287 lines
99 KiB
Text
287 lines
99 KiB
Text
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
|
|
<head>
|
|
<!-- For pinger, set start time and add meta elements. -->
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books">
|
|
<meta name="ncbi_pdid" content="book-part">
|
|
<meta name="ncbi_acc" content="NBK611985">
|
|
<meta name="ncbi_domain" content="statpearls">
|
|
<meta name="ncbi_report" content="reader">
|
|
<meta name="ncbi_type" content="fulltext">
|
|
<meta name="ncbi_objectid" content="">
|
|
<meta name="ncbi_pcid" content="/NBK611985/?report=reader">
|
|
<meta name="ncbi_pagename" content="Thrombotic Microangiopathy and the Kidney - StatPearls - NCBI Bookshelf">
|
|
<meta name="ncbi_bookparttype" content="chapter">
|
|
<meta name="ncbi_app" content="bookshelf">
|
|
<!-- Logger end -->
|
|
|
|
<!--component id="Page" label="meta"/-->
|
|
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Thrombotic Microangiopathy and the Kidney - StatPearls - NCBI Bookshelf</title>
|
|
<meta charset="utf-8">
|
|
<meta name="apple-mobile-web-app-capable" content="no">
|
|
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
|
|
<meta name="jr-col-layout" content="auto">
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="StatPearls [Internet]">
|
|
<meta name="citation_title" content="Thrombotic Microangiopathy and the Kidney">
|
|
<meta name="citation_publisher" content="StatPearls Publishing">
|
|
<meta name="citation_date" content="2025/01/17">
|
|
<meta name="citation_author" content="Abdullah Jalal">
|
|
<meta name="citation_author" content="Mohammad Atari">
|
|
<meta name="citation_author" content="Mohamed Hassanein">
|
|
<meta name="citation_author" content="Anuja Java">
|
|
<meta name="citation_pmid" content="39937948">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK611985/">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="Thrombotic Microangiopathy and the Kidney">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="StatPearls Publishing">
|
|
<meta name="DC.Contributor" content="Abdullah Jalal">
|
|
<meta name="DC.Contributor" content="Mohammad Atari">
|
|
<meta name="DC.Contributor" content="Mohamed Hassanein">
|
|
<meta name="DC.Contributor" content="Anuja Java">
|
|
<meta name="DC.Date" content="2025/01/17">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK611985/">
|
|
<meta name="description" content="Thrombotic microangiopathy (TMA) is a clinical syndrome characterized by endothelial injury and thrombotic occlusion of the microvasculature, leading to end-organ damage. This systemic disorder can affect any organ system, including the brain, heart, and gastrointestinal tract. However, the kidney is the most frequently affected organ.[1]">
|
|
<meta name="og:title" content="Thrombotic Microangiopathy and the Kidney">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="Thrombotic microangiopathy (TMA) is a clinical syndrome characterized by endothelial injury and thrombotic occlusion of the microvasculature, leading to end-organ damage. This systemic disorder can affect any organ system, including the brain, heart, and gastrointestinal tract. However, the kidney is the most frequently affected organ.[1]">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK611985/">
|
|
<meta name="og:site_name" content="NCBI Bookshelf">
|
|
<meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-statpearls-lrg.png">
|
|
<meta name="twitter:card" content="summary">
|
|
<meta name="twitter:site" content="@ncbibooks">
|
|
<meta name="bk-non-canon-loc" content="/books/n/statpearls/article-169704/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK611985/">
|
|
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&subset=latin" rel="stylesheet" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
|
|
<meta name="format-detection" content="telephone=no">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css//books_print.min.css" type="text/css" media="print">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
|
|
<style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style>
|
|
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
|
|
<meta name="ncbi_phid" content="CE8CA1057C91B2910000000000070005.m_5">
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
|
|
<body>
|
|
<!-- Book content! -->
|
|
|
|
|
|
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK611985/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
|
|
<style type="text/css">.st0{fill:#939598;}</style>
|
|
<g>
|
|
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
|
|
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
|
|
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
|
|
</g>
|
|
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"></div><div class="body"><div class="t">Thrombotic Microangiopathy and the Kidney</div><div class="j">StatPearls [Internet]</div></div><div class="tail"></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-cmap-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK611985/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK611985/&text=Thrombotic%20Microangiopathy%20and%20the%20Kidney"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-cmap-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">In Page Navigation</div></div><div class="cnt lol f1"><a href="/books/n/statpearls/?report=reader">Title Information</a><a href="/books/n/statpearls/toc/?report=reader">Table of Contents Page</a><a href="#_NBK611985_">Thrombotic Microangiopathy and the Kidney</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK611985/?report=classic">Switch to classic view</a><a href="/books/NBK611985/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK611985%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8CA1057C91B2910000000000070005.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">✘</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK611985_"><span class="title" itemprop="name">Thrombotic Microangiopathy and the Kidney</span></h1><p class="contribs">Jalal A, Atari M, Hassanein M, et al.</p><p class="fm-aai"><a href="#_NBK611985_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="article-169704.s1"><h2 id="_article-169704_s1_">Introduction</h2><p>Thrombotic microangiopathy (TMA) is a clinical syndrome characterized by endothelial injury and thrombotic occlusion of the microvasculature, leading to end-organ damage. This systemic disorder can affect any organ system, including the brain, heart, and gastrointestinal tract. However, the kidney is the most frequently affected organ.<a class="bibr" href="#article-169704.r1" rid="article-169704.r1">[1]</a></p><p>Historically, TMA syndromes were classified as either thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS) based on neurologic or kidney involvement, respectively.<a class="bibr" href="#article-169704.r1" rid="article-169704.r1">[1]</a> Subsequent discoveries led to further refinement of this classification, with TTP characterized by a genetic or acquired deficiency of a disintegrin-like metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) and HUS most commonly associated with Shiga toxin-producing <i>Escherichia coli</i>. Cases of HUS with a genetic component leading to activation of the alternative complement pathway are called “atypical” HUS.<a class="bibr" href="#article-169704.r1" rid="article-169704.r1">[1]</a><a class="bibr" href="#article-169704.r2" rid="article-169704.r2">[2]</a> The term atypical HUS has also been used to describe cases that are not TTP or classic HUS.<a class="bibr" href="#article-169704.r3" rid="article-169704.r3">[3]</a> Please see StatPearls' companion review, "<a href="https://www.statpearls.com/point-of-care/22741" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Hemolytic Uremic Syndrome</a>," for further information. However, this nomenclature is imprecise, as the term atypical HUS is broadly used to describe heterogeneous disorders with distinct pathophysiology and treatments. Hence, as our understanding of complement dysregulation and its role in various forms of TMA has evolved, longstanding efforts have been made to revise the nomenclature towards a more etiology-based classification system.<a class="bibr" href="#article-169704.r2" rid="article-169704.r2">[2]</a><a class="bibr" href="#article-169704.r4" rid="article-169704.r4">[4]</a><a class="bibr" href="#article-169704.r5" rid="article-169704.r5">[5]</a></p></div><div id="article-169704.s2"><h2 id="_article-169704_s2_">Etiology</h2><p>TMAs have commonly been classified into TTP/ADAMTS13 deficiency TMA (congenital or acquired), primary TMA (occurring due to dysregulation of the complement system due to genetic or acquired abnormalities), and secondary TMA (occurring secondary to various triggers or associated diseases).<a class="bibr" href="#article-169704.r6" rid="article-169704.r6">[6]</a> With primary TMAs, approximately 50% to 70% of patients have mutations in complement genes or regulatory proteins.<a class="bibr" href="#article-169704.r6" rid="article-169704.r6">[6]</a><a class="bibr" href="#article-169704.r7" rid="article-169704.r7">[7]</a><a class="bibr" href="#article-169704.r8" rid="article-169704.r8">[8]</a> These mutations have incomplete penetrance and often require a “second hit” or environmental trigger to cause TMA.<a class="bibr" href="#article-169704.r7" rid="article-169704.r7">[7]</a></p><p>In contrast to primary TMA, genetic abnormalities in complement or regulatory proteins are typically less common in those with secondary complement-mediated (CM)-TMA. Consequently, after the environmental trigger or underlying disease process is controlled, secondary CM-TMAs often resolve and have a much lower risk of recurrence. Thus, the additive benefits of anticomplement therapy in secondary TMAs are contentious and should be considered on a case-by-case basis.<a class="bibr" href="#article-169704.r6" rid="article-169704.r6">[6]</a><a class="bibr" href="#article-169704.r8" rid="article-169704.r8">[8]</a></p><p>More recently, a working group of international multispecialty TMA experts supported by the National Kidney Foundation (NKF) proposed a new etiology-based classification for TMA. Specifically, the expert panel recommended discarding the term “atypical" HUS since it is nonspecific and does not reflect the underlying pathophysiology. Below is the proposed etiology-based classification for TMA from the NKF Working Group.<a class="bibr" href="#article-169704.r4" rid="article-169704.r4">[4]</a></p><p>
