{"id":17280,"date":"2018-10-18T13:54:42","date_gmt":"2018-10-18T17:54:42","guid":{"rendered":"https:\/\/www.med.unc.edu\/medicine-dev\/?post_type=podcast&#038;p=17280"},"modified":"2023-11-14T12:40:23","modified_gmt":"2023-11-14T17:40:23","slug":"hemophilia-key","status":"publish","type":"episode","link":"https:\/\/www.med.unc.edu\/medicine\/news\/chairs-corner\/podcast\/hemophilia-key\/","title":{"rendered":"Hemophilia &#8211; with Dr. Nigel Key"},"content":{"rendered":"<header>\n<figure id=\"attachment_25949\" class=\"thumbnail wp-caption alignright\" style=\"width: 210px\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-25949 size-medium\" src=\"https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/03\/Key-Nigel-Faculty-Photo-200x300.jpg\" alt=\"Nigel S. Key, MB, ChB, FRCP \" width=\"200\" height=\"300\" \/><figcaption class=\"caption wp-caption-text\">Nigel S. Key, MB, ChB, FRCP<\/figcaption><\/figure>\n<p id=\"description\" class=\".documentDescription\">What is hemophilia? Dr. Nigel Key discusses this genetic disease with Dr. Ron Falk. They talk about how the disease is inherited, the effectiveness of the treatment, and what&#8217;s on the horizon for gene therapy. Dr. Key is the Harold R. Roberts Distinguished Professor of Medicine in the Division of Hematology and Oncology, and is the Director of the UNC Hemophilia and Thrombosis Center.<\/p>\n<\/header>\n<div id=\"content-area\">\n<div id=\"parent-fieldname-text\" class=\"plain\">\n<div class=\"alert alert-gray\">\n<p>\u201cThe life expectancy in 1960 was eleven years of age for a hemophilia patient with severe disease. Now, it\u2019s basically normal\u2014with good treatment, in developed countries, it\u2019s basically normal.&#8221;<\/p>\n<p>\u2013 Dr. Nigel Key<\/p>\n<\/div>\n<\/div>\n<\/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\/01\/hemophilia-whatisit.mp3'>A deficiency in clotting factors<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/hemophilia-symptoms.mp3'>Hemophilia symptoms & testing<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/hemophilia-treatment.mp3'>Hemophilia treatment<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/hemophilia-concerns.mp3'>Special concerns & life expectancy today<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/hemophilia-gene-therapy.mp3'>Gene therapy for hemophilia<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/hemophilia-more-info.mp3'>Access to treatment & 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\\\/01\\\/hemophilia-whatisit.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"A deficiency in clotting factors\",\"caption\":\"\",\"description\":\"\\\"hemophilia-whatisit\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"3:29\"},\"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\\\/hemophilia-symptoms.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Hemophilia symptoms & testing\",\"caption\":\"\",\"description\":\"\\\"hemophilia-symptoms\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"3:47\"},\"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\\\/hemophilia-treatment.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Hemophilia treatment\",\"caption\":\"\",\"description\":\"\\\"hemophilia-treatment\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"2:32\"},\"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\\\/hemophilia-concerns.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Special concerns & life expectancy today\",\"caption\":\"\",\"description\":\"\\\"hemophilia-concerns\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"5:18\"},\"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\\\/hemophilia-gene-therapy.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Gene therapy for hemophilia\",\"caption\":\"\",\"description\":\"\\\"hemophilia-gene-therapy\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"6:28\"},\"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\\\/hemophilia-more-info.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Access to treatment & more information\",\"caption\":\"\",\"description\":\"\\\"hemophilia-more-info\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"2:30\"},\"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><strong>Ron Falk, MD:<\/strong>\u00a0Hello, and welcome to the Chair\u2019s Corner from the Department of Medicine at the University of North Carolina. This is our series where we discuss different genetic diseases with physicians who treat patients with these conditions. Today, we will talk about hemophilia.