The Trends for Nationwide Blood Collection and the Supply of Blood in Korea during 2002∼2006

Background: The recent trends for blood collection and the blood supply were analyzed. Methods: Data from the annual reports of the Korean Red Cross from 2002 to 2006 were analyzed. Results: The number of donors in 2002∼2003 was about 2,530,000, but this decreased to 2,300,000 in the past 3 years with the population’s donation rate being 4.7%. By age, those donors between 16∼29 years made up 83% of all the donors. As donor verification became possible in real-time, blood collection from the registered deferral donors was decreased. Blood drawn by the KRC made up 98% of all the blood collected in Korea. Plasma collection for fractionation had recently decreased because of the blood shortage for transfusion in hospitals. The collection of single donor platelets has increased to up to 25% of all the platelets used in Korea. The supply of pre-storage leuko-reduced RBCs had increased. The inventory levels of blood components were lower than the proper levels for most of the days in 2006. The rate of discarding outdated blood components was markedly decreased due to a shortage of blood. The positive rate in screening tests for transfusion-related infection was an average of 2.4%. By nucleic acid tests,which were initiated from 2005, 14 cases during the window period (10 cases of HCV and 4 cases of HIV) were detected. Conclusion: For insuring a safe supply of blood, the donor information systems and up-to-date tests were deemed to become of good quality. However, the blood shortage should be resolved as soon as possible to maintain a consistent blood supplyope

International Comparison of Blood Product Prices

Background: Due to the slowing of population growth, population ageing, and more aggressive medical treatment, Korea will be faced with the challenge of blood shortage. One solution to the blood shortage problem is to take advantage of the multicomponent collection technique. However, clinical application is limited due to the low prices of blood products. In this study, we compared the prices of blood products in 6 major countries. Methods: Prices of leukoreduced red blood cells (RBC), platelet concentrate (PC), fresh frozen plasma (FFP), cryoprecipitate (CRYO), and apheresis platelets (AP) were compiled from US, United Kingdom, Japan, Australia, Spain, and Korea. Adjusted prices using per capita gross domestic product (GDP) and purchasing power parity (PPP) were estimated and analyzed. Results: The RBC price in Korea was only 30% of the mean RBC price of the other 5 countries. Considering per capita GDP and PPP, the RBC prices in Korea were estimated up to 41% and 46%, respectively. The PPP adjusted price of PC, FFP, and AP of Korea was 70%, 72%, and 70% of mean price of the other 5 countries. Price ratios of PC, FFP, and CRYO to RBC were 0.59, 0.63, and 0.57, which were higher than the means of the other 5 countries (0.38, 0.47, and 0.32). Conclusion: Considering per capita GDP and PPP, blood product prices in Korea were cheaper than the mean prices of the other 5 countries. For adoption of multicomponent collection, the prices of blood products should be raised, especially the price of RBCs.ope

Evaluation of fluorescence polarization assay for the assessment of fetal lung maturity