|
|
<b>Known Etiology</b>
|
|
</p><p>Thrombotic thrombocytopenic purpura (ADAMTS13 deficiency)</p><ul><li class="half_rhythm"><div>Hereditary
|
|
<ul><li class="half_rhythm"><div>Mutation in <i>ADAMTS13</i> gene</div></li></ul>
|
|
</div></li><li class="half_rhythm"><div>Acquired
|
|
<ul><li class="half_rhythm"><div>Autoantibodies to ADAMTS13</div></li></ul>
|
|
</div></li><li class="half_rhythm"><div>Please see StatPearls' companion review, "<a href="https://www.statpearls.com/point-of-care/30097" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Thrombotic Thrombocytopenic Purpura,</a>" for further information.</div></li></ul><p>Complement-mediated TMA</p><ul><li class="half_rhythm"><div>Genetic CM-TMA</div></li><li class="half_rhythm"><div>Acquired factor H autoantibody-associated TMA</div></li><li class="half_rhythm"><div>Nongenetic CM-TMA</div></li></ul><p>Genetic nonCM-TMA</p><ul><li class="half_rhythm"><div>Includes diacylglycerol kinase epsilon-TMA, TSEN-TMA, interferon-TMA, EXOSC3-TMA</div></li><li class="half_rhythm"><div><i>MMACHC</i> gene mutations increase the risk of cobalamin deficiency-associated TMA.</div></li></ul><p>Metabolic-associated TMA</p><ul><li class="half_rhythm"><div>Cobalamin deficiency: This deficiency can present in childhood and adulthood (as noted above, the risk is increased with mutations in the <i>MMACHC</i> gene).</div></li></ul><p>
|
|
<b>Predisposing Conditions</b>
|
|
</p><p>These forms may need additional diagnostic tests such as genetic predispositions, complement dysregulation, metabolic disease, or other testing to further define their etiology. Overlap with categories above from "Known Etiology" also exists. For example, infection-associated TMA often causes abnormal complement activation, and many patients who develop TMA after a hematopoietic stem cell transplant have a genetic predisposition to abnormal complement regulation.<a class="bibr" href="#article-169704.r7" rid="article-169704.r7">[7]</a></p><ul><li class="half_rhythm"><div><b>Transplant-associated TMA</b>
|
|
<ul><li class="half_rhythm"><div>Hematopoietic stem cell transplant: TMA occurs in up to 40% of allogeneic stem cell transplants.<a class="bibr" href="#article-169704.r9" rid="article-169704.r9">[9]</a><b> </b>This condition occurs due to an underlying genetic predisposition (hit 1), use of a conditioning regimen that includes chemotherapeutic agents and total body irradiation (hit 2). Associated conditions (eg, use of calcineurin inhibitors [CNIs] /mammalian target of rapamycin [mTOR], infections) can further activate the complement system<b>.</b></div></li><li class="half_rhythm"><div>Solid organ transplant: TMA after solid organ transplant can be multifactorial due to drugs (particularly CNI or mTOR use), infections, or antibody-mediated rejection. TMA has been reported to occur in up to 14% of patients after a kidney transplant, about 4% after a liver transplant, and 2.3% after a lung transplant. Complement gene mutations increase the risk of developing TMA. TMA commonly occurs in the first 3 months after transplant but can appear at any time in the posttransplant course. Posttransplant TMA can be recurrent or de novo. Recurrent TMA is almost always complement-mediated (due to underlying genetic mutations), while de novo TMA may be complement-mediated or secondary to the associated conditions or triggers mentioned above. Complement activation may also play a role in de novo TMAs.<a class="bibr" href="#article-169704.r10" rid="article-169704.r10">[10]</a></div></li></ul>
|
|
</div></li></ul><ul><li class="half_rhythm"><div><b>Pregnancy-associated TMA</b>
|
|
<ul><li class="half_rhythm"><div>Preeclampsia. Please see StatPearls' companion reviews, "<a href="https://www.statpearls.com/point-of-care/30096" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Thrombocytopenia in Pregnancy</a>" and "<a href="https://www.statpearls.com/point-of-care/27640" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Preeclampsia</a>." Pregnancy and the postpartum period are considered a high-risk time for TMA development. Pregnancy-associated TMAs include TTP, HELLP (hemolysis, elevated liver enzymes, and low platelet count), atypical hemolytic uremic syndrome (aHUS)/CM-TMA, and TMA associated with antiphospholipid syndrome.</div></li><li class="half_rhythm"><div>Pregnancy, particularly the postpartum period, is considered one of the major triggers for CM-TMA as the levels of many complement proteins (which increase during pregnancy) decrease during the postpartum period. Complement activation can also occur due to an imbalance in the production between anti-angiogenic (soluble Feline McDonough sarcomas, like tyrosine kinase-1) and pro-angiogenic factors (vascular endothelial growth factor [VEGF] and placental growth factor).<a class="bibr" href="#article-169704.r11" rid="article-169704.r11">[11]</a><a class="bibr" href="#article-169704.r12" rid="article-169704.r12">[12]</a></div></li><li class="half_rhythm"><div>HELLP syndrome is a serious pregnancy complication. Please see StatPearls' companion reference, "<a href="https://www.statpearls.com/point-of-care/30096" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HELLP Syndrome.</a>"</div></li><li class="half_rhythm"><div>Triggering of catastrophic antiphospholipid syndrome, aHUS, or TTP can also occur during pregnancy. Please see StatPearls' companion reference, "<a href="https://www.statpearls.com/point-of-care/17705" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Antiphospholipid Syndrome.</a>"</div></li></ul>
|
|
</div></li></ul><ul><li class="half_rhythm"><div><b>Hypertension-associated TMA</b>
|
|
<ul><li class="half_rhythm"><div>Hypertension is speculated to cause TMA due to the mechanical shear stress on the endothelium. Although hypertension could be the cause in some patients, investigating for other etiologies is strongly recommended, as complement abnormalities have been identified in 35% to 65% of patients who develop TMA in the setting of malignant hypertension. TMA features will persist in these patients despite blood pressure control beyond 48 to 72 hours. Therefore, identifying these patients is important from both therapeutic and prognostic standpoints because they can benefit from complement inhibition.<a class="bibr" href="#article-169704.r13" rid="article-169704.r13">[13]</a></div></li></ul>
|
|
</div></li></ul><ul><li class="half_rhythm"><div><b>Drug-induced TMA </b>
|
|
<ul><li class="half_rhythm"><div>This may be immune-mediated or direct toxicity-mediated. Immune-mediated TMA occurs due to the production of antibodies against the drug (or its metabolite). This condition is often associated with sudden onset of severe symptoms within hours or days after drug exposure. These antibodies can interact with platelets or circulating factors and cause endothelial injury. Direct toxicity-mediated TMA occurs due to cumulative effect dose and can occur at any time after being on the medication.<a href="https://www.statpearls.com/Keywords/UserViewPopup/172980#link_36509342" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">[6]</a><a class="bibr" href="#article-169704.r14" rid="article-169704.r14">[14]</a></div></li><li class="half_rhythm"><div>Mechanisms include direct endothelial damage and interruption of various pathways, such as VEGF, mTOR pathway, or deregulation of transcription factors (eg, nuclear factor-kappa B). TMA after an mTOR or calcineurin inhibitor (eg, drugs specifically relevant to transplant) use can also occur due to arteriolar vasoconstriction and endothelial injury, which can result in Von Willebrand factor multimer release, thereby causing platelet aggregation and complement activation (due to the complement-coagulation crosstalk).<a class="bibr" href="#article-169704.r15" rid="article-169704.r15">[15]</a></div></li><li class="half_rhythm"><div>Common drugs that are associated with TMA include the following:
|
|
<ul><li class="half_rhythm"><div>Chemotherapeutic agents: tyrosine kinase inhibitors, vascular endothelial growth factor (VEGF) inhibitors, immune checkpoint inhibitors <a class="bibr" href="#article-169704.r14" rid="article-169704.r14">[14]</a></div></li><li class="half_rhythm"><div>Immunosuppressive agents: calcineurin inhibitors, interferon-β, sirolimus</div></li><li class="half_rhythm"><div>Antibiotics: penicillin, ciprofloxacin, levofloxacin, metronidazole, nitrofurantoin <a href="https://www.statpearls.com/Keywords/UserViewPopup/172980#link_36509342" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">[6]</a></div></li><li class="half_rhythm"><div>Illicit drugs: cocaine, ecstasy</div></li></ul>
|
|
</div></li></ul>
|
|
</div></li></ul><ul><li class="half_rhythm"><div><b>Vasculitis/autoimmune disease associated TMA</b>
|
|
