대한내과학회지 : 제 82 권제 1 호 2012 http://dx.doi.org/10.3904/kjm.2012.82.1.67 폐농양과동반된간문맥혈전증 1 예 왈레스기념침례병원내과 박성남 임주견 김영묵 Portal Vein Thrombosis with a Lung Abscess Sung Nam Park, Ju Kyeon Yim, and Yeong Muk Kim Department of Internal Medicine, Wallace Memorial Baptist Hospital, Busan, Korea Portal vein thrombosis (PVT) is an uncommon cause of presinusoidal hypertension and can result from cirrhosis, malignancy, infection, inflammation, and congenital and acquired thrombophilic states. Infectious and inflammatory causes include pylephlebitis, omphalitis, diverticulitis, pancreatitis, cholecystitis, appendicitis, and inflammatory bowel disease. However, PVT induced by a lung abscess has not been reported. We experienced a 50-year-old male complaining of right upper quadrant pain, fever, and coughing. A lung abscess and PVT were revealed by computed tomography and abdominal Doppler ultrasonography. The PVT resolved, in part, after an 8-day course of antibiotic therapy. We report a case of PVT as a complication of a lung abscess and review the literature. (Korean J Med 2012;82:67-72) Keywords: Portal vein thrombosis; Lung abscess; Protein S 서론간문맥혈전증은문맥압항진증을유발하는드문원인으로주로간경변, 간암에동반되어발생하지만일부는아직원인을알수없는경우도많다 [1]. 간문맥혈전증의원인은국소적원인과전신적원인으로나눌수있고국소적원인으로는간경변, 종양, 감염, 염증등이있고전신적원인으로는유전또는후천혈전성향인자가작용한다 [2]. 간문맥혈 전증형성과연관된감염은신생아제대염, 게실염, 맹장염, 췌장염, 담관염, 결핵성임파선염등주로복강내감염혹은염증과관계된다 [1,2]. 간문맥혈전증의원인에대해여러논문에서보고된바있으나전신적감염을동반한경우는매우드물며폐농양과동반된예는외국에서도거의보고된바가없다. 이에저자들은폐농양에동반된간문맥혈전증을폐농양치료만으로일부호전된예를경험하였기에보고하는바이다. Received: 2011. 2. 14 Revised: 2011. 3. 11 Accepted: 2011. 3. 28 Correspondence to Yeong Muk Kim, M.D. Divison of Gastroenterology, Department of Internal Medicine, Wallace Memorial Baptist Hospital, 374-75 Namsan-dong, Geumjeong-gu, Busan 609-728, Korea Tel: +82-51-580-2000, Fax: +82-51-580-1048, E-mail: lovetoje@hanmail.net - 67 -
