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1 대한수혈학회지 : 제 29 권제 1 호, 2018 The Korean Journal of Blood Transfusion Vol. 29, No. 1, 73-78, April pissn eissn Case Report ABO 부적합수혈에의한급성용혈수혈반응 : 치명적증례보고및문헌검토 임현호 1 ㆍ김경희 1 ㆍ안규대 1 ㆍ정인화 1 ㆍ손영기 2 동아대학교의과대학진단검사의학교실 1, 동아대학교의과대학내과학교실 2 Acute Hemolytic Transfusion Reaction due to ABO-Incompatible Blood Transfusion: A Fatal Case Report and Review of the Literature Hyeon-Ho Lim 1, Kyeong-Hee Kim 1, Gyu-Dae An 1, In-Hwa Jeong 1, Young-Ki Son 2 Departments of Laboratory Medicine 1, Internal Medicine 2, Dong-A University College of Medicine, Busan, Korea A 77-year-old female patient who was suspected to have had an acute hemolytic transfusion reaction was admitted to the emergency room. She received one unit of type A red blood cells in a type B patient during a total knee arthroplasty operation at another medical institution. ABO-incompatible transfusion was carried out due to an identification error between the patient and blood product. At the time of admission, acute hemolytic reaction, lactic acidosis, and disseminated intravascular coagulation were observed. She was admitted to the intensive care unit and received continuous renal replacement therapy. She maintained renal function and was moved to the general ward on the 7th day. Complications such as pulmonary edema, gastrointestinal bleeding, and ischemic colitis persisted, and the patient died on the 111th after admission. This case is the first report of death due to an ABO-incompatible transfusion in Korea. Efforts to establish a safe transfusion environment are necessary not only at individual medical institutions but also at the national level. (Korean J Blood Transfus 2018;29:73-78) Key words: ABO incompatible transfusion, Hemolytic transfusion reaction, Transfusion safety 서론 Landsteiner가 ABO 혈액형군을발견하여수혈의학의과학적기틀을마련한이후, 수혈요법은임상적으로유용하며중요한치료방법으로발전되어왔다. 하지만의료인의실수로인한 ABO 혈 액형불일치수혈 (ABO-incompatible blood transfusion) 은주요수혈부작용의하나로지속적으로발생되고있다 [1,2]. ABO 불일치수혈은급성용혈수혈반응을야기할수있으며입원이나중환자실치료혹은사망에까지이르게할수있다. 2009년일본에서설문조사한연구에따르면 Received on February 11, Revised on March 13, Accepted on March 14, 2018 Correspondence to: Kyeong-Hee Kim Department of Laboratory Medicine, Dong-A University College of Medicine, 32 Daeshingongwon-ro, Seo-gu, Busan 49201, Korea Tel: , Fax: , progreen@dau.ac.kr, ORCID: This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright C 2018 The Korean Society of Blood Transfusion

