Manual ESR System을이용하여 ESR을측정하였다. Westergren 140

5 Fig. 4. Comparison of two methods for ESR measurements : Test 1 vs. Westergren method. A, Linear regression graph showing the correlation between the Westergren ESR test results(x-axis) and those of the Test 1(y-axis) in the low(<60mm) and high( 60mm) ESR groups before Fabry correction. B, The correlation between two methods in the low(<40mm) and high( 40mm) ESR groups after Fabry correction. Fig. 5. Adolfo Romero 등의보고에서나타난 LSRBw (Westergren ESR) 와 LSRBt (Test-1 ESR) 의상관관계 (ρ:0.917, P<0.01) 법의 ESR 측정치는적혈구용적률이 ESR에미치는영향을보정하기위하여 Fabry의교정식에따라교정하였으며, 교정전과교정후의두방법간의상관성을알아보기위하여혈색소, 적혈구용적률및 ESR값을기준으로분석하여보았다. 혈색소의경우는전체대상군과 9.0g/dL 이상군과이하군으로, 적혈구용적률의경우는전체대상군과 24% 이상군과이하군의세가지대상군으로분류하였고, ESR의경우는교정전은 60mm를기준으로이상군과이하군으로 Fabry 교정치는 40mm를기준으로이상군과이하군의두가지대상군으로나누어두방법간의상관관계를알아보았다. 혈색소와적혈구용적률에의해분류된세가지대상군에서는교정전이나교정후모두두방법간의상관관계가매우높은것으로나타났는데, 이러한결과는다른연구자들 (Shin 등, 1999; Plebani 등, 1998; Romero 등, 2003) 의결과와비교하여보았을때, 상관계수는약간낮게나타났지만비슷하게높은상관성을보여주었다. 저자들의실무경험으로는혈색소치가참고범위에들어가는환자들에비해혈색소치가낮은빈혈환자에서는두방법간의측정값이심한차이를보이는경우가많아, 이러한사실이통계적으로유의성이있는지를알아보고자본연구를수행하게된것인데예상과는달리통계적으로유의한차이를발견할수없었다. 이러한실제경험적인자료와본연구결과에서나타난차이는분석대상을 ICSH 기준에따라적혈구용적률이 35% 이하인환자만을대상으로하여 35% 이상인정상군이분석대상에서제외됨으로써상대적으로적혈구용적률이높은정상군과비교하지못한데서그원인을찿아볼수있을것이다. 이러한추론의근거는본연구결과에자료를제시하진않았지만, 분석대상군을적혈구용적률에상관없이무작위로추출하여 297명의 ESR 값을측정한다음혈색소 9.5g/dL 이상군과이하군으로나누어비교해보았을때 9.5g/dL 이하군이이상군보다상관계수가상대적으로낮게나타난것으로알수있다 (r=0.910 > r=0.762). 141

