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Case report
Atypical hemolytic uremic syndrome: An unusual postoperative complication
Síndrome urémico hemolítico atípico: una complicación postoperatoria infrecuente
S. Mota
Corresponding author
jordana_mota_717@hotmail.com

Corresponding author.
, C. Filipe, A.L. Almeida
Departamento de Anestesiología, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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it can be subdivided into typical and atypical forms&#46; Typical HUS is a syndrome of thrombocytopenia&#44; renal dysfunction&#44; and microangiopathic haemolytic anaemia &#40;MAHA&#41; associated with Shiga toxin-producing <span class="elsevierStyleItalic">Escherichia coli</span>&#46; The atypical form is not related to Shiga toxins and accounts for around 5&#8211;10&#37; of all cases of HUS&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#8211;5</span></a> AHUS has a poorer prognosis&#44; with death rates as high as 25&#37; and progression to end-stage renal disease in half of all patients&#46; In the typical form&#44; in contrast&#44; 3&#37; of patients develop end-stage renal disease&#44; and 25&#37; present reduced renal function&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">AHUS is currently thought to be a consequence of dysregulation of the complement system associated with mutations causing excessive complement activation on the surface of the renal microvasculature&#46; However&#44; further environmental and possible genetic triggers are needed for disease presentation&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;5&#8211;7</span></a> Approximately 60&#37; of individuals with aHUS also have an inherited and&#47;or acquired abnormality affecting components of the complement pathway&#46; These include mutations of genes encoding complement regulators &#40;factor H&#44; factor I&#44; CD46 and thrombomodulin&#41; and&#47;or complement activators &#40;C3 and factor B&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;5&#44;7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We present the case of a patient presenting with MAHA&#44; and describe the differential diagnosis&#44; its therapeutic implications&#44; and follow-up&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Clinical case</span><p id="par0025" class="elsevierStylePara elsevierViewall">A 46-year-old female&#44; ASA II&#44; with a history of vertical sleeve gastrectomy without complications&#44; and trazodone 50<span class="elsevierStyleHsp" style=""></span>mg and alprazolam 0&#46;25<span class="elsevierStyleHsp" style=""></span>mg for depression&#44; was scheduled for pericystectomy for hydatid cyst of the liver&#46; The preoperative analytical workup was unremarkable&#44; except for slight normocytic normochromic anaemia &#40;haemoglobin 10&#46;2<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#41;&#46; This was not considered relevant for the present surgical indication&#44; and a study of its aetiology was postponed for after surgery&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Surgery lasted for 4<span class="elsevierStyleHsp" style=""></span>h and 30<span class="elsevierStyleHsp" style=""></span>min&#44; with no intraoperative complications or observations of note&#44; and the patient was transferred to the post-anaesthesia care unit&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In the immediate postoperative period&#44; she became oliguric&#44; with decreased urinary output in the following hours&#44; and dark urine&#46; She was calm&#44; cooperative&#44; hemodynamically stable&#44; and with no clinical signs of haemorrhage&#46; Seven hours later&#44; we noticed a progressive fall in haemoglobin levels &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Fluid therapy and blood transfusion were initiated&#46; Although the patient remained asymptomatic&#44; haemoglobin levels continued to decline&#46; When haemoglobin had fallen to below 7<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; 1 unit of packed red cells &#40;PRCs&#41; was administered &#40;between 7 and 8<span class="elsevierStyleHsp" style=""></span>h after surgery&#41;&#46; Given the persistent decline of haemoglobin &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; 3 more units were administered over a 17-h period from the end of surgery &#40;total 4 units&#41;&#46; No vasoactive drugs were needed&#46; Blood panels showed decreased platelet count&#44; increased creatinine values&#44; increased LDH&#44; and increased total bilirubin &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Coagulation studies were unremarkable&#46; Urine analysis showed bilirubinuria&#44; haemoglobinuria and proteinuria&#46; Peripheral blood smear showed schizocytes&#44; considered indicative of MAHA&#46; Abdominal and renal ultrasound were unremarkable&#46; The patient was asymptomatic&#44; in other words&#44; with no current or recent history of diarrhoea&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The surgical team denied intraoperative rupture of the hydatid cyst&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Given the coexistence of MAHA&#44; thrombocytopenia and acute renal failure&#44; aHUS was suspected&#44; and PEX was initiated as soon as possible &#40;within the first 24<span class="elsevierStyleHsp" style=""></span>h after surgery&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">After PEX was started&#44; there was no further need for PCRs&#46; Kidney function initially improved&#44; albeit only slightly&#44; in response to therapy&#44; but serum creatinine values remained high &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; She was admitted for continuing haemodialysis and PEX for 2 weeks&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Further studies of genetic mutations and immunological causes of MAHA