대한수혈학회지 : 제 22 권제 3 호, 2011 심부전환자에서수혈관련급성폐손상의진단 1 예 홍윤지 1 ㆍ김정아 1 ㆍ최규태 1 ㆍ이경훈 1 ㆍ박경운 1,2 ㆍ송정한 1,2 ㆍ한규섭 1 = Abstract = 서울대학교의과대학검사의학교실 1, 분당서울대학교병원진단검사의학과 2 Diagnosis of Transfusion-Related Acute Lung Injury (TRALI) in a Heart Failure Patient Yun Ji Hong 1, Jung Ah Kim 1, Qute Choi 1, Kyunghoon Lee 1, Kyoung Un Park 1,2, Junghan Song 1,2, Kyou Sup Han 1 Department of Laboratory Medicine, Seoul National University College of Medicine 1, Seoul, Department of Laboratory Medicine, Seoul National University Bundang Hospital 2, Seongnam, Korea A 71-yr old man with known coronary heart disease complained of dyspnea and severe sweating one hour after of one unit of packed Red Blood Cells (prbc). Although the heart failure was secondary to the remote acute myocardial infarction, except inflammatory lesion in his toes, he had remained asymptomatic for a long time. Observed as having clear lungs a few hours before, the patient suffered an acute hypoxic episode (SpO 2 =61%) and a resulting chest x-ray revealed bilateral pulmonary infiltrates. Confused as the cause of the acute deterioration, he was transferred to the intensive care unit and received managed lung care by mechanical ventilation as well as other conservative care methods. Two days after the acute hypoxic event there was apparent clinical improvement, and he was weaned from ventilator support. His amelioration resulted in subsequent diagnosis of Transfusion-Related Acute Lung Injury (TRALI). TRALI is underdiagnosed in patients due to its nebulous nature. Evaluating patients exhibiting symptoms of bilateral lung infiltrate after blood for TRALI, and subsequent reporting of the diagnosis results, will help reveal the actual frequency of incidence of TRALI, and prevent additional events by tracing the blood donor. (Korean J Blood Transfus 2011;22:271-276) Key words: Transfusion-related acute lung injury, TRALI, Heart failure 서론수혈관련급성폐손상 (-related acute lung injury, TRALI) 은 1951년에처음그개념의 일부가도입되었고, 1) 1983년에이르러다섯증례의분석을통해수혈후발생하는급성저산소증과비심장성폐부종을수혈관련급성폐손상이라고정의하게되었다. 2) 처음개념이소개될때부 접수일 :2011년 8월 9일, 수정일 :2011년 11월 19일, 승인일 :2011년 11월 22일책임저자 : 박경운 463-707 경기도성남시분당구구미로 166 분당서울대학교병원진단검사의학과 TEL: 031) 787-7692, FAX: 031) 787-4015, E-mail: m91w95@dreamwiz.com - 271 -
대한수혈학회지 : 제 22 권제 3 호 터헌혈혈액속에존재하는사람백혈구항원에대한동종항체 (anti-human leukocyte antigen antibody) 가원인으로생각되었고, 2) 이후여러원인이제시되어왔다. 현재는사람백혈구항원에대한동종항체, 사람과립구항원에대한동종항체 (anti-human neutrophil antigen antibody) 및혈액저장에따른지질 (blood storage-related lipid) 이그주요원인으로알려져있다. 3) 초창기에는수혈관련급성폐손상의진단을위해검사소견에비중을두었지만, 최근에는임상적진단에무게를두고있다. 4) 최근이질환에대한관심이증가하면서선진국에서는수혈연관성이환과사망에있어기존의수혈전파성감염질환보다더비중있게다뤄지고있는반면, 4) 아직국내에서는수혈관련급성폐손상에대한보고가드물다. 여기에는정확한진단과신속한보고체계의부재가일부영향을끼치고있는것으로보인다. 저자들은최근수혈직후호흡곤란증상과양측성폐침윤을보인증례를경험하고이를보고하고자한다. 