<ul><li class="half_rhythm"><div>Autoimmune diseases commonly associated with TMA include systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and scleroderma. TMA has also been reported to be associated with immunoglobulin A nephropathy, antineutrophil cytoplasmic antibodies-associated vasculitis, membranous nephropathy, and focal segmental glomerulosclerosis.</div></li><li class="half_rhythm"><div>The pathophysiology of TMA in these diseases is multifactorial. Deficiency of early complement components (such as C1q, C2, or C4) in SLE can promote the generation of autoantibodies that can form immune complexes and trigger complement activation. Neutrophil extracellular traps (NETs) have also been implicated to play a role in TMA pathogenesis in these conditions since NETs incorporate complement components such as C3 cleavage products, properdin, and factor B, which can together form a C3 convertase leading to excessive complement activation. Genetic defects in the complement pathway genes have also been identified in a subset of these patients.<a class="bibr" href="#article-169704.r16" rid="article-169704.r16">[16]</a><a class="bibr" href="#article-169704.r17" rid="article-169704.r17">[17]</a></div></li></ul>
|
|
</div></li></ul><ul><li class="half_rhythm"><div><b>Cancer-associated TMA</b>
|
|
<ul><li class="half_rhythm"><div>TMA in patients with cancer can be due to chemotherapy or due to the direct effect of the tumor.<a class="bibr" href="#article-169704.r18" rid="article-169704.r18">[18]</a><a class="bibr" href="#article-169704.r19" rid="article-169704.r19">[19]</a></div></li><li class="half_rhythm"><div>Cancers associated with TMA typically include the following:
|
|
<ul><li class="half_rhythm"><div>Solid organ malignancy: breast, lungs, stomach, prostate, and ovaries</div></li><li class="half_rhythm"><div>Hematologic: monoclonal gammopathies and lymphoproliferative disorders (leukemia, lymphoma) </div></li></ul>
|
|
</div></li><li class="half_rhythm"><div>Possible mechanisms involve abnormal angiogenesis in the marrow that can lead to endothelial injury of the marrow vasculature by direct invasion. Additionally, microvascular tumor emboli, procoagulants produced by tumor cells, and impaired fibrinolysis have also been implicated. TMA associated with hematologic malignancies is speculated to be either due to monoclonal immunoglobulins causing direct endothelial injury, functioning like anti-complement antibodies, or inhibiting <i>ADAMTS13</i>.</div></li></ul>
|
|
</div></li></ul><ul><li class="half_rhythm"><div><b>Infection-associated TMA</b>
|
|
<ul><li class="half_rhythm"><div>TMA can be associated with a wide range of infections, including the following: Shiga toxin-producing <i>Escherichia coli,</i> pneumococcal, influenza, human immunodeficiency virus, COVID, dengue virus, or cytomegalovirus infection.</div></li><li class="half_rhythm"><div>Shiga toxin binds to endothelial cells and releases tissue factor and von Willebrand factor, thereby creating a prothrombogenic environment.</div></li><li class="half_rhythm"><div>Pneumococcal and influenza infections are known to cause the production of neuraminidase, which cleaves sialic residues from red cells and platelets and decreases factor H binding, leading to endothelial damage and impaired complement regulation.<a class="bibr" href="#article-169704.r20" rid="article-169704.r20">[20]</a></div></li><li class="half_rhythm"><div>Other mechanisms of infectious disease-associated TMA can include the activation of platelets, generation of thrombin, or development of <i>ADAMTS13</i> inhibitors.<a class="bibr" href="#article-169704.r21" rid="article-169704.r21">[21]</a><a class="bibr" href="#article-169704.r22" rid="article-169704.r22">[22]</a></div></li></ul>
|
|
</div></li></ul></div><div id="article-169704.s3"><h2 id="_article-169704_s3_">Epidemiology</h2><p>CM-TMA is a rare disease. Annual incidence rates are variable due to imprecise nomenclature affecting cohort inclusion or exclusion criteria and difficulty of diagnosis but typically range from 0.2 to 2 cases per million depending on age and geographic region.<a class="bibr" href="#article-169704.r4" rid="article-169704.r4">[4]</a><a class="bibr" href="#article-169704.r23" rid="article-169704.r23">[23]</a><a class="bibr" href="#article-169704.r24" rid="article-169704.r24">[24]</a> Furthermore, the etiology of the disease varies based on age. CM-TMA has more diverse etiologies in adults, as noted in the preceding section. Among children, there is no gender discrepancy, while in adults, a female preponderance is present, particularly in the child-bearing years.<a class="bibr" href="#article-169704.r25" rid="article-169704.r25">[25]</a><a class="bibr" href="#article-169704.r26" rid="article-169704.r26">[26]</a><a class="bibr" href="#article-169704.r27" rid="article-169704.r27">[27]</a> Extra-renal manifestations are common and occur in 20% of cases.<a class="bibr" href="#article-169704.r28" rid="article-169704.r28">[28]</a></p></div><div id="article-169704.s4"><h2 id="_article-169704_s4_">Pathophysiology</h2><p>The underlying pathophysiology of TMA involves endothelial injury causing microthrombi formation and platelet consumption. These microthrombi can mechanically damage erythrocytes to form schistocytes, in addition to causing ischemic end-organ damage. TTP has a genetic (homozygous or heterozygous gene variants) or acquired (inhibitory autoantibodies) deficiency of ADAMTS13. Under normal circumstances, endothelial cells release von Willebrand factor (vWF), folded ultra-large multimers, from Weibel-Palade bodies. With blood flow, shear stress unfolds vWF and exposes cleavage sites for <i>ADAMTS13</i> to snip into smaller multimers. With reduced <i>ADAMTS13</i> activity, the Von Willebrand factor unfolds and adheres to circulating platelets to form thrombi, further increasing shear stress, platelet aggregation, and microthrombi formation, eventually leading to ischemic tissue damage.</p><p>In CM-TMA, there are genetic (complement gene mutations) or acquired factors (autoantibodies) that cause dysregulation of the complement system's alternative pathway, leading to endothelial injury. Other pathophysiological mechanisms include direct toxicity or immune-mediated injury in drug-induced TMA, platelet activation, thrombin generation, complement evasion, and direct endothelial invasion in infection-associated TMA. Metabolic causes of TMA have also been described, along with varied underlying pathophysiological mechanisms.<a class="bibr" href="#article-169704.r6" rid="article-169704.r6">[6]</a><a class="bibr" href="#article-169704.r8" rid="article-169704.r8">[8]</a></p></div><div id="article-169704.s5"><h2 id="_article-169704_s5_">Histopathology</h2><p>Biopsies are often not performed with severe thrombocytopenia; biopsies may be skewed towards those without hemolytic uremic syndrome or TTP.<a class="bibr" href="#article-169704.r3" rid="article-169704.r3">[3]</a> The kidney-related histopathologic features reflect endothelial injury occurring in the glomeruli or arterioles. In the acute phase, the glomerular capillary wall thickens from endothelial cell swelling, subendothelial accumulation of acellular material, and mesangiolysis. Microthrombi may be present in glomerular capillaries, although their absence does not exclude the diagnosis. Generally, there is no mesangial or endocapillary hypercellularity. If arterioles are involved, they may have fibrinoid necrosis (especially in afferent arterioles), and arterial/arteriolar intimal swelling may be present.<a class="bibr" href="#article-169704.r3" rid="article-169704.r3">[3]</a> </p><p>With chronicity, there is duplication or “double contouring” of the glioblastoma from new subendothelial basement membrane formation. This appears as a membranoproliferative pattern without immune deposits and requires further examination by immunofluorescence and electron microscopy. Additionally, an “onion-skinning” appearance of interlobular and arcuate arterioles may form from myointimal hyperplasia.<a class="bibr" href="#article-169704.r12" rid="article-169704.r12">[12]</a> Immunofluorescence will be negative for immunoglobulin or complement staining. Electron microscopy may show subendothelial electron-lucent material corresponding to the "double contours" seen in light microscopy; electron-dense deposits should not be seen.<a class="bibr" href="#article-169704.r3" rid="article-169704.r3">[3]</a> </p></div><div id="article-169704.s6"><h2 id="_article-169704_s6_">History and Physical</h2><p>TMA can be a very challenging diagnosis and consequently often goes unrecognized. Although the typical presentation involves non-immune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, less severe and incomplete presentations have been described. In addition, renal-limited forms of TMA exist that are only identified on a kidney biopsy and lack hematologic manifestations. Often, the earliest manifestation of disease may be new-onset or worsening of previously controlled hypertension. Hence, comprehensive history taking and a physical exam are essential to properly diagnosing this condition. </p><p>
|
|
<b>Triggering Factors</b>
|
|
</p><p>A patient should be asked about these potential triggering factors:</p><ul><li class="half_rhythm"><div>Recent illnesses or infections</div></li><li class="half_rhythm"><div>Newly prescribed medications or illicit substance use</div></li><li class="half_rhythm"><div>Newly diagnosed or exacerbation of previously well-controlled hypertension</div></li><li class="half_rhythm"><div>Exacerbations of chronic illnesses (particularly autoimmune disorders, ie, lupus or antiphospholipid syndrome)</div></li><li class="half_rhythm"><div>History of malignancy</div></li><li class="half_rhythm"><div>Prior history or family history of TMA</div></li><li class="half_rhythm"><div>Unusual food consumption or exposure to potential food poisoning</div></li></ul><p>
|
|
<b>History</b>
|
|
</p><p>Immediate history may include fevers, chills, nausea, vomiting, diarrhea, palpitations, abdominal pain, bleeding from the gums, bruising, swelling of the extremities, discolored or decreased urine, and confusion.</p><p>
|
|
<b>Physical</b>
