View source for Hemolytic–Uremic Syndrome

<p><span style="color: #000000"><b>Hemolytic-uremic syndrome</b> (or <b>haemolytic-uraemic syndrome</b>), abbreviated <b>HUS</b>, is a disease characterized by hemolytic anemia, acute renal failure (uremia) and a low platelet count (thrombocytopenia). It predominantly but not exclusively affects children. Most cases are preceded by an episode of diarrhea caused by <i>E. coli</i> O157:H7, which is acquired as a foodborne illness. It is a medical emergency and carries a 5&ndash;10% mortality; of the remainder, the majority recover without major consequences but a small proportion develop chronic kidney disease and become reliant on renal replacement therapy.<sup id="cite_ref-pmid11691946_0-0" class="reference"><font size="2">[1]</font></sup> HUS was first defined as a syndrome in 1955.<sup id="cite_ref-pmid1816053_1-0" class="reference"><font size="2">[2]</font></sup><sup id="cite_ref-pmid13274004_2-0" class="reference"><font size="2">[3]</font></sup></span></p>
<p>&nbsp;</p>
<h2><span style="color: #000000"><span id="Signs_and_symptoms" class="mw-headline">Signs and symptoms</span></span></h2>
<h3><span style="color: #000000"><span id="In_children" class="mw-headline">In children</span></span></h3>
<p><span style="color: #000000">HUS is one of the thrombotic microangiopathies, a category of disorders that includes thrombotic thrombocytopenic purpura (TTP).</span></p>
<p><span style="color: #000000">The classic childhood case of HUS occurs after bloody diarrhea caused by a strain of <i>E. coli</i> that expresses verotoxin (also called shiga-like toxin) which is known as shiga toxin-producing <i>E. coli</i> (STEC) or enterohemorrhagic <i>E. coli</i> (EHEC). HUS follows an influenza-like or gastrointestinal (GI) prodrome with bleeding manifestations (especially hematemesis and melena), severe oliguria, hematuria, a microangiopathic hemolytic anemia, and (in some patients) prominent neurologic changes.<sup id="cite_ref-ReferenceA_3-0" class="reference"><font size="2">[4]</font></sup></span></p>
<p><span style="color: #000000">A somewhat less common form of HUS (~10% of cases) does not follow STEC infection and is thought to result from factor H deficiency (a complement regulatory protein) that results in uncontrolled complement activation after minor endothelial injury resulting in thrombosis.<sup id="cite_ref-4" class="reference"><font size="2">[5]</font></sup></span></p>
<p><span style="color: #000000">In the classical form (90% of cases), the STEC toxin enters the bloodstream and causes damage to the body's vascular endothelium. This is especially damaging to the kidney, where the toxin attaches to the glomerular endothelium and initiates a noninflammatory reaction leading to acute renal failure. Moreover, the generalized endothelial damage leads to platelet activation that causes thrombocytopenia (low platelet count). The renal glomerular endothelial cells express a receptor for the toxin. <sup id="cite_ref-5" class="reference"><font size="2">[6]</font></sup></span></p>
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<div style="width: 222px" class="thumbinner"><span style="color: #000000"><font size="2"><img class="thumbimage" alt="" width="220" height="182" src="http://upload.wikimedia.org/wikipedia/commons/thumb/3/3e/Shiga_toxin_type_2_%28Stx2%29_from_from_Escherichia_coli_O157-H7_PDB_1r4p.png/220px-Shiga_toxin_type_2_%28Stx2%29_from_from_Escherichia_coli_O157-H7_PDB_1r4p.png" /></font></span>
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<div class="magnify"><span style="color: #000000"><font size="2"><img alt="" width="15" height="11" src="http://bits.wikimedia.org/skins-1.17/common/images/magnify-clip.png" /></font></span></div>
<span style="color: #000000">Shiga-like toxin 2 (Stx2) from <i>Escherichia coli</i> O157:H7. From PDB 1R4P.</span></div>
