대한진단검사의학회지제 26 권제 5 호 2006 Korean J Lab Med 2006;26:369-73 원저 수혈의학 3 차의료기관에서의방사선조사혈액제제사용현황 김정현 김덕언 한양대학병원진단검사의학과 Irradiated Blood Usage in a Tertiary-care Hospital Jeong Hyun Kim.M.D. and Duck-An Kim. M.D. Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, Korea Background : Irradiated blood is used to prevent transfusion-associated graft-versus host disease in high risk patients. The guidelines for usage of irradiated blood components vary from one country to other according to their needs. But in Korea, little information is available on the current usage of and the guidelines for irradiated blood. Therefore, we analyzed the usage of irradiated blood components in Hanyang University Medical Center. Methods : Medical records were reviewed for 187 patients who had been transfused with irradiated blood products during the period from January 2004 to June 2005. And we investigated the proportion of irradiated blood products among the total number of blood products that were transfused during a one-year period. Results : Hematologic diseases and solid cancer patients comprised 63.7% and 24.6% respectively. The proportion of irradiated blood products among the total blood components were 25.7% of platelet concentrates, 61.4% of apheresis platelets, and 5.1% of packed red cells. Total transfused amount by disease categories and the average transfused units per patient of irradiated blood components were high in a group of patients with several hematologic diseases such as acute leukemia. Conclusions : The use of irradiated blood components takes a great proportion in total blood product transfusions and the majority of blood components were transfused to a group of patients with a few hematologic diseases. The proper use of blood should be guided by the promotion and education of a modified usage protocol for irradiated blood products and by a continuous data analysis. (Korean J Lab Med 2006;26:369-73) Key Words : Blood irradiation, GVHD, transfusion 서 론 수혈에의한이식편대숙주병은공혈자의림프구가수혈자의조 접 수 : 2006년 4월 26일 접수번호 : KJLM1944 수정본접수 : 2006년 7월 24일 게재승인일 : 2006년 8월 12일 교신저자 : 김덕언 우 133-792 서울시성동구행당동 17 한양대학병원진단검사의학과 전화 : 02-2290-8977, Fax: 02-2298-1735 E-mail: dukim@hanyang.ac.kr 직이나혈액세포를면역학적으로공격하여발생하는치명적인수혈부작용이다 [1, 2]. 발생기전은공혈자의혈액에존재하는 T 림프구가수혈자의면역체계에의해제거되지않고숙주조직을파괴시키며클론성증식을하는것으로이해되고있다. 이러한이식편대숙주병은주로면역기능이저하된환자의수혈시발생하며면역기능이정상인환자에서도수혈받은혈액의사람백혈구항원일배체형 (HLA haplotype) 에대하여하나를동형접합자로가지고있을경우, 또는살아있는 T 림프구가많이수혈되었을경우발생할수있다 [3, 4]. 이식편대숙주병이발생하면수혈후 369