|
|
</p><p>Physical findings also depend on the etiology but may involve the following organ systems. </p><ul><li class="half_rhythm"><div>Systemic findings: lethargy, fevers, confusion</div></li><li class="half_rhythm"><div>Dermatologic: (most common finding) petechiae, purpura, bruises, pallor (from anemia), jaundice (from hemolysis)</div></li><li class="half_rhythm"><div>Neurologic: focal deficits, seizures (in severe cases)</div></li><li class="half_rhythm"><div>Renal: hypertension, hematuria, oliguria</div></li><li class="half_rhythm"><div>Cardiovascular: tachycardia, edema</div></li><li class="half_rhythm"><div>Gastrointestinal: vomiting, diarrhea, blood in the stool (especially with Shiga toxin-related hemolytic uremic syndrome)</div></li></ul></div><div id="article-169704.s7"><h2 id="_article-169704_s7_">Evaluation</h2><p>TTP is a medical emergency requiring urgent intervention. Therefore, a predictive scoring system like PLASMIC or the French TMA scoring system can be used to assess its likelihood while <i>ADAMTS13</i> activity levels are pending. One suggestion is to treat anyone with a PLASMIC score greater than 5 empirically for TTP.<a class="bibr" href="#article-169704.r29" rid="article-169704.r29">[29]</a><a class="bibr" href="#article-169704.r30" rid="article-169704.r30">[30]</a><a class="bibr" href="#article-169704.r31" rid="article-169704.r31">[31]</a> Please see StatPearls' companion reference, "<a href="https://www.statpearls.com/point-of-care/30097" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Thrombotic Thrombocytopenic Purpura</a>," PLASMIC score section, for details on this scoring system.</p><p> <b>Laboratory evaluation</b></p><ul><li class="half_rhythm"><div>Complete blood count for anemia, thrombocytopenia (<150K or >25%-50% decrease from baseline), and reticulocytosis</div></li><li class="half_rhythm"><div>Hemolysis markers: lactate dehydrogenase, low haptoglobin, high indirect bilirubin</div></li><li class="half_rhythm"><div>Peripheral smear 1% or higher schistocytes
|
|
<ul><li class="half_rhythm"><div>Less than 1% of schistocytes can be present in chronic kidney disease, liver disease, and prosthetic valves.</div></li></ul>
|
|
</div></li><li class="half_rhythm"><div>Coagulation profile to rule out disseminated intravascular coagulation</div></li><li class="half_rhythm"><div>Coombs test to rule out immune hemolytic anemia</div></li><li class="half_rhythm"><div><i>ADAMTS13</i> level/activity</div></li><li class="half_rhythm"><div>Antiphospholipid antibody testing</div></li><li class="half_rhythm"><div>Vitamin B12 and homocysteine levels</div></li><li class="half_rhythm"><div>If indicated, testing for autoimmune diseases (eg, antinuclear antibody for lupus)</div></li><li class="half_rhythm"><div>Urinalysis for proteinuria and hematuria</div></li><li class="half_rhythm"><div>Stool studies (for STEC-HUS, and viral serologies)</div></li><li class="half_rhythm"><div>Complement investigations
|
|
<ul><li class="half_rhythm"><div>Genetic testing for complement variants (confirms a diagnosis of TMA and provides prognostic information regarding the risk of progression to end-stage renal disease, risk of relapse in the native kidney, or recurrence after a kidney transplant)</div></li><li class="half_rhythm"><div>Testing for acquired factors (commonly factor H autoantibody)</div></li><li class="half_rhythm"><div>Serum antigenic level of complement proteins (C3, C4, factor H, factor I, factor B, properdin) and cell surface expression of membrane cofactor protein (membrane cofactor protein, cluster of differentiation 46 using flow cytometry)</div></li><li class="half_rhythm"><div>Complement functional assays: 50% hemolytic complement (classical), alternative pathway method (alternative), hemolytic assays, recombinant production of the variant followed by in vitro functional assays</div></li></ul>
|
|
</div></li></ul><p>
|
|
<b>Kidney Biopsy</b>
|
|
</p><p>If clinical suspicion remains high and laboratory evaluation is equivocal, a kidney biopsy can be considered (if thrombocytopenia is not a limiting factor). Results from a French retrospective study reported a 45% incidence of renal-limited TMA.<a class="bibr" href="#article-169704.r32" rid="article-169704.r32">[32]</a></p></div><div id="article-169704.s8"><h2 id="_article-169704_s8_">Treatment / Management</h2><p>Management of TMA is variable depending on the etiology of the TMA or any potential genetic involvement.<a class="bibr" href="#article-169704.r6" rid="article-169704.r6">[6]</a> Management of TTP, particularly immune-mediated, typically involves therapeutic plasma exchange (TPE) and immunosuppression with corticosteroids with or without rituximab.<a class="bibr" href="#article-169704.r6" rid="article-169704.r6">[6]</a><a class="bibr" href="#article-169704.r7" rid="article-169704.r7">[7]</a><a class="bibr" href="#article-169704.r13" rid="article-169704.r13">[13]</a><a class="bibr" href="#article-169704.r33" rid="article-169704.r33">[33]</a> Additionally, caplacizumab can be considered; this medication is an immunoglobulin preventing the vWF-platelet glycoprotein Ib interaction and consequent microvascular thrombosis.<a class="bibr" href="#article-169704.r34" rid="article-169704.r34">[34]</a><a class="bibr" href="#article-169704.r35" rid="article-169704.r35">[35]</a></p><p>Congenital or hereditary forms of TTP are managed with plasma infusions to replenish <i>ADAMTS13</i> levels.<a class="bibr" href="#article-169704.r7" rid="article-169704.r7">[7]</a><a class="bibr" href="#article-169704.r12" rid="article-169704.r12">[12]</a><a class="bibr" href="#article-169704.r13" rid="article-169704.r13">[13]</a><a class="bibr" href="#article-169704.r33" rid="article-169704.r33">[33]</a> In severe cases, plasma exchange may be considered to remove vWF multimers.<a class="bibr" href="#article-169704.r12" rid="article-169704.r12">[12]</a> Additionally, case reports and results from a recent phase 3 study suggest a potential role for recombinant <i>ADAMTS13</i> in management.<a class="bibr" href="#article-169704.r12" rid="article-169704.r12">[12]</a><a class="bibr" href="#article-169704.r36" rid="article-169704.r36">[36]</a> </p><p>Addressing the underlying conditions or precipitating factors is an essential first step in TMAs associated with other etiologies.<a class="bibr" href="#article-169704.r6" rid="article-169704.r6">[6]</a> If the TMA persists or has a severe presentation, anti-complement therapy with eculizumab or the longer-acting eculizumab (both are C5 complement stabilizers) can be considered.<a class="bibr" href="#article-169704.r6" rid="article-169704.r6">[6]</a><a class="bibr" href="#article-169704.r37" rid="article-169704.r37">[37]</a> See <b>Table.</b> Different TMA Syndromes and Suggested Treatment Options, which highlights the different management options for different TMA syndromes.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figarticle169704table0"><a href="/books/NBK611985/table/article-169704.table0/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobarticle169704table0"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="article-169704.table0"><a href="/books/NBK611985/table/article-169704.table0/?report=objectonly" target="object" rid-ob="figobarticle169704table0">Table</a></h4><p class="float-caption no_bottom_margin">Table. Different TMA Syndromes and Suggested Treatment Options. </p></div></div></div><div id="article-169704.s9"><h2 id="_article-169704_s9_">Differential Diagnosis</h2><p>Early identification and treatment of thrombotic microangiopathies is essential. However, TMA is a heterogeneous disorder with diagnosis primarily dependent on nonspecific markers of endothelial injury. Thus, many disorders can mimic TMAs and must be differentiated to ensure appropriate and timely treatment. These disorders and specific investigations to differentiate them from TMA are summarized in <b>Table. </b>Differential Diagnosis of TMA below.</p><p> <b>Table.</b> Differential Diagnosis of TMA</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figarticle169704table1"><a href="/books/NBK611985/table/article-169704.table1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobarticle169704table1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="article-169704.table1"><a href="/books/NBK611985/table/article-169704.table1/?report=objectonly" target="object" rid-ob="figobarticle169704table1">Table</a></h4><p class="float-caption no_bottom_margin"><i>Differential diagnosis</i> <i>Investigation</i></p></div></div></div><div id="article-169704.s10"><h2 id="_article-169704_s10_">Prognosis</h2><p>TMA was previously associated with very high rates of morbidity and mortality. However, the introduction of anti-complement therapy, therapeutic plasmapheresis (TPE), and immunosuppressive therapies have led to significant decreases in these rates. While TTP was once a nearly fatal diagnosis, it still has a mortality rate of up to 20% with TPE and maximal treatment, leaving room for improvement.<a class="bibr" href="#article-169704.r34" rid="article-169704.r34">[34]</a><a class="bibr" href="#article-169704.r39" rid="article-169704.r39">[39]</a><a class="bibr" href="#article-169704.r35" rid="article-169704.r35">[35]</a><a class="bibr" href="#article-169704.r39" rid="article-169704.r39">[39]</a></p><p>Similarly, CM-TMA was reported to have a 25% mortality, 50% risk of progression to end-stage renal disease (ESRD), and a 60% to 90% risk of recurrence with subsequent allograft loss in the absence of timely treatment.<a class="bibr" href="#article-169704.r39" rid="article-169704.r39">[39]</a><a class="bibr" href="#article-169704.r40" rid="article-169704.r40">[40]</a> With anti-complement therapy, comparable improvements have been observed in reducing morbidity and mortality. Results from a United Kingdom cohort study reported that eculizumab therapy had improved 5-year ESRD-free survival in patients with complement gene mutations or factor H autoantibodies from 40% to 85%.