were requested&#46; ADAMTS13 activity was normal&#46; Anti-ADAMTS13 antibody&#44; direct Coombs test&#44; anti-ds-DNA antibody&#44; anti-ANA antibody and anti-Scl70 antibody were negative&#44; all but ruling out a TTP or immunological cause &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46; HIV testing was negative&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Mutations in complement factor H &#40;CFH&#41; associated with factor H deficiency were detected&#58; c&#46;3172T&#62;C &#40;p&#46;Tyr1058His&#41; and c&#46;3178G&#62;C &#40;p&#46;Val1060Leu&#41;&#44; and polymorphisms &#40;p&#46;Gln1076Glu&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Creatinine values gradually decreased over the course of 30 days &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The patient was followed up by the nephrologist&#44; and after 6 months creatinine levels had normalised&#44; without returning to baseline values &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; After 3 years&#44; there was no worsening of renal function and no other complications were observed&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">AHUS appears to be a &#8220;two-hit&#8221; disease&#44; involving a presumed &#8220;trigger&#8221; that leads to inflammation and is thought to increase complement activation&#44; and a &#8220;second hit&#8221; that may involve an autoantibody or a genetic modifier&#46; Genetic mutations play a role in the pathogenesis of aHUS&#44; and more than 50&#37; of patients with aHUS have causative mutations in complement genes&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#8211;8</span></a> The pathogenesis appears to involve 3 stages&#58; a triggering event &#40;e&#46;g&#46; transplantation&#44; pregnancy&#44; etc&#46;&#41;&#59; activation of the complement cascade and&#47;or coagulation pathway&#44; leading to thrombus formation&#59; and a dysregulation loop&#44; with complement overactivation&#44; which leads to thrombi formation&#46; Altered function of the coagulation pathway may be caused by genetic variants in coagulation genes&#44; leading to enhanced formation or decreased degradation of thrombi&#44; promoting thrombosis leading to activation of the complement system&#46; Genetic variants in complement genes and&#47;or acquired factors&#44; such as CFH autoantibodies&#44; lead to inadequate&#47;ineffective complement regulation&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">After reviewing several previous case reports&#44; we hypothesize that any surgery could act as a &#8220;trigger&#8221;&#46; In 2013&#44; a case of aHUS was reported after laparoscopic hemicolectomy&#46; According to the authors&#44; after the case of postoperative HUS in a child reported by Maki in 1968&#44; only posttransplant HUS cases have been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> In 2013&#44; an anaesthetist reported a case of HUS after orthopaedic surgery&#44; but in a patient with a 2-week history of diarrhoea and confusion&#44; which therefore may not exclude &#8220;typical&#8221; HUS&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In 2014&#44; a C3 mutation was discovered in a patient who presented aHUS after correction of Fallot tetralogy&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> In 2016&#44; a patient undergoing myomectomy also presented aHUS&#44; which was treated with eculizumab&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; this is the second case of post-surgery non-transplant aHUS with a reported mutation&#44; in this case&#44; in CFH&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Although it is a rare postoperative complication&#44; aHUS should be considered as a possible cause of MAHA &#40;with haemoglobin &#60;10<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; increased LDH&#44; and presence of fragmented red cells in peripheral smear&#41; and acute kidney injury after surgical procedures associated with thrombocytopenia &#40;platelets &#60;150&#44;000&#47;&#956;L&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;5&#44;7</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">PEX is the first-line treatment for aHUS in adults&#44; and should be started within 24<span class="elsevierStyleHsp" style=""></span>hours of diagnosis&#44; with supportive treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a> The objectives are to replace mutant elements of the complement with normal elements in order to eliminate pro-inflammatory and thrombogenic factors responsible for symptoms&#44; and to preserve renal function&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;4</span></a> Only 1 or 2 plasma volumes should be exchanged per day&#44; or 20&#8211;30<span class="elsevierStyleHsp" style=""></span>ml&#47;kg of body weight can be infused once a day in the first week and then progressively tapered from 5 to 3 sessions per week&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Some patients who respond to PEX may need long-term therapy to maintain remission&#46; Some of these together with non-responders have been selected for clinical trials&#44; for instance&#44; with monoclonal therapy &#40;eculizumab &#8211; anti-C5 monoclonal antibody&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a> Some authors claim that this could be the new gold standard therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Patients with a pathogenic complement gene mutation are potentially at risk of disease recurrence&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">After 3 years of follow-up&#44; end-stage renal disease or death occurs in &#62;50&#37; of aHUS patients&#44; with or without plasma-based therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In our patient&#44; presumptive diagnosis of aHUS was made&#44; and PEX was initiated before the genetic defect was found&#46; PEX was suspended on the 15th postoperative day&#44; and the patient was clinically and analytically monitored&#46; The patient has been kept under observation&#44; with no specific therapy&#44; for 3 years to date&#44; with normal &#40;but not baseline&#41; creatinine levels&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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          "identificador" => "xres1042064"
