대한내과학회지 : 제 92 권제 2 호 2017 https://doi.org/10.3904/kjm.2017.92.2.155 Interpretation of diagnostic test 철결핍빈혈진단과최신치료경향 건국대학교의학전문대학원내과학교실종양혈액내과 김성용 Iron Deficiency Anemia: Diagnosis and Treatment Sung-Yong Kim Division of Hematology/Oncology, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea 서론철결핍 (iron deficiency) 은체내로의철흡수에비하여철의요구량이나소실이많아체내철의양이감소된것을말하며, 철결핍이계속진행되어적혈구생성이떨어져빈혈이생기는경우철결핍빈혈 (iron deficiency anemia) 이라한다. 철결핍빈혈은국내남자의 2%, 여자의 22% 정도에서발생하는발생빈도가가장높은빈혈이다 [1]. 흔하고치료가쉬운질환이지만, 잘못된진단을하거나정확한원인규명없이치료를하는경우잘못된치료를하게되거나빈혈을증상으로나타내는숨겨진질환을놓칠수있으니진단에신중하여야한다. 종종위장관출혈로인한빈혈을모두철결핍빈혈로진단하는경우가있는데, 위장관출혈이있더라도철결핍이없는경우철결핍빈혈이아니며철투여가필요없거나투여하여도효과를기대하기어렵다. 원인에대한치료와더불어시행되는철보충은경구또는정맥주사투여로이루어진다. 경구투여는가격이싸고심각한부작용이없다는점에서더선호되고있지만위장관부작용의빈도가높고장기간복용을해야한다는단점이있다. 반면에혈관천자를해야하는단점이있지만위장관부작용이없고몇차례의 투여만으로부족한철을단시간에보충할수있는주사철제제가최근적극적으로이용되고있다 [2]. 이글에서는주로철결핍빈혈의진단시유의할점, 특수한상황에서의환자접근법, 주사치료의장단점과방법을다루고자한다. 진단및원인철결핍빈혈의심과검사결과의해석빈혈환자중망상적혈구 (reticulocyte) 가증가되지않는소구성빈혈 (microcytic anemia) 환자는철결핍빈혈가능성이높기때문에반드시철결핍을의심하여야한다. 그외성장기청소년, 임산부, 하지불안증후군 (restless leg syndrome), 만성신부전, 용혈빈혈, 출혈환자의경우는소구성빈혈이아니더라도철결핍을의심하여철관련검사를하는것이추천된다. 철관련검사는혈청페리틴 (serum ferritin), 혈청철 (serum iron), 총철결합능 (total iron binding capacity), 트랜스페린 (transferrin) 을포함하여야하며, 전형적인철결핍빈혈은혈청페리틴과혈청철이감소하면서총철결합능과트랜스페린은증가한다 (Table 1). 반면에감염이나염증, 만성신부전 Correspondence to Sung-Yong Kim, M.D., Ph.D. Division of Hematology/Oncology, Department of Internal Medicine, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea Tel: +82-2-2030-7539, Fax: +82-2-2030-7749, E-mail: sykim@kuh.ac.kr Copyright c 2017 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 155 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- The Korean Journal of Medicine: Vol. 92, No. 2, 2017 - Table 1. Laboratory tests for iron status Test Iron deficiency Functional iron deficiency Irondeficiency anemia Anemia of chronic disease IDA + ACD Normal value Serum iron, μmol/l Low Low-normal Low Low Low 10-30 Transferrin saturation, % 16 Low-normal < 16 Low-normal Low-normal 16-45 Ferritin, μg/l < 30 Normal < 10 > 100 < 100 40-300 in male 20-200 in female Hemoglobin, g/dl Normal Normal Low Low Low > 13 in man > 12 in woman MCV, fl Normal Normal < 80 Low-normal Low 80-95 stfr/log ferritin NA NA > 2 < 1 > 2 NA IDA, iron deficiency anemia; ACD, anemia of chronic disease; MCV, mean corpuscular volume; stfr, soluble transferrin receptor; NA, not applicable. 과같은질환에의한빈혈은혈청페리틴이정상또는상승하고총철결합능과트랜스페린은감소한다. 