- The Korean Journal of Medicine: Vol. 82, No. 1, 2012 - 증례환자 : 이〇〇, 남자, 50세주소 : 상복부통증현병력 : 내원 1개월전부터야간발한증상이있었고보름전부터마른기침이있었던분으로내원 3일전상복부에통증과압통이있어내원하였다. 과거력 : 특이과거력없었다. 사회력 : 20갑년의흡연력있었다. 가족력 : 특이사항은없었다. 문진소견 : 발열, 오한, 전신쇠약, 식욕부진호소하였으며의식상태는명료하였다. 진찰소견 : 활력징후는혈압은 100/60 mmhg, 맥박은 108 회 / 분, 호흡수는 22회 / 분, 체온은 38 였으며, 좌하폐야에서수포음이청진되었고, 우상복부에압통이있었다. 검사실소견 : 입원당시말초혈액검사에서백혈구 19,100/mm 3 ( 호중구 87.6%, 림프구 5.9%), 혈색소 9.8 g/dl, 헤마토크리트 30.4%, 혈소판 385,000/mm 3 였고, 혈청생화학검사에서혈청총단백 7.1 g/dl, 알부민 3.1 g/dl, 글로불린 4.0 g/dl, AST/ALT 59/54 U/L, 총빌리루빈 1.0 mg/dl, 알칼리포스파 타제 1713 IU/L ( 정상 103-335 IU/L), 감마-글루타밀트랜스펩티다제 554 U/L ( 정상 8-73 U/L), 췌장아밀라제 36 IU/L, 리파제 35 IU/L, 혈액요소질소 6.0 mg/dl, 크레아티닌 0.7 mg/dl, Na/K 135/4.4 meq/l, 젖산탈수소효소 172 U/L, 총콜레스테롤 136 mg/dl, C-반응성단백질 23.61 mg/dl, 공복혈당 98 mg/dl, 칼슘 8.7 mg/dl, 적혈구침강률 114 mm/hr이었다. 간염바이러스표지자검사에서 B형간염표면항원 (HBs Ag) 음성, HBs Ag에대한항체양성, C형간염바이러스에대한항체음성이었다. 혈액응고검사에서 PT 12.4초 (INR 1.1), aptt 26.5초이었다. 면역혈청검사에서루푸스항응고인자음성, 단백 C 활동성 67%, 단백 S 활동성 36%, antithrombin III 80 mg/dl, 이외항핵항체, 항카디오리핀항체, 핵주위항중성구세포질항체 (p-anca), 세포질항중성구세포질항체 (c-anca), Factor V Leiden mutation 모두음성이었다. 방사선소견 : 단순흉부방사선사진및흉부전산화단층촬영 (Fig. 1) 에서양폐하엽에음영증가소견보였고좌하엽에공기액체층이관찰되는직경 4 cm 크기의공동성병변을보였다. 복부전산화단층촬영 (Fig. 2) 에서간문맥의혈전증소견을보였고간경변증이나간종양의소견은없었다. 복부도플러초음파 (Fig. 3) 에서간문맥혈전증보였고, 혈류저하 A B Figure 1. Chest posterioanterior radiograph and computed tomography (CT) scan on admission. (A) Chest radiograph shows increased opacity in both lower lung fields. (B) Chest CT shows about a 4-cm cavitary lesion with air-fluid in the left lower lung. - 68 -
- Sung Nam Park, et al, Portal vein thrombosis with lung abscess - Figure 2. Abdominal computed tomography (CT) scanon admission. Abdominal CTshows an abnormal low-density lesion indicative of a filling defect (thrombus) in the portal vein (arrow) and splenic vein (arrow head). 소견보였다. 미생물및조직소견 : 혈액배양검사와객담배양검사에서균이배양되지않았다. 내시경소견 : 내원당시시행한상부소화관내시경검사에서위체부에서다발성궤양과출혈성위염소견보였다. 임상경과및치료 : 내원당시시행한검사에서폐농양에동반된간문맥혈전증으로진단후항생제치료시작하였으며흑색변있어시행한내시경소견상다발성궤양과출혈소견보여항응고요법은바로시행하지못하였다. 내원 3일째상복부통증의호전보였으며내원 8일째시행한초음파소견에서간문맥의혈전은호전양상보이나남아있었다 (Fig. 4). 흑색변없어지고내시경소견상호전양상보여정맥헤파린주사시작하고 3일후와파린을병용투여하여 INR 2-3으로유지한후와파린단독으로항응고제투여를계속하였다. A B C Figure 3. Initial abdominal and Doppler ultrasound. (A) Ultrasound of the abdomen shows hypoechoic thrombosis (arrow) in the left and right main portal veins. (B) Doppler ultrasound of the abdomen shows decreased portal flow in the left and right main portal veins. (C) Ultrasound of the abdomen shows a hypoechoic thrombus (arrow head) in the right main portal vein. - 69 -