          "titulo" => "Abstract"
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              "identificador" => "abst0005"
              "titulo" => "Introduction and objectives"
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              "identificador" => "abst0010"
              "titulo" => "Clinical case"
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              "identificador" => "abst0015"
              "titulo" => "Conclusion"
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          "identificador" => "xpalclavsec994824"
          "titulo" => "Keywords"
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          "titulo" => "Resumen"
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            0 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Introducci&#243;n y objetivos"
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            1 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Caso cl&#237;nico"
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            2 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Conclusi&#243;n"
            ]
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        3 => array:2 [
          "identificador" => "xpalclavsec994823"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Clinical case"
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        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Discussion"
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        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Conflicts of interest"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2017-10-17"
    "fechaAceptado" => "2017-12-19"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec994824"
          "palabras" => array:4 [
            0 => "Atypical haemolytic uremic syndrome"
            1 => "Complement factor H"
            2 => "Postoperative period"
            3 => "Plasma exchange"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec994823"
          "palabras" => array:4 [
            0 => "S&#237;ndrome ur&#233;mico hemol&#237;tico at&#237;pico"
            1 => "Factor H del complemento"
            2 => "Periodo postoperatorio"
            3 => "Intercambio de plasma"
          ]
        ]
      ]
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    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Thrombotic thrombocytopenic purpura and atypical haemolytic uremic syndrome &#40;aHUS&#41; are acute&#44; rare&#44; life-threatening thrombotic microangiopathies that require swift management&#46; We report a case of acute microangiopathic haemolytic anaemia &#40;MAHA&#41; presenting in perioperative setting&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Clinical case</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">After hepatic pericystectomy for hydatid cyst&#44; a 46-year-old female developed MAHA&#44; thrombocytopenia and acute renal failure in the immediate postoperative period&#46; &#8220;aHUS&#8221; was considered and immediate plasma exchange was initiated&#46; Plasma exchange was performed for 2 weeks with remission of renal dysfunction&#46; Further evaluation of genetic mutations and immunological causes for MAHA were sought&#46; Mutations in complement factor H associated with factor H deficiency were identified&#44; which are associated with increased risk of aHUS&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conclusion</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">MAHA is a rare postoperative condition&#44; requiring rapid differential diagnosis and treatment&#46; Anaesthetists should bear in mind aHUS as a possible cause of MAHA&#44; especially concerning immediate care for these patients&#46;</p></span>"
        "secciones" => array:3 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Clinical case"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Conclusion"
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      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introducci&#243;n y objetivos</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La p&#250;rpura trombocitop&#233;nica tromb&#243;tica y el s&#237;ndrome ur&#233;mico hemol&#237;tico at&#237;pico &#40;SHUa&#41; son microangiopat&#237;as tromb&#243;ticas agudas&#44; infrecuentes y potencialmente fatales que requieren una gesti&#243;n r&#225;pida&#46; Reportamos un caso de anemia hemol&#237;tica microangiop&#225;tica aguda &#40;MAHA&#41; que se present&#243; en el entorno perioperatorio&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Caso cl&#237;nico</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Tras la realizaci&#243;n de periquistectom&#237;a hep&#225;tica debida a quiste hidat&#237;dico&#44; una mujer de 46 a&#241;os desarroll&#243; MAHA&#44; trombocitopenia e insuficiencia renal aguda durante el periodo postoperatorio inmediato&#46; Se consider&#243; la posibilidad de SHUa&#44; inici&#225;ndose intercambio de plasma inmediato&#46; Se realiz&#243; intercambio de plasma durante 2 semanas&#44; con remisi&#243;n de la disfunci&#243;n renal&#46; Posteriormente se evaluaron las mutaciones gen&#233;ticas y las causas inmunol&#243;gicas de MAHA&#46; Se identificaron mutaciones en el factor H del complemento asociadas a deficiencia del factor H&#44; que est&#225;n asociadas a un incremento del riesgo de SHUa&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusi&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">MAHA constituye una situaci&#243;n postoperatoria infrecuente&#44; que requiere un r&#225;pido diagn&#243;stico diferencial y tratamiento&#46; Los anestesi&#243;logos deber&#225;n considerar el SHUa como causa posible de MAHA&#44; especialmente en lo referente al cuidado inmediato de estos pacientes&#46;</p></span>"
