{"id":19303,"date":"2019-01-23T14:23:17","date_gmt":"2019-01-23T19:23:17","guid":{"rendered":"https:\/\/www.med.unc.edu\/medicine\/?post_type=podcast&#038;p=19303"},"modified":"2023-06-06T13:57:05","modified_gmt":"2023-06-06T17:57:05","slug":"tma-saha","status":"publish","type":"episode","link":"https:\/\/www.med.unc.edu\/medicine\/news\/chairs-corner\/podcast\/tma-saha\/","title":{"rendered":"Thrombotic Microangiopathy (TMA) &#8211; with Dr. Manish Saha"},"content":{"rendered":"<figure id=\"attachment_4233\" class=\"thumbnail wp-caption alignright\" style=\"width: 250px\"><img loading=\"lazy\" decoding=\"async\" class=\"size-medium wp-image-4233\" src=\"https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2018\/12\/tma-saha-image2-240x300.jpeg\" alt=\"Manish Saha, MD\" width=\"240\" height=\"300\" srcset=\"https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2018\/12\/tma-saha-image2-240x300.jpeg 240w, https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2018\/12\/tma-saha-image2-819x1024.jpeg 819w, https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2018\/12\/tma-saha-image2-768x960.jpeg 768w, https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2018\/12\/tma-saha-image2-1228x1536.jpeg 1228w, https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2018\/12\/tma-saha-image2-600x750.jpeg 600w, https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2018\/12\/tma-saha-image2-301x376.jpeg 301w, https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2018\/12\/tma-saha-image2.jpeg 1550w\" sizes=\"auto, (max-width: 240px) 100vw, 240px\" \/><figcaption class=\"caption wp-caption-text\">Manish Saha, MD<\/figcaption><\/figure>\n<p>Dr. Manish Saha talks with Dr. Ron Falk about thrombotic microangiopathy, or TMA. They discuss two types of TMA, thrombotic thrombocytopenic purpura and hemolytic syndrome, and the symptoms associated with each. They also talk about the testing and treatment for TMA. Dr. Saha is an Assistant Professor of Medicine in the Division of Nephrology and Hypertension.<\/p>\n<div class=\"alert alert-grey\">\n\u201cThe early symptoms are very vague. They may have malaise, weakness, and headache. Most of the time they get hospitalized because when the bloodwork is done, the platelet count is severely low in these patients, and sometimes so dangerously low they get admitted to the hospital. That\u2019s when additional blood tests are done and ADAMTS13 and other evaluations are done, and when they are picked up.&#8221;<\/p>\n<p>\u2013 Dr. Manish Saha on when TMA is often diagnosed\n<\/p><\/div>\n<!--[if lt IE 9]><script>document.createElement('audio');<\/script><![endif]-->\n\t<div class=\"wp-playlist wp-audio-playlist wp-playlist-light\">\n\t\t\t<div class=\"wp-playlist-current-item\"><\/div>\n\t\t<audio controls=\"controls\" preload=\"none\" width=\"1118\"\n\t\t\t><\/audio>\n\t<div class=\"wp-playlist-next\"><\/div>\n\t<div class=\"wp-playlist-prev\"><\/div>\n\t<noscript>\n\t<ol>\n\t\t<li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/03\/tma-saha.mp3'>Thrombotic Microangiopathy (TMA) - Full-Length<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/tma-whatisit.mp3'>Types of TMA<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/tma-enzyme.mp3'>The role of enzyme ADAMTS13<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/tma-hus.mp3'>Hemolytic uremic syndrome (HUS)<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/tma-testing.mp3'>Testing for TMA<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/tma-treatment.mp3'>Treating TTP & HUS<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/tma-prognosis.mp3'>Prognosis, inheritance & more information<\/a><\/li>\t<\/ol>\n\t<\/noscript>\n\t<script type=\"application\/json\" class=\"wp-playlist-script\">{\"type\":\"audio\",\"tracklist\":true,\"tracknumbers\":true,\"images\":true,\"artists\":true,\"tracks\":[{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/03\\\/tma-saha.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Thrombotic Microangiopathy (TMA) - Full-Length\",\"caption\":\"\",\"description\":\"\\\"Thrombotic Microangiopathy (TMA) - with Dr. Manish Saha\\\" from Thrombotic Microangiopathy (TMA) - with Dr. Manish Saha by UNC Department of Medicine - Dr. Ron Falk. Released: 2018. Genre: \\\"Easy Lemon (30 second)\\\" Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 3.0 License http:.