2 Korean J Blood Transfus Vol. 29, No. 1, 73-78, Apr 년부터 2004년까지 ABO 부적합수혈에의해총 17명의예방가능한사망이발생하였고또한, ABO 부적합수혈의원인으로는환자와혈액제제의확인오류가가장흔하며절반을차지하였다고보고하였다 [3]. 국내수혈부작용보고기구인한국혈액안전감시체계 (Korean Hemovigilance System) 에따르면 2008년 4월부터 2012년 11월까지 ABO 부적합수혈로인한급성용혈수혈반응이 12건보고되었고사망보고는없었다 [4] 년전혈수혈후급성용혈작용에의한사망 1예 [5] 가보고되어있으나, 수혈된혈액의 ABO 혈액형이보고되지않아 ABO 부적합수혈의여부가명확하지않다. 추가로 1978년김등 [6] 이보고한 ABO 부적합수혈에의한급성신부전치료경험을제외하면 ABO 부적합수혈현황에대한체계적인문헌보고가드물다 안전수혈캠페인 [4] 과같은안전한수혈에대한인식증가와교육, 우수검사실신임인증제도및의료기관인증평가에서의수혈관련심사가강화되었다. 그럼에도불구하고 ABO 부적합수혈에의한급성용혈수혈반응이사망의주요원인이된예를경험하였기에안전한수혈을위한체계확립을위해문헌고찰과함께증례를보고하고자한다. 증례 77세여자환자가급성용혈수혈반응이의심되어응급실을통해서전원되었다. 내원당시환자는호흡곤란및오한을호소하였고, 황달이관찰되었다. 의식은명료하였고, 생체징후는혈압 120/70 mmhg, 심박수 99 회 / 분, 호흡수 22회 / 분, 체온 37.3 o C로관찰되었다. 당일타의료기관에서좌측슬관절전치환술수술중 B형 RhD 양성인환자에게 A형 RhD 양성농축적혈구 1단위가수혈되는실수가발생하였다. 사고는혈액제제와 환자확인과정의오류로인하여발생하였다. 환자는과거병력상 5개월전담낭절제술을시행받았다. 내원당시급성용혈반응, 젖산산증 (Lactic acidosis), 파종성혈관내응고 (Disseminated intravascular coagulation) 의소견을보였다. 입원시환자의검사실소견중혈색소혈증 (hemoglobinemia), 합토글로빈의감소, LDH의증가는급성용혈성반응을시사하였다. 또한프로트롬빈시간, 활성화부분트롬보플라스틴시간연장, 섬유소원분해산물, D-이합체증가, 섬유소원의감소는파종성혈관내응고소견과일치하였다 (Table 1). 내원후바로중환자실로입실하여지속적신대체요법 (continuous renal replacement therapy) 을시행하며신장기능을보호하였고 LDH 수치도 3,878 IU/L에서입원 7일째 608 IU/L로감소하여일반병동으로이동하여치료를지속하였다. 주요혈청학적소견은내원 1일째시행한직접항글로불린검사 (Direct antiglobulin test, DAT) 는 IgG에서 2 Table 1. Laboratory findings at admission Test Patient Value Reference range Hematocrit (%) Hb (g/dl) Plasma hemoglobin (mg/dl) Haptoglobin (mg/dl) PT (sec) PT (%) PT (INR) APTT (sec) Fibrinogen (mg/dl) Antithrombin III (%) FDP ( g/ml) > D-dimer ( g/ml FEU) > LDH (IU/L) Creatinine (mg/dl) Hb, hemoglobin

3 임현호외 : ABO 부적합수혈에의한급성용혈수혈반응 : 치명적증례보고및문헌검토 +, C3d에서 +/ 로약양성결과를보였고 2일뒤음성으로전환되었다. 내원 17일째항-A 동종응집소가 1:512까지상승하였으나이후점차감소하였다 (Table 2). 수혈은입원초기혈구형검사와혈청형검사가일치하지않는 ABO 불일치를보여적혈구제제는 O형, 혈소판및혈장제제는 AB 형으로수혈하였고, B형으로완전히전환된이후내원 60일에환자의혈액형인 B형으로수혈을시행하였다. 환자에게투여된총혈액량은 O형 RhD 양성적혈구제제 18단위, B형 RhD 양성적혈구제제 9단위, AB형신선동결혈장 10단위, B형신선동결혈장 33단위, AB형농축혈소판 26단위, B형농축혈소판 40단위, AB형성분채집혈소판 2 단위, AB형동결침전제제 8단위, B형동결침전제제 8단위이었다. 급성용혈수혈반응에따른신장손상, 파종성혈관내응고는회복되었지만폐부종, 위장관출혈, 허혈성대장염, 경련발작등의합병증이지속적으로발생하여내원 111일에 사망하였다. 