Hoxworth

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What is convalescent plasma? What is the rarest blood type? How much blood is used during a trauma or surgery? Get the answers to your most pressing blood banking questions and listen to In the Know with Dr. Oh!

Headshot of Dr. David Oh and red and white logo reading "In the Know with Dr. Oh"

Hoxworth Blood Center, an internationally recognized leader in transfusion medicine, takes you inside the world of blood banking!  Hoxworth's Chief Medical Officer, Dr. David Oh, covers all aspects of blood donation and transfusion medicine. Tune in and learn about new advancements in the field of blood banking, get answers to our most frequently-asked questions, and uncover the truths behind the most common rumors, myths and fabrications about blood donation.

Have a burning question for Dr. Oh? Contact us at hoxworthintheknow@uc.edu. 

Podcast Episode Transcripts

Alecia Lipton (00:27):

This is Alecia Lipton, and you're listening to in the know with Dr. Oh presented by Hoxworth Blood Center, University of Cincinnati. Our series of podcast will feature Dr. David Oh, our Chief Medical Officer, covering all aspects of blood donation and transfusion medicine. Most importantly, we will discuss how all this impacts you, the listener. Today's episode of In the Know with Dr. Oh focuses on convalescent plasma. First and foremost, Dr. Oh, what is convalescent plasma?

Dr. Oh (00:59):

Plasma is the plasma that we collect from a person who has been infected with COVID-19 and recovered. So COVID-19 convalescent plasma essentially contains the antibodies that can neutralize the virus from people who have recovered

Alecia Lipton (01:15):

Well, we're in blood banking and we've collected red blood cells, whole blood, platelets and plasma. But with the COVID 19 pandemic of 2020, we saw a new aspect come into blood banking, where we had to start collecting convalescent plasma. When did we start doing that?

Dr. Oh (01:35):

So it's actually not a new therapy. It was used over a hundred years ago in the flu epidemic of 1918. We started collecting COVID 19 convalescent plasma in April of this year,

Alecia Lipton (01:46):

When we first started working with the convalescent plasma in April of this year, we were doing that as part of an FDA study. Could you tell us a little bit about that?

Dr. Oh (01:57):

FDA has been very helpful in helping us to collect convalescent plasma and distribute it for people who need it. They provided a guidance, uh, which we pretty much use as a rule, a book to, or a playbook to help us in terms of collecting and distributing the product. We asked that donors who are interested in donating convalescent, plasma, contact us, and we evaluate their symptoms. And if they have any test results, that's very helpful in terms of us allowing them to go ahead and donate complex supplies.

Alecia Lipton (02:29):

And it looks like in about August the FDA then released some of the barriers so that it was easier for physicians to order convalescent plasma.

Dr. Oh (02:40):

In the pandemic we collected convalescent plasma. And the only way that patients could actually receive pelvis plasma was through three different mechanisms and they all had to be FDA approved protocols. So one was what we call an EIND and that's for individual patients. So a physician would see a patient that they wanted to treat and would actually have to contact FDA for permission to use the convalescent plasma. FDA was great in terms of being able to turn around those requests very rapidly, typically within a day. And, but you can imagine that the paperwork involved in that was pretty cumbersome. And that was a difficult process for both FDA and for individual doctors who were requesting. So the Mayo Clinic had a study, which had a lot of interest. It actually became an EAP or an extended access protocol, so that many hospitals across the country could use it and allow more patients to be able to get a convalescent plasma.

The Mayo clinic EAP was reviewed and approved by FDA, and actually FDA started recommending that physicians who requested plasma under an EIND start using the Mayo EAP because it was an easier process for them to get the convalescent plasma. Um, the other mechanism, the third mechanism was actually for individual hospitals or hospital groups to construct their own clinical trial. So this was an option that required a lot of work on behalf of the hospitals, but a couple of different hospitals in the Cincinnati area (Christ system and TriHealth system) developed their own protocols. And these had to be approved by FDA as well. And once those individual protocols were approved, then they could start enrolling patients to get convalescent plasma under the specific requirements of that specific protocol.

Alecia Lipton (04:25):

It sounds as if Hoxworth really worked hand in hand with the area hospitals and the FDA at the forefront of the COVID-19 and convalescent plasma usage.

Dr. Oh (04:34):

That's one of the great things about Hoxworth Blood Center. We have a very close relationship with our hospitals and we're able to work out some of these types of details. We are the only blood collector and supplier in this primary area. So all of the different hospitals in Cincinnati and the surrounding tri-state area, essentially get all of their blood from Hoxworth Blood Center. So we can help them directly with any special requests that they have or special processes such as this, we work closely with Christ Hospital and TriHealth in terms of helping them with their protocols and making sure that the convalescent plasma portion of those made sense. And we also worked with the UC health system with multiple studies that they were working on as well.

Alecia Lipton (05:17):

So you mentioned that Hoxworth Blood Center supplies blood to over 30 hospitals in the tri-state region. So does that mean no matter which hospital you're in at this point in time, if you are diagnosed with COVID-19, you have the ability to get convalescent plasma?

Dr. Oh (05:33):

Yeah, essentially we have been providing convalescent plasma to all the hospitals that we provide typical blood products to. And so that's essentially all of the hospitals in the area that includes the Mercy system, TriHealth, UC Health, Children's Hospital, Christ. So essentially if you or a loved one are receiving convalescent plasma in the Cincinnati area, you've gotten it from Hoxworth Blood Center.

Alecia Lipton (05:59):

When somebody has recovered from COVID-19 and they're considering, you know, I can go donate. Now, I've been symptom-free for 14 days. Does everybody have those antibodies or are there some people who might not have antibodies?

Dr. Oh (06:11):

There are people who, when we test do not seem to have antibodies, we perform antibody testing, which was not actually available in April for us to use. So initially we were accepting donors who had a test positive for COVID-19 at the time of diagnosis. It's hard to remember, but it was very difficult to get testing back then. So we were very fortunate when we had donors who had this type of test results. If we didn't have a test result because of a lack of testing availability, we actually held those convalescent plasma units that we collected until we were able to, to bring on, uh, an antibody test of our own. When we do do that testing the vast majority of people who report that they have had a COVID-19 infection, uh, do have, uh, antibodies that we are able to detect. And we actually want that level to be high enough for us to be able to have a lot of antibodies when we transfuse those to people who are actively infected

Alecia Lipton (07:07):

When somebody is contemplating, whether or not they should donate convalescent plasma, of course, we want them to pre-register for that on our website. And that is hoxworth.org/covid-19. So again, that's hoxworth.org backslash COVID dash 19. And why is it that we need people to register ahead of time? Why can't they just walk in the door and say, hi, I'm here to donate convalescent plasma?

Dr. Oh (07:35):

With all of our blood donations, even our standard blood products, we really would like for our donors to make appointments ahead of time, we have a limited amount of staff and equipment. So we really need to make sure when a donor arrives that we have availability for them so that their wait time is actually minimized for COVID-19. There's an extra level of qualification that has to happen because we don't want to be collecting people who won't have high levels of antibody. So oftentimes we really want to have documentation if it's at all available that the person was actively diagnosed with COVID-19.

Alecia Lipton (08:10):

You talked about having documentation that there was a positive diagnosis of COVID-19. Uh, what is it that you're looking for? Is it a doctor's note? Test results? What would the donor need to collect?

Dr. Oh (08:22):

We would prefer to have an actual lab result. If they have had a, for instance, nasal pharyngeal swab, that was positive. That's actually probably the best thing we could have. We also will accept, uh, doctors attestation that a person was infected, you know, early on. It was very difficult to get this documentation, but now it's actually pretty easy. I think for, for people to get that and testing has become much more available. So that testing is usually available.

Alecia Lipton (08:48):

I think one thing that's important for our listeners to know is that when you come and donate blood at blood center, we do a variety of, um, I believe 19 different tests on every unit of blood that's collected, but we do not currently test for COVID-19 or antibodies.

Dr. Oh (09:06):

That's correct. So for the general population, who's donating blood, we do not test for COVID-19. This is something that I think a few blood centers are doing, but really in terms of, you know, our function and our mission that COVID-19... Having people donate just to get results for COVID-19 was something that we did not feel like we should be, um, trying to do. The testing is not foolproof as well. So we really want people to have had a clinical symptoms and infection. If, if that's been, uh, documented for them before we would try to collect them for convalescent plasma.

Alecia Lipton (09:41):

And then the actual donation process, what is it like when you're coming in to do a convalescent plasma donation?

Dr. Oh (09:49):

Typically we have two major ways that people donate blood. One is whole blood and that's I think what most people traditionally think about when they think of blood donation. So oftentimes these are in a mobile setting, a donor will have a blood collected into a bag that actually has multiple empty bags connected to it. And it's a pretty rapid collection process. We collect about 500 milliliters of blood. Oftentimes you'll see that blood rocking on a scale that mixes the blood as it, as it weighs it, that is not the way we collect convalescent plasma, the other major mechanism, or a way that people donate is through automated devices. And so this is the way we currently collect platelets and we can collect plasma as well as we do that. A convalescent plasma, a donor will qualify just as they do for a whole blood donation, and then they will donate so that the blood goes into a device and we use disposable kits for every single donor that comes through. So, so the blood is kept separated from the actual machinery. The automated device will spin that blood at high speeds and allow us to actually layer out and collect the specific portion that we're interested in. Platelet donors will actually have platelets collected at the interface between the plasma and the red cells and for convalescent plasma donors, we're actually going to skim at the plasma level. So it's a very efficient way for us to collect that plasma and then return all of the other blood components back to the donor.

Alecia Lipton (11:18):

So it's very efficient. Also, as the donor, you're getting back some fluids as well. So, um, you leave feeling great. You're hydrated. How long does the process typically take? Is it the same with whole blood or is it as long as a platelet donation?

Dr. Oh (11:32):

It's kind of in between those two? So it's about an hour for most people, I would say whole blood is actually about 10 minutes in terms of the actual from needle to end of collection. But of course, with all of these donation types, there is an interview process, a questionnaire that needs to be answered and a recovery time in the, uh, after donating and what we call our canteen. So people can have some juice and cookies before they head out the door.