\",\"meta\":{\"artist\":\"UNC Department of Medicine - Dr. Ron Falk\",\"album\":\"Thrombotic Microangiopathy (TMA) - with Dr. Manish Saha\",\"genre\":\"\\\"Easy Lemon (30 second)\\\" Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 3.0 License http:\",\"year\":\"2018\",\"length_formatted\":\"16:32\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/tma-whatisit.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Types of TMA\",\"caption\":\"\",\"description\":\"\\\"tma-whatisit\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"2:42\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/tma-enzyme.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"The role of enzyme ADAMTS13\",\"caption\":\"\",\"description\":\"\\\"tma-enzyme\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"2:05\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/tma-hus.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Hemolytic uremic syndrome (HUS)\",\"caption\":\"\",\"description\":\"\\\"tma-hus\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"3:37\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/tma-testing.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Testing for TMA\",\"caption\":\"\",\"description\":\"\\\"tma-testing\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"1:34\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/tma-treatment.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Treating TTP & HUS\",\"caption\":\"\",\"description\":\"\\\"tma-treatment\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"3:43\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/tma-prognosis.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Prognosis, inheritance & more information\",\"caption\":\"\",\"description\":\"\\\"tma-prognosis\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"1:51\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}}]}<\/script>\n<\/div>\n\t\n<p>&nbsp;<\/p>\n<p><strong>Ron Falk, MD: <\/strong>Hello, and welcome to the Chair\u2019s Corner from the Department of Medicine at the University of North Carolina.<\/p>\n<p>This is our series where we discuss different genetic diseases with physicians who treat patients with these conditions. Today, we will talk about thrombotic microangiopathy, or TMA.<\/p>\n<p>We welcome Dr. Manish Saha, who is an Assistant Professor of Medicine in our Division of Nephrology and Hypertension. Welcome, Dr. Saha.<\/p>\n<p><strong>Manish Saha, MD:<\/strong> Thank you.<\/p>\n<h3><span class=\"blue\">Types of TMA<\/span><\/h3>\n<p><strong>Falk:<\/strong> What is thrombotic microangiopathy? What is TMA?<\/p>\n<p><strong>Saha:<\/strong> TMA, as the name suggests, is thrombosis or blood clots in small blood vessels of our body. These blood vessels are called arterioles or capillaries. Clinically, it is manifested as low platelet counts, also known as thrombocytopenia, because the platelet gets consumed in the clots. Then something called non-immune-mediated, or mechanical destruction of your red blood cells, giving rise to a low hemoglobin and making you anemic. If these blood clots form in any organ, you have organ-specific dysfunction. If it happens in the kidney, you have kidney injury. If it happens in the brain, you have neurological symptoms.<\/p>\n<p><strong>Falk:<\/strong> There are many types of thrombotic microangiopathies, many types of TMA. There are two of them that we should spend a little more time on. One of them is known as thrombotic thrombocytopenic purpura\u2014can\u2019t say that fast three times! It has an abbreviation known as TTP. What is TTP?<\/p>\n<p><strong>Saha:<\/strong> The clinical syndrome of TMA is shared by many disease entities, including what you said, TTP\u2014as the name suggests, thrombotic thrombocytopenic purpura. It was originally described over sixty years ago, the patient had features of small blood clots in the blood vessels. They also had low platelet count\u2014hence the name thrombocytopenia, and they had a purpuric rash. That\u2019s how the name was initially coined. Now, TTP manifests as TMA with neurological syndrome\u2014neurological symptoms of headache, confusion, signs and symptoms of stroke, and other features. It is one of the causes of TMA.