<\/p>\n<p>We welcome\u00a0<a title=\"\" href=\"https:\/\/unclineberger.org\/people\/profiles\/nigel-s-key\" target=\"_blank\" rel=\"noopener\">Dr. Nigel Key<\/a>, the Harold R. Roberts Distinguished Professor of Medicine in our Division of Hematology and Oncology. Dr. Key is the Director of the\u00a0<a href=\"https:\/\/www.med.unc.edu\/htcenter\" target=\"blank\" rel=\"noopener\">UNC Hemophilia and Thrombosis Center<\/a>. Welcome, Dr. Key.<\/p>\n<p><strong>Nigel Key, MB, ChB, FRCP:<\/strong>\u00a0Thank you.<\/p>\n<h3><span class=\"blue\">A deficiency in clotting factors<\/span><\/h3>\n<p><strong>Falk:<\/strong>\u00a0What is hemophilia?<\/p>\n<p><strong>Key:<\/strong>\u00a0Hemophilia is an inherited disorder which causes a tendency to bleed easily. It affects about one in every ten thousand of the population. There may be twenty-five thousand patients with hemophilia in the United States.<\/p>\n<p><strong>Falk:<\/strong>\u00a0There are two different kinds of hemophilia, right? Hemophilia A and hemophilia B.<\/p>\n<p><strong>Key:<\/strong>\u00a0Yes, indeed. Hemophilia is a genetic deficiency of one of the coagulation factors or clotting factors that we all use on a daily basis, from when we cut ourselves shaving to prevent excessive bleeding or to prevent bleeding after surgery. Hemophilia A is a deficiency of factor VIII (factor eight), clotting factor eight, and hemophilia B is a deficiency of clotting factor IX (factor nine). Hemophilia A is about four times as common as hemophilia B.<\/p>\n<p><strong>Falk:<\/strong>\u00a0When were those conditions first recognized?<\/p>\n<p><strong>Key:<\/strong>\u00a0Well, it\u2019s an interesting history, because the inheritance pattern, there are references to hemophilia going back to what is called the Babylonian Talmud in the Jewish faith. It is around the time of Christ, particularly the manifestation of excessive bleeding or even death with circumcision. It wasn\u2019t called hemophilia, of course, but it was clearly hemophilia.<\/p>\n<p><strong>Falk:<\/strong>\u00a0Because hemophilia A or factor eight deficiency is more common, is that why it was recognized earlier than hemophilia B or factor nine deficiency?<\/p>\n<p><strong>Key:<\/strong>\u00a0It wasn\u2019t appreciated actually, that there were two types of hemophilia, because they look exactly the same in terms of how they behave and the inheritance pattern, and so on, so it\u2019s just called hemophilia. It wasn\u2019t until the 1900\u2019s that it was realized there were two different subtypes. Otherwise, they look identical in a clinical sense.<\/p>\n<p><strong>Falk:<\/strong>\u00a0How are they inherited?<\/p>\n<p><strong>Key:<\/strong>\u00a0They are inherited in a pattern that is called X-linked recessive. What that means, is that there are a number of disorders in medicine, and hemophilia A and B are examples of them, where women can be carriers of the gene for hemophilia, but are not generally affected. They can pass it on to male offspring who then may inherit the gene from their mother and develop hemophilia. \u201cX-linked\u201d refers to the fact that it\u2019s on the X chromosome. Women have two X chromosomes and men only have one, so what I usually say to patients who are a carrier, is that you have one well-functioning X chromosome, and one that has the hemophilia gene, and whether your son has hemophilia depends on the toss of the dice as to whether he gets the \u201cgood\u201d or \u201cbad\u201d X chromosome.<\/p>\n<h3><span class=\"blue\">Hemophilia symptoms &amp; testing<\/span><\/h3>\n<p><strong>Falk:<\/strong>\u00a0The symptoms of both hemophilia A and B are identical.<\/p>\n<p><strong>Key:<\/strong>\u00a0Yes.<\/p>\n<p><strong>Falk:<\/strong>\u00a0What are those? Bleeding, as you point out, from common causes.<\/p>\n<p><strong>Key:<\/strong>\u00a0Right. Something we haven\u2019t mentioned so far is that hemophilia comes in different flavors. What I mean by that, is the severity of the disease determines the clinical presentation\u2014the age of presentation and what the manifestations of the disease are.<\/p>\n<p>That is to say, that severe hemophilia, which accounts for about half of the patients with hemophilia, have less than one percent of whether it be factor eight or factor nine. These are patients who generally will present early in childhood. When they start to walk, these children will develop bleeds into joints and the parents will recognize this. Frequently, they present before that. They may have presented with bleeding from circumcision or something of that nature.<\/p>\n<p>There\u2019s also a problem in that some children with hemophilia present as an abused child, to the social services, because of a lot of bruising, when in fact they\u2019re not abused children\u2014it comes to light that there is a reason for that. Thankfully, about two thirds of the time, the hemophilia is anticipated because of a family history, but even when you have perfect family history, about a third of the cases are new cases, they are what is called \u201cspontaneous genetic mutation.