Alecia Lipton (11:57):

Yeah, that's the best part of the day, the juice and cookies. You did bring up something very important there, and that was the personal interview prior to donation and also filling out the donor questionnaire. So I think it's important that listeners know that when you're donating convalescent plasma, you're still going through that questionnaire process and there are still criteria that you need to meet. And that would be things such as travel medication and lifestyle restrictions, correct?

Dr. Oh (12:26):

That's definitely true. So unfortunately, sometimes we'll have donors who come in and are very excited to donate, whether it's convalescent, plasma or other blood products. And then through the interview process, we are unable to collect blood from them because they're ineligible for one reason or another. It's hard to understand sometimes why we would defer somebody for specific types of travel or for specific risk factors for a transfusion transmitted diseases, or even for donor safety reasons. But these questions are actually fairly uniform throughout all blood collectors. We use essentially what we call AABB, which is an organization over blood banks, donor history questionnaire, which has been approved by FDA. So you'll have a similar experience wherever you donate in terms of the types of questions that we ask. And the reasons for that are really regulatory in nature.

Alecia Lipton (13:17):

No. When people come to donate blood, they can't donate blood every day. Um, there are safety mechanisms put in place so that safe for you, the donor. So for whole blood, you can donate every 56 days. Platelets, you can donate every two weeks. What is the rule for convalescent plasma donors? How often can they donate?

Dr. Oh (13:36):

Yeah, this is a new product for us. So we've had work in terms of what we feel is appropriate for donation intervals. And you will see actually see some differences between different blood centers that are collecting convalescent plasma. At Hoxworth, we have decided to collect every seven days, a new convalescent plasma donor for up to four donations. So essentially for a month, we collect once a week, at most. After that fourth donation, we ask the donors to come back every 14 days. This is a change from earlier where we were asking people to come back every 28 days. But when we've looked at the antibody levels of our donors, we see that they do decrease over time. And that the best opportunity for us to collect plasma is early on in infection or as early as possible. Uh, for the first several months, at least. Many people will actually continue to have a good antibody levels over an extended period of time. But many people will have a more dramatic drop. And then we really would not want to use their plasma because the antibody levels are not as high as they could be.

Alecia Lipton (14:40):

Thank you for listening to in the note with Dr. Oh brought to you by Hoxworth Blood Center, University of Cincinnati for additional information, visit us online at www.hoxworth.org!

This is Alecia Lipton, and you're listening to in the know with Dr. Oh presented by Hoxworth Blood Center, University of Cincinnati. Our series of podcast will feature Dr. David Oh, our Chief Medical Officer, covering all aspects of blood donation and transfusion medicine. Most importantly, we will discuss how all this impacts you, the listener. Today's episode of In the Know with Dr. Oh focuses on convalescent plasma. First and foremost, Dr. Oh, what is convalescent plasma?

Dr. Oh (00:59):

Plasma is the plasma that we collect from a person who has been infected with COVID-19 and recovered. So COVID-19 convalescent plasma essentially contains the antibodies that can neutralize the virus from people who have recovered

Alecia Lipton (01:15):

Well, we're in blood banking and we've collected red blood cells, whole blood, platelets and plasma. But with the COVID 19 pandemic of 2020, we saw a new aspect come into blood banking, where we had to start collecting convalescent plasma. When did we start doing that?

Dr. Oh (01:35):

So it's actually not a new therapy. It was used over a hundred years ago in the flu epidemic of 1918. We started collecting COVID 19 convalescent plasma in April of this year,

Alecia Lipton (01:46):

When we first started working with the convalescent plasma in April of this year, we were doing that as part of an FDA study. Could you tell us a little bit about that?

Dr. Oh (01:57):

FDA has been very helpful in helping us to collect convalescent plasma and distribute it for people who need it. They provided a guidance, uh, which we pretty much use as a rule, a book to, or a playbook to help us in terms of collecting and distributing the product. We asked that donors who are interested in donating convalescent, plasma, contact us, and we evaluate their symptoms. And if they have any test results, that's very helpful in terms of us allowing them to go ahead and donate complex supplies.

Alecia Lipton (02:29):

And it looks like in about August the FDA then released some of the barriers so that it was easier for physicians to order convalescent plasma.

Dr. Oh (02:40):

In the pandemic we collected convalescent plasma. And the only way that patients could actually receive pelvis plasma was through three different mechanisms and they all had to be FDA approved protocols. So one was what we call an EIND and that's for individual patients. So a physician would see a patient that they wanted to treat and would actually have to contact FDA for permission to use the convalescent plasma. FDA was great in terms of being able to turn around those requests very rapidly, typically within a day. And, but you can imagine that the paperwork involved in that was pretty cumbersome. And that was a difficult process for both FDA and for individual doctors who were requesting. So the Mayo Clinic had a study, which had a lot of interest. It actually became an EAP or an extended access protocol, so that many hospitals across the country could use it and allow more patients to be able to get a convalescent plasma.

The Mayo clinic EAP was reviewed and approved by FDA, and actually FDA started recommending that physicians who requested plasma under an EIND start using the Mayo EAP because it was an easier process for them to get the convalescent plasma. Um, the other mechanism, the third mechanism was actually for individual hospitals or hospital groups to construct their own clinical trial. So this was an option that required a lot of work on behalf of the hospitals, but a couple of different hospitals in the Cincinnati area (Christ system and TriHealth system) developed their own protocols. And these had to be approved by FDA as well. And once those individual protocols were approved, then they could start enrolling patients to get convalescent plasma under the specific requirements of that specific protocol.

Alecia Lipton (04:25):

It sounds as if Hoxworth really worked hand in hand with the area hospitals and the FDA at the forefront of the COVID-19 and convalescent plasma usage.

Dr. Oh (04:34):

That's one of the great things about Hoxworth Blood Center. We have a very close relationship with our hospitals and we're able to work out some of these types of details. We are the only blood collector and supplier in this primary area. So all of the different hospitals in Cincinnati and the surrounding tri-state area, essentially get all of their blood from Hoxworth Blood Center. So we can help them directly with any special requests that they have or special processes such as this, we work closely with Christ Hospital and TriHealth in terms of helping them with their protocols and making sure that the convalescent plasma portion of those made sense. And we also worked with the UC health system with multiple studies that they were working on as well.

Alecia Lipton (05:17):

So you mentioned that Hoxworth Blood Center supplies blood to over 30 hospitals in the tri-state region. So does that mean no matter which hospital you're in at this point in time, if you are diagnosed with COVID-19, you have the ability to get convalescent plasma?

Dr. Oh (05:33):

Yeah, essentially we have been providing convalescent plasma to all the hospitals that we provide typical blood products to. And so that's essentially all of the hospitals in the area that includes the Mercy system, TriHealth, UC Health, Children's Hospital, Christ. So essentially if you or a loved one are receiving convalescent plasma in the Cincinnati area, you've gotten it from Hoxworth Blood Center.

Alecia Lipton (05:59):

When somebody has recovered from COVID-19 and they're considering, you know, I can go donate. Now, I've been symptom-free for 14 days. Does everybody have those antibodies or are there some people who might not have antibodies?

Dr. Oh (06:11):

There are people who, when we test do not seem to have antibodies, we perform antibody testing, which was not actually available in April for us to use. So initially we were accepting donors who had a test positive for COVID-19 at the time of diagnosis. It's hard to remember, but it was very difficult to get testing back then. So we were very fortunate when we had donors who had this type of test results. If we didn't have a test result because of a lack of testing availability, we actually held those convalescent plasma units that we collected until we were able to, to bring on, uh, an antibody test of our own. When we do do that testing the vast majority of people who report that they have had a COVID-19 infection, uh, do have, uh, antibodies that we are able to detect. And we actually want that level to be high enough for us to be able to have a lot of antibodies when we transfuse those to people who are actively infected

Alecia Lipton (07:07):

When somebody is contemplating, whether or not they should donate convalescent plasma, of course, we want them to pre-register for that on our website. And that is hoxworth.org/covid-19. So again, that's hoxworth.org backslash COVID dash 19. And why is it that we need people to register ahead of time? Why can't they just walk in the door and say, hi, I'm here to donate convalescent plasma?

Dr. Oh (07:35):

With all of our blood donations, even our standard blood products, we really would like for our donors to make appointments ahead of time, we have a limited amount of staff and equipment. So we really need to make sure when a donor arrives that we have availability for them so that their wait time is actually minimized for COVID-19. There's an extra level of qualification that has to happen because we don't want to be collecting people who won't have high levels of antibody. So oftentimes we really want to have documentation if it's at all available that the person was actively diagnosed with COVID-19.

Alecia Lipton (08:10):

You talked about having documentation that there was a positive diagnosis of COVID-19. Uh, what is it that you're looking for? Is it a doctor's note? Test results? What would the donor need to collect?

Dr. Oh (08:22):

We would prefer to have an actual lab result. If they have had a, for instance, nasal pharyngeal swab, that was positive. That's actually probably the best thing we could have. We also will accept, uh, doctors attestation that a person was infected, you know, early on. It was very difficult to get this documentation, but now it's actually pretty easy. I think for, for people to get that and testing has become much more available. So that testing is usually available.

Alecia Lipton (08:48):

I think one thing that's important for our listeners to know is that when you come and donate blood at blood center, we do a variety of, um, I believe 19 different tests on every unit of blood that's collected, but we do not currently test for COVID-19 or antibodies.

Dr. Oh (09:06):

That's correct. So for the general population, who's donating blood, we do not test for COVID-19. This is something that I think a few blood centers are doing, but really in terms of, you know, our function and our mission that COVID-19... Having people donate just to get results for COVID-19 was something that we did not feel like we should be, um, trying to do. The testing is not foolproof as well. So we really want people to have had a clinical symptoms and infection. If, if that's been, uh, documented for them before we would try to collect them for convalescent plasma.

Alecia Lipton (09:41):

And then the actual donation process, what is it like when you're coming in to do a convalescent plasma donation?

Dr. Oh (09:49):

Typically we have two major ways that people donate blood. One is whole blood and that's I think what most people traditionally think about when they think of blood donation. So oftentimes these are in a mobile setting, a donor will have a blood collected into a bag that actually has multiple empty bags connected to it. And it's a pretty rapid collection process. We collect about 500 milliliters of blood. Oftentimes you'll see that blood rocking on a scale that mixes the blood as it, as it weighs it, that is not the way we collect convalescent plasma, the other major mechanism, or a way that people donate is through automated devices. And so this is the way we currently collect platelets and we can collect plasma as well as we do that. A convalescent plasma, a donor will qualify just as they do for a whole blood donation, and then they will donate so that the blood goes into a device and we use disposable kits for every single donor that comes through. So, so the blood is kept separated from the actual machinery. The automated device will spin that blood at high speeds and allow us to actually layer out and collect the specific portion that we're interested in. Platelet donors will actually have platelets collected at the interface between the plasma and the red cells and for convalescent plasma donors, we're actually going to skim at the plasma level. So it's a very efficient way for us to collect that plasma and then return all of the other blood components back to the donor.

Alecia Lipton (11:18):

So it's very efficient. Also, as the donor, you're getting back some fluids as well. So, um, you leave feeling great. You're hydrated. How long does the process typically take? Is it the same with whole blood or is it as long as a platelet donation?

Dr. Oh (11:32):

It's kind of in between those two? So it's about an hour for most people, I would say whole blood is actually about 10 minutes in terms of the actual from needle to end of collection. But of course, with all of these donation types, there is an interview process, a questionnaire that needs to be answered and a recovery time in the, uh, after donating and what we call our canteen. So people can have some juice and cookies before they head out the door.

Alecia Lipton (11:57):

Yeah, that's the best part of the day, the juice and cookies. You did bring up something very important there, and that was the personal interview prior to donation and also filling out the donor questionnaire. So I think it's important that listeners know that when you're donating convalescent plasma, you're still going through that questionnaire process and there are still criteria that you need to meet. And that would be things such as travel medication and lifestyle restrictions, correct?

Dr. Oh (12:26):

That's definitely true. So unfortunately, sometimes we'll have donors who come in and are very excited to donate, whether it's convalescent, plasma or other blood products. And then through the interview process, we are unable to collect blood from them because they're ineligible for one reason or another. It's hard to understand sometimes why we would defer somebody for specific types of travel or for specific risk factors for a transfusion transmitted diseases, or even for donor safety reasons. But these questions are actually fairly uniform throughout all blood collectors. We use essentially what we call AABB, which is an organization over blood banks, donor history questionnaire, which has been approved by FDA. So you'll have a similar experience wherever you donate in terms of the types of questions that we ask. And the reasons for that are really regulatory in nature.

Alecia Lipton (13:17):

No. When people come to donate blood, they can't donate blood every day. Um, there are safety mechanisms put in place so that safe for you, the donor. So for whole blood, you can donate every 56 days. Platelets, you can donate every two weeks. What is the rule for convalescent plasma donors? How often can they donate?

Dr. Oh (13:36):

Yeah, this is a new product for us. So we've had work in terms of what we feel is appropriate for donation intervals. And you will see actually see some differences between different blood centers that are collecting convalescent plasma. At Hoxworth, we have decided to collect every seven days, a new convalescent plasma donor for up to four donations. So essentially for a month, we collect once a week, at most. After that fourth donation, we ask the donors to come back every 14 days. This is a change from earlier where we were asking people to come back every 28 days. But when we've looked at the antibody levels of our donors, we see that they do decrease over time. And that the best opportunity for us to collect plasma is early on in infection or as early as possible. Uh, for the first several months, at least. Many people will actually continue to have a good antibody levels over an extended period of time. But many people will have a more dramatic drop. And then we really would not want to use their plasma because the antibody levels are not as high as they could be.

Alecia Lipton (14:40):

Thank you for listening to in the note with Dr. Oh brought to you by Hoxworth Blood Center, University of Cincinnati for additional information, visit us online at www.hoxworth.org!

Alecia Lipton (00:29):

You are listening to In the Know with Dr. Oh, and today's episode focuses on convalescent plasma. If you have recovered from COVID-19 and you've been symptom-free for at least 14 days, we encourage you to go online and register to make a convalescent plasma donation. And you can do that www.hoxworth.org/covid-19. So I was looking at the figures this morning, Dr. Oh, and it looks like Hoxworth, since April, has distributed over 2,622 units of convalescent plasma, and we've collected just over 3,052 units from prospective donors. Can you give us an idea of current usage? Where are we at with our usage and in this area, especially as the diagnosis of COVID-19 is creeping up?

Dr. Oh (01:35):

Today is, uh, early December. So we are experiencing a third spike and not just here locally, but nationally, there have been more COVID-19 infections recently than there ever have been, uh, previously, uh, in the pandemic. So initially when we started collecting in April, uh, we were just distributing a few units per day to the hospitals. Um, that reached kind of an early baseline in September, where we were distributing about eight units per day to our hospitals. Over the past few weeks, we had multiple days where we were distributing over 60 units to the hospitals per day. So as a result of that, we asked our hospitals to start transfusing one unit of convalescent plasma per patient, uh, rather than oftentimes they would give two units. And so to make sure that our supply lasted longer, this is consistent with the way that convalescent plasma is transfused throughout the country. So it's either one or two units per patient, typically, per course. Um, so I think that was a very reasonable. And so recently we have had, I would say, uh, a 400% increase in terms of the amount of convalescent plasma that's been distributed, and it keeps going up as, um, more and more people become infected with COVID-19.

Alecia Lipton (03:00):

I've seen many Different graphs shared through the media about what the anticipated growth is for COVID-19 positive cases. And it looks like that's going to continue through January. Are you seeing the same thing, do you think we're going to need to continue to have more and more convalescent plasma donors?

Dr. Oh (03:19):

You know, there aren't a ton of different medications that physicians have in their armament against COVID-19 infection. So we've been very happy that we've been able to help with convalescent plasma. As you mentioned earlier, in August of this year, a convalescent plasma received an EUA status, which is an emergency use authorization, so that it was found over tens of thousands of transfusions, um, throughout the pandemic to that point, that safety profile was really good for this. So there was very little risk for people to receive convalescent plasma efficacy was reasonable to expect as well. So it makes sense as a model that antibiotics would help in terms of neutralizing virus and, and help with course. And there have been many, many anecdotal reports of, uh, really rapid improvement after convalescent plasma. So with the likely efficacy of the product, as well as a very high safety level, uh, it became one of those drugs that, uh, clinicians could start ordering without having to have their patients participate in the FDA approved trial because they had established, um, and gained so much experience with the use through the EAP study and other mechanisms

Alecia Lipton (04:36):

That's great that they product is much more widely available now for patients in need. You mentioned that the current protocol is to administer one unit of the convalescent plasma per patient. Is it recommended that that be done earlier in their illness or do they do that when they're more critically ill?

Dr. Oh (04:54):

I think most of us believe that when a patient receives convalescent plasma earlier in their course, it's more beneficial. So we definitely don't want to give convalescent plasma if somebody is very mild in terms of symptoms and, and likely won't require hospitalization or, you know, uh, more intensive treatment, which many people have fairly mild symptoms where I think it probably works best and has most efficacy is early in hospitalization as a person becomes closer to having to require ventilation or to be put on a ventilator if we can give convalescent plasma in that time period, I think that there are probably cases where the patient does not go on to become ventilator dependent, which I think is a bad sign for them, a marker for them as they go forward. So if we use it judiciously, uh, and I've heard, you know, many reports of, of this being the way that it's been used and, and with good results. So it's probably early in hospitalization before the person gets on a ventilator.

Alecia Lipton (05:58):

For listeners out there, you have a positive Diagnosis of COVID-19 and you have recovered and you have been symptom-free for at least 14 days, we do encourage you to go online and register to be a convalescent plasma donor. You can do that at www.hoxworth.org/covid-19. With Hoxworth, we're always talking about how we need donors. We need to have blood on the shelf before the need arises. And that's also very true with convalescent plasma. So we can't let people say, Oh, well, I'll donate when someone in my family needs convalescent plasma, can you explain the rationale for having the product on the shelf before it's needed?

Dr. Oh (06:39):

It seems fairly simple to just collect plasma and then have it available. But we do have to do a lot of preparation for the products, as well as testing that's performed on every single donation that occurs. We don't recommend a directed donation of convalescent plasma at this time. The safety of convalescent plasma has been shown through tens of thousands of, of transfusions to this point. So we would not really want people to, to try to direct their plasma. It, it ends up adding a lot of complication to the process that really is not necessary.

Alecia Lipton (07:11):

And you also have to be able to match up those blood types, correct?

Dr. Oh (07:15):

That's correct. You may have heard for red cells, that O is the universal donor. For plasma, AB is actually the universal donor, and there's only about 4% of the population is blood type AB I think in desperate times when AB is not available, clinician may make the decision to use A plasma, but it's a, it's usually something we try to avoid as much as possible. So if we, especially when we get AB donors to donate their plasma, that's usually the most, uh, the most efficient.

Alecia Lipton (07:47):

And recently it's been hard to turn on the news without hearing about COVID-19 convalescent plasma, different treatments that are being used to treat those with the COVID-19 virus. Is the convalescent plasma therapy similar to what President Trump received during his stay in the hospital?

Dr. Oh (08:05):

Yeah, my understanding is that president Trump did receive some antibodies treatments, uh, that were developed and available for him in limited amounts. So other people have not been easily able to get those therapies, uh, that he was, but the mechanism is generally the same with convalescent plasma and, and some of the treatments that he received and that the antibody should neutralize the COVID-19 virus, and so work in a similar manner.

Alecia Lipton (08:32):

When we've talked before about this type of therapy, you explained to me that it's a concept called passive immunity. And can you explain how that works and how the infected person then develops antibodies?

Dr. Oh (08:46):

Typically for a person let's say, who has never been exposed to COVID-19, let's say somebody gets infected with that after an exposure. So that would develop antibodies as part of their immune response. And that's the way our body tends to deal with micro-organisms that we encounter. Uh, and so, um, you, you actively develop antibodies to fight off this infection. It's actually the same thing after getting a vaccination. Uh, and the reason we get vaccinated is so that we form antibodies against, um, the virus or bacteria that we're concerned about. So that is a natural, active immune response. If you take plasma from somebody who has actually developed those antibodies and give them to somebody who has not previously been exposed to the virus or bacteria that you're worried about, you give those antibodies to that recipient in a passive manner, because it's just transfused. So your body actually hasn't developed those antibodies on their own, but those antibodies are present in the plasma that's transfused, and that can help to neutralize the virus until your own body then is able to mount a response. And then you become actively immunized as well after exposure to the virus itself.