고찰본증례는 ABO 부적합수혈에의한급성용혈수혈반응에따른합병증으로환자가사망한국내첫문헌보고이다. B형의환자에게실수로 A형적혈구가수혈된후급성용혈수혈반응의전형적인임상소견과검사실적소견이관찰되었다. 용혈성수혈반응의초기에혈구형검사와혈청형검사가일치하지않는 ABO 불일치를보였기때문에 O형적혈구와 AB형혈장제제를사용하였다. ABO 불일치 (mismatched) 혈액제제의수혈에따른혼란을최소화하고자 B형적혈구와혈장제제의수혈은내원 60일째에시행되었다. ABO 부적합수혈에의한사망사고는국내에서는문헌보고가없었지만, 외국에서는수혈로인한사망사고의가장흔한원인중의하나로많 Table 2. Serologic findings after an erroneous transfusion of a unit of blood group A RBC into B patient Serologic test Days after transfusion of ABO-incompatible RBCs* Patient RBCs ABO grouping Anti-A 1+ Negative Negative Negative Anti-B 4+ +/ +/ 1+ DAT polyspecific 1+ Negative Negative 1+ +/ IgG 2+ +/ +/ C3d +/ Negative Negative Patient serum Reverse grouping A cell +/ B cell Negative Negative Negative Negative Titer of anti-a 1:1 1:512 1:256 1:64 *The transfusion of type B red blood cell and type B fresh frozen plasma were performed on the 60th day of admission

4 Korean J Blood Transfus Vol. 29, No. 1, 73-78, Apr 은보고가있어왔다. 영국의수혈부작용보고체계인 SHOT (The Serious Hazards of Transfusion) 의 20주년기념보고에따르면, 1996년 2005년동안 ABO 부적합수혈로인해 15건의사망과 51건의심각한상해가발생하였고, 2006년 2016년에는사망과심각한상해가각각 5건, 29건으로감소하였다고하였다. 2016년에는총 3건의 ABO 부적합수혈이 SHOT에보고가되었는데그중두사건에서의료기관에서시행하는첫번째수혈의경우에는 ABO 혈액형검사용검체와교차시험용검체를분리하여두번의채혈을실시하는것이지켜지지않아서다른환자의혈액을채혈하여 ( wrong blood in tube ) 발생하였다고한다 [7]. 1990년에서 1999년까지미국뉴욕주에서적혈구수혈과관련된오류를분석한결과 ABO 부적합과연관된오류는 237건으로 1/38,000의빈도를보였다고하였다. 그중 111건 (47%) 은부작용이발생하고않았고, 급성용혈수혈반응이 96건 (41%), 기저질환에의한사망은 8건 (3%) 의결과를보고하였다 [8]. ABO 부적합수혈이발생된 48명환자의임상적경과를분석한연구에서 50 ml 이하의수혈이이루어진경우에는사망이없었지만, 50 ml를초과한경우에는 16.7% (6/36) 에서사망하였다고보고하였다. ABO 부적합수혈의빠른인지와수혈의중단이 ABO 부적합수혈에따른증상이나증후를최소화하고사망을예방할수있다 [9]. 본증례는수술실에서 50 ml을초과하는 1단위의 ABO 부적합적혈구가수혈되어급성용혈수혈반응이발생하고사망에이르게되었다. 수혈은다양한직종이참여하고여러단계의연속된과정에의해서이루어지는의학적치료방법이다. 안전한수혈이이루어지도록하기위해서많은노력을기울이고있지만수혈오류를예방할수있는완벽한방법은아직까지없다. 수혈은손목밴드확인시스템, 혈액채취과정, 수혈전 검사, 혈액의불출및운반, 수혈전환자확인단계, 수혈시행의단계로이루어지며, 이들개별과정은수혈오류가발생할수있는결정적인단계들이다 [10]. 수혈전환자확인단계는실수가발생하면수혈오류로바로이어질수있기때문에핵심단계라고할수있다. 수령된혈액과수혈처방등문서를확인하는단계와환자의손목밴드나환자의등록번호와혈액을확인하는단계로나뉘어질수있는데후자가더욱중요하다. 본증례의오류도수혈전환자확인단계에서발생하였다. 일본에서도설문방식에의한 ABO 부적합수혈의원인조사에서환자와혈액제제의확인오류가가장흔하였고절반을차지하였다고보고하였다 [3]. 수혈의안전성을해칠수있는핵심실수에대한 Maskens 등 [11] 의전향적분석에서검체라벨링실수가 37.5% 로가장흔하고, 혈액의부적절한처방이 28.8% 를차지하였다. 이것은 2001년부터 2005년기간동안미국식품의약국에보고된심각한사고로이어질뻔하였던수혈 ( near hit ) 의원인분석에서라벨링실수가가장흔하게나타난것과일치되는내용이다 [9]. 이러한라벨링실수는잘못된 ABO 혈액형검사로이어지게되고부정확한혈액제제의수혈 ( Incorrect blood component transfused, IBCT) 에이르게된다. 11,570 건의 SHOT 보고중에서 IBCT가 3,000여건을초과하여가장높은빈도로보고되는것 [12] 과연관지을수있겠다. 이처럼수혈오류의주된위험은의료진에있으며, 기본에충실한안전수혈절차를익히는것이필요하다 안전수혈캠페인 은의료기관에서의첫수혈인경우 ABO 혈액형검사용검체와교차시험용검체를각각분리하여채혈 (2 회채혈 ), 2명의검사자에의한독립적 ABO 혈액형검사, 수혈전환자확인은 2명의의료인이함