증례 환자는 71세남자로 5년전급성심근경색으로관상동맥중재시술 (percutaneous coronary intervention) 을받았고, 3년전대장암과식도암을함께진단받고 Ivor Lewis 수술과부분대장절제술을받았다. 5개월전에는 ST분절비상승심근경색으로진단받고, 응급실통하여입원하여응급중재적관상동맥성형술을시행받았다. 이후퇴원을고려하던중의인성심부정맥혈전및동맥폐쇄로인한발가락의허혈성병변이발생하여수회의조직제거술을시행받으며장기간재원중이었다. 세번째조직제거술을받은다음날, 정규혈액검사에서혈색소 8.6 g/dl의소견을보여 B+ 농축적혈구 1 단위를수혈받았다. 수혈이종료되고한시간후에환자는흉부의불편감과중증의발한을호소하였고불안정한활력징후 ( 수축기혈압 130 mmhg, 이완기혈압 61 mmhg, 심박수 104회 / 분, 호흡수 25회 / 분 ) 를보였으며동맥혈가스검사상호흡부전 (SaO 2 30.7%, PaCO 2 40.4 mmhg, PaO 2 23.3 mmhg) 소견을나타내었다. 청진상폐전체에서미약한악설음이들렸고경정맥확장은관찰되지않았다. 흉부방사선소견에서이전에시행한검사와확연하게구별되는미만성폐침윤을보였으나 (Fig. 1), 오한이나열감을호소하지는않았으며호흡기검체및혈액검체에서균은배양되지않았다. 증상발생직후에시행한심전도에서는동성빈맥과이전부터존재하던우각차단소견이관찰되었다. 심장성원인을배제하기위해심장효소검사및전기화학발광면역분석법을이용한 N-terminal pro B-type natriuretic peptide (NTproBNP, Roche diagnostics, Rotkeuz, Switzerland) 검사를시행하였고, 그결과는 Table 1과같았다. 그외에급성용혈성수혈부작용을의심할만한특이소견은없었고, 발진이나가려움증등의주관적인증상도관찰되지않았다. 환자는불안정한활력징후와호흡부전이확인된직후, 중환자실에입실하여기관삽관과기계환기뿐만아니라이뇨제와같은다른보존적치료도함께시행하였다. 하지만, 환자의호전양상이섭취량및배설량이나체중의변화와는독립된양상을보였는데, 환자는수혈을받은당일의섭취량 / 배설량은 1,285 ml이었고, 흉부방사선촬영상호전을보인이틀후의섭취량 / 배설량은 +200 ml였다. 심장초음파검사상확인한박출계수 (ejection fraction) 는한달전 (34.1%) 과비교하였을때큰차이가없었다 ( 박출계수, 33.5%). 이후증상소실과함께검사소견의빠른호전을보여 - 272 -
심부전환자에서수혈관련급성폐손상의진단 Fig. 1. Chest radiographs. (A) Chest PA, 6 hours before blood. (B) Chest AP, 4 hours after the time the patient developed dyspnea after, showing bilateral lung infiltrates. (C) Chest AP, 2 days after, showing apparent improvement of lung infiltrates. Table 1. Cardiac marker test before and after of a unit of packed red blood cells 13 days before A day before 90 min after 5 hr after CK (IU/L) 67 CK-MB* (ng/ml) 2.3 2.6 4.5 Troponin I (ng/ml) 0.672 0.44 0.522 NT-proBNP (pg/ml) 7,356.0 6,978.0 Abbreviations: CK, creatinine kinase; NT-proBNP, N-terminal pro B-type natriuretic peptide. *Reference range: 0 2.8 ng/ml, WHO Acute myocardial infarction cutoff: 5 ng/ml, Reference range: 0 0.045 ng/ml, WHO Acute myocardial infarction cutoff: 0.6 ng/ml, Reference range: 97.5 th percentile in reference group, 349 pg/ml; 95 th percentile in NYHA II congestive heart failure, 6,567 pg/ml. 비로소수혈관련급성폐손상으로진단되었고 (Fig. 1, Table 2), 이틀간의중환자실치료후일반병동으로전동되었다. 고찰수혈관련급성폐손상은처음에는수혈후 6시 간내에생기는급성호흡곤란과양측성폐침윤이있으면서순환혈액량과부하를배제할수있는경우로정의되었고, 헌혈혈액내에존재하는수혈자의백혈구항원에대한항체가그원인으로제시되었다. 2) 이후다양한진단기준이제시되었는데, 2004년토론토에서열렸던 Canadian Consensus Conference에서는위의세가지기준과 - 273 -
대한수혈학회지 : 제 22 권제 3 호 Table 2. Arterial blood gas analysis showing decreased partial oxygen pressure in arterial blood (PaO 2) and respiratory acidosis after of a unit of packed red blood cells followed by gradual improvement 90 min after 120 min after (just before intubation) 180 min after (60 min after intubation) 1 day after (1 day after intubation) 2 days after (just before extubation) 3 days after (1 day after extubation) ph 7.275 7.287 7.321 7.411 7.467 7.386 PaCO 2 (mmhg) 40.4 35.0 31.6 28.6 25.2 31.0 PaO 2 (mmhg) 23.3 51.2 79.0 132.1 91.8 113.0 HCO 3 18.3 16.4 16.0 17.7 17.8 18.2 BE (mmol/l) 8 9.4 8.8 5.8 4.9 6.1 SaO 2 (%) 30.7 79.7 93.9 98.9 97.5 98.2 O 2 delivery device Facial mask with partial rebreathing reservoir Facial mask with partial rebreathing reservoir MV MV MV Nasal prong Oxygen flow rate 10 L/min 10 L/min FiO 2 0.6 FiO 2 0.35 FiO 2 0.25 2 L/min Abbreviations: BE, base excess; MV, mechanical ventilation. 함께 1) 저산소증 (PaO 2 /FiO 2 300 또는대기중측정한 pulse oximetry <90% 또는합당한임상적근거 ) 및 2) 기저급성폐손상의배제및급성폐손상을일으킬만한위험요인의배제를진단기준으로내세우고있다. 5) 또한기저질환이복잡하여급성폐손상의원인을명확하게알수없는경우를위해 possible TRALI 라는개념을도입하였는데, 이는급성폐손상이수혈이외에도적어도한개이상의다른위험요인과연관되어있을때적용할수있다. 5) 이개념의도입을통해수혈관련급성폐손상이실제보다과소평가되어보고되는문제점을개선하여질병의병태생리의연구에도움을주고, 동일헌혈자의혈액이또다른환자에게수혈되는것을미리예방할수있을것으로전망된다. 6) 미국의 National Heart, Lung, and Blood Institute (NHLBI) 의위원회에서도유사한진단기준을제 시하였는데, 7) 초창기에수혈관련급성폐손상의진단을위해검사소견에비중을둔반면, 최근에는임상적진단에그초점을두고있다. 4) 실제로보고되는일부증례에서임상양상만으로수혈관련급성폐손상을진단한경우를확인할수있다. 8) 국내에서는 2005년의첫보고이래, 현재까지수혈자 5명에서이질환이보고되었는데, 2명에서는환자의혈청내에서수혈전에는존재하지않았던사람백혈구항원에대한동종항체를확인해간접적으로헌혈혈액내의항체존재를확인하였고, 9) 나머지 3명은임상양상을바탕으로수혈관련급성폐손상을진단하였다. 10,11) 저자들이보고하는증례의경우에수회의급성심근경색으로인한심부전으로인해심장성폐부종과수혈관련급성폐손상의감별이필요했으나, 발병시간과환자의임상상을통해수혈관련급성폐손상을진단할수있었다. 환자의경우수 - 274 -
심부전환자에서수혈관련급성폐손상의진단 혈종료 1시간후에갑작스럽게증상을호소하였는데, 급성폐손상이 2시간이내에발생하는경우다른원인에의한호흡부전의악화를배제할수있는근거로삼을수있기때문이다. 4) 환자는심근경색후심부전및의인성동맥폐쇄로인한발가락병변으로장기재원하면서, 급성증상이해결된이후에는수혈후호흡곤란을호소하기까지약 5개월간비교적안정적인임상경과를보였다. 순차적으로시행한심장표지자검사결과 (Table 1) 에서보듯이급성심근경색을배제할수있었고, 증상발생후시행한 NT-proBNP 검사에서도수혈전보다오히려감소한값을보여폐침윤의원인으로심부전의악화를제외할수있었다. 급성폐손상을일으키는위험요인과별개로, 순환혈액량의과부하에의한호흡곤란과수혈관련급성폐손상을감별하는것은매우어려운일이나, 이뇨제의사용에도폐손상이지속된다면수혈관련급성폐손상으로진단하는것이합당한일이다. 5) 실제로이번증례의경우치료에대한반응을확인한후뒤늦게수혈관련급성폐손상으로진단되어복합기저질환이있는환자에서이질환을진단하는것이조심스러움을확인할수있었다. 이번증례는임상적으로수혈관련급성폐손상이강하게의심되지만헌혈자의검체를통한원인확인이어려운경우에환자를통해수혈부작용의진단에접근하는예가될수있다. 수혈관련급성폐손상은그임상양상과진단기준의모호함으로인해진단이쉽지않지만, 기존문헌에알려진발생빈도를고려했을때국내에서이를과소평가하고있다는사실을항상염두에두어야할것이다. 10) 요약 기저질환으로관상동맥질환이있는 71세남자환자가농축적혈구 1단위를수혈받은후호흡부전과발한이발생하였다. 환자는과거급성심근경색으로인한심부전이있었지만, 발가락의허혈성손상으로인한염증을제외하고는오랜기간동안무증상상태를유지중이었다. 수혈수시간전에는정상이었던흉부방사선검사소견이수혈후급성저산소증 (SpO 2=61%) 과함께양측성폐침윤을보였다. 급성악화의원인파악및치료를위해환자는중환자실에입실하여기관삽관및기계환기로보존적치료를시행받았고, 이후빠른호전을보여비로소수혈관련급성폐손상으로진단되었다. 환자는이틀간의중환자실치료후일반병동으로전동되었다. 수혈관련급성폐손상은그성상이모호하여실제발생보다과소평가되는면이있다. 수혈후폐침윤이있는환자에서수혈관련급성폐손상에대한적극적인의심과진단이될경우적극적인보고를통해이질환에의한추가적인수혈부작용을줄일수있을것으로생각된다. 참고문헌 1. Barnard RD. Indiscriminate : a critique of case reports illustrating hypersensitivity reactions. N Y State J Med 1951;51: 2399-402 2. Popovsky MA, Abel MD, Moore SB. Transfusion-related acute lung injury associated with passive transfer of antileukocyte antibodies. Am Rev Respir Dis 1983;128:185-9 3. Silliman CC, Ambruso DR, Boshkov LK. Transfusion-related acute lung injury. Blood 2005;105:2266-73 - 275 -
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