Alecia Lipton (10:01):

One of our goals of the In the Know with Dr. Oh Podcast series is to let our listeners know about transfusion medicine, convalescent plasma, blood donation, and how it will impact them as the listener. Right now, we're hearing a lot about social distancing, especially with the third spike in COVID-19. Is it safe to come in and donate right now?

Dr. Oh (10:25):

That's a great question. Um, you know, early in the pandemic, in the state of Ohio, uh, I know that there were a lot of travel restrictions that were placed. And at that time, we made a point and, um, the governor supported this to, to make a distinction about blood donation in that we still do require and need people to come out and donate blood as kind of a medical necessity. So, we take precautions at our collections sites. We social distance as much as possible. Of course you can't keep six, six feet away and and be able to, uh, collect blood from somebody. But we have all of our staff and, and people who come into those facilities wear masks at all times. And we try to keep exposures, you know, as low as possible. So, uh, we do encourage people to come out, uh, during this time period, I can't say it's, you know, absolutely. You know, the safest thing you can do that the safest thing people can do is just stay home and not leave their house, but it is reasonable for people to come out with a specific intent to donate blood, to help others. It is a medical necessity for us, and it is something that I think we are still encouraging people to do.

Alecia Lipton (11:41):

We encourage people to make wise decisions in their daily business. We have to go to the grocery store, we have to go to work. We have to go to the gas station and just doing social distancing, we can still accomplish those tasks. And it's the same with blood donation. It is a medical necessity. And as long as you're practicing good hygiene and social distancing, then coming to donate blood and or convalescent plasma should be safe for you.

Dr. Oh (12:08):

Yeah. You know, Alecia, even with the pandemic going on right now and all the precautions that we're taking surgeries are still happening and people still need blood. People have cancer. They, they go on chemotherapy. There's still the need for other blood products like red cells, platelets and plasma that's not convalescent plasma for patients who are, who are having the blood blood requirements. Blood transfusion is actually the number one procedure that's performed at hospitals. So this has continued at a rate pre COVID 19. And so in addition to having to collect all the convalescent plasma that we are, and having to social distance and having less, uh, ability to collect on mobiles, because we're social distancing, we still have the same blood needs from the hospitals as before. So, it's very challenging for us in this time to provide not only the convalescent plasma, but also the other blood products that people need.

Alecia Lipton (13:05):

Is there anything that would prevent somebody from donating convalescent plasma other than our typical guidelines for travel and medication and lifestyle?

Dr. Oh (13:16):

That's a great question. So if somebody qualifies with all the questions that we ask, we actually do a lot of testing after the donation as well. So one of the things that we do do is we test for a lot of infectious disease markers. Occasionally a donor will have a positive infectious disease marker. That actually does not mean that they have, uh, the infectious disease that we're testing for! We use very sensitive tests. Unfortunately, sometimes we have donors who are not actually infected who have what we call false positives to that process. And then we notify them that unfortunately they're unable to donate blood going forward. Uh, sometimes we will recommend that they see their physicians if the results are worrisome, but many of these tests, unfortunately we know, are very, very sensitive and we'll sometimes have people that test falsely positive right now.

We're actually having a lot of, uh, false, positive syphilis tests, uh, nationwide, which it sounds really scary, but all of these tests are required to be performed as a process in, in releasing blood for transfusion. And then we want to be as safe as possible so that there are no transfusion transmissions as much as possible through, uh, through blood transfusion. Uh, and so, um, actually people who are having false positives for syphilis testing, uh, we encourage to come back in eight, eight weeks and we actually send them a letter. Part of the testing processes also to prevent a rare transfusion reaction called TRALI, which is actually a pulmonary reaction where the recipient will have trouble breathing after a transfusion of some blood products, especially those that contain a lot of plasma. These reactions are very rare, but they have been associated with donors who have actually been pregnant.

And, uh, actually donors who have actually been pregnant multiple times are at higher association with recipients who receive plasma from them. So we've started screening blood donors for antibodies to what we call HLA. And these are not a problem for them at all in terms of life and, and clinical significance for the donor themselves. But because of this association, with this rare, uh, transfusion reaction, we have not been using blood or plasma or platelets that has been collected from donors who have these antibodies. That can be quite high percentage of women, donors who have had pregnancies, especially if they've had multiple children. Uh, and so up to even 20 to 30% of, of women who have had three or more children. So it's not, unfortunately it's not uncommon for somebody to come out, try to donate blood with us and especially plasma or platelets, and then be told, Oh, unfortunately you can't continue to donate those products in the future

Alecia Lipton (16:03):

Because you can't donate one product. That doesn't mean that you can't donate at all. Correct?

Dr. Oh (16:08):

That's correct. So, uh, if we detect these antibodies and so essentially we ask a question on our questionnaire, if you ever been pregnant, and if they answer that, yes, then we will perform an additional test. If, for people who have never been pregnant or who are males, um, they typically do not have these antibodies. So they are not actually screened for this. We would actually ask those donors who have an anti HLA antibodies to donate, uh, red cells for us and whole blood. So those red cells can be used without significant increase in risk for recipients

Alecia Lipton (16:40):

Patients in the hospital don't get a holiday from illness. There's still cancer. There's still surgeries. There's still traumas and people still need those blood and platelet transfusions. So it's important that we continue to have people come in and donate blood. If you're interested in donating blood, you can call Hoxworth at (513) 451-0910 or visit www.hoxworth.org to schedule your blood or platelet donation. Again, if you have recovered from COVID-19 and you're interested in making a convalescent plasma donation, you do need to pre-register online and you do that www.hoxworth.org/covid-19.

Alecia Lipton (00:40):

Hi, I'm Alecia Lipton. And today you're listening to in the know with Dr. Oh brought to you by Hoxworth Blood Center. Today's episode is going to focus on the eligibility for donating blood and the deferrals that may come with that. Dr. Oh, can you start out by talking about how the blood center is regulated?

Dr. David Oh (00:58):

Sure. Blood centers across the United States are highly regulated. Uh, when we create blood, FDA actually considers it to be a drug. So we have to make sure that we adhere to what we call a CGMP or current good manufacturing practices. What we put on a label as on a unit of blood actually really needs to reflect the contents of that bag, the same way as if you buy a medication at your pharmacy, uh, you'd want the label to reflect the contents of each bottle.

Alecia Lipton (01:27):

Okay. And I think what's important about that is that people realize that Hoxworth, isn't just sitting there making up rules. These are rules that are mandated by the Food and Drug Administration.

Dr. David Oh (01:37):

That's correct. So FDA, I always consider as our friends, they make sure that the drugs that are manufactured are up to a very high quality level and are safe for people who receive them. They create regulations for us in the CFR code of federal regulations. They also release guidances for industry, which we adhere to whenever they're released and so multiple times a year, we'll get a new guidance on specific areas of concern for the FDA, and we make sure that we comply with them.

Alecia Lipton (02:07):

Okay. I think a good takeaway from that, as you said, the FDA is our friend and I think that's important. They're there to make sure that, you know, the blood or whatever is being manufactured, whether it be blood, platelets or plasma is safe for the person receiving it and that it's also safe for the person to be giving it.

Dr. David Oh (02:25):

Yeah. Their rules and regulations really allow us to know what is expected from us. And we make sure to comply with that. You'll notice if you've donated at different blood centers across the country, that the questions that we use are all very similar. Those have been created through the industry in coordination and collaboration with FDA. And anytime we have questions, the FDA has to review those SOPs or forms that we create to make sure that they're comfortable.

Alecia Lipton (02:53):

So Hoxworth Blood Center is the steward of the local blood supply for the tri-state, being Ohio, Kentucky, and Indiana. And part of our mission is not only to supply that blood, but to make sure that it is a safe supply.

Dr. David Oh (03:06):

That's correct. So there is a lot of testing that goes on, uh, after you donate a unit of blood. Some people will say, Oh my goodness, you guys, we're giving our blood and we're not getting any money for it at all. How difficult can it be, you know, to your job. And there's a lot that happens after you donate to make sure that that is safe for a person to receive as a transfusion. There are a number of infectious disease marker tests that have to be performed. And we have to make sure that the parameters of the bag that we collect are adequate for release.

Alecia Lipton (03:41):

What are some of the disease markers that we test for?

Dr. David Oh (03:43):

There are specific infectious disease markers and tests that have been approved specifically for the use and purpose of testing blood donors, I'll list off a few of them...hepatitis B, HIV, hepatitis C. Those are kind of the major viruses that we're really concerned with and, and were a definite problem in terms of safety in the eighties. The development of tests has been a real step forward in terms of safety, where the current risk of contracting HIV or hepatitis C through blood transfusion, it's about one in 2 million transfusions that occur. So it's very, very safe.

Alecia Lipton (04:23):

I've heard people in the past say, well, you've asked us all these screening questions. Why then are you doing these medical tests also? Can you tell us the validity of the testing? Why do we go that extra step?

Dr. David Oh (04:35):

So that's a great question. There actually, a couple layers of safety that we have established for the blood industry. Uh, one is the donor history questionnaire. So we want to make sure that when you're answering all these crazy questions that are asking all about your social life, that by asking those questions, we're actually decreasing the number of people who may actually be infected with, uh, one of the transfusion transmitted infections that we're concerned with.

Alecia Lipton (05:02):

I know that a lot of times our donors will have questions for us about, "can I donate if I'm taking specific medications?" Obviously you can't donate. If you're taking a blood thinner, that would not be good. We wouldn't want you to bleed too fast. Um, but I think a lot of people are surprised to know that they can donate blood if they're taking antidepressants, birth control pills, even aspirin for a whole blood donor is okay. Um, can you talk a little bit about medication restrictions?

Dr. David Oh (05:31):

So this is a very difficult area. You can imagine for each blood center, if we had to evaluate every single drug that's out available for people, including even over the counters, it's very difficult for us to create a questionnaire for donors to complete and, uh, and even a reference to keep that up-to-date. So we really, again rely on our friends at FDA. Um, they have worked with an organization called AABB, which, uh, used to be known as the American Association of Blood Banks. They have created a donor history questionnaire and a list of medications that are of more concern for us, for donors. So that is actually available. If you go to the internet, you can actually Google that up for AABB and then blood donation medications, and you'll be able to find the most current list of medications.