철결핍빈혈을진단하는데가장중요하고믿을만한검사는혈청페리틴이며, 감소된경우철결핍을진단하는데무리가없다. 하지만혈청페리틴이정상인경우철결핍빈혈의진단이어려워지는데, 페리틴은감염이나염증으로인해상승하는급성기반응물질 (acute phase reactant) 이기때문에철결핍이있더라도혈청페리틴이정상이거나상승할수있기때문이다. 따라서감염, 염증, 간질환, 심부전, 악성질환이있는경우나적혈구생성인자 (erythropoietin) 를투여중인만성신부전환자와같은기능적철결핍 (functional iron deficiency) 이있는경우는혈청페리틴이정상이더라도철결핍이없다고단정할수없어다른검사결과나임상적특징을살펴보고종합적으로판단할수밖에없다. 철결핍과만성질환빈혈 (anemia of chronic disease or inflammation) 과같은다른빈혈이동반되었을경우철결핍진단이어렵다. 철결핍의진단을위한첫번째방법으로는골수검사를통하여철염색 (iron stain) 을하여저장철의부족을확인하면진단할수있다. 확실하고정확한방법이지만실제로적용하는경우는많지않다. 두번째방법으로는보편화된검사는아니지만혈청트랜스페린수용체 (serum transferrin receptor) 를측정하여만성질환빈혈과감별을할수있다. 혈청트랜스페린수용체는적혈구생성능 (erythropoiesis) 을간접적으로시사하는검사로철결핍의경우증가하며만성질환빈혈에서는감소한다. 혈청트랜스페린수용체와페리틴결과를이용하여트랜스페린수용체-로그페리틴지수 (serum transferrin receptor-log ferritin index) 를계산하 면만성질환빈혈이있더라도철결핍빈혈이동반되어있다고판단할수있다 [3]. 세번째는트랜스페린포화도 (transferrin saturation) 와페리틴을이용한방법이다. 만성신질환환자의경우트랜스페린포화도가낮으면서 (< 30%) 혈청페리틴이 100 ng/ml 미만, 심부전환자의경우낮은트랜스페린포화도와혈청페리틴이 300 ng/ml 미만인경우철결핍빈혈이동반되었다고추정할수있다고하였다 [3-5]. 이세가지방법은시행하기어렵거나정확도가높지않기때문에현실적으로는철결핍의감별이매우어려우며임상적인판단이오히려중요하다. 원인규명을위한병력청취및검사철결핍빈혈은원인을교정하여야근본적인치료가되기때문에반드시원인을찾아야한다. 크게철소실, 철요구량증가, 철흡수장애로나뉘며, 성별및연령대에따라그원인들이달라이를고려하여병력청취와검사들을시행하여야한다 (Table 2). 남성환자와노인환자의철결핍빈혈의가장흔한원인은만성적인출혈로, 반드시위장출혈에관련된문진과내시경검사및대변잠혈검사를진행하여야한다. 만성출혈을시사하는위내시경소견으로는궤양, 미란, 혈관형성이상 (angiodysplasia) 과종양이고, 대장내시경소견으로는치질, 게실, 궤양, 혈관형성이상, 장염 ( 염증성장질환, 결핵성장염, 감염성장염등 ) 과종양이다. 대변잠혈검사는비용이적게들고, 비침습적일뿐아니라내시경에서접근하지못하는부위에서도출혈이있는지알수있고, 위염, 십이지장염과같은염증이단순한흡수장애외출혈을동반되고있는지도감별할 - 156 -
- Sung-Yong Kim. Iron deficiency anemia - Table 2. Causes of iron deficiency Cause Chronic blood loss Decreased absorption Drug-related Increased demand Example Gastointestinal tract: esophagitis, erosive gastritis, peptic ulcer, diverticulitis, cancer, inflammatory bowel diseases, angiodysplasia, hemorrhoids, obscure source Genitourinary system: menorrhagia, intravascular hemolysis (autoimmune hemolytic anemia, damaged heart valve, cold antibody, march hemoglobinuria, microangiopathic hemolysis) Systemic bleeding: hemorrhagic telangiectasia, self-induced hemorrhage Gastrectomy, duodenal bypass, bariatric surgery, Helicobacter pylori infection, atrophic gastritis, inflammatory bowel disease, congestive heart failure Glucocorticoids, aspirin, NSAIDs, proton-pump inhibitor Infancy, rapid growth (adolescence), menstrual blood loss, pregnancy (second and third trimesters), blood donation NSAIDs, non-steroidal anti-inflammatory drugs. 수도있는검사이기때문에매우유용하다. 