        "secciones" => array:3 [
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            "titulo" => "Introducci&#243;n y objetivos"
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          1 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Caso cl&#237;nico"
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            "identificador" => "abst0030"
            "titulo" => "Conclusi&#243;n"
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    "NotaPie" => array:1 [
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mota S&#44; Filipe C&#44; Almeida AL&#46; S&#237;ndrome ur&#233;mico hemol&#237;tico at&#237;pico&#58; una complicaci&#243;n postoperatoria infrecuente&#46; Rev Esp Anestesiol Reanim&#46; 2018&#59;65&#58;351&#8211;355&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Differential diagnosis of microangiopathic haemolytic anaemia &#40;MAHA&#41;&#46; <span class="elsevierStyleItalic">Abbreviations</span>&#58; aHUS&#44; atypical haemolytic uremic syndrome&#59; CFH&#44; complement factor H&#59; TTP&#44; thrombotic thrombocytopenic purpura&#46;</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">BUN&#58; Blood urea nitrogen&#59; LDH&#58; lactic dehydrogenase&#46;</p>"
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                  \t\t\t\t</th><th class="td" title="table-head  " colspan="12" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Time</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Preoperative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="11" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Postoperative</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Immediate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">7<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">9<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">17<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">7 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">15 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 month&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 year&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="13" align="left" valign="top"><span class="elsevierStyleItalic">Blood panels</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Haemoglobin &#40;12&#8211;15<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Haematocrit &#40;36&#8211;46&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Platelets &#40;150&#8211;400<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">362&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">271&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">115&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">234&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">366&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">313&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">224&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">214&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">202&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">210&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BUN &#40;7&#46;9&#8211;20&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Creatinine &#40;0&#46;55&#8211;1&#46;02<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>LDH &#40;&#60;247<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">181&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">527&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2395&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2203&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2534&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">336&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">307&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">187&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">140&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">143&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">172&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total bilirubin &#40;0&#46;3&#8211;1&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                          "etal" => true
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                            2 => "Y&#46; Iwata"
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                      "doi" => "10.1155/2014/784943"
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                          "etal" => true
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                            0 => "F&#46; Bu"
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                            2 => "N&#46;C&#46; Meyer"
                            3 => "K&#46; Wang"
                            4 => "C&#46;P&#46; Thomas"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2013050453"
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                        "tituloSerie" => "J Am Soc Nephrol"
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                            0 => "R&#46;A&#46; Brodsky"
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                    0 => array:2 [
                      "doi" => "10.1182/blood-2015-06-640995"
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                        "tituloSerie" => "Blood"
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                        "paginaInicial" => "2459"
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ISSN: 23411929
Original language: English
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es en pt

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