Alecia Lipton (06:18):

One of the things when I was looking through the list, and I like how you explain that if there is a drug that could potentially cause a problem with pregnancy, that a good rule of thumb is maybe you can't donate blood if you're taking that. And when I was looking through the list, I saw that a lot of the acne medications like Accutane or some of the hair loss medications like Propecia, you can not donate blood if you're taking those. And also on those labels, it has very clear statements, that if you're a pregnant woman or if you're planning on pregnancy, that you should not take those medications.

Dr. David Oh (06:52):

So every time somebody comes and donates, we actually give them this list of medications that they need to look at before they donate and see if they are taking any of them within the time limits that are listed.

Alecia Lipton (07:03):

And I imagine that that list with the FDA changes quite rapidly as new drugs are being released to the public.

Dr. David Oh (07:11):

Yeah. With COVID-19 emerging worldwide about a year ago, FDA took some long awaited steps to look at donor eligibility. There's a real concern that we would not have enough blood for patients in the hospital who need blood, but use and need continues even with COVID-19, taking up other medical resources. So, FDA relaxed, uh, or reduce the intervals for many conditions, as kind of long awaited measures that the industry supports and should not affect donor safety. So travel to areas that are known to have a malarial risk was a big change from 12 months to three months. And many of the changes were decreased from 12 months to three months in terms of bovine insulin. Um, there was concern for mad cow disease, and that's when a lot of these restrictions occurred.

Dr. David Oh (08:14):

One was for bovine insulin, and the other was for travel in Europe and exposure at military bases. Uh, but now if you were previously deferred for those reasons, we're asking you not to just show up at donor centers and donate, but to give us a call if you've donated at Hoxworth before and been told not to donate because of any of these reasons. We have a deferral evaluation process where within a few weeks, we can remove deferrals if it's appropriate based on a lot of these changes that have occurred recently. So, yeah. So if you've been told you can't donate before, you can contact us at www.hoxworth.org and start the process.

Alecia Lipton (08:58):

Right? That's a great point. We want you to call ahead of time so that we can start you in the process to get you to be eligible, to donate. Again, we don't want you to make that special trip in and then be told we need to do some paperwork and have you come back. So you can always give us a (513)451-0910 or visit us at www.hoxworth.org. You have been listening to In the Know with Dr. Oh, brought to you by Hoxworth Blood Center.

Alecia Lipton (00:29):

You're listening to the second part of our episode of In the Know with Dr. Oh. We're talking about eligibility and deferrals on today's episode. I'm Alecia Lipton and I'm joined here in the studio with Dr. Oh! Dr. Oh, we were just talking about, um, some of the testing and the disease markers. Can you elaborate a little bit more on that?

Dr. David Oh (01:02):

Thank you. Yeah, you know, one of the big breakthroughs in terms of blood safety was development of testing for viral transmitted diseases and one of the big ones was HIV, right? So that was such a huge issue in the eighties. And it's still a big concern for us. In 1985 an antibody test was developed for HIV, which was amazing given the short time that we had, and the knowledge that we had about the virus at the time. It was developed very rapidly, and these antibody tests are actually tests that will look for antibodies that people will have formed after exposure to, uh, in this case, HIV. They had a window period of approximately 22 days or actually about 30 days. The tests have gotten much better over time.

Dr. David Oh (01:58):

So we have much more faith in the antibody tests that have been developed. They have built both become more specific and sensitive. So by specificity, it means that there are less false positives that occur with the antibody test, but they still do occur. And sensitivity means that the ability to detect a virus in almost everybody who has the infection. The second great breakthrough in terms of HIV testing occurred in the late 1990s and early two thousands with the development of what we call NAT testing or Nat testing, which essentially very similar to PCR testing. So for HIV, we look for the RNA associated with HIV infection and we're able to detect that and decrease the window period, which is the period between exposure and the time that those tests will be positive. So from the antibody testing, about 30 days to, um, Nat testing, which brought that down to about less than 10 days was it was a real dramatic increase in terms of blood safety. So back in the, in the heyday of HIV, before we even had an antibody test, the risk of HIV in certain areas of the country, were as high as one in a hundred units, which is just really scary. Today, again, as I said, previously, the risk is about one in 2 million units. And I actually think it's much less than that. Since 2000 there have been, uh, probably less than five cases of HIV transmission that have occurred through blood transfusion.

Alecia Lipton (03:24):

And that's nationwide.

Dr. David Oh (03:26):

Yes, yes. And those cases are not well known or publicized. Um, they're just so rare now, it's very rare for that.

Alecia Lipton (03:35):

That's definitely a different world than what it was in the early 1980s.

Dr. David Oh (03:39):

Yeah. I did want to mention, so if you are a donor and you've gotten a letter from us saying that you have had a false positive for HIV... For years and years, it was very difficult to have those donors come back and donate. Again, there is a donor reentry process that is available now, if you just had the positive antibody test. On some occasions, we, we can't reenter people and for some people, the testing will remain positive and it's not due to exposure to HIV. We would know with the, the Nat test is, is exquisitely sensitive and specific. Um, so that's actually the, the, the really great tests that we have. But we're still performing both tests to make sure that people who are, especially who are people who are on antiretroviral medications today, where the HIV may not be directly detected through PCR processes, that we would know that people were exposed previously and have antibody formation.

Dr. David Oh (04:32):

So we're still, we're still using both tests. I often get the question: Why would an antibody test be positive, right, to either HIV or hepatitis B or hepatitis C or any of the other infectious diseases we test for? And I try to explain it this way, and, and this is how I think of it. So, uh, scientifically I think in general, this makes sense. But if you've ever had a car key and you go out to a parking lot and you see a car--this actually happened to me once I, I had a blue Prius and I used to live in California. So they're all over the place. And I stuck the key in a car that wasn't mine. It looked just like mine, but it wasn't mine. And the key went in. And, um, and that's sometimes what will happen is that an antibody test will try to detect a specific antibody.

So we know it should just fit for this one infection. But we create so many different antibodies and we can have broad reactivity. So sometimes you'll have an antibody that was directed to something completely different or a different substance in your serum that can cause interference and can cause, cause it to look like you have an antibody match for what you're looking for. In some cases that's a once in a lifetime thing and the next time we test you, there's no reactivity. In other cases, you may have been exposed to something that looks enough like the antigen that you're testing for where that reactivity will continue to occur. And because we have to test every single donation with all these different tests, if you have a positive test, even though we do additional testing, those units are not able to be transfused. And we would just ask those donors not to donate in the future.

Alecia Lipton (06:08):

Okay, great. And that is just for the overall safety of the blood?

Dr. David Oh (06:12):

Yes. So as we're trying to create these processes to create, you know, safe, transfusable products, anytime there's a hiccup in the process, we would rather be safe and not use that blood, versus going through a bunch of different double checks and saying, okay, it's okay to use in case there was an error that occurred along the way.

Alecia Lipton (06:30):

Excellent. You've mentioned how the testing has gotten so good in recent years, that we can catch those little minute antibodies regardless to what disease we're looking at. In the early 1980s, I think it was maybe 85, they put into place that men who had previously had sex with other men were a lifetime deferral. In 2017, that was then changed and it was made a 12 month deferral. And then earlier this year, um, the FDA came back again and made a new change. Um, and now it is a three month deferral. So three months since their last sexual intercourse with another man.

Dr. David Oh (07:12):

Yeah. Uh, sexual contact actually, I think is how they define that. So, so this is a very sensitive area. So, I'll present this as well as I can, and I hope nobody gets upset with this discussion. But I think one of the reasons I wanted to do this podcast, uh, was to be able to kind of share some of the current thinking and the reasons for why we do certain things. So initially, you know FDA did require when we talked about the donor history questionnaire, right. I think the question was essentially if you had sexual contact with another, if you're a male who had sexual contact with another male, any time since 1977, then that would be a lifetime deferral. And with the level of testing that was available at that time with as many as one in a hundred units that could conceivably, you know, transmit HIV before we had a good test,

Dr. David Oh (08:02):

I think that, uh, you know, we had to be as careful as possible and try to restrict anyone who had a significant risk for HIV from donating blood. So really that's a, you know, recipient safety issue. Then we have been fortunate with the development of testing, as you've said, especially with antibody testing in 1985, and then the nucleic acid testing that evolved in 1999 or 2000, to, to bring that window period down to less than 10 days from the time of exposure to having our tests turn out positive. So with that, I think it was time to kind of reevaluate this rule in terms of deferral since 1977 for any MSM and sexual contact. I don't want to go into a lot of the details of that on our podcast, but you can go and look on Google and all this stuff is available.

Dr. David Oh (08:55):

In the guidance for industry, FDA provides a really nice background for the rationale for these different policies that are in place. They did reduce that from a one-time ever since 1977 MSM contact to 12 months. And I think that that was very reasonable at the time because many of our other deferrals for behavioral activities that would increase risk for hepatitis or HIV were at 12 months. So for, for example, if you got a tattoo--I always bring this up, or even a blood transfusion that was screened with the current testing that we have, so the blood transfusions are extremely safe now, related to HIV and hepatitis risks--it would be a 12 month deferral after either of those exposures. So if you got a tattoo at a non-licensed parlor, it would be a 12 month deferral.

Dr. David Oh (09:51):

And, and really, I think we felt as an industry, gosh, 12 months seems like a long time with the really much better sensitivity of our testing nowadays. So FDA did make that change to, to reduce from 12 month period to a three month period. And with the change for MSM, they made changes for tattoos and for a bunch of other things as well, that I think the industry was really waiting for. Some of these, uh, it's a two-edged sword, right? So we want to make blood as safe as possible, but we also want it to be available for people when they need it, need it. And the travel 12 month issues were really causing a lot of problems, uh, in terms of being able to keep a healthy blood supply across the country.

Alecia Lipton (10:32):

I think the travel is an important thing to bring up because we are so travel centric right now. Not as much with COVID-19, but prior to that people were vacationing, they were going on cruises. You would hear about church groups going on mission trips, and oftentimes they would be in an area considered a malarial zone. And then that would defer them for 12 months.

Dr. David Oh (10:54):

Yes, yes. The risk of malaria transmission through blood transfusion is actually...the incidence is actually very, very low. So I think that's another reason we can feel a little more secure in, in easing some of these restrictions, the estimates are that there may be two cases to three cases a year. But again, it's, it's difficult to sometimes find the data for you as well. So it's not a very common incidence for sure.

