hemolytic uremic syndrome ( hus ) is a common cause of acute renal injury in young children . it is characterized by microangiopathic hemolytic anemia , thrombocytopenia , and acute renal injury1 ) . the etiology of hus is variable , including infection , genetic disorder , medication , and other systemic diseases , of which infection is the most common cause of the disease1 ) . most cases of diarrhea - associated hus ( d(+ ) hus ) are caused by shiga toxin - producing bacteria , such as shiga toxin - producing escherichia coli ( stec ) with serotype o157 , o111 , or o2612 ) . patients with hus require careful supportive care , including management of fluid and serum electrolyte balance , control of hypertension , and early dialysis in anuric or significantly oliguric states2 ) . however , there are no specific recommended therapies to ameliorate the course of the disease . in addition , it has been reported that erythropoietin synthesis is reduced in patients with hus , contributing to aggravation of the anemia3 ) . therefore , hus with anemia is the standard indication for rbc transfusion to avoid cardiac or pulmonary complications . about 80% of patients with hus require packed rbc transfusion4 ) . here , we report a case of a male child with severe hemolytic anemia due to diarrhea - associated hus , whose parents refused packed rbc transfusion because they are jehovah 's witnesses . instead of packed rbc transfusion , we treated him with rhuepo with iron , folic acid , and vitamin b12 supplements . a 31-month - old male was transferred from a local children 's hospital to yeungnam university medical center in daegu , korea . for 3 days before transfer , he had been admitted to a local children 's hospital for fever , abdominal pain , and bloody diarrhea . based on suspected bacterial colitis , he received intravenous third - generation cephalosporin medication for empirical treatment , but the symptoms did not improve . at the time of admission , the patient was treated with fluid management and antibiotics management based on a diagnosis of colitis with dehydration . initial laboratory investigation revealed leukocytosis ( white blood cell , 17,760/l ) , normal hemoglobin level ( hb , 13.3 g / dl ) , platelet count of 15010/l , blood urea nitrogen ( bun ) level of 11.01 mg / dl , and increased serum creatinine ( cr ) level of 0.85 mg / dl . abdominal computed tomography revealed pancolitis and small amount of ascites and pleural effusion , and there was no evidence of a condition that required surgical treatment . the patient still presented with an ill and lethargic appearance and a large amount of bloody diarrhea on the second day of admission . follow - up laboratory tests showed decreased hemoglobin level of 11.9 g / dl , thrombocytopenia ( platelet count 4010/l ) and decreased renal function with a serum cr level of 1.86 mg / dl . estimated cr clearance was 28.5 ml / min/1.73 m and fractional na excretion was 2.2% implying intrinsic renal failure . hemolytic markers showed a raised reticulocyte level of 3.12 % , raised lactate dehydrogenase of 1,448 u / l , and reduced haptoglobin level of 3 mg / dl ( normal range , 22164 mg / dl ) . schistocytes and blurred cells were observed in peripheral blood smear , suggestive of microangiopathic hemolytic anemia ( fig . 1 ) . a diagnosis of diarrhea - associated hus was made , and the patient received careful supportive treatment with no further antibiotics . on the third day , the oliguric state persisted with rapidly increased bun and serum cr level to 40.3 mg / dl and 3.93 mg / dl , respectively . however , the patient 's parents refused transfusion of any blood products , including packed rbc , because they were jehovah 's witnesses . hemodialysis was performed with a priming process using 20% albumin on days 3 and 4 with the parents ' consent . as the anemia progressed , we were unable to perform hemodialysis due to concerns about further blood loss and hypovolemia . the hemoglobin level decreased to 3.6 g / dl at the lowest on day 9 . eventually , we used high - dose rhuepo therapy to manage the severe anemia . erythropoietin  ( recormon , roche , basel , switzerland ) was administered at a dose of 300 iu / kg / day for the first five consecutive days , after which the same dose was administered every other day . in addition , intravenous iron ( 3 mg / kg / day , daily ) , folic acid ( 1 mg / day , daily ) , and vitamin b12 ( 1 mg / day , daily ) were given together . the hb level increased steadily and was normalized 1 week after discharge ( hb , 12.1 g / dl ) ( fig . , the serum cr level and the results of urinalysis recovered to the normal range . during high - dose rhuepo therapy , the patient showed stable vital signs . common adverse events related to rhuepo therapy , such as flu - like symptoms , hypertension , thrombocytosis , thrombosis , allergic reaction , or seizure , were not observed in this case . echocardiography revealed mild left atrial enlargement and mild left ventricular hypertrophy but normal ventricular function . initial stool culture on sorbitol - containing macconkey agar detected enterohemorrhagic e. coli serotype o26 and polymerase chain reaction specific for shiga toxin ( stx1 and stx2 ) was positive . patients with d(+ ) hus