- 대한내과학회지 : 제 82 권제 1 호통권제 617 호 2012 - A B Figure 4. Follow-up abdominal and Doppler ultrasound. (A) After 8 days, ultrasound of the abdomen shows a partially decreased thrombus (arrow) in the right main portal vein. (B) Doppler ultrasound of the abdomen shows improved portal flow in the right main portal vein. 고찰간문맥혈전증은국소적이고, 전신적인혈전을유발하는인자들이야기하지만간경변증이중요한인자로여겨진다. 대상성간경변증을가진환자들에서혈전증의발생률은 0.6% 에서 16% 로다양하게보고된다 [3,4]. 비대상성간경변증을가진환자들에서는발생률이더높고특히간암환자들에게서는 35% 까지도보고된다. 간경변증이없는환자들의발생률은문헌상으로잘보고되어있지않지만서구에서는모든문맥압항진증환자의약 5-10% 로보고된다 [5]. 선진국에서특히소아에서발생한문맥압항진증의 1/3 이상이감염의합병증과연관된다고보고된다 [6]. 간문맥혈전증의원인은국소적인것과전신적인것으로나눌수있고, 국소적인원인은간경변증, 간암등의암성원인, 감염, 염증등이있고전신적인원인은선천적인원인과후천적인원인으로나눌수있다. 선천적인원인질환에는 Factor V Leiden mutation, prothrombin gene mutation, 단백 C,S 결핍, Antithrombin III 결핍등이있고후천적인것에는악성종양, 경구피임제, 임신, 골수증식질환, 항인지질항체증후군, 고호모시스테인혈증, 발작성야간혈색소뇨증등이있다. 국소적인원인으로는문맥염, 신생아제대염, 패혈증, 결핵성임파선염같은감염과게실염, 췌장염, 담낭염, 충수돌기염, 소화성궤양천공, 복부둔탁손상, 수술에의한간문맥계의손상, 염증성장질환같은염증이있다 [2]. 심한전 신적감염증이간문맥혈전증원인의 8% 를차지한다는보고도있다 [1]. 본증례환자는폐농양으로인한전신적감염증과단백 S 결핍을제외하고는간문맥혈전증의다른원인을찾을수없었다. 폐농양으로인한패혈증시혈전생성기전은잘알려져있지않지만패혈증상태에서는내독소가응고작용을활성화시키고, 혈액응고와섬유소용해작용간의불균형이초래되어혈액과응고성상태에이르게된다. 응고작용의활성화뿐아니라, 단핵세포들의표면위로조직인자의표현과혈전형성의내피하혈관벽교원질의노출에의한혈관벽과염증세포들과의상호작용이염증에의한혈전형성에기여하게된다 [7,8]. 단백 S는단백 C와인지질에대한친화력을증강시켜응고인자 Va와 VIIIa를불활성화시킴으로써혈액응고를억제하는역할을하는보조인자로작용한다 [9]. 단백 S 결핍은선천적혹은후천적으로유발될수있다. 선천적단백 S 결핍증은상염색체우성으로유전되며동형접합인경우영아기에사망하게되지만이형접합인경우주로반복적인정맥혈전증의임상형태를보이는것으로알려져있다. 후천적단백 S 결핍은임신, 간질환, 신증후군, 와파린투여, 세균감염, 악성종양, 경구피임제사용등으로올수있다 [10]. 또한문맥혈전으로인해간혈류가줄어들고 portosystemic shunting 으로인해 protein S같은항응고인자의합성이저해될수도있다 [11]. 혈중단백 S의약 60% 는다른단백질 (C4b-BP) 과 - 70 -