6 ESR을기준으로 ( 교정전 60mm, 교정후 40mm 기준 ) 낮은군과높은군을비교했을때에는두방법간의상관성에상당한차이가있음을보여주었다. 즉 ESR이낮은군에비해높은군에서상대적으로상관성이낮음을확인할수있었다 ( 교정전 ; r=0.701 > r=0.542, 교정후 ; r=0.690 > r=0.347). 이러한결과를다른보고자의결과와비교해보면, Shin 등 (1999) 과 Plebani 등 (1998) 의보고에서는 ESR이높은군에서도상관성이좋은것으로보고하고있으나, Romero 등 (2003) 의보고에서는 ESR이낮은군과높은군을따로구분하여비교하진않았으나상관관계를분석한 Scattergram(Fig. 5) 을보면 ESR이높은군에서분산점들이선형회귀선에서멀리떨어져있음을보여주었다. 이상의결과로미루어볼때, Test-1 자동 ESR 기기가혈색소나적혈구용적률이낮은환자에서도 Westergren 방법과의상관성이좋은것으로나타나, Test-1 기기에의한 ESR 측정법이임상적으로신뢰할수있고또한고유한장점인신속성과미량의검체를이용한다는점에서매우효율적인것으로판단된다. 그러나 ESR이높은환자들에서는 ESR이낮은정상군에비해상관성이떨어지는것으로나타나추가적인연구가요망되며, Test-1과 Westergren ESR 값이심한차이를보이는경우올바른문제해결방법이무엇인지에대하여관련전문가들사이에진지한연구검토가이루어져야할것으로사료된다. V. 결론 본연구는 2004년 7월 12일부터 8월 22일까지충남대학병원과충북대학병원의진단검사의학과에의뢰된 ESR 검체중 ICSH(1988) 기준에따라적혈구용적률값이 35% 이하인 191명의환자 ( 남자 97명, 여자 94명 ) 를대상으로자동 ESR 기기인 TEST-1과 ICSH의표준법인 Westergren 결과를비교평가하였다. Westergren ESR은 Fabry 공식을이용하여교정전과교정후의 ESR 값을산출하여 Test-1과의상관관계를분석하였다. 전체가검물을대상으로 Test-1과 Westergren법사이의상관성을분석해본결과교정전이나교정후모두상관성이매우높은것으로나타났다. 혈색소값을 9.0g/dL 이상군과이하군, 적혈구용적률을 24% 이상군과이하군으로으로나누어두방법간의상관성을비교할때도교정전이나교정후모두상관성이매우높은것으로나타났 다. 그러나 ESR을교정전 60mm와교정후 40mm를기준으로높은군과낮은군을비교하였을때에는, 혈색소나적혈구용적률을기준으로비교했을때와는달리교정전이나교정후모두 ESR이낮은군보다높은군에서상관성이떨어지는것으로나타나이에대한추가연구와문제해결책이제시되어야할것으로생각된다. 참고문헌 1. Caswell M, Stuart J. Assessment of Diesse Ves-matic automated system for measuring erythrocyte sedimentation rate. J Clin Pathol 44: , Fabry TL. Mechanism of erythrocyte aggregation and sedimentation. Blood 70: , Giavarina D, Capuzzo S, Cauduro F, Carta M, Soffiati G. Internal quality control for erythrocyte sedimentation rate measured by TEST-1 Analyzer. Clin Lab 48(9-10): , Hertzman A.Evans TI, Sanders KM, et al. Effects of blood storage on the erythrocyte sedimentation rate. J Rheumaatod 20: , International Committee for Standardization in Haematology. Guidelines on selection of laboratory tests for monitoring the acute phase response. J Clin Pathol 41: , International Council for Standardization in Haematology. ICSH recommendations for measurement of erythrocyte sedimentation rate. J Clin Pathol 46: , Kallner A. On the temporal development of erythrocyte sedimentation rate using sealed vacuum tubes. Am J Hematol 37: , Patton WN, Meyer PJ, Stuart J. Evaluation of sealed vacuum extraction method (Seditainer) for measurement of erythrocyte sedimentation rate. J Clin Pathol 42: , Plebani M, De Toni S, Sanzari MC, Bernardi D, Stockreiter E. The TEST 1 automated system: a new method for measuring the erythrocyte sedimentation rate. Am J Clin Pathol 110(3): , Romero A, Munoz M, Ramirez G. Length of 142

7 sedimentation reaction in blood: a comparison of the test 1 ESR system with the ICSH reference method and the sedisystem 15. Clin Chem Lab Med 41(2): , Shin KS, Kim JS, Son BR. Evaluation of the Test 1 for measuring erythrocyte sedimentation rate. J Clin Pathol and Quality Control 21: , Van Leeuwen MA, van Rijswijk MH. Acute phase proteins in the monitoring of inflammatory disorders. Baillieres Clim Rheumatol 8: , Westergren A. Studies of the suspension stability of the blood in pulmonary tuberculosis. Acta Med Scand 54: , Zlonis M. The mystique of the erythrocyte sedimentation rate: a reappraisal of one of the oldest laboratory tests still in use. Clin Lab Med 13: ,

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012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar