Transcript
Speaker: IVIG, of course, is short for intravenous gamma globulin. What you're getting is a normal part of human beings. It's very good as an emergency treatment. It's not so good as a way to maintain the count over time.
Speaker: Welcome to the PDSA podcast, Bruised But Not Broken, Living with ITP. The diagnosis of a bleeding disorder like immune thrombocytopenia may leave you wondering, how can I really live my life with ITP?
Speaker: PDSA's podcast, Bruised But Not Broken, Living With ITP, brings empowering stories, the latest research and treatment updates, lifestyle tips, and answers to the real-life questions the ITP community is asking.
Speaker: Here's your host for this episode, Barbara Pruitt.
Speaker: Today we will be continuing our series on ITP treatments. I'm sure all of you have heard of IVIG. It is one of the first line treatments given to patients with a diagnosis of ITP.
Speaker: Today i have not one, but two experts on IVIG. I'd like to introduce someone who has been on my podcast previously, Dr. James Bussell and Dr. Charlotte Cunningham-Rundles.
Speaker: Let me tell you a little bit about Dr. Boussell. Dr. Boussell is a professor of pediatrics, medicine, and obstetrics at the Weill Medical College of Cornell University in New York City.
Speaker: The great majority of Dr. Boussell's work and publications have been centered around the diagnosis and especially the treatment of patients with ITP. This includes children, adults, pregnant women with ITP, HIV-infected patients with thrombocytopenia, and fetuses affected by autoimmune and alloimmune thrombocytopenia.
Speaker: He has worked with IVIG, IV anti-D, rituximab, and also the TPO agents. In 2012, he received the King Faisal Prize for Medicine, also known as the Arab Nobel Prize.
Speaker: Dr. Bussell also serves on the PDSA Board of Medical Advisors. Also joining us is Dr. Charlotte Cunningham-Rundles.
Speaker: She is the David S. Gotsman Professor of Immunology at the Mount Sinai School of Medicine in New York. She is a professor of medicine and pediatrics, a member of the Immunology Institute, and she directs the Immunodeficiency Clinic at Mount Sinai.
Speaker: She is also the program director of the Allergy Immunology Fellowship Training Program. Dr. Cunningham Rundles is an expert in more than 150 primary immune deficiency diseases.
Speaker: which are conditions that result from genetic defects of the immune system. Her research has been supported by the U.S. Public Health Service, the Food and Drug Administration, and the National Institutes of Health, Division of Allergy, Immunology, and Transplantation.
Speaker: Welcome to Bruised But Not Broken, Living with ITP. I asked both of you to join me today, not only because you are experts in the topic of IVIG, but coincidentally, you are husband and wife.
Speaker: So welcome. Barbara, you left out a whole slew of awards that Charlotte's received. And a whole slew of awards you've received too. too many mention for Charlotte.
Speaker: I'm sure. And too many to mention for you. To start off with, this is a question for both of you. Explain what IVIG is and how is it obtained?
Speaker: IVIG, of course, is short for intravenous gamma globulin, but you don't have to give it intravenously these days. You can also give it subcutaneously or even intramuscularly.
Speaker: But it's a solution that comes from normal blood donors who have given their blood for various purposes, perhaps in a blood drive or perhaps at another location.
Speaker: But the gamma globulin is the protein part of this in the serum. which then contains all the antibodies, and that's really what gamma globulin is. It's a solution comes from normal human blood. By the way, a minimum of 1,000 donors have to have been included in that lot.
Speaker: So that the idea would be that you have basically all the antibodies you could possibly want, and that's what those solutions contain. Wow. So when someone donates blood, do they automatically take the gamma globulin out of that to add to a batch of IVIG or is it kept in the regular blood?
Speaker: In the United States, it's usually obtained by doing what's called plasmapheresis. When they take some of your blood out, separate the plasma, give you the red cells and everything else back so they can get more plasma and more gamma globulin per donation.
Speaker: In Europe, it's a little more like what you just said. They donate a unit of blood, they get red cells, they get platelets, and they get the plasma, of which they can remove the gamma globulin from if they want.
Speaker: But basically, it comes from normal donors or a person who is willing to have the plasma phoresis procedure. So if you went in to donate blood, Do they give you that option? do you want plasmapheresis or you know about that prior to doing it?
Speaker: You know about that ahead of time. You would be recruited specifically for one for plasmapheresis or if you donated blood, they probably wouldn't normally in the United States collect gamma globulin from it.
Speaker: Okay. So if it's taking a thousand different donations, that's quite a lot of work and quite a lot of work behind the scenes. Remember, it's all pooled together so that different donations are pooled into one large, I don't know, you want to call it a vat, into one location by the companies that produce the gamma globulin.
Speaker: This is so, let's say one person has a lot of antibodies to measles and another person has a lot of antibodies to chickenpox, not so much to measles.
Speaker: So when it all ends up together from over a thousand different donors, not just donations, you hopefully get a pretty even amount of almost everything.
Speaker: Wow. It sounds remarkable to say the least. So how does it exactly work for the treatment of ITP? I know it is used as one of the first-line treatments. And what is its effect when it comes to itp We think the dominant effect is that it slows the destruction of the antibody-coated platelets.
Speaker: But exactly how the mechanism works is still being widely debated. I think a fair amount of the way it works is also that it leads to the rapid destruction of the IgG antibodies to platelets, and therefore the platelets survive better also.
Speaker: But it's a very complicated thing, many, many theories about how it might work. So I know since it is a first-line therapy,
Speaker: Is it something that's used predominantly right when you're diagnosed or is it something that's used repetitively? It's often used when you're diagnosed.
Speaker: Right now, and this is hopefully going to change as a result of the new ASH guidelines, which we can come back to if you want. Steroids are given to almost everybody in the beginning.
Speaker: And then some people, in addition, get IVIG. That's because it brings up the platelet count faster. And if you use the two together, you're more sure of getting the count to start coming up.
Speaker: So you could give it to somebody who's bleeding more, has a lower platelet count for another reason is more at risk, like maybe they're on an anticoagulant as an example.
Speaker: Or sometimes if you are going to hospitalize somebody and you're going to keep them until the platelets come up, you might give them the IVIG just to get their count up faster so they can be discharged sooner.
Speaker: It's also used, though, pretty much at any point if somebody gets a very low count and there's concern about it because other treatments don't work nearly as fast.
Speaker: Right. So if someone was to present themselves, if they're an ITP patient and goes to the emergency room with a bad bloody nose and their treatment that they're using hasn't worked, it's a good chance they might give them IVIG.
Speaker: Yeah. It's certainly not the only option, but that kind of situation is when they would be most likely to use it, not at diagnosis. Okay. Now, are there other conditions that they give IVIG Other disorders or Well, the the main reason it started to be used so much in the United States, or another main reason was that if you don't have enough antibody of your own, or if you're immune deficient, then you're going to need gamma globulin for that purpose.
Speaker: And the other thing is some of the treatments for cancer, for example, will cut down your ability to make an antibody. And in that case, you also become immune deficient.
Speaker: And if you're lacking antibody, then gamma globulin, intravenous gamma globulin, or subcutaneously delivered gamma globulin, you know, is obviously what you're going to be needing. Just to clarify one thing about that, when you use it the way that Charlotte just described, to give somebody antibodies they don't have, you can give it subcutaneously.
Speaker: Virtually nobody that I'm aware of gives it that way for ITP because potentially the platelet count would come up more slowly and it might not work as well, although remarkably, there's no really good data on that.
Speaker: Finally, there's an answer to your original question. There's other, let's call them autoimmune diseases in which IVIG is often helpful. The main ones presently would be neurologic ones.
Speaker: like chronic inflammatory demyelinating polyneuropathy or myasthenia gravis or whatever. Usually in conditions like that, when more specific, easier to administer treatments get developed, IVIG drops out of favor a little and other treatments take over.
Speaker: Right. Well, when a person gets the IVIG, is the response fairly quick as far as the platelet count being elevated? Yeah. um If you have somebody who responds, it's often literally overnight.
Speaker: Okay. And how long would you expect that jump to last? Okay. Well, that's a great question because usually it doesn't last very long, depending on how where your cutoff is for defining lasting.
Speaker: Typically, you could expect around two weeks, maybe a little longer in some people. So it's very good if you think of it that way. It's very good as an emergency treatment.
Speaker: It's not so good as a way to maintain the count over time. Right. Okay. So if if a person was having an unusual period of bleeding, that might be a good thing to use, but not not on a regular basis necessarily.
Speaker: How do you determine how much to give a person? How much IVIG? If you're asking about the dose of IVIG for ITP,
Speaker: In general, the initial studies from Switzerland used 400 milligrams per kilogram, or that's the same as 0.4 grams per kilogram of body weight.
Speaker: It's often used at a higher dose than that, a gram per kilo. with the thought that it'll bring the platelet count up faster and higher and do it in one sitting. And the trade-off is you may be more likely to get headaches and or if you're going to get headaches, to have them be more severe.
Speaker: So the larger a person you are it's likely that your dosage would be much larger. It depends on your body weight. If you're immune deficient, however, you know, and you're not treating that person just for the low platelets,
Speaker: then that means that that gamma globulin is going to have to be repeated. In other words, either subcutaneously, weekly usually, or perhaps monthly. And you have to continue to get it. if you If you don't have it on your own, then you're going to need it periodically. Okay. I understand that. If you do have other immune disorders, correct?
Speaker: Yeah. Right. When you are an ITP patient, are there patients that use IVIG as their only treatment? Like maybe if they if their counts go way down or is it used in conjunction with whatever treatment they're on or with another treatment?
Speaker: I would say most commonly it's used in conjunction. Like you might give the IVIG to get the platelet count to come up because another treatment might take a week or two or three or four before it works. So you wouldn't want to leave somebody at a very low count, especially if they're having some bleeding while you're waiting for that.
Speaker: I think it's relatively very infrequent to have them just get IVIG on a regular basis for their ITP. Okay. That makes sense since it is short-lasting and being used more for a sudden onset or either a drop in your platelet count or if you become very symptomatic.
Speaker: Now, you said that the gamma globulin is pooled. Are there differences with the different manufacturers that make the gamma globulin? I mean, should that be something that a patient would consider to only get it from XYZ or a certain manufacturer?
Speaker: It's not really going to happen that way because, first of all, they're all very carefully controlled by the FDA to make sure that they all contain a very large stock of antibody of very specific sorts, measles, mumps, rubella, making certain that the quality of each one meets a certain standard.
Speaker: The other thing to make gamma globulin, you have to add a certain amount of material, a little bit of salt or other amino acid, so that the gamma globulin doesn't clump up.
Speaker: In other words, to get it into a good, smooth solution, it's got to also be made that way. So different manufacturers have taken different tactics that way. Oftentimes, it's not the patient's choice. It's the one that's available in the infusion center that they're attending.
Speaker: Or perhaps their insurance will stipulate that a certain brand of gamma globulin is going to be used because that's the one that the insurance company will pay for. bar Let me ask Charlotte a question about that.
Speaker: What about IGA deficient patients and aren't there some patients you've had who basically do much better with one preparation and have less reactions than another?
Speaker: Well, two things. There is an IgA depleted preparation because a rare immune deficient patient who has zero IgA in their own blood can actually make a reaction if they're given an IVIG that contains some degree of IgA as well.
Speaker: So there can be a reaction. So there's one company that's made an IgA depleted product exactly for that reason. But the other thing is that for reasons that are slightly and unclear, if you have a patient who's continuously needing gamma globulin and needs it every month or at various stipulated intervals, then for some reason, it doesn't seem to work very well to completely change the brand every time.
Speaker: So when you order the brand, it's generally through the insurance and it's once per year, and it's generally not going to change for that entire year and maybe not even ever. We seem to get along with one brand sometimes quite well, and switch shopping and changing is just not exactly a good idea. They're not exactly generic, if you see what I mean, you know, like switching one to the other.
Speaker: There could be little differences between the different manufacturers, right? There are distinct differences amongst all of them, yes. Okay. Okay. I know that when you talk to anybody about IVIG, they're always concerned about the side effects.