<a class="bibr" href="#article-169704.r4" rid="article-169704.r4">[4]</a><a class="bibr" href="#article-169704.r41" rid="article-169704.r41">[41]</a></p><p>With anti-complement therapy, hematologic response typically occurs within 1 week and kidney recovery within 30 days (but can occur up to 6-12 months after treatment).<a class="bibr" href="#article-169704.r4" rid="article-169704.r4">[4]</a><a class="bibr" href="#article-169704.r40" rid="article-169704.r40">[40]</a><a class="bibr" href="#article-169704.r41" rid="article-169704.r41">[41]</a> However, age at presentation, early disease recognition and initiation of eculizumab, presence of complement gene mutations, and severity of kidney injury are among key predictors of treatment response. Despite anti-complement therapy, 30% of patients may develop advanced chronic kidney disease (stage 3-5), and 20% may be left with permanent kidney injury.<a class="bibr" href="#article-169704.r4" rid="article-169704.r4">[4]</a><a class="bibr" href="#article-169704.r39" rid="article-169704.r39">[39]</a></p></div><div id="article-169704.s11"><h2 id="_article-169704_s11_">Complications</h2><p>If left untreated, TMA can lead to widespread organ damage, including thrombotic complications, kidney fibrosis, kidney failure, and ESRD requiring dialysis with poor outcomes. Anticomplement therapy carries the risk of infections and is costly, posing a significant physical and psychological burden on patients and their families. Even after kidney transplantation, some forms of TMA can recur, worsening outcomes.</p></div><div id="article-169704.s12"><h2 id="_article-169704_s12_">Deterrence and Patient Education</h2><p>Patients should be educated regarding TMA causes, underlying pathophysiology, workup, treatment, and outcomes of TMA to ensure a shared decision-making approach and improve outcomes. As disease recurrence is common, patients should be educated about symptoms indicating recurrent anemia or thrombocytopenia. </p></div><div id="article-169704.s13"><h2 id="_article-169704_s13_">Enhancing Healthcare Team Outcomes </h2><p>Thrombotic microangiopathy (TMA) is a clinicopathological entity that can result in multiple end-organ damage. The complex pathophysiology underlying TMA mandates efficient and expedient collaboration between different healthcare teams, facilitating the implementation of an appropriate diagnostic approach and management strategy for patients with TMA. The wide spectrum of organ involvement in TMA highlights the cardinal role of different healthcare teams and subspecialties in delivering the optimum patient care needed.</p><p>Delay in the diagnosis and treatment of TMA carries a poor prognosis with increased morbidity and mortality, stressing the importance of prompt identification of patients with TMA. Therapeutic interventions of TMA are largely dependent on the cause, including supportive care, plasma exchange in patients with TTP, the use of complement inhibitors in CM-TMA, and addressing underlying conditions or discontinuing causative drugs when applicable. These therapeutic techniques pose the risk of significant and sometimes fatal complications; however, the collaboration and clear communication between various medical teams and providers, with the clear determination of different team members' roles, can help healthcare teams enhance patient outcomes and deliver adequate and safe patient care.</p><p>Early identification and management of thrombotic microangiopathy and kidney involvement are imperative in reducing morbidity and mortality. The care of patients with this condition necessitates a collaborative approach among healthcare professionals to ensure patient-centered care and improve overall outcomes. Nephrologists, hematologists, pathologists, emergency medicine, critical care, advanced clinicians, nurses, pharmacists, and other healthcare professionals involved in the care of these patients should possess the essential clinical skills and knowledge to diagnose and manage focal onset seizures accurately. This includes expertise in recognizing the varied clinical presentations and understanding the nuances of laboratory and biopsy findings are crucial. Patient and caregiver education about triggering factors, medication compliance, and symptoms of recurrence are essential to prevent morbidity.</p><p>A strategic approach is equally crucial, involving evidence-based strategies to optimize treatment plans and minimize adverse effects. Ethical considerations must guide decision-making, ensuring informed consent and respecting patient autonomy in treatment choices. Each healthcare professional must be aware of their responsibilities and contribute their unique expertise to the patient's care plan, fostering a multidisciplinary approach. Effective interprofessional communication is paramount, allowing seamless information exchange and collaborative decision-making among the team members.</p><p>Care coordination plays a pivotal role in ensuring that the patient's journey from diagnosis to treatment and follow-up is well-managed, minimizing errors and enhancing patient safety. By embracing these principles of skill, strategy, ethics, responsibilities, interprofessional communication, and care coordination, healthcare professionals can deliver patient-centered care, ultimately improving patient outcomes and enhancing team performance in the management of thrombotic microangiopathy and kidney disease. </p></div><div id="article-169704.s14"><h2 id="_article-169704_s14_">Review Questions</h2><ul><li class="half_rhythm"><div>
|
|
<a href="https://www.statpearls.com/account/trialuserreg/?articleid=169704&utm_source=pubmed&utm_campaign=reviews&utm_content=169704" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Access free multiple choice questions on this topic.</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<a href="https://www.statpearls.com/articlelibrary/commentarticle/169704/?utm_source=pubmed&utm_campaign=comments&utm_content=169704" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Comment on this article.</a>
|
|
</div></li></ul></div><div id="article-169704.s15"><h2 id="_article-169704_s15_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="article-169704.r1">Salvadori M, Bertoni E. Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations. <span><span class="ref-journal">World J Nephrol. </span>2013 Aug 06;<span class="ref-vol">2</span>(3):56-76.</span> [<a href="/pmc/articles/PMC3832913/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3832913</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24255888" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24255888</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="article-169704.r2">GASSER C, GAUTIER E, STECK A, SIEBENMANN RE, OECHSLIN R. [Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia]. <span><span class="ref-journal">Schweiz Med Wochenschr. </span>1955 Sep 20;<span class="ref-vol">85</span>(38-39):905-9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/13274004" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 13274004</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="article-169704.r3">Kim YJ. A new pathological perspective on thrombotic microangiopathy. <span><span class="ref-journal">Kidney Res Clin Pract. </span>2022 Sep;<span class="ref-vol">41</span>(5):524-532.</span> [<a href="/pmc/articles/PMC9576460/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9576460</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35791743" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35791743</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="article-169704.r4">Nester CM, Feldman DL, Burwick R, Cataland S, Chaturvedi S, Cook HT, Cuker A, Dixon BP, Fakhouri F, Hingorani SR, Java A, van de Kar NCAJ, Kavanagh D, Leung N, Licht C, Noris M, O'Shaughnessy MM, Parikh SV, Peyandi F, Remuzzi G, Smith RJH, Sperati CJ, Waldman M, Walker P, Vivarelli M. An expert discussion on the atypical hemolytic uremic syndrome nomenclature-identifying a road map to precision: a report of a National Kidney Foundation Working Group. <span><span class="ref-journal">Kidney Int. </span>2024 Sep;<span class="ref-vol">106</span>(3):326-336.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/39174192" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 39174192</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="article-169704.r5">Karmali MA, Petric M, Lim C, Fleming PC, Arbus GS, Lior H. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. <span><span class="ref-journal">J Infect Dis. </span>1985 May;<span class="ref-vol">151</span>(5):775-82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3886804" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3886804</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="article-169704.r6">Java A, Burwick R, Chang A. Thrombotic Microangiopathies and the Kidney. <span><span class="ref-journal">Adv Kidney Dis Health. </span>2024 May;<span class="ref-vol">31</span>(3):255-264.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/39004465" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 39004465</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="article-169704.r7">Genest DS, Patriquin CJ, Licht C, John R, Reich HN. Renal Thrombotic Microangiopathy: A Review. <span><span class="ref-journal">Am J Kidney Dis. </span>2023 May;<span class="ref-vol">81</span>(5):591-605.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/36509342" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36509342</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="article-169704.r8">Kavanagh D, Ardissino G, Brocklebank V, Bouwmeester RN, Bagga A, Ter Heine R, Johnson S, Licht C, Ma ALT, Noris M, Praga M, Rondeau E, Sinha A, Smith RJH, Sheerin NS, Trimarchi H, Wetzels JFM, Vivarelli M, Van de Kar NCAJ, Greenbaum LA., Forum Participants. Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum. <span><span class="ref-journal">Kidney Int. </span>2024 Dec;<span class="ref-vol">106</span>(6):1038-1050.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/39395628" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 39395628</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="article-169704.r9">Schoettler ML, Carreras E, Cho B, Dandoy CE, Ho VT, Jodele S, Moissev I, Sanchez-Ortega I, Srivastava A, Atsuta Y, Carpenter P, Koreth J, Kroger N, Ljungman P, Page K, Popat U, Shaw BE, Sureda A, Soiffer R, Vasu S. Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplantation-Associated Thrombotic Microangiopathy: A Report on Behalf of the European Society for Blood and Marrow Transplantation, American Society for Transplantation and Cellular Therapy, Asia-Pacific Blood and Marrow Transplantation Group, and Center for International Blood and Marrow Transplant Research. <span><span class="ref-journal">Transplant Cell Ther. </span>2023 Mar;<span class="ref-vol">29</span>(3):151-163.</span> [<a href="/pmc/articles/PMC10119629/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10119629</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36442770" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36442770</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="article-169704.r10">Brocklebank V, Wood KM, Kavanagh D. Thrombotic Microangiopathy and the Kidney. <span><span class="ref-journal">Clin J Am Soc Nephrol. </span>2018 Feb 07;<span class="ref-vol">13</span>(2):300-317.</span> [<a href="/pmc/articles/PMC5967417/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5967417</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29042465" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29042465</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="article-169704.r11">Yonekura Collier AR, Zsengeller Z, Pernicone E, Salahuddin S, Khankin EV, Karumanchi SA. Placental sFLT1 is associated with complement activation and syncytiotrophoblast damage in preeclampsia. <span><span class="ref-journal">Hypertens Pregnancy. </span>2019 Aug;<span class="ref-vol">38</span>(3):193-199.</span> [<a href="/pmc/articles/PMC6707710/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6707710</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31291799" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31291799</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="article-169704.r12">Urra M, Lyons S, Teodosiu CG, Burwick R, Java A. Thrombotic Microangiopathy in Pregnancy: Current Understanding and Management Strategies. <span><span class="ref-journal">Kidney Int Rep. </span>2024 Aug;<span class="ref-vol">9</span>(8):2353-2371.</span> [<a href="/pmc/articles/PMC11328568/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC11328568</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/39156177" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 39156177</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="article-169704.r13">Palma LMP, Sridharan M, Sethi S. Complement in Secondary Thrombotic Microangiopathy. <span><span class="ref-journal">Kidney Int Rep. </span>2021 Jan;<span class="ref-vol">6</span>(1):11-23.</span> [<a href="/pmc/articles/PMC7575444/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7575444</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33102952" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33102952</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="article-169704.r14">Lee KY, Pan SY, Huang TT, Lin WC, Chiang YC. Drug-induced thrombotic microangiopathy after adjuvant chemotherapy in malignant ovarian germ cell tumor: A case report and literature review. <span><span class="ref-journal">Taiwan J Obstet Gynecol. </span>2024 Nov;<span class="ref-vol">63</span>(6):944-947.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/39482010" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 39482010</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="article-169704.r15">Chatzikonstantinou T, Gavriilaki M, Anagnostopoulos A, Gavriilaki E. An Update in Drug-Induced Thrombotic Microangiopathy. <span><span class="ref-journal">Front Med (Lausanne). </span>2020;<span class="ref-vol">7</span>:212.</span> [<a href="/pmc/articles/PMC7256484/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7256484</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32528969" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32528969</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="article-169704.r16">Java A, Kim AHJ. The Role of Complement in Autoimmune Disease-Associated Thrombotic Microangiopathy and the Potential for Therapeutics. <span><span class="ref-journal">J Rheumatol. </span>2023 Jun;<span class="ref-vol">50</span>(6):730-740.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/36642429" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36642429</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="article-169704.r17">Lee KH, Kronbichler A, Park DD, Park Y, Moon H, Kim H, Choi JH, Choi Y, Shim S, Lyu IS, Yun BH, Han Y, Lee D, Lee SY, Yoo BH, Lee KH, Kim TL, Kim H, Shim JS, Nam W, So H, Choi S, Lee S, Shin JI. Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review. <span><span class="ref-journal">Autoimmun Rev. </span>2017 Nov;<span class="ref-vol">16</span>(11):1160-1173.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28899799" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28899799</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="article-169704.r18">Valério P, Barreto JP, Ferreira H, Chuva T, Paiva A, Costa JM. Thrombotic microangiopathy in oncology - a review. <span><span class="ref-journal">Transl Oncol. </span>2021 Jul;<span class="ref-vol">14</span>(7):101081.</span> [<a href="/pmc/articles/PMC8065296/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8065296</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33862523" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33862523</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="article-169704.r19">Falanga A, Schieppati F, Russo L. Pathophysiology 1. Mechanisms of Thrombosis in Cancer Patients. <span><span class="ref-journal">Cancer Treat Res. </span>2019;<span class="ref-vol">179</span>:11-36.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31317478" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31317478</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>20.</dt><dd><div class="bk_ref" id="article-169704.r20">Hopkins CK, Yuan S, Lu Q, Ziman A, Goldfinger D. A severe case of atypical hemolytic uremic syndrome associated with pneumococcal infection and T activation treated successfully with plasma exchange. <span><span class="ref-journal">Transfusion. </span>2008 Nov;<span class="ref-vol">48</span>(11):2448-52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18673349" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18673349</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>21.</dt><dd><div class="bk_ref" id="article-169704.r21">Lopes da Silva R. Viral-associated thrombotic microangiopathies. <span><span class="ref-journal">Hematol Oncol Stem Cell Ther. </span>2011;<span class="ref-vol">4</span>(2):51-9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21727765" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21727765</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>22.</dt><dd><div class="bk_ref" id="article-169704.r22">Java A, Apicelli AJ, Liszewski MK, Coler-Reilly A, Atkinson JP, Kim AH, Kulkarni HS. The complement system in COVID-19: friend and foe? <span><span class="ref-journal">JCI Insight. </span>2020 Aug 06;<span class="ref-vol">5</span>(15)</span> [<a href="/pmc/articles/PMC7455060/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7455060</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32554923" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32554923</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>23.</dt><dd><div class="bk_ref" id="article-169704.r23">Yan K, Desai K, Gullapalli L, Druyts E, Balijepalli C. Epidemiology of Atypical Hemolytic Uremic Syndrome: A Systematic Literature Review. <span><span class="ref-journal">Clin Epidemiol. </span>2020;<span class="ref-vol">12</span>:295-305.</span> [<a href="/pmc/articles/PMC7075343/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7075343</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32210633" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32210633</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>24.</dt><dd><div class="bk_ref" id="article-169704.r24">Lapeyraque AL, Bitzan M, Al-Dakkak I, Francis M, Huang SS, Kaprielian R, Larratt L, Pavenski K, Ribic C, Tosikyan A, Licht C, Philibert D. Clinical Characteristics and Outcome of Canadian Patients Diagnosed With Atypical Hemolytic Uremic Syndrome. <span><span class="ref-journal">Can J Kidney Health Dis. </span>2020;<span class="ref-vol">7</span>:2054358119897229.</span> [<a href="/pmc/articles/PMC6984425/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6984425</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32047641" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32047641</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>25.</dt><dd><div class="bk_ref" id="article-169704.r25">Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. <span><span class="ref-journal">Orphanet J Rare Dis. </span>2011 Sep 08;<span class="ref-vol">6</span>:60.</span> [<a href="/pmc/articles/PMC3198674/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3198674</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21902819" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21902819</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>26.