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<p><span style="color: #000000">The typical pathophysiology involves the shiga-toxin binding to proteins on the surface of glomerular endothelium and inactivating a metalloproteinase called ADAMTS13, which is also involved in the closely-related thrombotic thrombocytopenic purpura (TTP).<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup> Once the ADAMTS13 is disabled, multimers of von Willebrand Factor (vWF) form and initiate platelet activation and cause microthrombi formation.<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup> The arterioles and capillaries of the body become obstructed by the resulting complexes of activated platelets which have adhered to endothelium via large multimeric vWF. The growing thrombi lodged in smaller vessels destroy red blood cells (RBCs) as they squeeze through the narrowed blood vessels, forming schistocytes, or fragments of sheared RBCs. This mechanism, known as microangiopathic hemolysis,<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup> has been likened to the effect of a cheesewire or garotte across the vessel lumen. The presence of schistocytes is a key finding that helps to diagnose HUS.<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup></span></p>
<p><span style="color: #000000">The consumption of platelets as they adhere to the thrombi lodged in the small vessels can lead to severe thrombocytopenia.<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup></span></p>
<p><span style="color: #000000">As in the related condition TTP, reduced blood flow through the narrowed blood vessels of the microvasculature leads to reduced blood flow to vital organs, and ischemia may develop.<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup> The kidneys and the central nervous system (brain and spinal cord) are the parts of the body most critically dependent on high blood flow, thus they are the most likely organs to be affected. However, in comparison to TTP, the kidneys tend to be more severely affected in HUS, and the central nervous system is less commonly affected.<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup></span></p>
<p><span style="color: #000000">In contrast with typical disseminated intravascular coagulation seen with other causes of septicemia and occasionally with advanced cancer, coagulation factors are not consumed in HUS (or TTP) and the coagulation screen, fibrinogen level, and assays for fibrin degradation products such as &quot;D-Dimers&quot;, are generally normal despite the low platelet count (thrombocytopenia).<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup></span></p>
<p><span style="color: #000000">HUS occurs after 2-7% of all <i>E. coli</i> O157:H7 infections<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from May 2010"><font size="2">[<i>citation needed</i>]</font></sup>. Children and adolescents are commonly affected.<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup> Grossly, the kidneys may show patchy or diffuse renal cortical necrosis. Histologically, the glomeruli show thickened and sometimes split capillary walls due largely to endothelial swelling. Large deposits of fibrin-related materials in the capillary lumens, subendothelially, and in the mesangium are also found along with mesangiolysis. Interlobular and afferent arterioles show fibrinoid necrosis and intimal hyperplasia and are often occluded by thrombi.<sup id="cite_ref-ReferenceA_3-1" class="reference"><font size="2">[4]</font></sup></span></p>
<h3><span style="color: #000000"><span id="In_adults" class="mw-headline">In adults</span></span></h3>