Alecia Lipton (11:22):

So with the FDA relaxation we have now, men who've had sexual contact with other men, they now have a three month deferral, as opposed to 12 months. We also have individuals who've traveled in malarial zones, they're now down to a three month deferral, so we're kind of making things the same.

Dr. David Oh (11:40):

It's really exciting. Actually, the director at Hoxworth is a physician. I think he'll, he's okay with us talking about this. Dr. Cancelas, he's Spanish and he's spent time in Europe, and so was unable to donate because of the variant CJD risk and the donor rules. So those have been relaxed because the incidence of CJD has just really....vCJD has just really plummeted worldwide. And so I think that was a very welcome change for people who do a lot of traveling, who have spent time in Europe, for our military people who have spent time on U.S. bases. It's a huge ability for, for those people who are, are typically great donors and, you know, are really giving, to be able to give blood again. So we do have a process for that. Again, we ask people not to just show up at the donor centers, but to contact us and make sure that we can remove the deferral and do the legwork that we need to, to be able to make sure it's good for them to come and donate.

Alecia Lipton (12:44):

One deferral that's also exciting: Previously, if you were a breast cancer survivor, you were deferred from donating blood. And a lot of times, if you're a survivor of any type of cancer you want to give back, you want to help other people. And now once you are cancer free for one year, then you can donate again. Correct?

Dr. David Oh (13:03):

That's correct. Yeah. And the primary reason for that 12 month deferral, we want to make sure that, that for the donor, that, you know, they're clear in terms of not needing to have urgent medical care, and we've already taken a unit of blood from them. So 12 months is just to make sure that, you know, everything looks like it's going well for them. There have been no cases that I'm aware of transfusion transmitted cancers, carcinomas. So I think we feel secure in that, that if that were a real concern, we'd see, we'd have seen cases for sure by now. We do ask people who have had primary leukemias or lymphomas to, to not donate, but in terms of adenocarcinomas or other types of cancers, um, uh, those people are eligible to come back after a year, considered cancer-free.

Dr. David Oh (13:57):

Every time you come and donate, we do a fingerstick evaluation for hemoglobin hematocrit to make sure that it is safe for the donor to donate the fingerstick tests are not the best out there.

I will tell you, but for us to, to operationally collect blood FDA has approved this process for us to evaluate donors. I would say that, you know, people who donate blood, especially the red stuff, so whole blood or red cell donations really need to look at their iron levels. And especially for women who have blood loss occurring during the, during their reproductive years. So I do recommend in general that donors who are frequent donors, even frequent platelet donors, consider taking a multivitamin, a daily multivitamin that contains iron. It's not surprising if a donor ends up having iron low iron issues, um, because they're a frequent donor. It is a cause of iron loss. And so we want to be careful with our donors. We want to encourage them. Yeah. If you donate frequently, make sure you take a daily multivitamin with iron.

Alecia Lipton (15:11):

Okay, great. Other than the multivitamin, um, we can also get iron from the food we eat. Um, are there any recommendations you can give for that as far as, you know, a good, um, high iron diet? Yeah.

Dr. David Oh (15:22):

Yeah, sure. So you can look on the internet. I know everybody has a different diet process, right. So I don't want to tell people what to eat. Of course the foods with high iron are great. The studies have actually shown though that, um, if you're a frequent blood donor, supplementation is a better way to go. It's very difficult to get enough iron just from diet to be able to compensate if you're a frequent blood donor.

Alecia Lipton (15:44):

Okay. And then this would be, um, an over the counter supplement you could get.

Dr. David Oh (15:48):

Yeah. That's typically what we recommend is over the counter, you could get just iron itself or you can get a multivitamin with iron. And I think most people today are, are looking at, you know, multivitamins as something. So just make sure you have a good iron content in it. Okay.

Alecia Lipton (16:01):

Okay. Talking about iron and making sure that our donors have a healthy iron store, for individuals, once they turn 16 and they can donate, if they're a female, we're only going to let them donate once a year until they're age 19. And if you're a male, you can donate twice a year. Why do we have that difference? And why at 19 do we then said, well, you could donate four times a year?

Dr. David Oh (16:25):

Yeah. So there were some concerns, especially that's a kind of a sensitive time in terms of our maturation, right? So that we didn't want people to be iron deficient as we're collecting people at, at fairly young ages. So I think it's a general process that many, many blood centers across the country started recommending in terms of decreased amounts of blood that are donated before the age of 18, really. And so we have that policy now for 16 to 18 year olds. We may actually relax it a little bit for 18 year olds as we kind of go forward, so those years between 16 and 17.

Dr. David Oh (17:00):

Most of the States across the country allow blood donors to donate at age 17 without any parental consent or those types of issues... That's written into state laws. And those laws were developed , I think, earlier in terms of war efforts and community supporting a blood donation, uh, to support the country, uh, and, and they've remained on the books, uh, when people donate age 16, typically there's a parental consent that we have, uh, signed, uh, as well. We do want to be very sensitive with those donors.

Alecia Lipton (17:35):

Thank you for listening to, In the Know with Dr. Oh brought to you by Hoxworth Blood Center, University of Cincinnati. For additional information, visit us online at www.hoxworth.org.

Alecia Lipton (00:40):

I'm Alecia Lipton, and you're listening to In the Know with Oh presented by Hoxworth Blood Center, University of Cincinnati. Each episode will contain facts about blood donation. Hoxworth Blood Center is the steward for the local blood supply in the tri-state region. And I'm excited to say, I just looked at numbers and we are now collecting over 100,000 blood products a year, and those are used to help save lives in over 30 tri-state hospitals. In the studio with us today, of course, is Dr. Oh and then we have a special guest, Dr. Oh, could you do the introductions?

Dr. David Oh (01:16):

Thank you very much, Alecia. I'm so pleased to have Caroline Alquist with us today. She is our medical director over the TID laboratory and therapeutic apheresis, and we'll discuss a little bit more what that means today. There may be a lot of alphabet soup going forward, and so we'll try to clarify as we go. Caroline has been with us for less than a year, but it feels like she's been with us forever and that's a good thing. Um, so we're very pleased to have her. Can you please share with us a little bit of your history in terms of your education and how you came to occupy that role you have here today?

Dr. Caroline Alquist (01:53):

I actually Cincinnati native. I grew up here in Hyde Park and attended Ursuline Academy in Blue Ash. After which time I left and went down to Wake Forest for university, and then followed that up with grad school, getting my MD and PhD at Louisiana State University of New Orleans. After that, I went into a pathology residency there as well, which was a phenomenal opportunity to do both anatomic and clinical pathology training. And from there I segued to Dartmouth Hitchcock Medical Center, where I actually studied transfusion medicine and blood banking…great opportunity to work with some of the leaders in the field, specifically, given their interests, in managing our blood supply when we have scarce resources. Afterwards, I returned back to New Orleans to work for Oschner, um, where I got a great chance to really develop my skills in histocompatibility, HLA in particular. I stayed there for a few years, but  the call of my family got me to come back and I was really excited for the opportunity to join Hoxworth six months ago and, and really join this team.

Alecia Lipton (02:53):

We're thrilled to have you here with us. And I think, you know, we should mention that not only are you an MD, but you also have a PhD as well.

Dr. Caroline Alquist (03:00):

Yeah. I had a great opportunity in grad school to pursue both degrees. Um, it was an opportunity that I couldn't pass up and I'm really glad I followed that path.

Dr. David Oh (03:08):

I think we should call you Dr. Dr. Alquist. We mentioned that you were medical director of TID at Hoxworth. So what does that mean? TID?

Dr. Caroline Alquist (03:20):

There are a lot of letters in what I do. TID is actually transplantation immunology division. It's known as HLA in a lot of centers. Essentially what we're looking at is the immunology of transplant, specifically how the human body interprets self and non-self. HLA just stands for human leukocyte antigen, which is just the first place we discovered the HLA molecules. That's actually the fuzz on all of our cells. What it is really is a name tag, it's a name tag, our immune system uses to say, do you belong to me or should I kick you out? So what TID does is, is we figure out what organs and what bone marrow best match your compliment of HLA antigens. And we really help the clinical teams select the best matches for when a bone marrow transplant donor's available, or when a deceased donor solid organ, or even a living donor solid organ becomes available. And that's the predominant bulk of our business. However, we do also do some business looking at disease associations and pharmacogenetics, meaning some HLA fuzz can actually have a huge impact on how you respond to different drugs or whether or not you're going to be predisposed to get certain diseases, like narcolepsy or celiac disease.

Dr. David Oh (04:33):

Most people think of Hoxworth Blood Center as a collection center. These are definitely other activities. What do you think in terms of having this at a blood center? I know when I was at Stanford, before I came here, we had an HLA laboratory as well. And actually our former director ended up taking a position there, allowing you to come to us, which is awesome. So what do you think about the synergies that are, are present for a TID laboratory, HLA laboratory located in a blood center?

Dr. Caroline Alquist (04:58):

TID is really a study of blood. So it makes sense that we're, we're situated within a blood center environment. I think being a physician in HLA, it'd be pretty lonely to not be surrounded by my transfusion medicine counterparts, with which I'm on the phone with all the time. So it's a lot easier, I think quite frankly, to be in the same building with people that I can bounce ideas off of and get more clinical information about cases and, and discuss things professionally in a more comfortable environment.

Dr. David Oh (05:26):

You know, the other thing about Hoxworth that's really interesting is that we are part of the University of Cincinnati. Is that important for what you do in the TID area?

Dr. Caroline Alquist (05:34):

It is nice to have a university so close by because HLA is something a lot of people don't know a lot about. However, it does have its fingers in all the different specialties. So being so close to a university setting gives me the opportunity to look into interdisciplinary research options and, and to be there for my clinical teams across all the specialties, being part of a university makes me feel, I know that I'm always accessible to my customers. However, the university system really reinforces that feeling and makes those opportunities even easier to come by.

Alecia Lipton (06:08):

Part of the mission for Hoxworth Blood Center is not only to save lives, but it's also to educate. So having that relationship or being part of the university really kind of brings everything together. In layman's terms since I'm the only one in the room without MD, after my name, to me, I think what TID a good explanation would be. It's keeping you from rejecting that organ. It's making sure that the organs you're getting are the best match for you. Would that be a good explanation?

