대한진단검사의학회지제 27 권제 1 호 2007 Korean J Lab Med 2007;27:1-6 원저 진단혈액학 미성숙혈소판분획을이용한혈소판감소증진단법의임상적유용성 조용곤 1,2 이재현 1 김달식 1,2 이혜수 1,2 최삼임 1,2 전북대학교의과대학진단검사의학교실

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1 대한진단검사의학회지제 27 권제 1 호 2007 Korean J Lab Med 2007;27:1-6 원저 진단혈액학 미성숙혈소판분획을이용한혈소판감소증진단법의임상적유용성 조용곤 1,2 이재현 1 김달식 1,2 이혜수 1,2 최삼임 1,2 전북대학교의과대학진단검사의학교실 1, 전북대학교임상의학연구소 2 Clinical Usefulness of the Simple Technique to Diagnose Thrombocytopenia Using Immature Platelet Fraction Yong Gon Cho, M.D. 1,2, Jae Hyun Lee, M.D. 1, Dal Sik Kim, M.D. 1,2, Hye Soo Lee, M.D. 1,2, and Sam Im Choi, M.D. 1,2 Department of Laboratory Medicine 1, Chonbuk National University Medical School; Research Institute of Clinical Medicine 2, Chonbuk National University, Jeonju, Korea Background : Immature platelet fraction (IPF) is the percentage of reticulated platelet (RP) of total platelet count. We measured an IPF reference range using XE-2100 blood cell counter with upgraded software (Sysmex, Japan) and evaluated the clinical utility of this parameter for the laboratory diagnosis of thrombocytopenia due to an increase in peripheral platelet destruction. Methods : Peripheral blood samples collected into K2EDTA (Beckton Dickinson, USA) were analyzed at Chonbuk National University Hospital. One hundred forty-two samples from apparently healthy adults (all routine full blood count parameters including platelets within the healthy reference range) were used to establish a normal reference range for IPF. The patients were classified into 3 groups including hypoplastic (consisted of 22 patients undergoing chemotherapy with falling platelet counts and 14 with aplastic anemia), cirrhotic (40 with cirrhosis of liver), and idiopathic thrombocytopenic purpura (ITP) (14 with ITP) groups. Results : An IPF reference range in healthy individuals was established as %, with a mean of 1.7%. A significant increase in IPF values was found in the ITP patient group. The cut-off value of IPF was 6.1% and its sensitivity and specificity were 92.9%, and 82.9% respectively. Reproducibility was good. Conclusions : A rapid, inexpensive automated method for measuring IPF is feasible and should become a standard parameter in evaluating thrombocytopenic patients. (Korean J Lab Med 2007;27:1-6) Key Words : Reticulated platelet, Immature platelet fraction, Idiopathic thrombocytopenic purpura, Aplastic anemia 서 론 미성숙혈소판분획 (immature platelet fraction, IPF) 은자동화 접수 : 2006 년 5 월 30 일접수번호 : KJLM1954 수정본접수 : 2006 년 12 월 11 일게재승인일 : 2006 년 12 월 11 일교신저자 : 조용곤우 전북전주시덕진구금암동 전북대학교의과대학진단검사의학교실전화 : , Fax: cyk6772@chonbuk.ac.kr 기기에서측정되는망상혈소판 (reticulated platelet, RP) 의백분율 을가리키며, 형광염색을통해세포질내에 RNA성분을갖고있는미성숙혈소판의수를총혈소판수에대한백분율 로나타낸것이다. RP% 는많은논문을통해혈소판감소환자에서혈소판조혈을반영하는지표로사용될수있으며특히, 골수의생산저하에의한경우와말초에서의파괴증가에의한경우를구별하는데유용하다고보고되었다 [1-5]. 그러나, 정상인에서의 RP% 의참고범위가보고자에따라 3% 에서 20% 까지매우다양하였고, 측정과정이매우복잡하여임상적으로적용되기어려웠다 [6]. 최 1