</dt><dd><div class="bk_ref" id="article-169704.r26">Sullivan M, Erlic Z, Hoffmann MM, Arbeiter K, Patzer L, Budde K, Hoppe B, Zeier M, Lhotta K, Rybicki LA, Bock A, Berisha G, Neumann HP. Epidemiological approach to identifying genetic predispositions for atypical hemolytic uremic syndrome. <span><span class="ref-journal">Ann Hum Genet. </span>2010 Jan;<span class="ref-vol">74</span>(1):17-26.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20059470" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20059470</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>27.</dt><dd><div class="bk_ref" id="article-169704.r27">Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. <span><span class="ref-journal">Clin J Am Soc Nephrol. </span>2010 Oct;<span class="ref-vol">5</span>(10):1844-59.</span> [<a href="/pmc/articles/PMC2974386/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2974386</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20595690" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20595690</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>28.</dt><dd><div class="bk_ref" id="article-169704.r28">Zhang K, Lu Y, Harley KT, Tran MH. Atypical Hemolytic Uremic Syndrome: A Brief Review. <span><span class="ref-journal">Hematol Rep. </span>2017 Jun 01;<span class="ref-vol">9</span>(2):7053.</span> [<a href="/pmc/articles/PMC5472348/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5472348</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28626544" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28626544</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>29.</dt><dd><div class="bk_ref" id="article-169704.r29">Vyas A, Isaac S, Kaur D, Yadav U. Role of the PLASMIC Score in the Management of Thrombotic Thrombocytopenic Purpura. <span><span class="ref-journal">Cureus. </span>2023 Mar;<span class="ref-vol">15</span>(3):e36188.</span> [<a href="/pmc/articles/PMC10104422/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10104422</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37065284" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37065284</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>30.</dt><dd><div class="bk_ref" id="article-169704.r30">Li A, Khalighi PR, Wu Q, Garcia DA. External validation of the PLASMIC score: a clinical prediction tool for thrombotic thrombocytopenic purpura diagnosis and treatment. <span><span class="ref-journal">J Thromb Haemost. </span>2018 Jan;<span class="ref-vol">16</span>(1):164-169.</span> [<a href="/pmc/articles/PMC5760324/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5760324</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29064619" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29064619</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>31.</dt><dd><div class="bk_ref" id="article-169704.r31">Fage N, Orvain C, Henry N, Mellaza C, Beloncle F, Tuffigo M, Geneviève F, Coppo P, Augusto JF, Brilland B. Proteinuria Increases the PLASMIC and French Scores Performance to Predict Thrombotic Thrombocytopenic Purpura in Patients With Thrombotic Microangiopathy Syndrome. <span><span class="ref-journal">Kidney Int Rep. </span>2022 Feb;<span class="ref-vol">7</span>(2):221-231.</span> [<a href="/pmc/articles/PMC8820983/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8820983</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35155861" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35155861</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>32.</dt><dd><div class="bk_ref" id="article-169704.r32">Maisons V, Duval A, Mesnard L, Frimat M, Fakhouri F, Grangé S, Servais A, Cartery C, Fauchier L, Coppo P, Titeca-Beauport D, Fage N, Delmas Y, Quérard AH, Seret G, Bobot M, Le Quintrec M, Ville S, von Tokarski F, Chauvet S, Wynckel A, Martins M, Schurder J, Barbet C, Sautenet B, Gatault P, Caillard S, Vuiblet V, Halimi JM., MATRIX Consortium Group. Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies. <span><span class="ref-journal">Kidney Int. </span>2024 May;<span class="ref-vol">105</span>(5):1100-1112.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/38431217" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 38431217</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>33.</dt><dd><div class="bk_ref" id="article-169704.r33">Hanna RM, Henriksen K, Kalantar-Zadeh K, Ferrey A, Burwick R, Jhaveri KD. Thrombotic Microangiopathy Syndromes-Common Ground and Distinct Frontiers. <span><span class="ref-journal">Adv Chronic Kidney Dis. </span>2022 Mar;<span class="ref-vol">29</span>(2):149-160.e1.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/35817522" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35817522</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>34.</dt><dd><div class="bk_ref" id="article-169704.r34">Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK., HERCULES Investigators. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. <span><span class="ref-journal">N Engl J Med. </span>2019 Jan 24;<span class="ref-vol">380</span>(4):335-346.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30625070" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30625070</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>35.</dt><dd><div class="bk_ref" id="article-169704.r35">Knoebl P, Cataland S, Peyvandi F, Coppo P, Scully M, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Minkue Mi Edou J, De Winter H, Callewaert F. Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study. <span><span class="ref-journal">J Thromb Haemost. </span>2020 Feb;<span class="ref-vol">18</span>(2):479-484.</span> [<a href="/pmc/articles/PMC7027866/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7027866</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31691462" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31691462</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>36.</dt><dd><div class="bk_ref" id="article-169704.r36">Scully M, Antun A, Cataland SR, Coppo P, Dossier C, Biebuyck N, Hassenpflug WA, Kentouche K, Knöbl P, Kremer Hovinga JA, López-Fernández MF, Matsumoto M, Ortel TL, Windyga J, Bhattacharya I, Cronin M, Li H, Mellgård B, Patel M, Patwari P, Xiao S, Zhang P, Wang LT., cTTP Phase 3 Study Investigators. Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura. <span><span class="ref-journal">N Engl J Med. </span>2024 May 02;<span class="ref-vol">390</span>(17):1584-1596.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/38692292" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 38692292</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>37.</dt><dd><div class="bk_ref" id="article-169704.r37">Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Frémeaux-Bacchi V, Kavanagh D, Nester CM, Noris M, Pickering MC, Rodríguez de Córdoba S, Roumenina LT, Sethi S, Smith RJ., Conference Participants. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. <span><span class="ref-journal">Kidney Int. </span>2017 Mar;<span class="ref-vol">91</span>(3):539-551.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27989322" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27989322</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>38.</dt><dd><div class="bk_ref" id="article-169704.r38">Jodele S, Dandoy CE, Lane A, Laskin BL, Teusink-Cross A, Myers KC, Wallace G, Nelson A, Bleesing J, Chima RS, Hirsch R, Ryan TD, Benoit S, Mizuno K, Warren M, Davies SM. Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab. <span><span class="ref-journal">Blood. </span>2020 Mar 26;<span class="ref-vol">135</span>(13):1049-1057.</span> [<a href="/pmc/articles/PMC7099329/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7099329</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31932840" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31932840</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>39.</dt><dd><div class="bk_ref" id="article-169704.r39">Connelly-Smith L, Alquist CR, Aqui NA, Hofmann JC, Klingel R, Onwuemene OA, Patriquin CJ, Pham HP, Sanchez AP, Schneiderman J, Witt V, Zantek ND, Dunbar NM. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue. <span><span class="ref-journal">J Clin Apher. </span>2023 Apr;<span class="ref-vol">38</span>(2):77-278.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/37017433" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37017433</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>40.</dt><dd><div class="bk_ref" id="article-169704.r40">Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. <span><span class="ref-journal">N Engl J Med. </span>2013 Jun 06;<span class="ref-vol">368</span>(23):2169-81.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23738544" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23738544</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>41.</dt><dd><div class="bk_ref" id="article-169704.r41">Brocklebank V, Walsh PR, Smith-Jackson K, Hallam TM, Marchbank KJ, Wilson V, Bigirumurame T, Dutt T, Montgomery EK, Malina M, Wong EKS, Johnson S, Sheerin NS, Kavanagh D. Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study. <span><span class="ref-journal">Blood. </span>2023 Oct 19;<span class="ref-vol">142</span>(16):1371-1386.</span> [<a href="/pmc/articles/PMC10651868/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10651868</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37369098" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37369098</span></a>]</div></dd></dl></dl></div><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_top_margin">
|
|
<b>Disclosure: </b>Abdullah Jalal declares no relevant financial relationships with ineligible companies.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_top_margin">
|
|