철분약제복용시위양성이있다는주장이있으나철분복용때문이아니고출혈포커스를찾지못하는환자일확률이더높으니양성으로나온다면반드시위장관출혈검사를진행하는것이좋다. 주의할점은대변잠혈검사는위음성이있어한차례검사하는것보다는몇차례반복적으로검사를하여야한다. 약물관련병력, 특히출혈위험도를높이는항혈소판제, 스테로이드, 비스테로이드항염증제, 항응고제복용을반드시확인하여야한다. 이런약제를복용중인환자들중에는대변잠혈검사에서는양성으로나오지만여러번의위내시경및대장내시경검사를비롯하여캡슐내시경을하여도출혈포커스를결국찾지못하는경우가있다 (obscure source). 이런경우는경과관찰을하는수밖에없고빈혈이갑자기심해지면다시출혈위치를찾는반복적인노력을하여야한다. 주기적인월경을하고있는젊은여성의경우는모두내시경을할필요는없다. 대신만성적인출혈을시사하는증상및소화기증상에대해서문진하여, 필요시내시경및대변잠혈검사를한다. 특히젊은여성환자는치핵출혈과같은항문출혈을잘이야기하지않는경우가많기때문에문진에꼭포함하여야한다. 월경과다가있는경우산부인과진찰이필수적이다. 그외철소실은투석중혈액소실, 용혈을통한헤모글로빈소실그리고혈뇨가있다. 따라서투석환자, 용혈환자, 그리고혈뇨환자는철관련검사를진행하여야한다. 의심만한다면진단이어렵지않지만이런환자는소구성빈혈이아니기때문에철결핍빈혈동반을놓치기쉽다. 적혈구형성인자를투여하는환자의경우기능적철결핍이있기때문에적혈구형성인자치료반응이미진한경우혈청페리틴이낮 지않더라도주사철을투여하여야한다. 철소실과함께철결핍의중요한원인중하나는흡수장애이다. 흔히놓치기쉬운원인이기때문에정확하고자세한문진이필요하다. 먹는음식을통한철흡수를위해서는위산이필요하고철은주로십이지장에서흡수되기때문에위나십이지장에질환이있거나수술한경우흡수장애를초래할수있다. 흡수장애가의심되는내시경적소견으로는위염, 특히헬리코박터감염위염과위축성위염이있고, 위또는십이지장수술소견 ( 위절제술이나십이지장우회수술 ) 이있다. 만성위축성위염의원인이되며철흡수에필요한위산을억제하는위산분비억제약물복용이지속적으로있었는지물어보아야한다 [6]. 그외심부전환자의경우만성염증뿐아니라철흡수장애를동반하여철결핍이생긴다고보고되고있어심부전여부를파악하여야한다 [7,8]. 철함유음식섭취부족은노인과채식주의자에서철결핍빈혈을일으키는원인이되므로식생활에관한문진을잘하여야하고, 성장이빠른신생아및청소년기는생리적요구량에비해상대적인섭취부족이원인이되니전형적인빈혈증상이아닌피곤함, 이식증 (pica) 과같은비특이적인증상이있으면철결핍을의심하여혈색소및페리틴검사를진행하는것이바람직하다. Helicobacter pylori 감염과철결핍빈혈 Helicobacter pylori 감염은위장관출혈을일으키거나, 위산조성의변화를일으켜철의흡수를억제시키거나세균자체가철을직접이용하기때문에철결핍빈혈을일으킬수있다. 메타분석에의하면헬리코박터감염된환자는감염되지않은사람에비해철결핍빈혈위험도가 2.8배가된다고보고 - 157 -
- 대한내과학회지 : 제 92 권제 2 호통권제 675 호 2017 - 하였고 [9], 헬리코박터의제균이철흡수를올리고철결핍빈혈치료에도움이되며 [10], 경구철치료에불응환자에서헬리코박터제균치료를통해좋은치료효과를얻었다고하였다 [11-13]. 제균에의한철결핍빈혈의호전효과는특히빈혈이심한환자에서뚜렷하였다 [14,15]. 이러한연구결과들은철결핍빈혈환자에서헬리코박터감염을검사및제균요법이철결핍의치료및재발방지에도움이된다는것을시사하고있다. 저자의경험에의하면철보충없이제균요법만으로는철결핍개선이매우느리거나없기때문에철보충을같이시행하는것을추천한다. 철보충치료수혈철결핍환자의대부분은빈혈이심하지않고경구또는주사철투여에교정되기때문에수혈이필요하지않는다. 하지만생체징후가불안정한심부전, 심허혈, 호흡부전그리고혈압저하를보이는환자는주사철투여로도빈혈을빠르게교정시킬수없기때문에반드시수혈로서빈혈을개선시켜야한다. 단, 노인심부전환자의경우한꺼번에많은양의수혈은갑작스런체액증가를일으켜호흡부전을악화시키거나심정지를일으킬수있기때문에수혈속도에주의를하여야한다. 정맥주사치료 1954년첫주사철제제인 high molecular weight iron dextran (HMWID) 는출시된이후심각한부작용이종종보고되었다 [16,17]. Labile-free iron 때문에생기는과민반응으로발열및오한이생기고심한경우혈압이떨어져승압제까지투여해야하는경우였다. 따라서주사철투여는환자의활 력상태를모니터하면서응급상황에대처하는약품이반드시준비되어야만가능하였고, 철결핍개선효과는좋았지만이런과민반응으로인해주사철제제는경구제제를사용할수없는환자에서만투여되어왔다. 1991년더이상 HMWID 는만들어지지않게되고, low molecular weight iron dextran (LMWID) 이제조되기시작하였다. 이후 ferric gluconate와 iron sucrose 와같은부작용이적은다른종류의주사용철제제도생산되기시작하였다. 하지만여전히과거의경험으로인해주사철투여에두려움이많고, 정맥천자의편견때문에아직까지도경구투여보다는제한적으로사용되고있다. 현재사용되고있는주사철제제와국내에서판매되고있는주사는표 3과같다. LMWID 를포함한현재이용가능한주사철제제는안전하다는후속연구가발표되자, 경구철보다는더효과적이고, 매일장기간복용할필요가없고, 소화기부작용이거의없는주사철제제가유럽과미국에서는점차이용이확대되고있다. 