Speaker: As all patients with ITP, when you come to talking about any treatment, they want to know what are the side effects. And my understanding, the the most common side effect with IVIG is headaches. Is that correct?
Speaker: That would be probably right. One thing that was very interesting in, the let's say, first half of the 1980s when Charlotte and I might each be presenting on IVIG at a meeting, and she described the side effects in the hypogammaglobulinemic patients who were getting it for their immune lack, and I was describing it for ITP. If you listen to the side effects, you often didn't think we were talking about the same thing.
Speaker: Because in ITP, like you said, mostly headaches. There can be other things. And in particularly in more elderly patients, some people would restrain the dose and let's say give a gram per kilo by giving it half a gram per kilo two days in a row.
Speaker: I think, and Charlotte, correct me if I'm wrong, the hypogamma patients are more likely to have fevers and that kind of acute reaction and have abdominal pain and things like that. It's a little different, you know, muscle pain, headaches. It's a little more systemic than just simply a headache.
Speaker: Part of the problem there if you take a person who's acutely ill, they need gamma globulin, but they're ill at that time. You give gamma globulin in high dose, you're probably going to have a reaction. Major.
Speaker: Because the gamma globulin goes in and says, oh, I see a bug. I think I'll get this out of here. So what you may have is you have actually an immune reaction, which is not comfortable. And so you can get around that by usually giving half the dose the first time just to get that person up to speed, so to speak.
Speaker: Okay. And make it more comfortable for them in the long run. And make it more comfortable. I mean, over time, you should be having no reactions. You know, the patient gets the gamma globulin and then goes out and has lunch or shops at Bloomingdale's.
Speaker: Right. Well, that's a perk, you know, to go shopping at Bloomingdale's after your IVIG. That sounds great. Barbara, one more thing about that is there are medications that can be given with the goal of reducing side effect.
Speaker: Okay. And what's that? um Typically, for ITP at least, you would use Tylenol, not say Motrin or Raspirin, because you don't want to impair the function of the platelets.
Speaker: Right. You could give prednisone or dexamethasone steroids, cut down inflammation, which includes headaches.
Speaker: And then sometimes you could use an antihistamine, although if you do, it's important to use one of the ones that doesn't make you sleepy. But exactly how well all of those work, does everybody need them, et cetera, et cetera, is not that well defined.
Speaker: Well, I've also heard that being very well hydrated prior to the infusion can be beneficial. Yeah, and some people actually do a little better if you infuse some normal saline or other water solution just before the infusion just to be sure they're hydrated.
Speaker: to be clear, though, that's something that I think virtually everybody with any experience would agree on. i don't think if we said, well, can you find data to prove this?
Speaker: I don't think it would be there, which doesn't make it wrong. I'm just commenting. It just seems to work a little better. Yeah. A patient could actually really start drinking a lot of fluids the day before the day of if they know they're getting it, and that could be helpful.
Speaker: Sure. And would it be reasonable if the patient said, could you give me a little bit of fluids, IV, prior to that? Is that something that a doctor would say, sure, why not? In some cases, some patients really re-need it. I mean, some of our patients have a certain amount of GI problems, in other words, gastrointestinal loss of fluid.
Speaker: And in that circumstance, it just probably works a little better if you make sure they're hydrated in advance. But most people don't require that. And just as a practical point, in this day of appointment and time medicine, if you were going to give somebody IVIG and you said, I've got your chair for three hours or four hours or whatever, it'd be nice to know ahead of time so you could plan for a slightly longer amount of time.
Speaker: You know, you'd order the infusion and get the ah saline or whatever it was up from the pharmacy in advance. Yeah. Right. and then it might be helpful to have it run a little bit slower. Would that be beneficial?
Speaker: Oh, of course, if you go very, very slowly. But I mean, the other side of the coin is most patients don't like to be sitting in a chair all afternoon either if they don't have to. And the slower is definitely true with the acute reactions.
Speaker: I don't think it's as clear for headaches, though it seems logical. And what would an acute reaction be? um with IVIG in an ITP patient?