<b>Disclosure: </b>Mohammad Atari declares no relevant financial relationships with ineligible companies.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_top_margin">
|
|
<b>Disclosure: </b>Mohamed Hassanein declares no relevant financial relationships with ineligible companies.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_top_margin">
|
|
<b>Disclosure: </b>Anuja Java declares no relevant financial relationships with ineligible companies.</p></div></dd></dl></dl></div></div></div><div class="fm-sec"><h2 id="_NBK611985_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Abdullah Jalal</span><sup>1</sup>; <span itemprop="author">Mohammad Atari</span><sup>2</sup>; <span itemprop="author">Mohamed Hassanein</span><sup>3</sup>; <span itemprop="author">Anuja Java</span><sup>4</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup> Mayo Clinic Rochester, Minnesota</div><div class="affiliation"><sup>2</sup> University of Mississippi Medical Center</div><div class="affiliation"><sup>3</sup> University of Mississippi Medical Center</div><div class="affiliation"><sup>4</sup> Washington University School of Medicine</div><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">January 17, 2025</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 2025, StatPearls Publishing LLC.<p class="small">
|
|
This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
|
|
(<a href="https://creativecommons.org/licenses/by-nc-nd/4.0/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">
|
|
http://creativecommons.org/licenses/by-nc-nd/4.0/
|
|
</a>), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.
|
|
</p></div></div><h3>Publisher</h3><p><a href="https://www.statpearls.com/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">StatPearls Publishing</a>, Treasure Island (FL)</p><h3>NLM Citation</h3><p>Jalal A, Atari M, Hassanein M, et al. Thrombotic Microangiopathy and the Kidney. [Updated 2025 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobarticle169704table0"><div id="article-169704.table0" class="table"><h3><span class="title">Table. Different TMA Syndromes and Suggested Treatment Options</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK611985/table/article-169704.table0/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__article-169704.table0_lrgtbl__"><table style="width: 800px;" class="no_top_margin"><tbody><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>TMA syndromes</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p><b>Treatment options</b></p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Immune TTP</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Therapeutic plasma exchange </p>
|
|
<p>Immunosuppression</p>
|
|
<p>Caplacizumab</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Congenital TTP</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Fresh frozen plasma</p>
|
|
<p>Therapeutic plasma exchange</p>
|
|
<p>Recombinant <i>ADAMTS13</i> <a class="bibr" href="#article-169704.r36" rid="article-169704.r36">[36]</a></p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Complement-mediated TMA</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Genetic CM-TMA</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Anti-complement therapy</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b> Acquired CM-TMA</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Anti-complement therapy</p>
|
|
<p>Therapeutic plasma exchange</p>
|
|
<p>Immunosuppression</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b> TMA associated with secondary causes</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p> <b>Treatment options</b></p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Infection-associated</b></p>
|
|
<p>Bacterial (<i>Streptococcus pneumoniae</i>, STEC)</p>
|
|
<p>Viral (ie, influenza, human immunodeficiency virus, dengue)</p>
|
|
<p>Protozoa (<i>Toxoplasma gondii</i>)</p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Supportive management</p>
|
|
<p>Treatment of underlying infection</p>
|
|
<p>Antibiotic use in STEC is controversial</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Drug-induced</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Drug withdrawal (if possible)</p>
|
|
<p>Can consider therapeutic plasma exchange with immune-mediated TMA</p>
|
|
<p>Some case reports describe using anti-complement therapy</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Cobalmin deficiency-associated</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Vitamin B12 repletion</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Mutation-associated non-complement mediated </b></p>
|
|
<p>DGKE-TMA, TSEN-TMA, INF-TMA, EXOSC3-TMA</p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Supportive care</p>
|
|
<p>Limited benefits of anti-complement therapy</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Pregnancy-associated</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Pre-eclampsia/HELLP</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Supportive care and fetal delivery, if feasible</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>TTP</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Can consider plasma infusion, therapeutic plasma exchange for TTP</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Postpartum TMA</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Consider anti-complement therapy</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Malignancy-associated</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Treatment of underlying malignancy</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Transplant-associated </b>(stem cell, solid organ transplant)</p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Supportive</p>
|
|
<p>Treat precipitating factors (ie, infections, drugs, rejection)</p>
|
|
<p>Anticomplement therapy with several ongoing trials of anti-complement therapy</p>
|
|
<p>Note: HSCT-TMA algorithm available at this reference <a class="bibr" href="#article-169704.r38" rid="article-169704.r38">[38]</a></p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Auto-immune associated (ie, SLE)</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Treat underlying condition:</p>
|
|
<ul><li class="half_rhythm"><div>Immunosuppression for SLE</div></li><li class="half_rhythm"><div>Consider TPE (if immune-mediated)</div></li><li class="half_rhythm"><div>Consider anti-complement therapy</div></li></ul>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Scleroderma renal crisis</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Angiotensin-converting-enzyme inhibitors (specifically captopril)</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<b>Catastrophic antiphospholipid syndrome</b>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Anticoagulation</p>
|
|
<p>Immunosuppression for antiphospholipid syndrome (corticosteroids)</p>
|
|
<p>Intravenous immunoglobulin or TPE</p>
|
|
<p>For refractory cases, a trial of rituximab or anti-complement therapy can be considered <a class="bibr" href="#article-169704.r12" rid="article-169704.r12">[12]</a></p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="width: 240.525px;vertical-align:top;">
|
|
<p><b>Malignant hypertension</b></p>
|
|
</td><td rowspan="1" colspan="1" style="width: 303.342px;vertical-align:top;">
|
|
<p>Supportive Care</p>
|
|
<p>Blood pressure management</p>
|
|
<p>Anti-complement therapy if no response to supportive care by 48 to 72 hrs.</p>
|
|
</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobarticle169704table1"><div id="article-169704.table1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK611985/table/article-169704.table1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__article-169704.table1_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p><b>Differential diagnosis</b></p>
|
|
</td><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p><b>Investigation</b></p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Disseminated Intravascular Coagulation</p>
|
|
</td><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>PT, PTT, fibrinogen, d-dimer</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Autoimmune disease (ie, antiphospholipid syndrome, systemic lupus erythematosus)</p>
|
|
</td><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Disease-specific antibodies (ie, anti-cardiolipin/anti-beta2 glycoprotein I antibodies, antinuclear antibody)</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Heart valve-induced hemolysis (ie, prosthetic valves, Heyde syndrome)</p>
|
|
</td><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Medical history</p>
|
|
<p>Echocardiogram</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Tick-borne illnesses (ie, babesiosis)</p>
|
|
</td><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Peripheral blood smear</p>
|
|
<p>Polymerase chain reaction</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Autoimmune hemolytic anemia</p>
|
|
</td><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Coombs test</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Viral infections (cytomegalovirus, human polyomavirus 1)</p>
|
|
</td><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Polymerase chain reaction</p>
|
|
</td></tr><tr><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Antibody-mediated rejection (antibody-mediated rejection)</p>
|
|
</td><td rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<p>Donor-specific antibodies Kidney biopsy Histologic features of antibody-mediated rejection</p>
|
|
</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
|
|
|
|
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal105 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
|
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
|
|
|
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
|
|
</html>
|