<p><span style="color: #000000">Adult HUS has similar symptoms and pathology, but is an uncommon outcome of the following: HIV; antiphospholipid syndrome (associated with lupus erythematosus and generalized hypercoagulability); postpartum renal failure; malignant hypertension; scleroderma; and certain drugs, including some chemotherapy drugs and other immunosuppressive agents (mitomycin, ciclosporin, cisplatin and bleomycin).</span></p>
<h3><span style="color: #000000"><span id="Atypical_cases" class="mw-headline">Atypical cases</span></span></h3>
<p><span style="color: #000000">A third category is referred to as familial HUS or atypical HUS (aHUS).</span></p>
<p><span style="color: #000000">It represents 5-10% of HUS cases<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from November 2008"><font size="2">[<i>citation needed</i>]</font></sup> and is largely due to mutations in the complement proteins factor H, membrane cofactor protein and factor I<sup id="cite_ref-pmid15661753_6-0" class="reference"><font size="2">[7]</font></sup> leading to uncontrolled complement system activation.</span></p>
<p><span style="color: #000000">Recurrent thromboses result in a high mortality rate.</span></p>
<p><span style="color: #000000">Most reported HUS cases during the 2011 Escherichia coli O104:H4 outbreak were atypical cases.</span></p>
<h2><span style="color: #000000"><span id="Diagnosis" class="mw-headline">Diagnosis</span></span></h2>
<p><span style="color: #000000">Clinically, HUS can be very hard to distinguish from thrombotic thrombocytopenic purpura. The laboratory features are almost identical, and not every case of HUS is preceded by diarrhea. HUS is characterized by the triad of hemolytic anemia, thrombocytopenia, and acute renal failure. The only distinguishing feature is that in TTP, fever and neurological symptoms are often present; but this is not always the case. A pericardial friction rub can also sometimes be heard on auscultation (uremic pericarditis). The two conditions are sometimes treated as a single entity called TTP/HUS.<sup id="cite_ref-pmid12544708_7-0" class="reference"><font size="2">[8]</font></sup><sup id="cite_ref-pmid11604563_8-0" class="reference"><font size="2">[9]</font></sup> However, some dispute this grouping, and TTP is now known to be caused by an acquired defect in the protein ADAMTS13.<sup id="cite_ref-pmid12823037_9-0" class="reference"><font size="2">[10]</font></sup></span></p>
<h2><span style="color: #000000"><span id="Treatment" class="mw-headline">Treatment</span></span></h2>
<p>&nbsp;</p>
<p><span style="color: #000000">Antibiotic treatment of <i>E. coli</i> O157:H7 colitis may stimulate further verotoxin production and thereby increase the risk of HUS.<sup id="cite_ref-10" class="reference"><font size="2">[11]</font></sup><sup id="cite_ref-pmid16918877_11-0" class="reference"><font size="2">[12]</font></sup></span></p>
<p><span style="color: #000000">Treatment is generally supportive, with dialysis as needed. Untreated HUS in adults, however, may progress to end-stage organ damage. Platelet transfusion may actually worsen the outcome.</span></p>
<p><span style="color: #000000">Since 2010, eculizumab has been used experimentally in the treatment of HUS, following approval from the European Medicines Agency in 2007.<sup style="white-space: nowrap" class="Template-Fact" title="This claim needs references to reliable sources from June 2011"><font size="2">[<i>citation needed</i>]</font></sup></span></p>
<p><span style="color: #000000">In most children with postdiarrheal HUS, there is a good chance of spontaneous resolution, so observation in a hospital is often all that is necessary, with supportive care such as hemodialysis where indicated. In children with neurological or other nonrenal involvement, and in adult cases, particularly when there is diagnostic uncertainty between HUS and TTP, plasmapheresis (plasma exchange) is the treatment of choice. This is generally performed daily until the platelet count is normal, using fresh frozen plasma as the replacement fluid for the patient's plasma which is removed. Plasmapheresis may reverse the ongoing platelet consumption.</span></p>