Speaker: I think generally that's not very common. Okay. It depends, especially, you know, like that there's no other factor there like the patient's not hypogammaglobulinemic but doesn't know it.
Speaker: um Ideally, everybody would have their levels checked before getting IVIG. If, as Charlotte described a minute ago, if they have a cold, then the molecules of IgG binding to the viral particles or whatever in the blood could definitely create a reaction.
Speaker: So there's things like that, but mostly that's not such a big problem. Okay. Well, it sounds safer than people can imagine. I think people get very freaked out about side effects and get very concerned. and This is in the setting. Sorry, I should have said one more thing.
Speaker: This is in the setting where current preparations more or less, I would say, stand on their head to not be transmitting any kind of infection.
Speaker: But that's, you know, you couldn't transmit HIV, you couldn't transmit hepatitis etc., but e cetera but something new, you know, or whatever, he couldn't absolutely guarantee.
Speaker: That would usually not be an acute reaction, though. That would be something that would develop over time. I think it's always important to tell the patient, too, what you're getting is a normal part of human beings.
Speaker: And it's more of the molecule that you will already have. Your body will not treat it as foreign because it's not foreign. A gamma globulin molecule is the same in a healthy person as it is in a person with ITP.
Speaker: And it's just a question of trying to get the counts and the person infused and give it in a reasonable period of time so that it doesn't take, for example, the entire day, which one could do, but, you know, nobody wants to do that.
Speaker: So it's not a foreign material. It's not a drug, if you see what I mean. It's not a drug. It's a biologic. In other words, it's biology. That's a very good point that you make, um saying that it is something that your body already has.
Speaker: You already have it, and you already have plenty of it. It's just that we need to interrupt that autoimmune circuit, or we need to replace a little bit more what you don't have enough of. Okay. Well, are there any other potential benefits to getting the IVIG aside from hopefully raising your platelet count?
Speaker: If we're talking about ITP, i mean, there is a little bit of literature that maybe in some people over a lot of repeated infusions, it will actually improve the disease.
Speaker: Why and how that happens is... a whole other issue. It could benefit, suppose you're getting it for ITP, but you also have another autoimmune disease, it might help that other disease also.
Speaker: But in principle, you're doing something short term to help yourself out until the cavalry arrives. Okay. Are you aware if there are any new developments or any advances in IVIG therapy that patients with ITP should be aware of? Is anything new coming around?
Speaker: There have been different things Charlotte can answer for the hypogamma setting, But in ITP, there's always a thought, well, you'll figure out the mechanism and then you'll get a better way to do it.
Speaker: The most obvious one in ITP and some other autoantibody-mediated autoimmune diseases are so-called FCRN inhibitors.
Speaker: FCRN basically recycles your IgG, so it lasts on average three to four weeks in the blood. If you block that recycling period, it might only last for three to five days, and that would mean if you have a disease driven by igg antibodies to something,
Speaker: that all of a sudden you're going to drop their level precipitously, you know, submarine with screen doors. Oh, boy. it'll um It'll mean that you'll potentially be doing a lot better.
Speaker: Sometimes that works really well. Sometimes it doesn't. And there are other molecules that are further away than those, but that's the most obvious one. Do you want to talk about the anti-infectives?
Speaker: Yeah, ah Jim is just reminding me to mention that some of the gamma globulins have ah ah little have been made specifically in order to reinforce certain antibodies. In other words, the there's a particular company that's gone to an effort to have a preparation with an increased amount of antiviral antibodies.
Speaker: There's another company that's gone to a lot of effort to remove some of the components that might lead to blood clotting. Oh, interesting. And so there's... some differences in these compounds and they are all have a unique niche, let's put it that way, in medicine.
Speaker: They're marked as different, right? They're not ones that anybody would give as a regular IVIG. You would. It's just that, of course, because they've gone to more effort to do certain manipulations, you know, they're more expensive. So insurance companies are going to need a letter of necessity to say, okay, I am choosing the one I want here.
Speaker: I don't want the other versions that you may think of. I'm giving this one. And specifically why you'd have to demonstrate the need. And you'd have to have a letter of necessity to to declaim that, yeah, to make that clear.