Dr. Caroline Alquist (06:37):

That's absolutely correct for a transplant with bone marrow. Of course, we're looking to match you, right? We want your fuzz to look just like the fuzz we're giving to you, with a certain amount of exceptions. However, with solid organ, we don't get deceased organs coming across our doorstep on a regular, predictable fashion. So we've really had to take a radically different approach. In solid organ, I'm never trying to match you. I'm really just trying to avoid things I know that your immune system doesn't like. It's called an antigen avoidance strategy. Meaning if you're on a list to get a solid organ, I want to know what antibodies you have so my lab will do that testing so that the algorithm that, that helps allocate organs knows that. And the idea is that you will never be offered an organ, which we know that you would not be really compatible with, antibody-wise.

Alecia Lipton (07:22):

How many hospitals do you currently work with?

Dr. Caroline Alquist (07:25):

I believe currently we work with 12 hospitals. I would have to fact check that... HLA is, uh, a pretty niche market. So we are, um, often picking up business for more far-flung hospitals, um, because we're, we're close, we're available, we're centrally located. And we're really lucky to have so many people interested in this field at Hoxworth. So we're a really good resource to really less-close hospital systems.

Dr. David Oh (07:52):

So let me ask, I know it's not a tremendous number of hospitals, but I think over 10, at least that we are certainly helping with. Can a hospital, uh, offer transplantation without the use of an HLA laboratory?

Dr. Caroline Alquist (08:08):

They can offer transplantation as long as they have access to an HLA laboratory. In the past, historically, you'd want at your HLA lab really close because a lot of transplants relied on this thing called a cross-match, meaning I literally mix the patient who wants the organs. I take their serum and I just mix it with the cells of the donor who you might want. And as long as they play nice in a test tube, you'd get the organ. As technology's advanced, we're actually able to do a lot of these cross matches virtually called the virtual cross-match, which makes physical proximity a lot less important, which is why we're able to help a lot of programs that are a lot further away because these virtual cross matches, we know correlates so beautifully with the physical cross-match results. There's no reason to prevent a patient in a far-flung location from getting that organ immediately if we can do the physical work on the backend next business day, but we know that what the result's going to be.

Dr. David Oh (09:02):

It seems like in organ transplantation, there's a big difference between a live transplant and an organ from a deceased donor. Can you talk a little bit about the different roles that you have in live transplantation versus a deceased organ transplantation?

Dr. Caroline Alquist (09:17):

Yeah, no, there are. So there's immediate use HLA, which is going to be our deceased donor organs, where we have to make a decision very quickly with the clinical team, whether or not it's a good compatible match. And then there's the bone marrow transplant and live organ donation. I call those less immediate stress, because we get to plan. We get to take our time and make sure things are thoughtfully matched and made optimal for both of the donor's safety and the recipient safety. For living donor transplant, where we're typically talking about kidney... Some programs, do do living liver, um, partial liver transplants as well, but currently at the university setting, which we work, um, the living donor population is really relegated to the kidney donations. And what's beautiful about it is if you would like to donate to a loved one, a friend and acquaintance, or even a far-flung stranger, you can submit your sample.

We can work you up, keep your identification anonymous, should you decide to remain anonymous and we can figure out the best match for you as a living organ donor. What's also amazing as you could even enter something called a chain, meaning you don't match the person you were hoping to donate for, but you can donate to someone else who's got a partner that can help you, or if the chain's even longer, you help someone who can help someone else who that third person can help you. And these amazing chains take a phenomenal infrastructure that really allows this to happen, but these chains allow living donation like never before.

Alecia Lipton (10:45):

Being part of Hoxworth, we're able to see that saving treatment, um, continue every day, whether it be through our donors coming in, or be it through the work of the work that you do in your lab.

Dr. David Oh (10:58):

Dr. Alquist, can you talk a little bit about the type of technology that you use in performing your, uh, your evaluation of samples?

Dr. Caroline Alquist (11:04):

Sure. So the HLA lab uses a really wide array of technology. HLA was developed, you know, decades ago, and we actually still use some of that original technology. So we're using anything from cytotoxicity assays, which is the real historical, um, stuff, but it's still quite useful. Um, cytotoxicity assays mean I literally mix your plasma or serum with the cells from your potential donor, and I see if your serum or plasma has antibodies that would kill or hurt those lymphocytes. And I look under a microscope and I say, Oh, that doesn't look good, or, they're playing nicely that we can proceed. That's a lymphocytotoxicity assay. We do use that technology, but we've added a lot of other cool stuff. So now more commonly, we use solid phase assays, which are going to be things called Luminex beads, meaning we've coated these synthetic beads with, with antibodies that are antigens rather that we know about.

And we mix it with your serum and plasma. And we see what antibodies floating around in your serum or plasma attach to those beads. I send it through a flow cytometer, and that tells me exactly how much antibody and what specificity it has within your blood. So that's a lot more convenient, right, than asking for live cells from a potential donor. Um, and we do that all the time to really determine what somebody's antibody profile is while they're waiting for a solid organ, or even if they're being worked up for a bone marrow transplant, because we never want to give you a bone marrow transplant from someone, if they have antigens to which you have pre-formed antibodies.

Dr. David Oh (12:36):

And next generation sequencing?

Dr. Caroline Alquist (12:38):

Yes. Lots of toys! So in addition to antibody studies, which are going to be your, you know, cytotoxicity and solid phase assays, we do a lot of typing as well. 'Cause we need to know what that fuzz is, what the HLA fuzz is. So there's a lot of methodologies we can use to look at HLA typing. We can use real-time PCR. We can use next-generation sequencing. All of these modalities are available depending on how quick you need your samples. Also different technologies give you a different resolution. So we can know down to the tiniest kink, what your fuzz looks like or where we can get a, uh, a grand picture before proceeding down any certain pathway.

Dr. David Oh (13:15):

So fascinating the rate of technology advances and keeping up. And so we need people like you to be able to direct our laboratories. I know, I know we have certain accreditations...and in Blood banking, we always think about AABB. Um, can you talk a little bit about ASHI and your qualification with that?

Dr. Caroline Alquist (13:33):

Sure! ASHI is the certifying body for histocompatibility and immunogenetics. It was designed really just to focus on HLA. So it is kind of considered the, the central accrediting body for all HLA labs in the United States. What's interesting is the only way to become an ASHI-approved director is its own pathway. So it does have its own board. Uh, it used to be known as the American Board of Histocompatibility and Immunogenetics; however they recently merged ABHI and ASHI, you know, more alphabet soup. It's now known as the American College of Histocompatibility and Immunogenetics. The whole process is that you enter either as an MD or a PhD with a board certification, which you can be, of course, the ASHI certification currently available. And you undergo a full background check, credentials verification, and you enter a directors-in-training program.

This director-in-training program then consists of at least two years of collecting cases and on the job education. What they want is you to be fully immersed in a histocompatibility lab, taking in those experiences in real time, while collecting interesting cases, they then ask you to submit 50 cases per area of interest. There's up to six areas you can submit in: solid organ living donor, solid organ deceased donor. You've got bone marrow transplant from a related donor, bone marrow transplant from unrelated donors, transfusion support, and histocompatibility for other purposes, there's always a waste basket. Um, and every group requires 50 cases to be submitted. And you need to do basically a book report on 10 of those cases for each division as well. So it's a huge amount of paperwork that used to be sent. Now you are able to send it on a jump drive, thankfully you can send it on a jump drive, um, back to the American Society for Histocompatibility or Immunogenetics, now known as the American College of Histocompatibility and Immunogenetics, um, and they actually send it out to reviewers.

So there are qualified directors all over the world that are willing to review those reams of paperwork to evaluate whether or not you truly know what you're talking about. Um, and that allows you to proceed to an oral interview phase. If they accept your, your portfolio and your oral interview will be all your reviewers plus, um, there's always a few extra people in the room to make sure everything proceeds as planned. And following that oral interview, should you pass it, there can be subsequent interviews. Um, you'll get a letter that says that you were officially accepted as an accredited and approved ACHI director. This is now known as being a fellow or associate of ACHI. So, because I took their board as well as my pathology boards and transfusion boards, I am considered a fellow of ACHI.

Dr. David Oh (16:25):

Wow.

Alecia Lipton (16:26):

Definitely one of the best of the best.

Dr. David Oh (16:30):

I appreciate your sharing that, I think it's important for people to kind of understand that real specialization that has to occur in the years of training that it takes to, to get to your level. Um, I would expect that you'd be like a 70 or 80 year old person sitting across from me, but you're actually very young. And so it's amazing that you've, you've done what you've done. So I really appreciate your spending time with us today.

Alecia Lipton (16:53):

Yeah. Thank you so much, Dr. Alquist. So this has been part one of our discussion with Dr. Ahlquist, stay tuned for part two. Again, this is In the Know with Dr. Oh presented by Hoxworth Blood Center.

Alecia Lipton (00:27):

Hi, I'm Alecia Lipton and you are listening to part two of our interview with Dr. Caroline Alquist from Hoxworth Blood Center. You are listening to In the Know with Dr. Oh, and this part of the episode, we're going to talk about therapeutic apheresis. Dr. Oh, can you tell us a little bit about therapeutic apheresis and then turn it over to Dr. Alquist and she can explain what that is at Hoxworth?

Dr. David Oh (00:52):

Sure. So therapeutic apheresis actually is a, is kind of an umbrella term? And it relates to a lot of processes and procedures that are done with fluid exchange. I would say it's different from dialysis, which uses a filter. We're actually collecting and re-infusing different fluids. And that could be plasma, that could be albumin, that could be red cells, that could be, in terms of collection, stem cells. So that's kind of a, an umbrella term that we use. Dr. Alquist is actually our director of therapeutic apheresis. We spoke to her last time, in relation to her the hat that she wears as our director of our HLA laboratory. But this is actually another big hat that you wear. So welcome!

Dr. Caroline Alquist (01:44):

Thank you for having me.

Dr. David Oh (01:46):

So maybe you can explain better what therapeutic apheresis is, and your role here at Hoxworth Blood Center.