<h2><span style="color: #000000"><span id="Prognosis" class="mw-headline">Prognosis</span></span></h2>
<p><span style="color: #000000">With aggressive treatment, more than 90% survive the acute phase. About 9% may develop end stage renal disease. About one-third of persons with HUS have abnormal kidney function many years later, and a few require long-term dialysis. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizures, blindness, paralysis, and the effects of having part of their colon removed. The overall mortality rate from HUS is 5-15%. Children and the elderly have a worse prognosis.<sup id="cite_ref-12" class="reference"><font size="2">[13]</font></sup></span></p>
<h2><span style="color: #000000"><span id="Epidemiology" class="mw-headline">Epidemiology</span></span></h2>
<p><span style="color: #000000">HUS has a peak incidence between six months and four years of age.<sup id="cite_ref-pmid11691946_0-1" class="reference"><font size="2">[1]</font></sup></span></p>
<p><span style="color: #000000">HUS and the <i>E. coli</i> infections which caused it have been the source of much negative publicity for the Food and Drug Administration (FDA), meat industries, and fast-food restaurants since the 1990s, especially in the Jack in the Box contaminations. It was also featured in the Robin Cook novel <i>Toxin</i>. In 2006, an epidemic of harmful <i>E. coli</i> emerged in the United States due to contaminated spinach. The known cases have been reported at 183, including 29 cases of HUS. In June, 2009, Nestle Toll House cookie dough was linked to an outbreak of E. coli 0157:H7 in the United States, which sickened 70 people in 30 states.[1]</span></p>
<p><span style="color: #000000">At least 18 people died presumably from hemolytic-uremic syndrome in the 2011 E. coli O104:H4 outbreak in Europe.<sup id="cite_ref-13" class="reference"><font size="2">[14]</font></sup></span></p>
<h2><span style="color: #000000"><span id="See_also" class="mw-headline">See also</span></span></h2>
<ul>
    <li><span style="color: #000000">Shigellosis</span></li>
    <li><span style="color: #000000">Microangiopathic hemolytic anemia</span></li>
</ul>
<h2><span id="References" class="mw-headline">References</span></h2>
<div style="list-style-type: decimal; -moz-column-count: 2; -webkit-column-count: 2; column-count: 2" class="reflist references-column-count references-column-count-2">
<ol class="references">
    <li id="cite_note-pmid11691946-0">^ <a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-pmid11691946_0-0"><sup><i><b><font color="#0645ad" size="1">a</font></b></i></sup></a> <a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-pmid11691946_0-1"><sup><i><b><font color="#0645ad" size="1">b</font></b></i></sup></a> <span class="citation Journal">Corrigan JJ, Boineau FG (November 2001). &quot;Hemolytic-uremic syndrome&quot;. <i>Pediatr Rev</i> <b>22</b> (11): 365&ndash;9. <a class="mw-redirect" title="PubMed Identifier" href="http://en.wikipedia.org/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a> <a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/11691946"><font color="#3366bb">11691946</font></a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Hemolytic-uremic+syndrome&amp;rft.jtitle=Pediatr+Rev&amp;rft.aulast=Corrigan+JJ%2C+Boineau+FG&amp;rft.au=Corrigan+JJ%2C+Boineau+FG&amp;rft.date=November+2001&amp;rft.volume=22&amp;rft.issue=11&amp;rft.pages=365%E2%80%939&amp;rft_id=info:pmid/11691946&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