<\/p>\n<p><strong>Falk:<\/strong> There used to be described what is known as a pentad, or five different features of TTP. What were those?<\/p>\n<p><strong>Saha:<\/strong> The pentad that was described, many years ago, included fever, low platelet count\u2014also known as thrombocytopenia, neurological symptoms, kidney injury and low hemoglobin or anemia. This pentad was described years ago, but recent studies show that less than five percent of patients with TTP had the pentad of symptoms. TTP does not need to present with all of these features\u2014they can just have one marker and still have TTP.<\/p>\n<h3><span class=\"blue\">The role of enzyme ADAMTS13<\/span><\/h3>\n<p><strong>Falk:<\/strong> One of the causes of TTP is an absence, or an inhibition of an enzyme known as ADAMTS13. There are various ways of pronouncing that acronym of a metalloproteinase. What is it?<\/p>\n<p><strong>Saha:<\/strong> ADAMTS13 is an enzyme that is made by the liver. It is called metalloprotease because it requires a metal like calcium or zinc for this action. So, if somebody has a vessel injury, the body makes another protein known as ultra large von Willebrand factor, which is a clotting factor. It helps in forming a clot at the site of injury of the blood vessel.<\/p>\n<p><strong>Falk:<\/strong> Which is normal\u2014that\u2019s what it\u2019s supposed to do.<\/p>\n<p><strong>Saha:<\/strong> This is normal. This is regulated, because you don\u2019t want this process to continue. Once the platelet plug is formed and the blood vessel is repaired, you want the process to stop there. That is where ADAMTS13 comes into play. What this enzyme does, it controls the process. The platelet plug is limited to the site of injury and it doesn\u2019t get unregulated.<\/p>\n<p><strong>Falk:<\/strong> Really, what ADAMTS13 does, is to chop up high molecular weight, or ultra-high molecular weight von Willebrand\u2019s factor, which comes out of cells known as endothelial cells. That\u2019s how you stop the process you described. How does one as an individual, then, not have enough of this enzyme?<\/p>\n<p><strong>Saha:<\/strong> In two ways. One is known as congenital TTP, where people have a defect in the genetic material that makes this enzyme. So, if you have a genetic mutation, you do not make enough of this enzyme. These patients present early in life, also known as congenital TTP. Adults can also have TTP, but usually they make enough of that ADAMTS13 enzyme, but there\u2019s an autoantibody that inhibits the action of ADAMTS13.<\/p>\n<h3><span class=\"blue\">Hemolytic uremic syndrome, HUS<\/span><\/h3>\n<p><strong>Falk:<\/strong> There\u2019s another leading cause of TMA, which is known as the hemolytic syndrome, or HUS. What is that?<\/p>\n<p><strong>Saha:<\/strong> HUS is hemolytic uremic syndrome. When it was initially described, they found that patients with TMA, instead of having neurological symptoms like in TTP, they have kidney failure. That\u2019s where the term \u201curemia\u201d was coined. Patients with TMA who primarily have kidney involvement have something called hemolytic syndrome. It can be caused mainly by two different entities. The first, and common one, is infections, and these infections are mainly from E. coli, shigella, pneumococcus, among other infections.<\/p>\n<p><strong>Falk:<\/strong> The most common one in the state of North Carolina, was at one point, a petting zoo at the North Carolina state fair. Petting goats that carried, on their fur, those bugs. You can also get those microorganisms or bacteria from food.<\/p>\n<p><strong>Saha:<\/strong> Yes, uncooked meat, including hamburgers , beef and other produces may be a source of this E.coli<\/p>\n<p><strong>Falk:<\/strong> It\u2019s the reason to cook hamburgers all the way through, it\u2019s the reason to wash things even like alfalfa sprouts really well, because otherwise those bacteria just aren\u2019t washed away.<\/p>\n<p><strong>Saha:<\/strong> Correct.<\/p>\n<p><strong>Falk:<\/strong> In addition to the infectious causes of hemolytic uremic syndrome, there is something else called the \u201catypical\u201d form, which is a genetic abnormality as well.