- 박성남외 2 인. 폐농양과동반된간문맥혈전증 1 예 - 결합되고 40% 정도만혈액응고억제효과를발휘하는자유형으로존재하는데 C4b-BP는급성기반응물질로서어떠한염증반응에서도증가할수있고이로인해단백 S 활성도를감소시킬수있다. 따라서급성기에측정된단백활성도감소는임상적으로큰의미를부여하기힘들고급성기이후에도지속적으로유리단백 S가감소된것이증명되어야혈전증의원인으로의미가있다고할수있다 [12]. 본증례의환자는특별한혈전증의과거력과가족력이없어문맥혈전증에의한혈류감소혹은폐농양에따른심한전신적감염증으로일시적단백 S 활동성의저하를보였을가능성이있으나환자사정으로감염호전후추가검사를시행할수없었다. 간문맥의혈전이형성되고 60일이내에나타나는증상을급성증상으로분류할수있는데주로복통, 발열, 오심등이나타날수있으나대부분증상이없거나비특이적이다. 만성의경우혈전이발생한간문맥주변의곁정맥 (collateral veins) 의발달과해면종 (portal cavernoma) 이형성되며정맥류출혈, 복수, 비장종대등의간문맥고혈압의증상과징후가나타난다 [2]. 간문맥혈전증의진단은복부초음파검사, 도플러초음파, 전산화단층촬영등을이용하여조기에진단가능하다. 복부색도플러초음파검사는 98% 의음성예측도를나타내고 [2] 최근에는내시경초음파, 복부자기공명영상, 복부자기공명혈관촬영술등을이용하여작은혈전도발견가능하고주변장기관련성등에더욱정확한검사를시행할수있다 [13]. 급성간문맥혈전증의치료목표는간문맥의완전한개통성을유지하여만성간문맥혈전증으로의진행을막고장간막정맥으로혈전이진행할수있는위험도를낮추어장간막허혈과경색을막는것이다. 초기간경변이있고간문맥고혈압의증거가없는경우를제외하고는일반적으로간경변환자에서는장기적인항응고요법은추천되지않고간경변이없는환자의경우는혈전으로인한정맥류출혈이나비장비대증혹은복수같은간문맥고혈압의증거의유무에따라다르다. 간문맥고혈압의증거가있는만성간문맥혈전증의경우에는과응고상태나이전의다른혈관에서혈전병력등이있으면장기간의항응고요법을강력히고려하지만조절되지않는정맥류출혈이있거나혈소판수치가 50,000/mm 3 이하일경우에는시행하지않는다. 간문맥고혈 압의증거가없는급성간문맥혈전증인경우는유발요인을알아내어치료하고전신적혹은국소적인혈전용해요법과외과적혈전제거술, 간내문맥전신순환연결술 (transjugular intrahepatic portosystemic shunt) 등을고려한다. 또한과응고상태를유발하는인자가있는지조사하여없으면 3-6개월후항응고요법을중단한뒤경과관찰하고과응고상태를유발하는인자가있다면장기적인혹은평생동안의항응고요법을고려한다 [2]. 하지만거대세포바이러스감염에동반된간문맥혈전증이나췌장염, 게질염에동반된장간막정맥혈전증의경우항응고제치료없이원인질환의호전과함께혈전증이호전된사례들이있어모든간문맥혈전증에이러한치료원칙을적용해야하는가에대해서는의문점이있다 [14-16]. 따라서폐농양같은감염에의해이차적으로발생한간문맥혈전증의경우에는항응고요법필요유무, 항응고제종료및사용기간등의치료지침에대한더많은연구가필요할것으로생각된다. 요 저자들은폐농양에합병된간문맥혈전증환자에서항응고요법없이항생제치료만으로폐농양의호전과함께일부용해된간문맥혈전증 1예를경험하였기에문헌고찰과함께보고하는바이다. 약 중심단어 : 간문맥혈전증 ; 폐농양 ; 단백 S REFERENCES 1. Rajani R, Björnsson E, Bergquist A, et al. The epidemiology and clinical features of portal vein thrombosis: a multicentre study. Aliment Pharmacol Ther 2010;32:1154-1162. 2. Parikh S, Shah R, Kapoor P. Portal vein thrombosis. Am J Med 2010;123:111-119. 3. Okuda K, Ohnishi K, Kimura K, et al. Incidence of portal vein thrombosis in liver cirrhosis: an angiographic study in 708 patients. Gastroenterology 1985;89:279-286. 4. Amitrano L, Guardascione MA, Brancaccio V, et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol 2004;40:736-741. 5. Onohara T, Takahashi I, Nishizaki T, Wakasugi K, Matsusaka T, Kume K. Superior mesenteric vein thrombosis due to diverticulitis and spontaneous thrombolysis after ilio-cecal resection: a case report. J Cardiovasc Surg (Torino) 2000; - 71 -
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