    <li id="cite_note-pmid1816053-1"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-pmid1816053_1-0"><font color="#0645ad">^</font></a></b> <span class="citation Journal">Anagnou NP, Papanicolaou N, Fessas P (1991). &quot;Recurrent attacks of hemolytic uremic syndrome&quot;. <i>Haematologia (Budap)</i> <b>24</b> (2): 101&ndash;5. <a class="mw-redirect" title="PubMed Identifier" href="http://en.wikipedia.org/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a> <a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/1816053"><font color="#3366bb">1816053</font></a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Recurrent+attacks+of+hemolytic+uremic+syndrome&amp;rft.jtitle=Haematologia+%28Budap%29&amp;rft.aulast=Anagnou+NP%2C+Papanicolaou+N%2C+Fessas+P&amp;rft.au=Anagnou+NP%2C+Papanicolaou+N%2C+Fessas+P&amp;rft.date=1991&amp;rft.volume=24&amp;rft.issue=2&amp;rft.pages=101%E2%80%935&amp;rft_id=info:pmid/1816053&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
    <li id="cite_note-pmid13274004-2"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-pmid13274004_2-0"><font color="#0645ad">^</font></a></b> <span class="citation Journal">GAsser C, Gautier E, Steck A, Siebenmann RE, Oechslin R (September 1955). &quot;Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia&quot; (in German). <i>Schweiz Med Wochenschr</i> <b>85</b> (38-39): 905&ndash;9. <a class="mw-redirect" title="PubMed Identifier" href="http://en.wikipedia.org/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a> <a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/13274004"><font color="#3366bb">13274004</font></a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Hemolytic-uremic+syndrome%3A++bilateral+necrosis+of+the+renal+cortex+in+acute+acquired+hemolytic+anemia&amp;rft.jtitle=Schweiz+Med+Wochenschr&amp;rft.aulast=GAsser+C%2C+Gautier+E%2C+Steck+A%2C+Siebenmann+RE%2C+Oechslin+R&amp;rft.au=GAsser+C%2C+Gautier+E%2C+Steck+A%2C+Siebenmann+RE%2C+Oechslin+R&amp;rft.date=September+1955&amp;rft.volume=85&amp;rft.issue=38-39&amp;rft.pages=905%E2%80%939&amp;rft_id=info:pmid/13274004&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
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    <li id="cite_note-5"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-5"><font color="#0645ad">^</font></a></b> Kumar et al., Robbins Basic Pathology, 8th Edition; <a class="internal mw-magiclink-isbn" href="http://en.wikipedia.org/wiki/Special:BookSources/9781416029731"><font color="#0645ad">ISBN 978-1-4160-2973-1</font></a></li>
    <li id="cite_note-pmid15661753-6"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-pmid15661753_6-0"><font color="#0645ad">^</font></a></b> <span class="citation Journal">Esparza-Gordillo J, Goicoechea de Jorge E, Buil A, <i>et al.</i> (March 2005). <a class="external text" rel="nofollow" href="http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&amp;pmid=15661753"><font color="#3366bb">&quot;Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32&quot;</font></a>. <i>Hum. Mol. Genet.</i> <b>14</b> (5): 703&ndash;12. <a title="Digital object identifier" href="http://en.wikipedia.org/wiki/Digital_object_identifier"><font color="#0645ad">doi</font></a>:<a class="external text" rel="nofollow" href="http://dx.doi.org/10.1093%2Fhmg%2Fddi066"><font color="#3366bb">10.1093/hmg/ddi066</font></a>. <a class="mw-redirect" title="PubMed Identifier" href="http://en.wikipedia.org/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a> <a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/15661753"><font color="#3366bb">15661753</font></a><span class="printonly">. <a class="external free" rel="nofollow" href="http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&amp;pmid=15661753"><font color="#3366bb">http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&amp;pmid=15661753</font></a></span>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Predisposition+to+atypical+hemolytic+uremic+syndrome+involves+the+concurrence+of+different+susceptibility+alleles+in+the+regulators+of+complement+activation+gene+cluster+in+1q32&amp;rft.jtitle=Hum.+Mol.+Genet.&amp;rft.aulast=Esparza-Gordillo+J%2C+Goicoechea+de+Jorge+E%2C+Buil+A%2C+%27%27et+al.%27%27&amp;rft.au=Esparza-Gordillo+J%2C+Goicoechea+de+Jorge+E%2C+Buil+A%2C+%27%27et+al.%27%27&amp;rft.date=March+2005&amp;rft.volume=14&amp;rft.issue=5&amp;rft.pages=703%E2%80%9312&amp;rft_id=info:doi/10.1093%2Fhmg%2Fddi066&amp;rft_id=info:pmid/15661753&amp;rft_id=http%3A%2F%2Fhmg.oxfordjournals.org%2Fcgi%2Fpmidlookup%3Fview%3Dlong%26pmid%3D15661753&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