\u201d It can be unexpected in a family that has no family history. Some of our patients are diagnosed very early, because it\u2019s anticipated and they could have hemophilia. It\u2019s picked up early with a blood test. Others sort of wait until they present with bleeding.<\/p>\n<p><strong>Falk:<\/strong>\u00a0If you have more than one percent of either factor eight or factor nine, the chances of having a milder disease becomes a reality. How much factor does one need?<\/p>\n<p><strong>Key:<\/strong>\u00a0Well, that\u2019s a good question, but it\u2019s generally what we call moderate hemophilia is about less than five percent\u2014a little bit, up to five percent of normal. Those patients can have the spontaneous bleeds that severe hemophilia patients get into joints and muscles. Mild hemophilia is considered over five percent. Those patients may not come to attention until adulthood or after surgery or something like that. I remember a professional hockey player that I diagnosed with mild hemophilia. We\u2019ve had instances like that. We\u2019ve had quite a few military who have been diagnosed with hemophilia who really haven\u2019t had a problem except when they\u2019ve been in surgery or had a major trauma.<\/p>\n<p><strong>Falk:<\/strong>\u00a0Then the disease becomes recognized.<\/p>\n<p><strong>Key:<\/strong>\u00a0Then it becomes\u2014hopefully\u2014recognized but it may well present late in life.<\/p>\n<p><strong>Falk:<\/strong>\u00a0How does one test for hemophilia?<\/p>\n<p><strong>Key:<\/strong>\u00a0I mentioned that there\u2019s a deficiency of either factor eight or factor nine in the blood. Fortunately, we have a very good test for that\u2014we can just measure the level and tell the percent of the clotting factor. Percentage of the average normal\u2014say, that the average person has one hundred percent, though it actually varies\u2014we can measure that in the blood and determine whether factor eight is one percent, three percent, five percent, with an accurate blood test.<\/p>\n<h3><span class=\"blue\">Hemophilia treatment<\/span><\/h3>\n<p><strong>Falk:<\/strong>\u00a0How do you treat these patients now? And later on, we\u2019ll talk about the exciting options of gene therapy. Currently, what\u2019s the most usual therapy?<\/p>\n<p><strong>Key:<\/strong>\u00a0The most usual therapy is replacement of the missing clotting factor, which has been really, and still is, the standard of care since the 1970\u2019s. Unfortunately, it has to be given intravenously, so patients who require it\u2014the severe and moderate patients\u2014are either trained to give it to themselves, or a family member. This means accessing a vein and keeping the factor at home, mixing it up and giving it when they think a bleed is coming on\u2014they\u2019re trained to do that. They start getting trained at about the age of seven or eight to actually do this. I don\u2019t know if there are other disorders in which patients are trained to give intravenous injections at home. This is the standard of care, it\u2019s long been the standard of care in hemophilia.<\/p>\n<p><strong>Falk:<\/strong>\u00a0Because it\u2019s so important to get the factor back in as quickly as possible. How do you actually get children, young adults, to learn to do this and then to give factor to themselves early enough? Putting in an IV doesn\u2019t feel good, but I suppose the pain from the bleeding is even worse.<\/p>\n<p><strong>Key:<\/strong>\u00a0Yes, well it starts earlier than that, because it\u2019s often the parents will have to do it for the first few years of life. Getting into veins in little chubby babies can be very difficult, so sometimes in early life there is a central venous access device that stays in, that the parent can access. We get them out as soon as possible and train them on vein infusion technique as soon as possible. This is something that a lot of our nurses do, but one of the great forums for teaching kids is hemophilia summer camp, where maybe a hundred children with hemophilia there, and they see one another doing it there. At seven or eight years old, they have an intensive experience with a nurse supervising and teaching them how to do it. Kids are really quite resilient and they frequently will do it for themselves at an early age.<\/p>\n<h3><span class=\"blue\">Special concerns &amp; life expectancy today<\/span><\/h3>\n<p><strong>Falk:<\/strong>\u00a0What do you do before an operation or a dental procedure? For somebody with severe disease, do you prophylactically give it to them?