2 2 조용곤 이재현 김달식외 2 인 근자동화기기를이용하여측정된 IPF 는안정된참고범위를나타 내며, 혈소판감소증의진단에도유용하다고보고되었다 [7, 8]. 이 에저자들은자동화기기를이용한 IPF 의참고범위를측정하고, 혈소판감소환자에서의임상적적용가능성을평가하고자하였다. 1. 대상 대상및방법 2006년 1월부터 4월까지전북대학교병원건강관리과에내원한환자와전북대학교의과대학에재학중인학생중혈액검사결과가정상치를벗어나지않은사람을대조군으로하고, 동일기간동안전북대학교병원에서혈액검사를시행하여말초혈액의혈소판수가 /L 미만인환자를실험군으로하였다. 대조군은총 142명 ( 남자 76명, 여자 66명 ) 이었고, 연령분포는 22-82세 ( 평균 ± 표준편차, 41.4±19.6) 였다. 환자군은총 90명 ( 남자 51명, 여자 39명 ) 이었고, 연령분포는 1-83세 (51.9±18.9) 였다. 환자는크게세종류의군으로나누었고, 제1군에는골수검사를통해재생불량성빈혈로진단된환자 14명과항암요법후골수검사를시행하여골수억제가확인된백혈병환자 22명 ( 골수생성저하군 ), 제2 군에는간경변증환자 40명 ( 간경변증환자군 ) 을포함시켰고, 제3 군에는특발성혈소판감소성자반증으로진단된환자 14명 (ITP 환자군 ) 을포함시켰다 (Table 1). Table 1. Causes of thrombocytopenia in patients Groups Causes N of Cases Hypoplastic Aplastic anemia 14 Chemotherapy 22 Cirrhotic Liver cirrhosis 40 ITP ITP 14 Total 90 Abbreviation: ITP, idiopathic thrombocytopenic purpura. 2. 혈소판수및 IPF 의측정 대조군과환자군의정맥으로부터 K 2EDTA가들어있는진공채혈관 (Becton Dickinson, Franklin Lakes, NJ, USA) 에전혈 3 ml를채혈한후혈소판수및 IPF 측정을시행하였다. Sysmex 사의 XE-2100은혈소판을두가지의형광염색시약인 polymethine과 oxazine으로염색한후유세포분석의원리에기초한광학 reticulocyte/platelet channel을통해수집하고, 전용소프트웨어 (XE IPF master, Sysmex, Kobe, Japan) 를이용하여 IPF 를계산할수있다. 형광염색시약들은혈소판의세포질내에있는 RNA성분을염색하고, 염색된혈소판들이기기내에장착되어있는반도체레이저로부터나오는빛을통과하면, 전방산란광과형광강도가측정된다. 이렇게측정된결과로부터 Fig. 1과같은혈소판산포도 (scattergram) 가그려지고, 컴퓨터알고리즘에의해성숙혈소판과미성숙혈소판의분획이결정된다. IPF는총혈소판수에대한미성숙혈소판의백분율로표시된다. 대조군의평균혈소판수는 246.5± /L이었고, 연령을 22-39세와 40-82세로나누어비교하였을때및성별간의유의한차이는없었다. 환자군중에서골수생성저하군의평균혈소판수는 30.9± /L이었고, ITP 환자군의평균혈소판수는 41.4± /L로두군간에유의한차이는없었지만, 간경 Table 2. Reproducibility results for 10 repeat analyses on six different individuals with varying platelet counts and IPF values Samples Mean platelet counts ( 10 9 /L) Mean IPF SD CV Normal ± Normal ± Low-PLT & high-ipf1 62.0± Low-PLT & high-ipf2 54.8± Low-PLT & low-ipf1 56.0± Low-PLT & low-ipf2 34.8± Abbreviations: IPF, immature platelet fraction; PLT, platelet. acv erythrocytes reticulocytes Forward light scatter Mature platelets are indicated in light blue dots IPF is indicated in green dots FSC FSC Fluorescence intensity SFL SFL Fig. 1. Optical platelet scattergram from a patient with high IPF value. Abbreviation: IPF, immature platelet fraction.