    <li id="cite_note-pmid12544708-7"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-pmid12544708_7-0"><font color="#0645ad">^</font></a></b> <span class="citation Journal">Coppo P, Bussel A, Charrier S, <i>et al.</i> (January 2003). <a class="external text" rel="nofollow" href="http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0025-7974&amp;volume=82&amp;issue=1&amp;spage=27"><font color="#3366bb">&quot;High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome&quot;</font></a>. <i>Medicine (Baltimore)</i> <b>82</b> (1): 27&ndash;38. <a title="Digital object identifier" href="http://en.wikipedia.org/wiki/Digital_object_identifier"><font color="#0645ad">doi</font></a>:<a class="external text" rel="nofollow" href="http://dx.doi.org/10.1097%2F00005792-200301000-00003"><font color="#3366bb">10.1097/00005792-200301000-00003</font></a>. <a class="mw-redirect" title="PubMed Identifier" href="http://en.wikipedia.org/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a> <a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/12544708"><font color="#3366bb">12544708</font></a><span class="printonly">. <a class="external free" rel="nofollow" href="http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0025-7974&amp;volume=82&amp;issue=1&amp;spage=27"><font color="#3366bb">http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0025-7974&amp;volume=82&amp;issue=1&amp;spage=27</font></a></span>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=High-dose+plasma+infusion+versus+plasma+exchange+as+early+treatment+of+thrombotic+thrombocytopenic+purpura%2Fhemolytic-uremic+syndrome&amp;rft.jtitle=Medicine+%28Baltimore%29&amp;rft.aulast=Coppo+P%2C+Bussel+A%2C+Charrier+S%2C+%27%27et+al.%27%27&amp;rft.au=Coppo+P%2C+Bussel+A%2C+Charrier+S%2C+%27%27et+al.%27%27&amp;rft.date=January+2003&amp;rft.volume=82&amp;rft.issue=1&amp;rft.pages=27%E2%80%9338&amp;rft_id=info:doi/10.1097%2F00005792-200301000-00003&amp;rft_id=info:pmid/12544708&amp;rft_id=http%3A%2F%2Fmeta.wkhealth.com%2Fpt%2Fpt-core%2Ftemplate-journal%2Flwwgateway%2Fmedia%2Flandingpage.htm%3Fissn%3D0025-7974%26volume%3D82%26issue%3D1%26spage%3D27&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
    <li id="cite_note-pmid11604563-8"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-pmid11604563_8-0"><font color="#0645ad">^</font></a></b> <span class="citation Journal">Medina PJ, Sipols JM, George JN (September 2001). <a class="external text" rel="nofollow" href="http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1065-6251&amp;volume=8&amp;issue=5&amp;spage=286"><font color="#3366bb">&quot;Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome&quot;</font></a>. <i>Curr. Opin. Hematol.</i> <b>8</b> (5): 286&ndash;93. <a title="Digital object identifier" href="http://en.wikipedia.org/wiki/Digital_object_identifier"><font color="#0645ad">doi</font></a>:<a class="external text" rel="nofollow" href="http://dx.doi.org/10.1097%2F00062752-200109000-00004"><font color="#3366bb">10.1097/00062752-200109000-00004</font></a>. <a class="mw-redirect" title="PubMed Identifier" href="http://en.wikipedia.org/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a> <a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/11604563"><font color="#3366bb">11604563</font></a><span class="printonly">. <a class="external free" rel="nofollow" href="http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1065-6251&amp;volume=8&amp;issue=5&amp;spage=286"><font color="#3366bb">http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1065-6251&amp;volume=8&amp;issue=5&amp;spage=286</font></a></span>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Drug-associated+thrombotic+thrombocytopenic+purpura-hemolytic+uremic+syndrome&amp;rft.jtitle=Curr.