5 임현호외 : ABO 부적합수혈에의한급성용혈수혈반응 : 치명적증례보고및문헌검토 께하는것이다. 이러한기본적인절차가충분히교육되고지켜진다면수혈오류가발생하지않을것이다. 하지만이러한기본적인절차는바쁜임상환경에서쉽게무시될수있다. 이러한인적오류 (human error) 를예방하기위해서최신의정보통신기술 (Information Technology) 을수혈현장에적용하는경우가증가하고있다 [13-15]. 무선주파수인식을통한자동인식기술인 RFID (Radio- Frequency Identification) 기술을수혈의학에적용할때의가이드라인까지발표되어있다 [16]. 하지만이러한최신의기술도오류를일으키거나실제도입시장벽이있을수도있다 [17,18]. 기술적인적용외에도수혈에참여하는의료인들의지속적인교육과평가, 수혈과정의능동적인평가, 혈액안전감시체계의활성화, 수혈관련질향상의업무를담당하는수혈안전책임자 (Transfusion Safety Officer) 를두고안전한수혈환경을추구하는의료기관들도있다 [19]. 수혈은다단계의과정을거치고, 여러직종의참여를필요로하는복잡한의료행위이다. 수혈오류를줄이고안전한수혈환경을이루기위한한가지의단일한방법은있을수가없다. 본증례는 ABO 부적합수혈에의한급성용혈수혈반응이사망의주요원인이된국내최초의문헌보고이다. 안전한수혈환경을구축하기위한노력은개별의료기관뿐만아니라국가적차원의논의와지원이필요한시점이다. 요약급성용혈수혈반응이의심되어응급실을통해서전원된 77세여자환자는타의료기관에서슬관절전치환수술중 B형환자에게 A형농축적혈구가 1단위잘못수혈되었다. 사고는혈액제제와환자확인과정의오류로인하여발생하였다. 내 원당시급성용혈반응, 젖산산증, 파종성혈관내응고소견을보였다. 중환자실로입실하여지속적신대체요법을시행하며신장기능을보호하였고 7일째일반병실로이동하였다. 급성용혈수혈반응에따른신장손상, 파종성혈관내응고는회복되었지만폐부종, 위장관출혈, 허혈성대장염등의합병증이지속적으로발생하여내원 111일에사망하였다. 본증례는 ABO 부적합수혈에의한급성용혈수혈반응이사망의주요원인인된국내최초의문헌보고이다. 안전한수혈환경을구축하기위한노력은개별의료기관뿐만아니라국가적차원의논의와지원이필요한시점이다. References 1. Stainsby D, Russell J, Cohen H, Lilleyman J. Reducing adverse events in blood transfusion. Br J Haematol 2005;131: Myhre BA, McRuer D. Human error - a significant cause of transfusion mortality. Transfusion 2000;40: Fujii Y, Shibata Y, Miyata S, Inaba S, Asai T, Hoshi Y, et al. Consecutive national surveys of ABO-incompatible blood transfusion in Japan. Vox Sang 2009;97: Cho D, Hyun J, Ryang DW. Prevention of ABO incompatible blood transfusion: '2-2-2 safe blood transfusion campaign'. Korean J Blood Transfus 2013;24: Kim PK, Cho KH. A case report of acute hemolytic reaction during blood transfusion. Korean J Anesthesiol 1973;6: Kim YL, Kim DK, Kim HS. A clinical experience upon acute renal failure due to mismatched blood transfusion. Korean J Anesthesiol 1978;11: Bolton-Maggs PHB. Serious hazards of transfusion - conference report: celebration of