3 미성숙혈소판분획을이용한혈소판감소증진단법의임상적유용성 3 변증환자군의평균혈소판수는 56.5± /L로나머지두군과의비교에서유의하게높은결과를나타내었다 (Table 2). 3. 재현성측정및저혈소판증검체에서의결과확인 IPF의측정재현성을알아보기위해서혈소판수가정상인 2명의검체와혈소판수가 /L 미만이면서높은 IPF 값을보인 2명의검체, 그리고혈소판수가 /L 미만이면서낮은 IPF 값을보인 2명의검체를선택하여 10회반복측정을시행하였다. 혈소판수가낮은경우잡음 (noise) 의영향을확인하기위하여검체를농축하여재검하고결과를비교하였다. 재검을위해검체를원심분리 (4,000 rpm 10분 ) 한후상층의혈장을제거하고남은검체를적절하게혼합하였다. 또한, 1명의정상인의혈액을자신의혈장으로혈소판검출한계까지배수희석하여 IPF 측정치가변화하는지를알아보았다. 4. 통계처리 IPF의대조군과환자군사이의평균값비교는 Mann-Whitney U test를이용하였고, 유의수준은 P<0.05로하였다. 또, 혈소판감소증의원인을가장잘구별하는 IPF의경계치 (cut-off) 를구하기위해 ROC 곡선을이용하였다. 결과 1. IPF의참고범위및혈소판감소원인에따른차이 정상분포를확인하였고, 참고범위는 ( 평균 1.7)% 이었고, 성별간의유의한차이는없었지만, 연령간의비교에서는 22-39세의결과가 40-82세의결과보다유의하게높았다. 골수생성저하환자군으로부터측정된 IPF의평균값은 3.7 ( )% 이었고, 간경변환자군의평균 IPF 값은 4.6 ( )% 이었으며, ITP 환자군의평균 IPF 값은 12.1 ( )% 이었다. 골수생성저하와간경변환자군간의차이는유의하지않았지만, ITP 환자군의결과는나머지두군과각각유의한차이를나타내었다 (P=0.0001) (Fig. 2). 2. IPF의진단적유용성환자군의 IPF 값을 ROC 곡선을이용하여민감도와특이도를조사한결과, 말초파괴증가로인한혈소판감소증의진단기준이되는 IPF 값은 6.1% 이었으며, 이때의민감도와특이도는각각 92.9%, 82.9% 이었다 (Fig. 3). 3. 측정재현성및저혈소판증검체의결과검정혈소판수가정상인검체에서 IPF의측정변이계수는평균 (acv) 17.4% 이었고, 혈소판수가 /L 미만으로감소되어있으면서높은 IPF 값을보인검체에서는 7.7% 이었으며, 혈소판수가 /L 미만이면서낮은 IPF 값을보인검체에서는 28.4% 이었다 (Table 2). 각환자군의검체를혈소판수에따라선별하여 7개의검체를농축하여재검한결과, 큰차이를보이지않았고, 정상인의혈액을배수희석하여측정한 IPF의결과도큰차이를보이지않았다 (Table 3, 4). 142명의대조군을대상으로측정된 IPF의결과는로그변환후 IPF Control Hypoplastic Cirrhotic ITP Sensitivity Cut-off: 6.1% Sensitivity: 92.9% Specificity: 82.9% Fig. 2. Comparison of mean IPF values between control and patients. Mean IPF from ITP group was significantly higher than those from control, hypoplastic, and cirrhotic groups (P<0.05). However, its difference between control and non-itp patients group was not significant. Abbreviations: IPF, immature platelet fraction; ITP, idiopathic thrombocytopenic purpura Specificity Fig. 3. ROC curve shows that the cut-off value (indicated as ) of IPF is 6.1%, its sensitivity and specificity are 92.9% and 82.9%, respectively.