특히경구약제부작용이있거나경구약제가효과가없는경우, 빠른철결핍빈혈개선이필요한경우, 만성신질환환자에서적혈구형성인자를투여하는경우가적응증이된다 (Table 4). 염증성장질환환자역시경구철에효과가없는경우가많고경구철에장의염증을악화시킬수도있다고발표가되어주사제제가일차약제로유럽에서권유되고있다 [18]. 그외경구철흡수가어려운십이지장의우회술이포함되거나경구철제제에소화기부작용이많은위수술을받은환자에서도적응증이된다. 최근산부인과영역에서도심한자궁출혈을보이는철결핍빈혈의경우경구철제제가철요구량을충족시킬수없기때문에보다효과적인주사제제가권유되고있다 [19]. 하지불안증후군 (restless leg syndrome) 에서도같은기간투여시주사철제제가효과적이고부작용도별로없었다고보고되었다 [20]. 항암치료를받 Table 3. Iron preparations for intravenous use Formulation Dose (infusion) Maximal dose (infusion) Ferric gluconate 125 mg (10-60 min) 250 mg (60 min) Iron sucrose 100-400 mg (2-90 min) 300 mg (2 hr) Iron dextran (LMW) 100 mg (2 min) 1,000 mg (1-4 hr) Ferumoxytol * 510 mg (> 1 min) 510-1,020 mg (15-60 min) Ferric carboxymaltose 750-1,000 mg (15-30 min) 750-1,000 mg (15-30 min) Iron isomaltoside 20 mg/kg (15 min) 20 mg/kg (15 min) LMW, low molecular weight. Ferumoxytol is not available in South Korea. - 158 -
- 김성용. 철결핍빈혈의진단과치료 - Table 4. Indications for parenteral iron therapy Established indication Failure of oral therapy Iron intolerance or with low iron levels that are refractory to treatment (e.g., after gastrectomy or duodenal bypass, with Helicobacter pylori infection, or with celiac disease, atrophic gastritis, inflammatory bowel disease, or genetically induced iron refractory iron deficiency anemia) Need for quick recovery (e.g., with severe iron deficiency in the second or third trimester of pregnancy or with chronic bleeding that is not manageable with oral iron, as may occur in patients with congenital coagulation disorders) Substitution for blood transfusions when not accepted by patient for religious reasons Use of erythropoiesis-stimulating agents in chronic kidney disease Potential indication Anemia of chronic kidney disease (without treatment of erythropoiesis-stimulating agents) Persistent anemia after use of erythropoiesis-stimulating agents in patients with cancer who are receiving chemotherapy Anemia of chronic disease unresponsive to treatment with erythropoiesis stimulating agents alone 는환자가철주사를맞는경우목표혈색소에더빠르게도달하였고, 적혈구형성촉진인자요구량도줄었다고보고하였다 [21]. 주사철의투여경로는정맥이다. 근육주사는현재더이상사용되지않는다. 근육주사시통증이있고, 투여된부위피부가착색이될수있으며, 투여부위의육종 (sarcoma) 발생이보고되었기때문이다. 정맥주사의가장흔한불편은정맥천자자체와투여반응 (infusion reaction) 이다. 급성부작용으로는오심, 구토, 두통, 홍조 (flushing), 근육통, 가려움증, 관절통, 흉부통, 등통증그리고저인산혈증 (hypophosphatemia) 이있으나모두일시적인부작용이며특별한조치없이사라지는것으로알려져있다. 