<\/p>\n<p><strong>Key:<\/strong>\u00a0Yes, exactly. Apart from these severe patients having spontaneous joint and muscle bleeds, we absolutely want to know when our patients are having procedures, be it dental or surgery, so that we can determine how to prevent them from having bleeding after the procedure. Frequently, that will involve infusion of a clotting factor given with an hour of the procedure.<\/p>\n<p><strong>Falk:<\/strong>\u00a0What issues or concerns do women have?<br \/>\n<strong>Key:<\/strong>\u00a0Well, the issue with women carriers is that, on average, they will have fifty percent of of factor eight, and that\u2019s plenty. But, there\u2019s a strange phenomenon in nature when we\u2019re the embryo in the womb\u2014it\u2019s called \u201clyonization\u201d\u2014it means that some women carriers are very skewed, they actually have factor eight or nine levels that are quite low. They can be five percent, ten percent\u2014they\u2019re a mild hemophiliac, so menstruation can be an issue, bleeding after procedures can be an issue. It\u2019s quite variable among women, because it\u2019s random how much factor eight or factor nine they end up with.<\/p>\n<p><strong>Falk:<\/strong>\u00a0How do patients deal with pain?<\/p>\n<p><strong>Key:<\/strong>\u00a0Let me preface the answers by saying that the care of hemophilia patients has dramatically changed over the last thirty years, where instead of just treating bleeds when they occur early, which might be twice a month for severe hemophilia patients, we\u2019re now in the era of what\u2019s called prophylaxis. Patients will take clotting factor on a regular basis throughout the week to prevent bleeds.<\/p>\n<p>I\u2019m seeing kids, young adults coming from pediatricians coming into our clinic, who are eighteen to twenty years old, with near-pristine joint function. I have a group of hemophilia patients who are forty-five years and above, many of whom have very destructive joint disease\u2014arthritis, and destructive joint disease that is beyond the point where clotting factor is going to do much, except prevent further bleeding, but certainly the joint is already damaged. It\u2019s a generational thing, really\u2014the biggest issue is trying to maintain compliance with young adults as they move into independence from Mom\u2014going to college, starting work, and so on, so that they understand the importance of prevention, essentially.<\/p>\n<p>To answer your question more directly, certainly chronic joint pain is an issue in hemophilia. There may be a situation where we try to identify a particular joint where it would be amenable to orthopedic procedure. We work a lot with our orthopedic colleagues, whether it be total joint replacement, hips and knees particularly, some ankles, some shoulders. There are other joint fusion procedures. It\u2019s important to have an orthopedist who understands hemophilia and its issues.<\/p>\n<p><strong>Falk:<\/strong>\u00a0What\u2019s the life expectancy for somebody in the more modern era, for somebody who is twenty years old right now, for example, and who does prophylactic therapy?<\/p>\n<p><strong>Key:<\/strong>\u00a0The life expectancy in 1960 was eleven years of age for a hemophilia patient with severe disease. Now, it\u2019s basically normal\u2014with good treatment, in developed countries, it\u2019s basically normal.<\/p>\n<p>We\u2019ve had a number of what\u2019s called twinning activities in developing countries throughout the world, and in my experience\u2014we\u2019re on our fourth one now with Zimbabwe\u2014if you go to Zimbabwe and look at the outcomes in hemophilia patients there, they are very different from here. You can see the effect of not having treatment on life expectancy and joint damage. We also did work in the Republic of Georgia, with Armenia, and with Ethiopia, and they\u2019re all in various stages of development of their hemophilia programs. The World Federation of Hemophilia, of which I used to be on the board, is a very effective organization at initiating care in these countries, but it can be remarkably successful, actually, despite the fact that it\u2019s a rare and expensive disease to treat, with the right advocacy and involvement of patient groups, particularly, as well as physicians, it can be very effective.<\/p>\n<h3><span class=\"blue\">Gene therapy for hemophilia<\/span><\/h3>\n<p><strong>Falk:<\/strong>\u00a0Gene therapy is on the horizon. Tell us about it.