370 김정현 김덕언 약 10-12일내에발열, 발진, 범혈구감소증, 간기능이상, 부종과전신적인수포등의임상적인증상이나타나며일단질환이발생하면효과적인치료방법이없으므로예방이필수적이다. 이식편대숙주병을일으키는혈액제제내의백혈구는성분별혈액제제에따라혈액한단위당약 10 6-10 9 개정도가포함되어있으므로 [5, 6] 이러한백혈구를제거하기위해여러가지방법이연구되어왔다 [7, 8]. 통상적으로이용하는여과법의경우 95% 이상의백혈구제거율을보이고있으나 [9] 수혈에의한이식편대숙주병은남아있는소수의림프구에의해발생할수있으며방사선조사혈액제제의사용이유일한예방법으로알려져있다 [10, 11]. 최근면역기능저하환자의증가와더불어 2005년 10월에변경된건강보험심사평가원의방사선조사혈액제제의사용기준확대에따라방사선조사혈액제제의사용량은급증할것으로보인다. 그러나국내에서는방사선조사혈액제제의사용현황에대한체계적인보고가드물고혈액사용지침에맞는적절한수혈이이루어지는지에대한구체적인조사가드물어이에방사선조사혈액제제에대한사용현황을조사하였다. 대상및방법 1. 대상 2004년 1월부터 2005년 6월까지 18개월간한양대학병원에입원하여방사선조사혈액제제를수혈받은 187명의환자를대상으로조사하였다. 출고된혈액제제중환자에게수혈되지않고폐기된혈액제제는조사대상에서제외하였다. 수혈받은환자들의대부분은혈액학적질환과악성종양으로치료중인환자들이었다. 2. 방법방사선조사혈액제제를수혈받은환자에대하여혈액제제의종류와, 수혈받은혈액량, 수혈받은시기와수혈당시환자의진단명을조사하여질환별수혈양상의추이를보았다. 또한 2004 년 1월부터 12월까지 1년간수혈된농축적혈구, 농축혈소판, 성분채집혈소판의총량을조사하여혈액제제의성분별로전체혈액제제에서방사선조사혈액제제가차지하는비율을파악하였다. 방사선조사혈액제제를수혈받은환자들의진단명과혈액제제의종류, 수혈시기, 수혈량에대한자료조사는병원정보시스템과혈액은행전산프로그램으로부터얻었으며진단명이여러개인경우의무기록을참조하여수혈받은원인에대한주진단명을기준으로조사하였다. 환자들의질병분류는국제질병분류 (international classification of disease, ICD) 제10판 [12] 에의거한한국표준질병사인분류에따른진단명으로산정하였다 [13]. 결 1. 수혈대상환자의구성 연구기간동안총 187명의환자가방사선조사혈액제제를수혈받았으며남자가 95명, 여자가 92명이었고환자들의평균연령은 47세였다. 10년단위로구분한연령별환자의분포는비교적고르게분포되어있었다. 수혈받은환자들의질환별분포를보면급성백혈병과림프종, 골수이형성증후군등의혈액학적요인에의한환자군이 63.7% 를차지하였다. 림프종을제외한고형암의경우전체환자의 24.6% 이었고결체조직질환이 3.2% 를차지하였다 (Table 1). 과 2. 1 년간수혈된혈액제제중방사선조사혈액제제가차지하는비율 2004년 1월부터 12월까지 1년간수혈된농축혈소판, 성분채집혈소판, 농축적혈구의전체혈액제제에대해방사선조사혈액제제가차지하는비율은각각농축혈소판의 25.7%, 성분채집혈소판의 61.4%, 농축적혈구의 5.1% 로나타났다 (Table 2). 3. 질환별방사선조사혈액제제의사용현황 고형암의경우 46명으로가장많은환자수를차지하였으며전체방사선조사혈액제제중농축혈소판의 4.6%, 성분채집혈 Table 1. Disease categories of the patients transfused with irradiated blood components Disease categories N. of patients (%) Acute myeloid leukemia 21 (11.2) Acute lymphocytic leukemia 13 (7.0) Non-classified leukemia 1 (0.5) Lymphoma 29 (15.5) Aplastic anemia 22 (11.8) Multiple myeloma 11 (5.9) Idiopathic thrombocytopenic purpura 6 (3.2) Myelodysplastic syndrome 5 (2.7) Other hematologic disease 11 (5.9) Solid cancer 46 (24.6) Connective tissue disease 6 (3.2) Others 19 (10.2) Total patients 187 (100) Table 2. Percentage of irradiated blood components to the total blood components for year 2004 N. of total N. (%) of irradiated blood units blood units Platelet concentrates 23,544 6,038 (25.7%) Platelet pheresis 1,174 721 (61.4%) Packed red cells 18,980 975 (5.1%)
3 차의료기관에서의방사선조사혈액제제사용현황 371 Table 3. Total amount of irradiated blood components used according to disease categories and percentage per total irradiated blood use Disease categories PC, unit (%) PP, unit (%) PRC, unit (%) Acute myeloid leukemia 2,400 (29.6) 448 (42.1) 430 (28.3) Acute lymphocytic leukemia 1,762 (21.8) 175 (16.5) 239 (15.8) Aplastic anemia 1,258 (15.5) 208 (19.6) 238 (15.7) Myelodysplastic syndrome 300 (3.7) 16 (1.5) 30 (2.0) Multiple myeloma 340 (4.2) 42 (4.0) 64 (4.2) Lymphoma 1,045 (12.9) 75 (7.1) 177 (11.7) Solid cancer 369 (4.6) 13 (1.2) 197 (13.0) Others 625 (7.7) 86 (8.1) 142 (9.4) Total 8,099 (100) 1,063 (100) 1,517 (100) Abbreviations: PC, platelet concentrate; PP, platelet pheresis; PRC, packed red cells. Lymphoma 13% MDS 4% MM 4% solid ca 5% Other 8% Fig. 1. Percentage of irradiated platelet concentrate usage according to disease categories. Abbreviations: AML, acute myeloid leukemia; ALL, acute lymphocytic leukemia; AA, aplastic anemia; MM, multiple myeloma; MDS, myelodysplastic syndrome; solid ca, solid cancer. 