우려되는과민반응 (hypersensitivity) 은매우드물지만 [22,23], 과민반응및사망이전혀없는것은아니다 [24]. 정맥주사를투여한경우감염에취약해진다는보고가있어감염기간동안주사치료는가능한피하는것으로권유되고있고 [25], 임신초기의안전성이연구되지못하였기때문에임신초기는피하는것이좋다. 또한철약제의과민반응과거력이있는경우금기이다 [26]. 철주사투여에과민반응및쇼크는 HMWID 에서보고되었고이후약제에는거의보고되지않고있으나각주사제제에따라권유되는주입속도와용량을지키는것이바람직하겠다 (Table 3). LMWID 의경우는주사투여후사망률이가장낮은것으로되어있으나 HMWID 와같이덱스트란이함유되어있기때문에시험투여 (test dose) 를권유하고있다 [24]. 주사철투여전항히스타민의선처치는오히려항히스타민자체가혈압을낮추는경우가있어철투여로인한과민반응으로오인되어불필요한처치및승압제투여까지될수있어권유하지않고있다 [27]. 주사철의총투여용량은빈혈을교정하기위한양과저장을위한양 (500-1,000 mg) 을더하여결정한다. 흔히사용하는계산식은 body weight in kilograms 2.3 hemoglobin deficiency (target hemoglobin level patient hemoglobin level) + 500 to 1,000 mg이다. 경구철은체내철이충분한경우흡수가거의되지않기때문에철과다가생기지않지만, 주사철은주입한양그대로체내에남게되므로필요이상투여시이차성혈색소증 (secondary hemochromatosis) 이생겨간부전, 심부전그리고내분비장애가생길수있으니혈청페리틴이 500 ng/ml (mcg/l) 를넘지않도록주의하여야한다. 경구치료경구철은대부분의철결핍빈혈환자의 1차치료선택이다. 가장좋은 (gold standard) 경구철은가격이싸고생체이용률 (bioavailability) 이높은 ferrous sulfate 이다. 다른경구철화합물로는 iron fumarate, iron gluconate, carbonyl iron 그리고 polysaccharide-iron complex 등이있다. 권장용량은철성분으로써 100-300 mg/day을 2-3차례나누어공복에복용한다. 처방시철성분 (elementary iron) 함량으로용량을계산하여야하며, 일부약제는국내보험급여용량대로처방하면투여해야할용량에미치지못하는경우도있으니확인하여야한다. 경구철약제는복용시철의산화성질로인하여위장관점막을자극하기때문에소화불량, 오심, 구토, 복통, 변비등의부작용이생길수있다. 한보고에의하면최대 70% 의환자에서위장관부작용이있다고하였다 [28]. 부작용은약용량과비례하니부작용이심하면감량할수있다. 공복복용시철의흡수가잘되지만위장관부작용도더잘생기므로위장관부작용이있다면식후또는식사와함께복용할 - 159 -
- The Korean Journal of Medicine: Vol. 92, No. 2, 2017 - 수도있다. 서방정약제는철이주로흡수되는십이지장을지나쳐흡수가잘되지않기때문에권유되지않고있지만상부위장부작용이적어사용되고있다 결 철결핍빈혈은가장흔히볼수있는빈혈로연령, 성별그리고과거수술력에따라원인이각각다르기때문에정확한문진과검사를통해원인을찾아서교정하는것이중요하다. 가임기여성의경우소화기증상이없으면내시경을반드시할필요는없지만그외의경우, 소화기출혈이가장흔한원인이기때문에내시경및대변잠혈검사를시행한다. 출혈이명확하지않은환자의경우흡수장애의원인이되는헬리코박터감염을확인하고제균하는것이치료및재발방지에도움이된다. 원인교정과함께철보충을해야한다. 경구치료는장기간의치료기간이필요하고소화기부작용이흔한반면, 정맥철투여는소화기부작용이없고, 짧은시간에철겹핍을교정시킬수있어적응증이되는환자에서는적극적으로사용하여야한다. 주사부작용은대부분일시적이지만권유되는용량, 투여속도그리고시험투여여부를잘지키는것이중요하다. 론 중심단어 : 철결핍빈혈 ; 진단 ; 치료 REFERENCES 1. Lee JO, Lee JH, Ahn S, et al. Prevalence and risk factors for iron deficiency anemia in the Korean population: results of the fifth KoreaNational Health and Nutrition Examination Survey. J Korean Med Sci 2014;29:224-229. 2. Auerbach M, Deloughery T. Single-dose intravenous iron for iron deficiency: a new paradigm. Hematology Am Soc Hematol Educ Program 2016;2016:57-66. 3. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011-1023. 4. Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436-2448. 5. Macdougall IC, Bock AH, Carrera F, et al. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant 2014;29:2075-2084. 