<\/p>\n<p><strong>Key:<\/strong>\u00a0Gene therapy has been the promise in hemophilia for fifteen years or more. Like most therapies in medicine, it\u2019s been two steps forward, one step back\u2014back to the lab, work this out\u2014two steps forward, one back, over that period. We kind of went through the glass ceiling about a year, eighteen months ago, where the essential major barriers have been largely overcome at this point. There is a rush, actually, from having academic endeavors in gene therapy in a few good centers, including our own. There is now, six or eight companies that are getting into clinical trials in gene therapy, recognizing that it\u2019s just around the corner. So, it\u2019s looking extremely viable and possible.<\/p>\n<p><strong>Falk:<\/strong>\u00a0How often do patients develop an immune response to either the factor that they\u2019re getting prophylactically, or even, I suppose, gene therapy approach?<\/p>\n<p><strong>Key:<\/strong>\u00a0Yes, that is the big bugaboo still in hemophilia. Many of our patients in the seventies and eighties, the big bugaboo then with plasma-derived clotting factor was blood-borne viruses, particularly HIV and hepatitis C. That era is done\u2014it\u2019s finished. We are using synthetic clotting factors, thank goodness. The big problem or major complication now is when a patient develops an antibody to the infused factor eight or factor nine.<\/p>\n<p><strong>Falk:<\/strong>\u00a0A foreign protein.<\/p>\n<p><strong>Key:<\/strong>\u00a0A foreign protein. In severe hemophilia, it\u2019s estimated that at some time in their life in severe hemophilia A, one in four patients or as much as one in three will develop an inhibitor. Fortunately, sometimes it goes away spontaneously. When it doesn\u2019t and it\u2019s high level, it\u2019s a major clinical challenge. It\u2019s pretty rare in hemophilia B, but we have a few cases.<\/p>\n<p><strong>Falk:<\/strong>\u00a0What can be done about this inhibitory antibody?<\/p>\n<p><strong>Key:<\/strong>\u00a0In severe hemophilia, these antibodies are picked up usually in the small children once their bodies start to get exposed to the clotting factor, in early life. The pediatricians will immediately try to actually get rid of this antibody, and the way they do it is through a process known as immune tolerance induction.<\/p>\n<p>What they do, is step up significantly the dosing and the frequency of factor eight infusions to train the patient\u2019s immune system to give up on making these antibodies against the clotting factor. When you go to the allergist with a bee sting allergy, they do something similar. They train your immune system to give up on making that life-threatening antibody that can cause bee sting allergies. It\u2019s sort of a good analogy to that, but it can take months to even years, and it\u2019s about seventy percent successful\u2014not always successful.<\/p>\n<p><strong>Falk:<\/strong>\u00a0There\u2019s a whole trial to get rid of peanut allergy by using a lot of peanut protein.<\/p>\n<p><strong>Key:<\/strong>\u00a0The immune system is interesting.<\/p>\n<p><strong>Falk:<\/strong>\u00a0If one thinks forward, what gene therapy could look like, how would it work?<\/p>\n<p><strong>Key:<\/strong>\u00a0Well, the way it works is that\u2014I mentioned the hemophilia patient has a gene which is inherited which is not making factor eight or factor nine as it should. Gene therapy is really another way of delivering the missing clotting factor. In that case, we fool the patient\u2019s genetic system into making the protein that it otherwise is defective in. The way this is done, it\u2019s essentially a virus, but it\u2019s not a virus that causes disease. It\u2019s sort of the Trojan horse\u2014you load it up with the gene for factor eight or factor nine, you inject it one time, intravenously, it\u2019s trained to go to the liver, where it sets up residence and starts producing factor eight or factor nine.<\/p>\n<p>In the last year, we\u2019re finding out that we can achieve essentially normal levels of either factor eight or nine. A few years ago, we were delighted to get to three percent or five percent. Of course, there\u2019s always provisos, but generally speaking, the results are looking very, very encouraging.<\/p>\n<p><strong>Falk:<\/strong>\u00a0Great. What a wonderful promise. How long does it take for that therapy to work?<\/p>\n<p><strong>Key:<\/strong>\u00a0Well, you start to see the patient making their own factor eight or nine within a week, actually, but it peaks out after several weeks\u2014three, four, five weeks, and it stays at that level. Some people are going to be getting fifteen percent, some are going to be getting eighty percent. There\u2019s a little bit of unpredictability as yet as to how high they will peak out at, but once it sort of hits its plateau, it generally stays there. The question is, Is one time good to go the rest of your life? We\u2019ll have to see\u2014from the hemophilia dogs here in Chapel Hill that they\u2019re about ten years out, and that\u2019s a very good model of human disease. It looks extremely promising, but it\u2019s not impossible that a second treatment could be required.