6 Korean J Blood Transfus Vol. 29, No. 1, 73-78, Apr years of UK haemovigilance. Transfus Med 2017;27: Linden JV, Wagner K, Voytovich AE, Sheehan J. Transfusion errors in New York State: an analysis of 10 years' experience. Transfusion 2000;40: Janatpour KA, Kalmin ND, Jensen HM, Holland PV. Clinical outcomes of ABOincompatible RBC transfusions. Am J Clin Pathol 2008;129: Heddle NM, Fung M, Hervig T, Szczepiorkowski ZM, Torretta L, Arnold E, et al. Challenges and opportunities to prevent transfusion errors: a Qualitative Evaluation for Safer Transfusion (QUEST). Transfusion 2012; 52: Maskens C, Downie H, Wendt A, Lima A, Merkley L, Lin Y, et al. Hospital-based transfusion error tracking from 2005 to 2010: identifying the key errors threatening patient transfusion safety. Transfusion 2014;54:66-73; quiz Bolton-Maggs PH, Cohen H. Serious Hazards of Transfusion (SHOT) haemovigilance and progress is improving transfusion safety. Br J Haematol 2013;163: Murphy MF, Fraser E, Miles D, Noel S, Staves J, Cripps B, et al. How do we monitor hospital transfusion practice using an end-to-end electronic transfusion management system? Transfusion 2012;52: Nuttall GA, Abenstein JP, Stubbs JR, Santrach P, Ereth MH, Johnson PM, et al. Computerized bar code-based blood identification systems and near-miss transfusion episodes and transfusion errors. Mayo Clin Proc 2013;88: Sandler SG, Langeberg A, Dohnalek L. Bar code technology improves positive patient identification and transfusion safety. Dev Biol (Basel) 2005;120: Knels R, Ashford P, Bidet F, Böcker W, Briggs L, Bruce P, et al. Guidelines for the use of RFID technology in transfusion medicine. Vox Sang 2010;98 Suppl 2: Snyder ML, Carter A, Jenkins K, Fantz CR. Patient misidentifications caused by errors in standard bar code technology. Clin Chem 2010;56: Coustasse A, Cunningham B, Deslich S, Willson E, Meadows P. Benefits and barriers of implementation and utilization of Radio- Frequency Identification (RFID) systems in transfusion medicine. Perspect Health Inf Manag 2015;12:1d 19. Dunbar NM, Szczepiorkowski ZM. How do we utilize a transfusion safety officer? Transfusion 2015;55:

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untitled 대한수혈학회지 : 제 26 권제 3 호, 2015 The Korean Journal of Blood Transfusion Vol. 26, No. 3, 266-272, December 2015 http://dx.doi.org/10.17945/kjbt.2015.26.3.266 pissn 1226-9336 eissn 2383-6881 Original Article