<\/p>\n<p><strong>Saha:<\/strong> Correct. Atypical HUS is when you have the same features, but it\u2019s not caused by an infection, but due to an unregulated activation of something called an alternate complement pathway. Complement pathway is one of our defense mechanisms that fights infections. A genetic defect or an antibody in one of these regulators lets this alternate complement pathway get activated uncontrollably and result in thrombotic microangiopathy.<\/p>\n<p><strong>Falk:<\/strong> In terms of the genetic causes of these thrombotic microangiopathies, there is the absence or deficiency of an enzyme that cleaves the protein that stops you from bleeding, and another genetic cause of the same kind of thrombotic microangiopathy is a defect in the way we control infection. So, both of these are genetic abnormalities that pertain to regulation of bleeding or regulation of infection\u2014handling infections.<\/p>\n<p><strong>Saha:<\/strong> Correct.<\/p>\n<p><strong>Falk:<\/strong> What is the most common place for a patient to discover that they have thrombotic microangiopathy? Is it because they are hospitalized for clotting and bleeding and having neurological dysfunction, or are patients picked up in the outpatient setting?<\/p>\n<p><strong>Saha:<\/strong> It\u2019s rarely picked up in the outpatient setting, because the early symptoms are very vague. They may have a malaise, weakness, and headache. Most of the time they get hospitalized because when the bloodwork is done, the platelet count is severely low in these patients, and sometimes so dangerously low they get admitted to the hospital. That\u2019s when additional blood tests are done and ADAMTS13 and other evaluations are done, and when they are picked up.<\/p>\n<h3><span class=\"blue\">Testing for TMA<\/span><\/h3>\n<p><strong>Falk:<\/strong> How do you test for these TMA\u2019s, and how accurate are those tests?<\/p>\n<p><strong>Saha:<\/strong> The initial part when you\u2019re diagnosing someone with TMA, you just need routine bloodwork, to make sure you have evidence of low platelet counts, called thrombocytopenia, and have mechanical destruction of RBC\u2019s, evident on peripheral smear as schistocytes, and you may have evidence of an organ dysfunction, like elevated creatinine because the kidneys are involved, or any other organ involvement.<\/p>\n<p>Once you know you have evidence of thrombotic microangiopathy, then the question is, is it TTP or HUS, or any other secondary cause? For TTP, you need to measure the ADAMTS13 activity level, and for HUS, you need to make sure there is no infection. If there is not, and you are looking for atypical HUS (complement mediated), then you need to study the genetic defects that exist in the regulators of alternate complement pathway.<\/p>\n<p><strong>Falk:<\/strong> How accurate are those tests?<\/p>\n<p><strong>Saha:<\/strong> For atypical HUS (complement mediated), you can only expect to get about fifty percent positivity in patients who clinically present with atypical HUS. In the other fifty percent of patients, it can be normal, but they can still have atypical HUS.<\/p>\n<p><strong>Falk:<\/strong> Not because there\u2019s not enough of it, but because it doesn\u2019t function well.<\/p>\n<p><strong>Saha:<\/strong> It doesn\u2019t function well, and maybe the testing we have now as of 2018 is not sensitive enough to pick up every mutation. Hopefully, with time it will improve. Also, we will find other causes.<\/p>\n<h3><span class=\"blue\">Treating TTP &amp; HUS<\/span><\/h3>\n<p><strong>Falk:<\/strong> How do you treat somebody with TTP?<\/p>\n<p><strong>Saha:<\/strong> Congenital TTP is usually treated by plasma infusion, meaning you\u2019re giving back to them normal ADAMTS13 that exists in blood. Patients who are adults and have adult-onset TTP, because it\u2019s caused by an autoantibody, need to do something called a plasma exchange.<\/p>\n<p><strong>Falk:<\/strong> You get rid of it.<\/p>\n<p><strong>Saha:<\/strong> You get rid of the antibody against ADAMTS13 , and you treat them with immunosuppression like steroids and other medications to stop antibody production.<\/p>\n<p><strong>Falk:<\/strong> How about HUS? How do you treat that?<\/p>\n<p><strong>Saha:<\/strong> HUS, if it\u2019s caused by an infection, you treat the infection and supportive therapy. If it is atypical HUS(complement mediated), then there is a specific drug , anti-complement 5 medication, also known as Eculizumab, that you may consider<\/p>\n<p><strong>Falk:<\/strong> That has really revolutionized the treatment, especially children with atypical HUS. It has made it so that their life expectancy is pretty good.