4 4 조용곤 이재현 김달식외 2 인 Table 3. IPF values of seven specimens before and after concentration No. Specimens Platelet count ( 10 9 /L) 고 Before 망상혈소판은세포질내에 RNA를함유하고있는미성숙혈소판으로, 골수의혈소판조혈상태를반영하는지표로알려져있다 [9, 10]. IPF는총혈소판수에대한망상혈소판의백분율로, ED- TA 전혈검체를이용하여자동화기기에서쉽게측정될수있다. 전혈을사용하므로산포도에서망상적혈구와망상혈소판의구분이문제될수있지만, 본연구에사용된 XE-2100 (Sysmex) 은적혈구군집 (cluster) 과혈소판군집사이에조각적혈구 (RBC fragments) 가있는경우나용혈과같이혈소판군집에비정상적인군집이있는경우에는 abnormal scattergram 이라는메시지를보여주므로새로운검체를적용하여극복할수있다. 또한성숙한혈소판과미성숙혈소판의구분은혈소판의크기와측정된형광강도사이에그려진도표상에서다수의정상검체를가지고자체적으로설정한 IPF 검출영역으로부터미성숙혈소판을정의함으로써가능하다. 만일, 검체내의혈소판수가낮을경우, 혈소판의분포영역이적어지고측정되는세포의수가적어짐으로써상대적으로잡음 (noise) 의영향을더크게받을우려가있지만, 장비회사의설명에따르면, 고정된검출영역을사용하기때문에큰영향이없다고되어있고, 본연구에서시행한농축및희석에의한검사의결과에서도큰차이를보이지않았다. 혈소판수가감소된환자중에서 ITP 환자군의 IPF 결과는골수생성저하군과간경변환자군의결과에비해모두유의하게높았고, 혈소판수가정상인대조군의결과에비해서도유의하게높은수치를나타내었으며, 이는 IPF의최근보고와도일치하는소견이었다 [7, 8]. 간경변증환자의경우에는골수생성저하군과유의한차이를보이지않았다. Romp 등 [11] 은골수생검소견과망상혈소판백분율과의관계를비교한결과골수내의거핵세포수의증가에따라말초혈액내의망상혈소판백분율이증가하는것으로골수거핵세포수를간접적으로예측할수있기때문에침습적인골수생검을하지않고, 말초혈액의채취만으로골수이식의생착판정을더쉽고빠르게시행할수있다고주장하였다. 본연구결과역시혈소판감소의원인에따라상이한 IPF 결과를나 찰 IPF After Groups AA LC ITP Abbreviations: IPF, immature platelet fraction; AA, aplastic anemia; LC, liver cirrhosis; ITP, idiopathic thrombocytopenic purpura. Table 4. IPF of serially diluted specimen Platelet counts ( 10 9 /L) IPF Diluting factor : : : : : :32 Unmeasurable unmeasurable 1:64 Abbreviation: IPF, immature platelet fraction. 타내었기때문에, IPF는혈소판회전율을반영하는지표로서혈소판회전율이증가된질환의진단및경과를살피는데유용할것으로생각된다. ROC 곡선을이용하여기준치를설정한보고들은망상혈소판백분율이각각의기준치에서 83-94% 의민감도와 % 의특이도를가진다고보고하였다 [12-14]. 본연구에서도 6.1% 의기준치에서 92.9% 의민감도와 82.9% 의특이도를보임으로써, IPF는혈소판감소증의원인진단에있어서민감도와특이도가우수한진단지표임을나타내었다. 그러나, IPF는유세포분석기를이용한망상혈소판백분율에비해낮은수치의참고범위를나타내었다. 이는혈소판내의 RNA 를염색하는형광색소로써, 유세포분석기를이용한측정법에서는 thiazole orange (TO) 가주로사용된반면, 본연구에서는 polymethine과 oxazine이사용되었기때문으로생각된다. TO는혈소판내의 RNA와결합후높은형광을나타내기때문에망상혈소판의측정에가장적합한형광색소로알려져있다 [15]. Auramine O (AO) 를이용하여자동화기기로측정된망상혈소판의참고범위는 0.98±0.41% 로 TO를이용한결과에비해유의하게낮았다 [16]. 본연구의결과도 ( 평균 1.7)% 로 AO를이용한결과와비슷하였다. 따라서, RNA 함유량이낮은혈소판은검출이불가능하기때문에, 골수생산저하나말초파괴의증가가미미할경우에는측정될수없을것으로생각되었다. 그러나, 본연구와동일한기기와방법을사용한최근연구 [7, 8] 에서는참고범위를각각 ( 평균 3.4)% 와 ( 평균 3.3)% 로보고하였다. 이결과들은본연구의결과에비해높은것으로, 이차이가대상에의한것인지, 실험방법의미세한차이에의한것인지를알기위해서는추가비교연구가필요할것으로생각된다. 저자들은동일검체를 10회반복측정하여얻어진 IPF 결과를가지고변이계수를구하였다. 제조사의권고에따라, 혈소판수가 /L 이상, /L 미만이면서 IPF가 3.0% 이상, 10.0 % 미만인검체는변이계수가 25% 이하인경우에재현성이있다 고판정하고, 혈소판수가 /L 미만이면서 IPF 가 10.0% 이상인검체는변이계수가 20% 이하를보이는경우에재현성이있다고판정하였다. 그결과, 혈소판수가정상인검체와혈소판수가 /L 미만이면서 IPF가 10.0% 이상인검체의변이계수는각각 17.4%, 7.7% 로재현성이있었고, 혈소판수가 / L 이상, /L 미만이면서 IPF가 3.0% 이상, 10.0% 미만