소판의 1.2%, 농축적혈구의 13.0% 를수혈받았다. 급성백혈병은농축혈소판, 성분채집혈소판, 농축적혈구모두에서가장많은양의방사선조사혈액제제를수혈받았으며 1인당수혈받은혈액제제의단위도가장높았다 (Table 3, 4). 전체방사선조사혈액제제중가장많은수혈량을차지하는농축혈소판에대해질환별수혈량을모식도로나타낸결과급성백혈병과무형성빈혈, 림프종, 다발성골수종등의혈액학적질환에서대부분의방사선조사혈액제제가수혈되었다 (Fig. 1). 고 수혈에관련된기초자료인혈액사용에관한보고는혈액의수급계획과건강보험심사평가원의기준자료로이용되고있다. 따라서국가마다혈액사용보고가성분혈액별또는임상적진단별로이루어져왔으며수시로개정되고있다 [14, 15]. 그러나 찰 AML 29% AA 16% ALL 21% Table 4. Average units of irradiated blood components transfused per person according to disease categories during an 18-month period Disease categories PC PP PRC Acute myeloid leukemia 114.3 21.3 20.5 Acute lymphocytic leukemia 135.5 13.5 18.4 Aplastic anemia 57.2 9.5 10.8 Myelodysplastic syndrome 60 3.2 6.0 Multiple myeloma 30.9 3.8 5.8 Lymphoma 36.0 2.6 6.1 Solid cancer 8.0 0.3 4.3 Other 15.6 2.2 3.6 Abbreviations: See Table 2. 방사선조사혈액제제의사용현황에대하여는국내에서구체적으로보고된바가드물어혈액의수급현황을파악하는데부족한점이많아이에대한자료를조사하고분석해보았다. 이번조사는 3차의료기관의 1년 6개월간의자료로서이를토대로몇가지사항을고려해볼수있었다. 방사선조사혈액제제가수혈된환자의질병분포는고형암환자가 24.6% 로높은비율을차지하였으나방사선조사혈액제제의수혈량은성분별혈액제제의종류에따라전체의 1.2-13.0% 가량으로낮았다. 급성백혈병의경우 1인당수혈받은혈액제제의평균단위수와전체혈액제제중차지하는비율이가장높았으며전체방사선조사혈액제제의 50% 정도가이들환자군에수혈되고있음을알수있었다 (Table 4). 이러한사실은방사선조사혈액제제제가급성백혈병이나림프종등혈액학적질환을가진소수의환자에게집중적으로투여되므로혈액의수급과관련된여러정책을시행시이러한혈액제제를처방하는의사나환자군을대상으로실시할때효과적으로이루어질수있음을뒷받침한다. 전체혈액제제중방사선조사혈액이차지하는비율은농축혈소판과성분채집혈소판제제에서각각 25.7% 와 61.4% 의비율을차지하는것으로나타났다 (Table 3). 특히혈소판농축액은미국이나일본의연구에서와마찬가지로가장많이이용되는혈액제제이므로 [16-18] 방사선조사혈액제제가전체혈액제제사용의상당부분을차지함을알수있다. 수혈에의한이식편대숙주병에대한보고는국내에서는차등에의해백혈병환자에서발생한경우가보고되어있으며국외에서는장기이식환자, 면역저하환자, 심혈관계수술환자등의수혈시발생한보고가있다 [19-22]. 본기관의자료조사에의하면조사기간동안지정수혈은 16건이있었으며이경우혈액은행에서관리하여전부방사선조사를하였다. 그러나신생아수혈이나심장수술등의경우에는임상의각과에서혈액제제요청을하므로방사선조사혈액제제가거의사용되지않았다. 따라서임상의들에게방사선조사혈액제제의올바른사용지침에대한교육이필요할것이다. 우리나라의경우실질적인지침이라할수있는건강보험심사
372 김정현 김덕언 평가원의방사선조사혈액제제의사용기준이최근변경되면서 (2005년 10월 ) 고형암의항암화학요법이나방사선요법기간중, 신생아수혈, 선천성면역결핍환자, 장기이식환자등의수혈에서그사용을인정하는쪽으로확대되었다. 이들중고형암의항암화합요법이나방사선요법의경우는이번조사에서도나타났듯이대상환자수가많으므로앞으로전체방사선조사혈액제제의수혈량증가에큰영향을미칠것으로예상된다. 혈액의공급은보통국가내에서헌혈자들이자발적으로헌혈한한정된혈액에대해이루어진다. 또한국가별로질병에대한역학분포나위험요인의분포도가다르므로국가별로실정에맞게혈액의수요량을예측하고이에맞게혈액공급계획을세우는것은중요하다. 방사선조사혈액제제사용의지침이되는이식편대숙주병의위험요인을가진면역저하환자군을정하는범위는국가마다조금씩다르며대상환자군을어느경우까지인정할것인지에대한논란은남아있다 [23]. 일본의경우다른나라에비하여사람백혈구항원일배체형의수가적어수혈에의한이식편대숙주병의위험성이크므로방사선조사혈액에대하여더광범위한지침을제시하고있으며지속적인개정이이루어지고있다 [24, 25]. 또한미국이나영국, 일본등다른나라의논문이나지침서등을보면혈액사업을담당하는기관에서임상적인사용지침뿐아니라감마선조사의용량, 필요장비, 실제적인방사선조사방법등에대하여도체계적으로언급하며지속적으로개정판을발표하고있으며 [25-27] 절대적인사용기준과상대적인사용기준등을구분하여환자의상황에맞게혈액사용이이루어질수있도록지침을제시하고있다. 우리나라의경우심사평가원의기준이실질적인지침으로사용되고있으나구체적인사용지침과수혈현황에대한자료조사가부족하다. 이번연구에서방사선조사혈액제제는전체혈액제제중차지하는비율이높고수혈대상환자군의차이가사용량에큰영향을미침을알수있었다. 추가적으로건강보험심사평가원의심사기준변경후방사선조사혈액제제의사용양상의변화에대한조사가필요할것으로생각된다. 