<\/p>\n<p><strong>Saha:<\/strong> Correct. Since the FDA approved it a couple of years ago, this is probably the only drug that is available that has revolutionized the treatment and the prognosis or outcome of atypical HUS.<\/p>\n<p><strong>Falk:<\/strong> Unfortunately, it is an extremely expensive drug.<\/p>\n<p><strong>Saha:<\/strong> It is very expensive, yes.<\/p>\n<p><strong>Falk:<\/strong> One that should really only be used if you know for sure that the person has an inherited complement deficiency.<\/p>\n<p><strong>Saha:<\/strong> Yes, only when the suspicion is very high, or you have evidence should you consider it.<\/p>\n<p><strong>Falk:<\/strong> Tell us a little bit more about this drug Eculizumab, which is an infusion given once a month that inhibits what is known as C5, or the fifth component of complement.<\/p>\n<p><strong>Saha:<\/strong> This drug is an infusion. There is no pill or subcutaneous version yet. There is induction phase, and there\u2019s a maintenance phase, and the dose vary according to your weight. This is a drug that inhibits complement factor 5. Patients is at risk for something known as Neisseria meningitis. They need to be vaccinated for all the serogroups that are recommended by the CDC, as well as antibiotic prophylaxis for the first few weeks at least, if not longer, when you\u2019re starting to be on Eculizumab infusion.<\/p>\n<p><strong>Falk:<\/strong> Then there\u2019s the maintenance phase.<\/p>\n<p><strong>Saha:<\/strong> Then there\u2019s the maintenance phase that is a little bit more complicated to see how long you should use it. It depends on, how is the patient responding to it? What is the recovery of the organ involvement? And what kind of mutation does the patient have?<\/p>\n<p><strong>Falk:<\/strong> In atypical HUS at this point, the question is not if the drug is useful, it\u2019s very, very useful and lifesaving, but when can one stop it? There is tremendous controversy about when you can stop that drug.<\/p>\n<p><strong>Saha:<\/strong> Yes, it is a wonderful drug for the right diagnosis, but there is no consensus on when you should stop it.<\/p>\n<p><strong>Falk:<\/strong> Or if you can.<\/p>\n<p><strong>Saha:<\/strong> Right, but even if you stop it for one reason or another, you should see your patients regularly with a very close follow-up.<\/p>\n<p><strong>Falk:<\/strong> The side effects of this drug are inhibiting part of the normal process of getting rid of infections, so the side effects, as you described, are lots of infectious diseases, but most commonly, bacteria that causes meningitis.<\/p>\n<p><strong>Saha:<\/strong> Correct, because it affects the complement pathway which is part of our defense mechanism against infection, the greatest worry is the bacteria known as Neisseria meningitis, causing infection in the brain known as meningitis.<\/p>\n<h3><span class=\"blue\">Prognosis, inheritance &amp; more information<\/span><\/h3>\n<p><strong>Falk:<\/strong> What is the overall quality of life then of somebody who has thrombotic microangiopathy?<\/p>\n<p><strong>Saha:<\/strong> If the disease is diagnosed early, and the treatment is appropriate, they should have a good life expectancy. At the same time, they are at risk for certain long-term chronic diseases. Patients, if they have kidney involvement, they are at risk for chronic kidney disease. If they had brain involvement, they\u2019re at risk for cognitive dysfunction and depression. If their heart was involved, they are at risk for cardiomyopathy, or heart problem, or hypertension. As you follow these patients regularly they should be screened for all these chronic disorders that they may develop over time.<\/p>\n<p><strong>Falk:<\/strong> Hopefully with good therapy, though, and routine follow-up, the life expectancy should be really pretty good.<\/p>\n<p><strong>Saha:<\/strong> Yes, it should be pretty good, if diagnosed and treated early.<\/p>\n<p><strong>Falk:<\/strong> What are the chances, then, if somebody has a genetic form of TTP, or atypical HUS, will pass that condition on to their children?