5 미성숙혈소판분획을이용한혈소판감소증진단법의임상적유용성 5 인검체의변이계수는 28.4% 로재현성이떨어짐을확인하였다. 그러나, 혈소판감소증의원인감별에영향을끼칠정도의변화는없었기때문에임상적으로적용하는데에는무리가없을것으로판단되었다. Briggs 등 [7] 에따르면, 혈소판수가정상이거나비정상적으로낮은검체의변이계수는각각 9.05%, 10.78% 이었고, IPF가높은검체는낮은변이계수를나타내고, IPF 가낮은검체는상대적으로높은변이계수를나타내었다. 본연구에서는비슷한혈소판수를가진 low-plt & high-ipf1, low-plt & high-ipf2, low-plt & low-ipf1의변이계수를비교해보았을때ipf가낮은검체는변이계수가높았고, IPF가높은검체는변이계수가낮아 Briggs 등 [7] 과동일한경향을보였다 (Table 2). 그러나, 낮은 IPF를보인 low-plt & low-ipf1와 low-plt & low-ipf2를비교해보았을때에는변이계수는모두높았고, 혈소판수에따른차이는보이지않았다. IPF는 CBC 검사와함께시행할수있기때문에, 채혈후검사가이루어지기까지의소요시간이길지않을것으로생각된다. 그러나채혈후지체시간이미치는영향은평가해야할필요가있다. 본연구에서는시행하지않았지만, Briggs 등 [7] 은채혈된검체를실온상태로보관하였을때측정된 IPF가 48시간까지안정하다고보고하였다. 요약배경 : 미성숙혈소판분획 (immature platelet fraction, IPF) 은총혈소판수에대한망상혈소판 (reticulated platelet) 의수를백분율 로나타낸것이다. 저자들은자동혈구계산기인 XE-2100 을이용하여 IPF의참고범위를측정하고, 혈소판감소증환자에서의임상적적용가능성을평가하였다. 방법 : 말초혈액검체는 K 2 EDTA가들어있는진공채혈관 (Becton Dickinson, USA) 에채혈되어전북대학교병원에서분석되었다. 전혈구계산결과정상을보인총 142명의검체가 IPF의참고범위를설정하는데사용되었다. 환자들은크게세종류의군으로나뉘어, 골수검사를통해재생불량성빈혈로진단된환자 14명과항암요법후골수검사를시행하여골수억제가확인된백혈병환자 22명은골수생성저하군이라하였고, 간경변증환자 40명은간경변증환자군, 특발성혈소판감소성자반증으로진단된환자 14 명은 ITP 환자군으로분류되었다. 결과 : 혈소판수가정상인대조군에서측정된 IPF의참고범위는 ( 평균 1.7)% 이었고, ITP 환자군에서측정된 IPF 결과가유의하게높았다. 골수생성저하군과 ITP 환자군을구별하는 IPF의경계치 (cut-off) 를 ROC 분석으로얻은결과, 6.1% 에서 92.9% 의민감도와 82.9% 의특이도를나타내었고, 검사의재현성은좋았다. 결론 : IPF를자동혈구계산기를이용하여측정하는방법은쉽고, 비용이적게들며, 신속하게결과를알수있는방법으로, 혈 소판감소증환자에서골수생성저하와말초파괴증가를구별하는데유용할것으로생각된다. 감사본연구의수행을위해 IPF master를제공하여준한국동강메디피아주식회사에감사한다. 참고문헌 1. Do JH, Park JS, Park TH, Lee EY, Son HC, Kim SH, et al. Clinical usefulness of measurement of reticulated platelets by thiazole orange in idiopathic thrombocytopenic purpura. Korean J Clin Pathol 1999; 19: ( 도정화, 박정선, 박태희, 이은엽, 손한철, 김순호등. 특발성혈소판감소성자반증에서 Thiazole Orange 염색에의한망상혈소판측정의임상적유용성. 대한임상병리학회지 1999;19: ) 2. Heo WB, Kim YK, Lee NY, Won DI, Suh JS. Estimate of thrombopoiesis by flow cytometric analysis of reticulated platelets in patients with severe thrombocytopenia. Korean J Lab Med 2005;25:7-13. ( 허운보, 김유경, 이난영, 원동일, 서장수. 중증혈소판감소증에서망상혈소판유세포분석을통한혈소판형성평가. 대한진단검사의학회지 2005;25: 7-13.) 3. Cho YG, Kim JH, Kim DS, Choi SI, Lee HS. Quantitation of the percentage of reticulated platelets to diagnose the cause of thrombocytopenia. Korean J Lab Med 2005;25: ( 조용곤, 김정현, 김달식, 최삼임, 이혜수. 혈소판감소증의감별진단에유용한망상혈소판백분율의측정법. 