또한수혈과관련된이식편대숙주병의발생양상을파악하여방사선조사혈액제제의수급과비용면에서균형을맞출수있도록지속적인현황조사가필요할것이다. 요약배경 : 방사선조사혈액제제는이식편대숙주병을예방하기위해사용되고있다. 이러한방사선조사혈액제제에대한사용지침이국가별로실정에맞게제시되고있으나우리나라의경우방사선조사혈액제제의사용현황과사용기준에대한자료가불충분하다. 따라서저자는한양대학병원의방사선조사혈액제제의사용현황을분석해보았다. 방법 : 2004년 1월부터 2005년 6월까지한양대학병원에입원하 여방사선조사혈액제제를수혈받은 187명의환자에대하여방사선조사혈액제제의종류와수혈량, 수혈받은시기, 그리고환자의진단명을조사하였다. 또한 2004년 1월부터 12월까지 1년간출고된혈액제제중농축혈소판, 농축적혈구, 성분채집혈소판의총량을조사하여이들중방사선조사혈액제제가차지하는비율을파악하였다. 결과 : 환자구성은혈액관련질환환자가 63.7%, 고형암환자가 24.6% 를차지하였다. 1년간출고된전체혈액제제중방사선조사혈액제제가차지한비율은농축혈소판의 25.7%, 성분채집혈소판의 61.4% 농축적혈구의 5.1% 이었다. 질환별수혈받은총량과 1인당수혈받은혈액제제의평균단위수에서급성백혈병을비롯한소수의혈액학적질환이높은비율을차지하는것으로나타났다. 결론 : 방사선조사혈액제제의사용은전체혈액제제중차지하는비율이높고, 대상환자군에따라혈액사용량에큰차이를보이며몇몇의혈액질환을가진소수의환자군에대부분의수혈이이루어지고있다. 앞으로변경된방사선조사혈액제제의사용지침에대한홍보와교육, 그리고지속적인자료조사를통해적절한혈액사용을유도해야할것이다. 참고문헌 1. Ohto H and Anderson KC. Survey of transfusion-associated graftversus-host disease in immunocompetent recipients. Transfus Med Rev 1996;10:31-43. 2. Seghatchian MJ and Ala F. Transfusion-associated graft-versus-host disease: current concepts and future trends. Transfus Sci 1995;16: 99-105. 3. Wagner FF and Flegel WA. Transfusion-associated graft-versushost disease: risk due to homozygous HLA haplotypes. Transfusion 1995;35:284-91. 4. Ahya R, Douglas G, Watson HG. Transfusion associated graft versus host disease in an immunocompetent individual following coronary artery bypass grafting. Heart 1998;80:299-300. 5. Cassens U, Greve B, Tapernon K, Nave B, Severin E, Sibrowski W, et al. A novel true volumetric method for the determination of residual leucocytes in blood components. Vox Sang 2002;82:198-206. 6. Kao KJ, Mickel M, Braine HG, Davis K, Enright H, Gernsheimer T, et al. White cell reduction in platelet concentrates and packed red cells by filtration: a multicenter clinical trial. Transfusion 1995;35:13-9. 7. Webb IJ and Anderson KC. Transfusion-associated graft-versushost disease. In: Scientific basis of transfusion medicine: Implications for clinical practice. 2nd Edition. Anderson KC, Ness PM, ed. Philadelphia: WB Saunders Company, 2000:420-6 8. Schroeder ML. Transfusion-associated graft-versus-host disease. Br
3 차의료기관에서의방사선조사혈액제제사용현황 373 J Hematol 2002;117:275-87. 9. Kim SI, Han KS, Kwon SW. A New, simple method for preparing leukocyte-poor red blood cells employing intestina1 clamp. Korean J Hematol 1990;25:181-5. ( 김상인, 한규섭, 권석운. 장감자를사용한새로운백혈구제거적혈구제조법. 대한혈액학회지 1990;25:181-5.) 10. Hayashi H, Nishiuchi T, Tamura H, Takeda K. Transfusion-associated graft-versus-host disease caused by leukocyte-filtered stored blood. Anesthesiology 1993;79:1419-21. 11. Przepiorka D, LeParc GF, Stovall MA, Werch J, Lichtiger B. Use of irradiated blood components: practice parameter. Am J Clin Pathol 1996;106:6-11 12. World Health Organization. International Statistical classification of disease and related health problems, 10th ed. Geneva: World Health Organization 1992. 