의학과/석사[한글] 호흡곤란증후군은 신생아의 주요 사망 원인이며 따라서 고위험군의 산모를 진료하는데 있어 필수적으로 태아의 폐성숙도를 평가하여야 한다. 이 질환의 발생율은 비교적 낮기 때문에 이를 진단하기 위해서는 진단적 민감도와 특이도가 특히 높은 검사 방법을 선택해 야 한다. 태아의 폐성숙도는 양수내 표면황성물질의 여러가지 성상에 대한 검사로 평가될 수 있다. 현재 많이 사용되고 있는 방법으로는 L/S ratio, 0.D. 650 검사, 포말생성검사 등이 있는데 최근 형광편광법을 이용한 TDx-FTM 자동분석기에 의한 검사방법이 소개되어 이 방법의 분석특성과 임상적 유용성을 평가하였다. TDx-FLM은 0-160 mg/g의 분석 범위내에서 우수한 직선성을 보였다. 표준물질을 사용한 검사의 정밀도도 우수하였다. 양수의 평균적인 albumin농도를 사용한 분석가능 하한치는 4.4 mg/g이었다. 혈액의 흔입에 의한 영향은 매우 커서 저농도에서는 위양성을, 중등도 이상의 농도에서는 위음성을 보일 수 있으므로 혈액이 흔입된 검체의 검사는 금해야 할 것으로 생각되었다. 임신 26-35주인 23명의 환자를 대상으로 한 검사 결과에서 TDx-FLM 값은 임신 후반기로 진행할수록 증가하는 양상을 보였으나 개인차가 심하였다.TDx-FLM 결과는 L/S ratio 및 0.D. 650 검사와 좋은 상관관계를 보였으며(r=0.8811, 0.7668), 포말생성검사화는 양성결 과에 불일치가 많았다. TDx-FLM 검사를 시행한 후 일주일 이내 분만이 이루어졌던 15예를 대상으로 임상적인 결과를 분석하였다. TDx-FLM의 폐성숙에 대한 cutoff 값을 70mg/g으로 설정하였을때 L/S ratio와의 일치율은 좋지 않았으며 (x = 0.38), 민감도는100%, 륵이도는 25%였다. 반면에 TDx-FLM의 폐성숙에 대한 cutoff 간을 50mg/g으로 낮추었을 때는 L/S ratio와 중등도의 일치율을 보였으며 (x= 0.50), 민감도는 lOO%. 특이도는 50% 였으므로 cutoff 값을 50 mg/g으로 조절할 필요가 있었다. 이상과 갈은 관찰에서 TDx-FLM검사는 분석특성이 뛰어나고, 자동화 밋 표준화가 가능하며, 조작이 간편하고 검사 시간이 �아서 응급검사가 가능하고 검사에 필요한 검체의 양이 적은 등의 장점이 있으므로 향후 적절한 cutoff 값을 설정한다면 임상적으로 유용하게 사용될 수 있는 검사라고 생각되었다. [영문] It Is essential to evaluate the fetal lung maturity in the management of high risk pregnancy because respiratory distress syndrome (RDS) is important for the cause of neonatal morbidity and mortal its. And the test for the diagnosis of this disease should be very sensitive and specific for RDS is a relatively rare disease. The majority of the tests for the assessment of fetal lung maturity eyaluates the various characteristics of amniotic fluids. Recently fluorescence depolarization technology for the assessment of fetal lung maturity (TDx-FLM) hart been introduced to clinical laboratory. The purpose of the study was to invegtigate the performance characteristics of the assay and to evaluate the clinical usefulness as a predictor of the RDS. The linearity of TOK-FLM in the assay range of 0-160 ng/g was excellent (r=0.99). Three different concentrations of control were used and the precision of the test in total was less then 7%. Within-run precision was less than 2% with each control. The lowest limit of the assay using 1.5 g/L albumin wag 4.4 77/g. The interference of 1% hemolysed blood was significant. At low surfactant to albumin (S/A)value, the blood contamination caused false elevation of the S/A value. while it caused significant. decrease of S/A value at medium and high S/A values. TDx-FLM was performed in 23 patients. There were marked individual variations. TDx-FLM correlated well with L/S ratio (r=0.88) and 0.D.650(r=0.77), but it frequently disagreed with the result of foam stability test espeoially when the grade was 2 or more. Of fifteen cases, delivered within seven days after the amniocentesis, RDS was dianosed in two babies and five were categorized as transient tachynea of newborn. When we set the cutoff for pulmonary maturity at 70mg/g according to manufacturer's guide, the agreement with L/S ratio was poor (%=0.38), and the diagnostic sensitivity and specificity wsa 100% and 25%, respectively. By lowering the cutoff to 50 mg/g, the test shewed improved agreement with L/S ratio (%=0.50) and the diagnostic sensitivity of 100% and specificity of 5O%. In conclusion, TDx-FLM test can be satisfactorily applied to a clinical laboratory as a first-line me predictor for fetal lung maturity.restrictio

Functional and expressional characteristics of marrow stromal cells in acute leukemia and aplastic anemia