+Opin.+Hematol.&amp;rft.aulast=Medina+PJ%2C+Sipols+JM%2C+George+JN&amp;rft.au=Medina+PJ%2C+Sipols+JM%2C+George+JN&amp;rft.date=September+2001&amp;rft.volume=8&amp;rft.issue=5&amp;rft.pages=286%E2%80%9393&amp;rft_id=info:doi/10.1097%2F00062752-200109000-00004&amp;rft_id=info:pmid/11604563&amp;rft_id=http%3A%2F%2Fmeta.wkhealth.com%2Fpt%2Fpt-core%2Ftemplate-journal%2Flwwgateway%2Fmedia%2Flandingpage.htm%3Fissn%3D1065-6251%26volume%3D8%26issue%3D5%26spage%3D286&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
    <li id="cite_note-pmid12823037-9"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-pmid12823037_9-0"><font color="#0645ad">^</font></a></b> <span class="citation Journal">Hosler GA, Cusumano AM, Hutchins GM (July 2003). <a class="external text" rel="nofollow" href="http://journals.allenpress.com/jrnlserv/?request=get-abstract&amp;issn=0003-9985&amp;volume=127&amp;page=834"><font color="#3366bb">&quot;Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathologic entities. A review of 56 autopsy cases&quot;</font></a>. <i>Arch. Pathol. Lab. Med.</i> <b>127</b> (7): 834&ndash;9. <a class="mw-redirect" title="PubMed Identifier" href="http://en.wikipedia.org/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a> <a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/12823037"><font color="#3366bb">12823037</font></a><span class="printonly">. <a class="external free" rel="nofollow" href="http://journals.allenpress.com/jrnlserv/?request=get-abstract&amp;issn=0003-9985&amp;volume=127&amp;page=834"><font color="#3366bb">http://journals.allenpress.com/jrnlserv/?request=get-abstract&amp;issn=0003-9985&amp;volume=127&amp;page=834</font></a></span>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Thrombotic+thrombocytopenic+purpura+and+hemolytic+uremic+syndrome+are+distinct+pathologic+entities.+A+review+of+56+autopsy+cases&amp;rft.jtitle=Arch.+Pathol.+Lab.+Med.&amp;rft.aulast=Hosler+GA%2C+Cusumano+AM%2C+Hutchins+GM&amp;rft.au=Hosler+GA%2C+Cusumano+AM%2C+Hutchins+GM&amp;rft.date=July+2003&amp;rft.volume=127&amp;rft.issue=7&amp;rft.pages=834%E2%80%939&amp;rft_id=info:pmid/12823037&amp;rft_id=http%3A%2F%2Fjournals.allenpress.com%2Fjrnlserv%2F%3Frequest%3Dget-abstract%26issn%3D0003-9985%26volume%3D127%26page%3D834&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
    <li id="cite_note-10"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-10"><font color="#0645ad">^</font></a></b> <a class="external text" rel="nofollow" href="http://www.emedicine.com/EMERG/topic238.htm"><font color="#3366bb">eMedicine - Hemolytic Uremic Syndrome : Article by William Shapiro</font></a></li>
    <li id="cite_note-pmid16918877-11"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-pmid16918877_11-0"><font color="#0645ad">^</font></a></b> <span class="citation Journal">Panos GZ, Betsi GI, Falagas ME (September 2006). <a class="external text" rel="nofollow" href="http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0269-2813&amp;date=2006&amp;volume=24&amp;issue=5&amp;spage=731"><font color="#3366bb">&quot;Systematic review: are antibiotics detrimental or beneficial for the treatment of patients with Escherichia coli O157:H7 infection?&quot;</font></a>. <i>Aliment. Pharmacol. Ther.