13. National Statistical Office. Korean standard classification of diseases. 3rd ed. Seoul: Korean Medical Record Association, 1994:1-114. ( 통계청. 한국표준질병사인분류, 제3판. 서울대한의무기록협회, 1994:1-114.) 14. Seo DH, Kang JW, Oh YC, Han KS, Kim SI. Utilization of blood components for transfusion by hospitals in Korea(1998-99). Korean J Blood Transfus 2001;12:11-8. ( 서동희, 강재원, 오영철, 한규섭, 김상인. 국내의료기관에서의혈액제제사용현황. 대한수혈학회지 2001;12: 11-8.) 15. Lim YA and Hyun BH. Blood Use According to Diagnoses in Hospitalized Adults of Ajou University Hospital. Korean J Clin Pathol 2001;21:79-85. ( 임영애및현봉학. 아주대병원입원성인환자의진단명에따른혈액사용분석. 대한임상병리학회지 2001;21:79-85.) 16. Lee SK, Jeon MJ, Shin JH, Suh SP, Ryang DW. Use of blood components, irradiated and filtered blood products in Chonnam niversity hospital. Korean J Blood Transfus 1997;8:231-8. ( 이상구, 전미정, 신종희, 서순팔, 양동욱. 전남대학교병원에서성분수혈, 혈액제제에대한방사선조사및백혈구제거필터사용현황. 대한수혈학회지 1997;8:231-8.) 17. McCullough J. The nation s changing blood supply system. JAMA 1993;269:2239-45. 18. Blood program in Japan. Blood Product Research Organization. 1995. 19. Cha MS, Lee KH, Min YH, Lee KG. Transfusion-associated graftversus-host disease in patients with acute leukemia. Korean J Dermatol 1996;34:345-9. ( 차명수, 이광훈, 민유홍, 이광길. 급성림프구성백혈병에서수혈후발생한이식편대숙주질환 1예. 대한피부과학회지1996;34:345-9.) 20. van der Mast BJ, van den Dorpel MA, Drabbels JJ, Claas FH, Weimar W. Transfusion-associated graft vs. host disease after donor-specific leukocyte transfusion before kidney transplantation. Clin Transplant 2003;17:477-83. 21. Aoun E, Shamseddine A, Chehal A, Obeid M, Taher A. Transfusion-associated GVHD: 10 years experience at the American University of Beirut-Medical Center. Transfusion 2003;43:1672-6. 22. Yasuura K, Okamoto H, Matsuura A. Transfusion-associated graftversus-host disease with transfusion practice in cardiac surgery. J Cardiovasc Surg 2000;41:377-80. 23. Hume H, Blanchette V, Strauss RG, Levy GJ. A survey of Canadian neonatal blood transfusion practices. Transfus Sci 1997;18:71-80. 24. Ohto H, Yasuda H, Noguchi M, Abe R. Risk of transfusion-associated graft-versus-host disease as a result of directed donations from relatives. Transfusion 1992;32:691-3. 25. Asai T, Inaba S, Ohto H, Osada K, Suzuki G, Takahashi K, et al. Guidelines for irradiation of blood and blood components to prevent post-transfusion graft-vs.-host disease in Japan. Transfus Med 2000;10:315-20. 26. Blood services committee. Guidelines for irradiation of blood and blood components. 2nd ed. New York: New York State council on human blood and transfusion services 2004. 27. Australian and New Zealand society of blood transfusion. Guidelines for gamma irradiation of blood components. 2nd ed. Australia: Australian & New Zealand society of blood transfusion inc. 2003.