6. Heidelbaugh JJ. Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications. Ther Adv Drug Saf 2013;4:125-133. 7. van Veldhuisen DJ, Anker SD, Ponikowski P, Macdougall IC. Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches. Nat Rev Cardiol 2011;8:485-493. 8. Cohen-Solal A, Damy T, Terbah M, et al. High prevalence of iron deficiency in patients with acute decompensated heart failure. Eur J Heart Fail 2014;16:984-991. 9. Muhsen K, Cohen D. Helicobacter pylori infection and iron stores: a systematic review and meta-analysis. Helicobacter 2008;13:323-340. 10. Ciacci C, Sabbatini F, Cavallaro R, et al. Helicobacter pylori impairs iron absorption in infected individuals. Dig Liver Dis 2004;36:455-460. 11. Choe YH, Kwon YS, Jung MK, Kang SK, Hwang TS, Hong YC. Helicobacter pylori-associated iron-deficiency anemia in adolescent female athletes. J Pediatr 2001;139:100-104. 12. Annibale B, Marignani M, Monarca B, et al. Reversal of iron deficiency anemia after Helicobacter pylori eradication in patients with asymptomatic gastritis. Ann Intern Med 1999;131:668-672. 13. Hershko C, Camaschella C. How I treat unexplained refractory iron deficiency anemia. Blood 2014;123:326-333. 14. Yuan W, Li Y, Yang K, et al. Iron deficiency anemia in Helicobacter pylori infection: meta-analysis of randomized controlled trials. Scand J Gastroenterol 2010;45:665-676. 15. Huang X, Qu X, Yan W, et al. Iron deficiency anaemia can be improved after eradication of Helicobacter pylori. Postgrad Med J 2010;86:272-278. 16. Wysowski DK, Swartz L, Borders-Hemphill BV, Goulding MR, Dormitzer C. Use of parenteral iron products and serious anaphylactic-type reactions. Am J Hematol 2010;85:650-654. 17. Hamstra RD, Block MH, Schocket AL. Intravenous iron dextran in clinical medicine. JAMA 1980;243:1726-1731. 18. Gasche C, Berstad A, Befrits R, et al. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis 2007;13:1545-1553. 19. Van Wyck DB, Mangione A, Morrison J, Hadley PE, Jehle JA, Goodnough LT. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion 2009;49:2719-2728. 20. Allen RP, Adler CH, Du W, Butcher A, Bregman DB, Earley CJ. Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Sleep Med 2011; 12:906-913. 21. Macdougall IC. Iron supplementation in nephrology and oncology: what do we have in common? Oncologist 2011;16-160 -
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