대한진단검사의학회지 2005;25: ) 4. Toba K, Fuse I, Koike T, Tsuchiyama J, Higuchi W, Niikuni K, et al. Clinical application of reticulated platelet analysis using the maticmodified thiazole orange method and flow cytometry. Rinsho Ketsueki 2000;41: Saxon BR, Blanchette VS, Butchart S, Lim-Yin J, Poon AO. Reticulated platelet counts in the diagnosis of acute immune thrombocytopenic purpura. J Pediatr Hematol Oncol 1998;20: Matic GB, Chapman ES, Zaiss M, Rothe G, Schmitz G. Whole blood analysis of reticulated platelets: improvements of detection and assay stability. Cytometry 1998;34: Briggs C, Kunka S, Hart D, Oguni S, Machin SJ. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. Br J? Haematol 2004;126: Abe Y, Wada H, Tomatsu H, Sakaguchi A, Nishioka J, Yabu Y, et al. A simple technique to determine thrombopoiesis level using immature platelet fraction (IPF). Thromb Res 2006;118: Ault KA, Rinder HM, Mitchell J, Carmody MB, Vary CP, Hillman

6 6 조용곤 이재현 김달식외 2 인 RS. The significance of platelets with increased RNA content (reticulated platelets). A measure of the rate of thrombopoiesis. Am J Clin Pathol 1992;98: Rinder HM, Munz UJ, Ault KA, Bonan JL, Smith BR. Reticulated platelets in the evaluation of thrombopoietic disorders. Arch Pathol Lab Med 1993;117: Romp KG, Peters WP, Hoffman M. Reticulated platelet counts in patients undergoing autologous bone marrow transplantation: an aid in assessing marrow recovery. Am J Hematol 1994;46: Richards EM and Baglin TP. Quantitation of reticulated platelets: methodology and clinical application. Br J Haematol 1995;91: Peterec SM, Brennan SA, Rinder HM, Wnek JL, Beardsley DS. Reticulated platelet values in normal and thrombocytopenic neonates. J Pediatr 1996;129: Joseph MA, Adams D, Maragos J, Saving KL. Flow cytometry of neonatal platelet RNA. J Pediatr Hematol Oncol 1996;18: Lee LG, Chen CH, Chiu LA. Thiazole orange: a new dye for reticulocyte analysis. Cytometry 1986;7: Watanabe K, Takeuchi K, Kawai Y, Ikeda Y, Kubota F, Nakamoto H. Automated measurement of reticulated platelets in estimating thrombopoiesis. Eur J Haematol 1995;54:

366 조용곤 김정현 김달식외 2 인 항암화학요법직후 [3, 7] 에는망상혈소판이감소되며, 항암요법후골수기능이회복 [3, 6] 되거나조혈모세포성장인자치료후 [8, 9] 에는혈소판수가증가하기수일전에증가된다고하였다. 또, 전자간증 [] 이나만성혈소판증가와관련된혈전증 [11

366 조용곤 김정현 김달식외 2 인 항암화학요법직후 [3, 7] 에는망상혈소판이감소되며, 항암요법후골수기능이회복 [3, 6] 되거나조혈모세포성장인자치료후 [8, 9] 에는혈소판수가증가하기수일전에증가된다고하였다. 또, 전자간증 [] 이나만성혈소판증가와관련된혈전증 [11 대한진단검사의학회지 : 제 2 권제 6 호 2 Korean J Lab Med 2; 2: 36-72 진단혈액학 혈소판감소증의감별진단에유용한망상혈소판백분율의측정법 조용곤 1,2 김정현 2 김달식 1,2 최삼임 1,2 이혜수 1,2 전북대학교의과대학진단검사의학교실 1, 전북대학교임상의학연구소 2 Quantitation of the Percentage of Reticulated

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