<\/p>\n<p><strong>Falk:<\/strong>\u00a0Amazing when one compares that to regular prophylactic infusion.<\/p>\n<p><strong>Key:<\/strong>\u00a0Yes.<\/p>\n<h3><span class=\"blue\">Access to treatment &amp; more information<\/span><\/h3>\n<p><strong>Falk:<\/strong>\u00a0What are the top questions or concerns that patients ask you?<\/p>\n<p><strong>Key:<\/strong>\u00a0Well, bear in mind that I\u2019m an adult treater, so I\u2019ll preface this with that sometimes as a pediatrician it may come as more of a shock to the family if there\u2019s no family history. Everybody wants a child who is one hundred percent healthy. The good news is that children born with hemophilia now can look forward to a very bright future. As an adult treater, these patients have had it their whole lives after all, except for some of the mild patients who show up later. It\u2019s unfortunate, but a reality that it\u2019s an expensive disease to treat, and having access to treatment, therapies is still a big issue from a medical insurance standpoint. It varies from state to state, the adult coverage, but we do everything we can do, but we spend a lot of time getting patients who don\u2019t have insurance or who have sub-adequate insurance, hooked up with a way to get them clotting factor, and somehow, we struggle through it. Many manufacturers have programs to help patients, so I\u2019d say having access to the treatment they need as it is in the developing world, is still a big concern here.<\/p>\n<p><strong>Falk:<\/strong>\u00a0Where can someone find more information about hemophilia\u2014a reliable source?<\/p>\n<p><strong>Key:<\/strong>I would say that the\u00a0<a class=\"external-link\" title=\"\" href=\"https:\/\/www.hemophilia.org\/\" target=\"_blank\" rel=\"noopener\">National Hemophilia Foundation<\/a>, which is based in New York and it\u2019s been around for fifty years or so, is a reliable source of monographs and educational materials. There is a system of hemophilia treatment centers throughout the US\u2014there\u2019s about 130 of them. In North Carolina, we have four, going on five, soon. These are not always just in the largest hospital, but they are designated to have special expertise in that area. The\u00a0<a class=\"external-link\" title=\"\" href=\"https:\/\/www.wfh.org\/\" target=\"_blank\" rel=\"noopener\">World Federation of Hemophilia<\/a>\u00a0also-it\u2019s a patient-based organization, as is the National Hemophilia Foundation. The National Hemophilia Foundation has chapters in every state, here in North Carolina it is called\u00a0<a class=\"external-link\" title=\"\" href=\"https:\/\/www.hemophilia-nc.org\/\" target=\"_blank\" rel=\"noopener\">Hemophilia of North Carolina<\/a>. These are reliable sources for patients to find out about the disease.<\/p>\n<p><strong>Falk:<\/strong>\u00a0Thank you so much, Dr. Key for spending time with us today.<\/p>\n<p><strong>Key:<\/strong>\u00a0You\u2019re welcome.<\/p>\n<p><strong>Falk:<\/strong>\u00a0Thanks so much to our listeners for tuning in. This episode completes our series focused on genetic diseases, but please stay tuned for new episodes. You can subscribe to the Chair\u2019s Corner on\u00a0<a href=\"https:\/\/itunes.apple.com\/us\/podcast\/unc-department-of-medicine-chairs-corner\/id1076686662?mt=2\" target=\"_blank\" rel=\"noopener\">iTunes<\/a>,\u00a0<a href=\"https:\/\/soundcloud.com\/chairscorner\" target=\"_blank\" rel=\"noopener\">SoundCloud<\/a>, or\u00a0<a href=\"https:\/\/www.facebook.com\/UNCDeptMedicine\" target=\"_blank\" rel=\"noopener\">like us on FaceBook<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>What is hemophilia? Dr. Nigel Key discusses this genetic disease with Dr. Ron Falk. They talk about how the disease is inherited, the effectiveness of the treatment, and what&#8217;s on the horizon for gene therapy. Dr. Key is the Harold R. Roberts Distinguished Professor of Medicine in the Division of Hematology and Oncology, and is the Director of the UNC Hemophilia and Thrombosis Center.<\/p>\n","protected":false},"featured_media":4153,"menu_order":0,"template":"","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","_links_to":"","_links_to_target":""},"podcast-category":[633,639],"class_list":["post-17280","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>Hemophilia - with Dr. Nigel Key | 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\/chairs-corner\/podcast\/hemophilia-key\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Hemophilia - with Dr. Nigel Key | Department of Medicine\" \/>\n<meta property=\"og:description\" content=\"What is hemophilia? 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