의학과/박사[한글]정상적인 조혈이 이루어지기 위해서는 골수의 미세환경을 이루고 있는 세포 요소들인 기질세포와 골수전구세포의 상호작용이 중요한 역할을 한다. 본 연구에서는 정상 조혈세포의 증식이 억제되거나 생성부전인 혈액 질환이 있을 때, 기질세포의 변화가 동반되거나 병인으로서 작용할 수 있을 것이라는 가정하에, 급성 백혈병 환자와 재생불량성 빈혈 환자의 골수와 정상인의 골수로부터 내피세포가 풍부한 기질세포를 분리하여 각 군 간의 조성 변화를 비교하고, 조혈모세포의 체외배양시 기능적인 차이를 보이는지와 유전자 표현상의 차이를 보이는지를 알아보고자 하였다. 급성 백혈병, 재생불량성 빈혈 환자 및 정상 골수 공여자의 골수로부터 내피세포가 풍부한 기질세포를 분리하여 배양하였으며, 이를 보급세포(feeder layer)로 하여 정상인의 조혈모세포 체외배양을 실시하였다. 분리된 기질세포의 성상을 비교하기 위하여 유세포분석 및 면역형광염색법으로 BODIPY-FL-AcLDL stain과 CD34, CD105, CD29, CD31, CD44, KDR 등의 발현 정도를 분석하였으며, DNA 칩을 이용한 유전자 발현 측정을 위하여 mRNA를 분리하였다. 정상 조혈모세포의 체외배양 성적은 배양 7일 및 14일째 조혈모세포의 수를 측정하고, 배양된 조혈모세포 가운데 CD34+CD38- 세포수를 측정함으로써 평가하였다. 유전자 프로파일 검사는 17,000개의 유전자가 배열된 마이크로어레이를 사용하여 시행하였으며, 정상과 백혈병, 백혈병과 재생불량성 빈혈, 재생불량성 빈혈과 정상의 세 가지 조합으로 각각 3회씩 반복하여 시행하였다. 골수기질세포는 골수로부터 분리한 직후 3-5%였으며, 이를 배양하여 보급세포로 사용할 수 있는 골수기질세포주를 확립할 수 있었다. 정상 골수로부터 채집한 골수기질세포를 24 well plate에 2 x104세포를 넣어 일차 배양시 plate에 90% 이상 차게 되는 시기는 약 5일이 소요된 반면, 급성백혈병과 재생불량성 빈혈의 경우 5일까지도 90%이상 증식하지 못했다. 골수기질세포의 단클론항체에 대한 성상 발현에 세 군간에 차이가 없었으나, 항CD34항체, 항KDR항체 등에 양성을 보여 혈관내피세포의 특성을 많이 가진 것으로 나타났다. 조혈모세포의 체외배양 성적은 정상인에 비하여 급성 백혈병 및 재생불량성 빈혈 환자의 기질세포의 증식능이 유의하게 감소하였으며, 재생불량성 빈혈군의 경우 분화 정도가 심하였다. 유전자 프로파일 검사 결과 세포 접촉이나 조혈촉진에 관한 대부분의 유전자 발현이 세 군간 차이가 없었으나, 급성 백혈병과 재생불량성 빈혈군에서 Jagged 1 유전자의 발현이 감소되어 있었으며, 재생불량성 빈혈군에서 Fibroblast Growth Factor 2 유전자의 발현이 증가되어 있었다. 이상과 같이 급성 백혈병과 재생불량성 빈혈 환자에서 정상인에 비하여 골수기질세포의 조혈촉진 기능이 감소되어 있음을 확인할 수 있었으며, 이들 세포의 표현형의 차이는 없었지만 일부 유전자의 표현 정도가 차이를 보임을 볼 수 있었기 때문에 향후 이들 유전자의 발현 정도의 차이가 골수의 조혈부전에 어떤 역할을 하는지 규명함으로써 이들 혈액 질환에서 골수기질세포의 역할이 보다 분명히 밝혀질 수 있으리라 생각된다. [영문]The interaction between the bone marrow stromal cells as a microenvironment and hematopoietic progenitor cells is the most important for the maintenance of normal hematopoiesis. In this study, under the hypothesis that marrow stromal cells will have some defect in supporting normal hematopoiesis in cases with acute leukemia and/or aplastic anemia, the phenotypic, functional, and expressional differences of bone marrow stromal cells from acute leukemia and aplastic anemia were analyzed in comparison with the stromal cells from normal marrow donors. The bone marrow stromal cells were isolated from the acute leukemia patients, aplastic anemia patients, and hematologically normal bone marrow donors. The stromal cells were cultured for 5 days to form the feeder layer for normal hematopoietic progenitor cell culture. The isolated stromal cells of each group were tested for the uptake of BODIPY conjugated acetylated low density lipoprotein (acLDL), CD34, CD105, CD29, CD31, CD44, and KDR by immunofluorescence or flow cytometry. To determine whether or not abnormalities exist in the bone marrow stroma in acute leukemia and aplastic anemia, the ability of marrow stromal cells to support hematopoiesis was analyzed by coculture of the immunomagnetically isolated normal cord blood hematopoietic progenitor cells and each stromal cell line as a feeder layer. After inoculation of normal marrow hematopoietic stem cells onto preformed, irradiated stromal cells, the number of the progenitor cells was counted after 7 and 14 days of each culture. The fraction of CD34+/CD38- cell population was also determined and evaluated in comparison with the initial proportion of the progenitor cells. The genetic profile of each stromal cell line was analyzed by 17,000-gene microarray analysis. Three kinds of combination - normal/acute leukemia, acute leukemia/aplastic anemia, and aplastic anemia normal - were analyzed three times respectively. The proportion of the CD45-/CD34+ stromal cell fraction after isolation from bone marrow was about 3-5%. After culture for 5 days, the stromal cells from normal and acute leukemia patients grew more than 90% of 24-well microplate, while the stromal cells from aplastic anemia patients did not. Neither the morphological cytological nor the phenotypic characteristics of the isolated stromal cells (acLDL uptake, CD34+, CD105+, CD29+, KDR+, CD31-, CD44-) did not show significant difference between groups and showed mostly the characteristics of endothelial cells. On coculture assay, the proliferative capacity of progenitor cells with acute leukemia and aplastic anemia originated feeder layer groups was much lower than that of normal feeder layer group. Moreover, there were significantly fewer CD34+/CD38- cells in aplastic anemia feeder layer group. In genetic profiling, most of the significant genes known to be important in cell adhesion and hematopoiesis regulation did not show significant differences between groups. However, the Jagged 1 gene expression was significantly reduced in acute leukemia and aplastic anemia group as well as Fibroblast Growth Factor 2 gene expression was upregulated in only aplastic anemia group. These findings suggest that some kind of gene expression changes, which can lead to the stromal defect in supporting hematopoiesis, and can make a role in the pathogenesis of the disease.ope