require careful supportive care . the volume status of patients should be monitored carefully to avoid fluid overload or depletion , especially in cases with vomiting , diarrhea , and decreased oral intake5 ) . maintaining renal perfusion and avoiding fluid overload oliguric patients , the indications for dialysis are similar to those in other forms of acute kidney injury , and early dialysis can be helpful . the patients can rapidly become profoundly anemic as a consequence of rbc hemolysis and inadequate erythropoietin synthesis3 ) . platelet transfusion is not recommended unless life - threatening hemorrhage occurs , or an invasive procedure is undertaken , because platelet transfusion can exacerbate thrombosis6 ) . studies of the use of steroids , antithrombotic agents ( aspirin , heparin , dipyridamole , and streptokinase ) , plasma infusion , plasma exchange , or synsorb - pk in hus patients have been reported ; however , none showed a significant treatment benefit7 ) . in addition , antibiotic therapy is discouraged in stec - infected patients , because it is known to have little benefit and to increase the risk of d(+ ) hus2 ) . jehovah 's witnesses decline therapeutic transfusion of the primary components of human blood based on their religious beliefs . these include stopping further blood loss , stimulating erythropoiesis using rhuepo , maintaining blood volume with intravenous fluids , and other forms of supportive care8 ) . clinical trials using bioartificial oxygen carriers , especially hemoglobin - based oxygen carriers , are currently ongoing9 ) . erythropoietin and its analogs are widely used for anemia in patients with chronic kidney disease and patients who receive chemotherapy . a previous study showed a consistent rise in reticulocyte count within 45 days and increased hemoglobin level and hematocrit within 7 days on treatment with rhuepo10 ) . the optimal dose and dosing regimens are unclear , especially in critically ill patients with severe blood loss or those with severe acute anemia who refuse transfusion . there have been reports of cases in which severe anemia was successfully treated with erythropoietin in patients who refused blood transfusion . however , such cases in children are rare , and in most of these cases anemia was caused by hemorrhage due to trauma or related to surgical procedures1112 ) . in our case , we referred the report from digieri et al.11 ) for the dose of rhuepo ( 300 iu / kg / day ) . to keep up with enhanced erythropoiesis , iron , folate , and vitamin b12 , erythropoietin is known to exert a renoprotective effect by suppressing renal tubular epithelial apoptosis , enhancing epithelial proliferation and hastening functional recovery in ischemic or drug - induced acute kidney injury13 ) . pape et al.14 ) reported that early administration of erythropoietin may attenuate anemia and reduce the requirement for rbc transfusion if administered early in the course of hemolytic anemia and renal failure in d(+ ) hus patients . however , a recent study showed that rhuepo therapy had no rbc transfusion - sparing effect in d(+ ) hus patients15 ) . therefore , further studies are needed to clarify the efficacy of rhuepo in d(+ ) hus . here , we reported the first case of successful rhuepo therapy in a jehovah 's witness child with severe anemia due to d(+ ) hus without rbc transfusion . in summary , rhuepo therapy can be effective in acute anemia due to d(+ ) hus , especially in patients in whom rbc transfusion is not possible . in addition to enhancing rbc production , a renoprotective effect of rhuepo therapy can be expected in patients with d(+ ) hus .
patients with hemolytic - uremic syndrome ( hus ) can rapidly develop profound anemia as the disease progresses , as a consequence of red blood cell ( rbc ) hemolysis and inadequate erythropoietin synthesis . 
 therefore , rbc transfusion should be considered in hus patients with severe anemia to avoid cardiac or pulmonary complications . 
 most patients who are jehovah 's witnesses refuse blood transfusion , even in the face of life - threatening medical conditions due to their religious convictions . these patients require management alternatives to blood transfusions . 
 erythropoietin is a glycopeptide that enhances endogenous erythropoiesis in the bone marrow . with the availability of recombinant human erythropoietin ( rhuepo ) , 
 several authors have reported its successful use in patients refusing blood transfusion . however , the optimal dose and duration of treatment with rhuepo are not established . 
 we report a case of a 2-year - old boy with diarrhea - associated hus whose family members are jehovah 's witnesses . 
 he had severe anemia with acute kidney injury . 
 his lowest hemoglobin level was 3.6 g / dl , but his parents refused treatment with packed rbc transfusion due to their religious beliefs . 
 therefore , we treated him with high - dose rhuepo ( 300 iu / kg / day ) as well as folic acid , vitamin b12 , and intravenous iron . 
 the hemoglobin level increased steadily to 7.4 g / dl after 10 days of treatment and his renal function improved without any complications . to our knowledge , this is the first case of successful rhuepo treatment in a jehovah 's witness child with severe anemia due to hus .