<\/p>\n<p><strong>Saha:<\/strong> Congenital TTP is usually transmitted as autosomal recessive disease. That means you need to get one copy of genetic defect from each parent, while atypical HUS can present in both autosomal dominant or autosomal recessive. If someone is affected by atypical HUS in autosomal dominant fashion, meaning there\u2019s a fifty percent chance that their offspring will have or will carry that mutation. This increases the risk of the disease but just carrying the mutation may not be enough to cause symptoms as a additional trigger may be required.<\/p>\n<p><strong>Falk:<\/strong> A secondary stimulus. Where can somebody find more information about TMA if they\u2019re looking on the web?<\/p>\n<p><strong>Saha:<\/strong> One of the websites is <a href=\"https:\/\/unckidneycenter.org\/kidneyhealthlibrary\/glomerular-disease\/thrombotic-microangiopathy-tma\" target=\"_blank\" rel=\"noopener noreferrer\">unckidneycenter.org<\/a>. Another one is <a href=\"https:\/\/www.ahus.org\" target=\"_blank\" rel=\"noopener noreferrer\">Atypical HUS Foundation<\/a>. A third one is <a href=\"https:\/\/ghr.nlm.nih.gov\/condition\/thrombotic-thrombocytopenic-purpura\" target=\"_blank\" rel=\"noopener noreferrer\">Genetics Home Reference<\/a>.<\/p>\n<p><strong>Falk:<\/strong> Thank you so much, Dr. Saha.<\/p>\n<p><strong>Saha:<\/strong> Thank you.<\/p>\n<p><strong>Falk:<\/strong> Thanks so much to our listeners for tuning in. Next time, we will be talking with Dr. Nigel Key on hemophilia. You can subscribe to the Chair\u2019s Corner on <a href=\"https:\/\/itunes.apple.com\/us\/podcast\/unc-department-of-medicine-chairs-corner\/id1076686662?mt=2\" target=\"_blank\" rel=\"noopener noreferrer\">iTunes<\/a>, <a href=\"https:\/\/soundcloud.com\/chairscorner\" target=\"_blank\" rel=\"noopener noreferrer\">SoundCloud<\/a>, or <a href=\"https:\/\/www.facebook.com\/UNCDeptMedicine\" target=\"_blank\" rel=\"noopener noreferrer\">like us on FaceBook<\/a>.<\/p>\n<div><\/div>\n<div class=\"alert alert-blue width:100% \">\n<p><strong>Visit these sites for more information:<\/strong><\/p>\n<ul>\n<li><a class=\"external-link\" title=\"\" href=\"https:\/\/www.ahus.org\" target=\"_blank\" rel=\"noopener noreferrer\">Atypical HUS Foundation<\/a><\/li>\n<li><a class=\"external-link\" title=\"\" href=\"https:\/\/unckidneycenter.org\/directory\/manish-saha\" target=\"_blank\" rel=\"noopener noreferrer\">Dr. Manish Saha\u2019s School of Medicine profile <\/a><\/li>\n<li><a class=\"external-link\" title=\"\" href=\"https:\/\/ghr.nlm.nih.gov\/condition\/thrombotic-thrombocytopenic-purpura\" target=\"_blank\" rel=\"noopener noreferrer\">Genetics Home Reference<\/a><\/li>\n<li><a class=\"external-link\" title=\"\" href=\"https:\/\/unckidneycenter.org\/kidneyhealthlibrary\/glomerular-disease\/thrombotic-microangiopathy-tma\" target=\"_blank\" rel=\"noopener noreferrer\">TMA educational information &#8211; UNC Kidney Center<\/a><\/li>\n<\/ul>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Dr. Manish Saha talks with Dr. Ron Falk about thrombotic microangiopathy, or TMA. They discuss two types of TMA, thrombotic thrombocytopenic purpura and hemolytic syndrome, and the symptoms associated with each. They also talk about the testing and treatment for TMA. Dr. Saha is an Assistant Professor of Medicine in the Division of Nephrology and Hypertension.<\/p>\n","protected":false},"featured_media":4233,"menu_order":0,"template":"","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","_links_to":"","_links_to_target":""},"podcast-category":[633,639],"class_list":["post-19303","episode","type-episode","status-publish","has-post-thumbnail","hentry","podcast-category-podcast-genetic-diseases-podcast","podcast-category-podcast","odd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Thrombotic Microangiopathy (TMA) - with Dr. Manish Saha | Department of Medicine<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/medicine\/news\/\/news\/chairs-corner\/podcast\/tma-saha\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Thrombotic Microangiopathy (TMA) - with Dr. Manish Saha | Department of Medicine\" \/>\n<meta property=\"og:description\" content=\"Dr. Manish Saha talks with Dr. Ron Falk about thrombotic microangiopathy, or TMA. 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