</i> <b>24</b> (5): 731&ndash;42. <a title="Digital object identifier" href="http://en.wikipedia.org/wiki/Digital_object_identifier"><font color="#0645ad">doi</font></a>:<a class="external text" rel="nofollow" href="http://dx.doi.org/10.1111%2Fj.1365-2036.2006.03036.x"><font color="#3366bb">10.1111/j.1365-2036.2006.03036.x</font></a>. <a class="mw-redirect" title="PubMed Identifier" href="http://en.wikipedia.org/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a> <a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/16918877"><font color="#3366bb">16918877</font></a><span class="printonly">. <a class="external free" rel="nofollow" href="http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0269-2813&amp;date=2006&amp;volume=24&amp;issue=5&amp;spage=731"><font color="#3366bb">http://www.blackwell-synergy.com/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0269-2813&amp;date=2006&amp;volume=24&amp;issue=5&amp;spage=731</font></a></span>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Systematic+review%3A+are+antibiotics+detrimental+or+beneficial+for+the+treatment+of+patients+with+Escherichia+coli+O157%3AH7+infection%3F&amp;rft.jtitle=Aliment.+Pharmacol.+Ther.&amp;rft.aulast=Panos+GZ%2C+Betsi+GI%2C+Falagas+ME&amp;rft.au=Panos+GZ%2C+Betsi+GI%2C+Falagas+ME&amp;rft.date=September+2006&amp;rft.volume=24&amp;rft.issue=5&amp;rft.pages=731%E2%80%9342&amp;rft_id=info:doi/10.1111%2Fj.1365-2036.2006.03036.x&amp;rft_id=info:pmid/16918877&amp;rft_id=http%3A%2F%2Fwww.blackwell-synergy.com%2Fopenurl%3Fgenre%3Darticle%26sid%3Dnlm%3Apubmed%26issn%3D0269-2813%26date%3D2006%26volume%3D24%26issue%3D5%26spage%3D731&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
    <li id="cite_note-12"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-12"><font color="#0645ad">^</font></a></b> <span class="citation book">Chu P, Hemphill RR (2004). &quot;222: Acuired hemolytic anemia&quot;. In Tintinalli JE, Kelen GD, Stapczynski JS. <i>Emergency Medicine: A Comprehensive Study Guide</i> (6th ed.). New York, NY: McGraw-Hill. <a title="International Standard Book Number" href="http://en.wikipedia.org/wiki/International_Standard_Book_Number"><font color="#0645ad">ISBN</font></a> <a title="Special:BookSources/0-07-138875-3" href="http://en.wikipedia.org/wiki/Special:BookSources/0-07-138875-3"><font color="#0645ad">0-07-138875-3</font></a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=222%3A+Acuired+hemolytic+anemia&amp;rft.atitle=Emergency+Medicine%3A+A+Comprehensive+Study+Guide&amp;rft.aulast=Chu+P%2C+Hemphill+RR&amp;rft.au=Chu+P%2C+Hemphill+RR&amp;rft.date=2004&amp;rft.edition=6th&amp;rft.place=New+York%2C+NY&amp;rft.pub=McGraw-Hill&amp;rft.isbn=0-07-138875-3&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
    <li id="cite_note-13"><b><a href="http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#cite_ref-13"><font color="#0645ad">^</font></a></b> <span class="citation news"><a class="external text" rel="nofollow" href="http://www.guardian.co.uk/world/2011/jun/02/e-coli-outbreak-uk-cases"><font color="#3366bb">&quot;E coli outbreak: three UK cases have rare strain&quot;</font></a>. <i>The Guardian</i>. 2 June 2011<span class="printonly">. <a class="external free" rel="nofollow" href="http://www.guardian.co.uk/world/2011/jun/02/e-coli-outbreak-uk-cases"><font color="#3366bb">http://www.guardian.co.uk/world/2011/jun/02/e-coli-outbreak-uk-cases</font></a></span>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=E+coli+outbreak%3A+three+UK+cases+have+rare+strain&amp;rft.jtitle=The+Guardian&amp;rft.date=2+June+2011&amp;rft_id=http%3A%2F%2Fwww.guardian.co.uk%2Fworld%2F2011%2Fjun%2F02%2Fe-coli-outbreak-uk-cases&amp;rfr_id=info:sid/en.wikipedia.org:Hemolytic-uremic_syndrome"><span style="display: none"> </span></span></li>
</ol>
</div>
<h2><span id="External_links" class="mw-headline">External links</span></h2>
<ul>
    <li><a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/books/NBK1367/"><font color="#3366bb">GeneReviews/NCBI/NIH/UW entry on Atypical hemolytic-uremic syndrome</font></a></li>
</ul>