Speaker: I just mean you never get one of these routinely without something that. probably won't because of the, it's just simple expense. Right. And generally for the IVIG, I mean, for the ITP population, you would get just the standard IVIG solution.
Speaker: The one that they have on the shelf, yeah. All right. Well, let me ask, is there anything else you want to explain or or talk about IVIG with ITP patients? Anything that we possibly did not cover?
Speaker: I think maybe one thing we didn't say is that, of course, like everything, not everybody responds. And I think that's relatively obvious, but we might infer things about someone's ITP, depending on if they do or don't respond.
Speaker: And I think you've probably covered this or would cover it elsewhere, but ITP is not a, quote, simple situation where the only thing that matters is the antiplatelet antibodies.
Speaker: And the more other things that are out there that are complicating the situation, maybe the less likely you would be to respond to IVIG. Doesn't mean it couldn't help you in conjunction with other things.
Speaker: Right. Well, that helps a lot. um And like you said, it's mostly in conjunction with another treatment that they're having and that it's given if your counts were to drop or or possibly also if you were, um would you think that if you were facing a minor surgical procedure, would that be something that they might give prior to that?
Speaker: Yeah, definitely. it all depends. There's not tons of data, but people have tried to make guidelines about what you do for what procedure, depending on your count and so on.
Speaker: So sure. Okay. Well, this has been great. And to have both of you on at the same time, you two are a wealth of information and I really appreciate you sharing that with us today.
Speaker: And I'm sure that this topic and this podcast being on IVIG will be one that will be listened to quite a bit by our ITP population. So I thank you again for participating and you all are so generous to be here with me today.
Speaker: So thank you. Thank you. Thank you. We're glad you're doing this for the ITP population. Well, hopefully it makes a difference in their life and in their journey.
Speaker: How do you live your life with a bleeding disorder like ITP? From working in the kitchen with knives, to navigating sharp corners in your house, going out to eat in a restaurant, traveling on a plane, attending a sporting event, even dancing at a wedding.
Speaker: ITP patient Barbara Pruitt shares her tips and tricks for moving through life with ITP for more than 60 years. Here's her lifestyle lesson for the day.
Speaker: Chances are, if you have ITP, you have probably gotten IVIG. Did you hear what Dr. Cunningham-Rundles said about IVIG? It is something that your body already has. You're just getting a large dose of it.
Speaker: So really, the side effects are slim. About 15 years ago, I was having some kind of a procedure done, and they wanted to give my platelets a boost. So I was scheduled for two days of IVIG,
Speaker: two days apart. After the first dose, I went home and proceeded to have a bad headache. I took Tylenol, but it didn't seem to help much.
Speaker: I called my doctor's office and the nurse called me back. She is the one that told me I needed to hydrate. I realized looking back that I hadn't been drinking many fluids for the previous day or two.
Speaker: So I started drinking water and eventually my headache went away. Two days later, when I went for my second IVIG, I had drank plenty of water the day before and the morning of.
Speaker: And you guessed it, I didn't have a headache. My advice is when receiving IVIG, make sure that you're really well hydrated.
Speaker: And in general, too, it's good for your health, especially during the heat of the summer. So keep your water bottle handy. That's it for today. Thanks for joining me on Bruised But Not Broken, Living with ITP.
Speaker: Hope to see you next time. until then, I'm wishing you lots of happy, healthy platelets. Thanks for listening to the PDSA podcast, Bruised But Not Broken, Living with ITP.
Speaker: made possible by our presenting sponsors, Amjet and Sanofi. Special thanks to Gus Majorga for composing our theme music.
Speaker: To see what's coming up, visit our website at pdsa.org and subscribe wherever you get your podcasts. Please share this podcast through social media with anyone who you think might benefit from the information and stories we share with the ITP and other platelet disorders community.
Speaker: As always, please speak with a healthcare professional before making any treatment decisions. But know that PDSA.org is a wealth of information and resources to help you navigate life with ITP and other platelet disorders.
Speaker: Remember, you are not alone.