Reassessment of a Dup(1)(q21q32), Trp(1)(q21q32) in a Case of Myelodysplastic Syndrome by CGH (Comparative Genomic Hybridization)

Acquired partial duplication or triplication of the long arm of human chromosome 1 has been observed rarely in myelodysplastic syndrome(MDS). We describe a dup(1)(q21q32), trp(1)(q21q32) in a patient with refractory anemia of MDS. A 51-year-old man was admitted for dyspnea. Five months ago, he was diagnosed with myelodysplastic syndrome (RA) and iron deficiency anemia and had been treated with iron vitamin Bl2, oxymetholone, and prednisolone. The karyotype of trypsin-Giemsa-banded metaphase cells obtained from bone marrow aspirates was 46,XY,dup(1)(q21q32)×2[5]/46,XY,try(1)(q21q32)[2]/46,XY,dup(1)(q21q32),trp(1)(q21q32)[2] and confirmed the amplification of 1q21-lq32 by CGH (comparative genomic hybridization). In this assay, test and reference DNAs are labeled with FITC and Texas Red, respectively and co-hybridized to normal metaphase chromosomes. Ratio profiles of each individual chromosome were analyzed using a Quips-XL software(Vysis, Downers Grove, IL, USA). The thresholds of gain and loss were defined 1.2 and 0.8, respectively.ope