Dr. Caroline Alquist (01:55):

Absolutely. So I joined Hawksworth about six months ago, and I have taken the role as the director of therapeutic apheresis, which is something I did in my previous job as well, managing the apheresis team. So what this involves really is, as Dr. Oh pointed out, this is the removal of a small amount of blood into essentially a giant centrifuge that's going to separate your blood into the heaviest to lightest components, like a Neapolitan sundae. You're going to have your red cells on the bottom, followed by your white cells and platelets, and then your yellow, which is your plasma, up top. Using this beautiful centrifugal separation, we have an electronic eyeball with an electronic straw that can remove the layer of interest.

So if you have antibodies you need to get rid of, we're going to take off from the yellow, right? Cause your antibodies live in your plasma. We're going to pull into a giant bag and throw it in the trashcan. Okay. And we'll replace it with a, with a substance known as albumin, which is a heat-treated human blood product. Or we can also use human FFP, or fresh frozen plasma, um, depending on your coagulation status.

Similarly, that little electronic eyeball and straw can drop down to your white cells and we can collect stem cells if that's what we're going for. And we do not throw that back in the trash. We would put that in a freezer until you're ready for them, or we can even transfuse those fresh. If you have too many platelets, we'll just take those off of you, throw those in the trash can. Same with if you have too many white cells in a case like leukemia, or if you have a red cell disorder like sickle cell disease, we can remove that whole red cell layer, replacing it with healthy donor red cells. And we infuse that all back to you.

Dr. David Oh (03:30):

That's a terrific explanation and description. So we use similar technology with our blood donors, to collect platelets and also to collect double red cells and occasionally plasma as well. So it's a very similar technology that we use for our blood donors. The difference I think, for what you're directing here at Hoxworth is that, it's actually for clinical indications. Can you talk a little bit about some of the procedures that we do use therapeutic apheresis or that we're involved with through our therapeutic apheresis department?

Dr. Caroline Alquist (04:02):

Sure! So Hoxworth offers a full complement of apheresis services. If I described it a few minutes ago, we do it. So we do offer, our most common procedures we do perform for other hospitals, are going to be therapeutic plasma exchange. That's going to be removal of any substance in the plasma that could be causing you harm. Additionally, we do red cell exchanges for our sickle cell population here in the tri-state area. Um, we also offer extra corporeal photopheresis, also known as ECP. It's a mouthful, I know. Essentially, this was designed to get sunshine in the body, all right? We knew a long time ago that sunshine was really good for cutaneous lymphomas. But once it went into the body and those cells got away from the sunshine, we didn't know how to get to them. We realized we can use our cool apheresis machine to pull out your white cells, expose them to UV light and reinfuse them. That's all it is. So we gave it a real fancy name for sunshine in the body. We use that commonly to treat graft versus host disease, following bone marrow transplant. However, it does have some interesting off label indications for rejection after lung transplant or heart transplant, which we've seen some success with.

Dr. David Oh (05:09):

Can we go through the different procedures that you talked about in a little bit more detail and, uh, kind of related to indication, so it would be used for, so I think you started with plasma exchange. Is there a classic disease that would require plasma exchange?

Dr. Caroline Alquist (05:25):

We do use it a lot for antibody-mediated rejection, which dovetails really nicely with my role in HLA. Um, essentially after transplant or before transplant, you could have antibodies we know that could be a problem with that transplant, be it solid organ or bone marrow transplant. And so, because I know HLA antibodies are floating around in your plasma, I can sip those off and throw them in the trash can. And if they're not there to cause problems, then we can prevent some of that damage. Typically the clinical team will also be utilizing drugs to prevent more antibody from being manufactured, but this gets rid of whatever's floating around at the time of the procedure. And I guess if we just work our way south, we'll start with plasma exchange.

Dr. David Oh (06:06):

Can you talk a little bit about TTP?

Dr. Caroline Alquist (06:08):

Oh, sure. TTP is another common indication that we use plasma exchange for.

Dr. David Oh (06:13):

I'm going to let you tell us what TTP stands for because my tongue always gets tripped up.....

Dr. Caroline Alquist (06:19):

Thrombocytopenic thrombotic purpura is essentially a disease that occurs when you suddenly develop an antibody to ADAMTS13. Okay. I know this is a whole lot of letters again, all right. This is a metalloproteinase that essentially is your lawnmower, lives in your blood. So you're constantly your endothelial cells that make up your vascular system are constantly pumping out a protein known as Von Willebrand's disease. Not only is that a mouthful, it's also the longest human protein produced, and that is constantly being grown on your endothelial cells like grass. ADAMTS13 is our fancy lawnmower that makes sure that those stay short. So if you develop an antibody, do your lawn mower, the grass gets out of hand and it starts occluding your vessels. Okay? And as that grass starts occluding your vessels, your platelets get stuck, your red cells get popped, and these patients are going to show up with really low platelets and anemia.

And the symptoms of low platelets are typically bleeding from the gums, strange bruising. Some people have some neurologic signs, typically as a result of clotting vessels in the brain, which can present with stroke-like symptoms. Other people just say they have headaches, or they have more ambiguous complaints, but that telltale sign is we're going to draw a CBC and we're going to see low platelets, a high LDH typically caused by those vascular occlusions, and some also contributed to, from the popping red cells. And we also are going to see a slight anemia. So if we know that you have an antibody to your lawnmower, and we need to get that out post haste, um, the best way to do it is throw that plasma away. So we use our therapeutic apheresis plasma exchange program to pull the plasma out into a waste bag, throw it in the trash can and give you healthy human plasma with functional lawnmowers included to start paring back the Von Willebrand factor proteins that have been expressed in your, in your vasculature.

Dr. David Oh (08:09):

Is this process a one and done, or is it something that patients will continue to do?

Dr. Caroline Alquist (08:13):

This is a process we're going to be doing until you recover. So typically for an indication like this, you would get a central line and we're going to do this daily until we get your platelet count higher than 150,000 per microliter. And your LDH has normalized, telling us that you're not really making as many clots in your organs and your platelet count is sustained at a safe level. After we reached that, it's depends on your clinical team, if they would like to do a taper, wean you off slowly, make sure you're not going to start dropping platelets again, or we could stop cold-turkey and see what happens. Different programs have different approaches. And so far there's not been a conclusive study which is the best way to go about it. It's interesting cause you produce this auto-antibody for unknown reasons, and it just goes away after awhile for unknown reasons. So it is kind of a weird transient disease that we do see fairly frequently

Dr. David Oh (09:04):

And often it comes back again in these people as well. So you can have a second case or refractory cases that do occur. So it's interesting, so with these patients, they have low platelet count and you know, this is, a lot of our audience are blood donors here. We actually don't use platelets as treatment for TTP, but we use plasma. So that's another donated product. Um, why do we use plasma instead of just albumin or other blood replacement?

Dr. Caroline Alquist (09:32):

So the reason we want to use human plasma is 'cause we have to give functional lawnmower activity back. We have to give that healthy ADAMTS13 back to start paring back that that protein that's being expressed. And we don't get platelets of course, because the only reason your platelets are low is they're getting stuck in the grass and causing clots. So we don't want to add more fuel to that fire.

Dr. David Oh (09:52):

So it's interesting, you know, as we asked blood donors to come in, sometimes we'll ask them to donate plasma. Sometimes we'll ask them to donate platelets. Sometimes we'll ask them to donate red cells. And it's because there are different indications for each of these different products and we have to have supply of each type in order to, to help patients with therapies. And with plasma, if you're an AB recipient, right, an AB patient, you really should just get AB plasma. If you're O, you can get any blood type. So it's a reverse of the universal red cell donor. The universal plasma donor is, is AB.

Alecia Lipton (10:27):

It's very important to mention that with these treatments, we need donors. There is not a substitute, there is not a medicine, there's nothing developed in the lab that we can give them. So we need those volunteer donors to come in on a regular basis, whether it be the red cells, the plasma, or the platelets.

Dr. David Oh (10:45):

Let's talk a little bit about sickle cell disease in red cell exchanges. That's the primary reason for that. Tell us a little bit about it.

Dr. Caroline Alquist (10:51):

Okay, yeah. Sickle cell disease is a great candidate for the therapeutic apheresis program. Essentially what we know is that at a certain level of sickled cells in your blood, you are more prone to having strokes or multiorgan damage, which can manifest in a lot of different ways, such as acute chest syndrome, which is the sudden pain in the chest caused by the sickle cells, occluding your vessels. We can see priapism, once again, it's those sickled cells occluding vessels. There's a whole host of things. There could even be a, a really bad pain crisis.

Dr. David Oh (11:25):

So, so who, who gets sickle cell typically?

Dr. Caroline Alquist (11:28):

So sickle cell disease is commonly seen in our African-American population.

Dr. David Oh (11:32):

And, and what's what happens in sickle cell? The red cells are not, uh, formed in the right shape. Is that right?

Dr. Caroline Alquist (11:41):

Yeah. Essentially what happens is those cells, when they experience any kind of de-oxygenation, they actually form a sickle like shape. And unfortunately, a sickle like shape does not nicely go through our vascular tubes, like our typical round or oval shaped red cell. So once they form that strange shape, they're more likely to get stuck. And when one gets stuck, it's like a log jam. And that causes a lot of problems, which is why most of our sickle cell patients, we have a goal to keep their hemoglobin S under 30%.

Dr. David Oh (12:09):

Yeah. So it's less likely to sickle then, and cause problems. And, and some people actually get regular red cell exchanges, even if they aren't currently having an exacerbation of disease, to prevent the adverse supply that can occur, like stroke. And so as we try to collect red cells, are there additional challenges that we have in terms of, of finding red cells that are compatible for, for these recipients?

Dr. Caroline Alquist (12:38):

Absolutely. So, as you can imagine, if these patients are constantly getting transfusions, there's a lot of possibility for them to develop antibody, right? 'Cause everybody's cells are covered in a different fuzz, like my HLA fuzz, but also in blood antigen fuzz. All fuzz can be interpreted by the immune system as foreign, if it doesn't match your, your name tag. Right? So what we're finding is many of our typically African-American sickle cell patients when they get repeated transfusions, if that blood is not from African-American donors, they're at a much higher risk of developing antibody, just because there's genetic variation and certain Euro or Asian donors are less likely to have the antigens that match in African-Americans patients. We do do a level of extended typing or matching here at the Hoxworth. We make sure that we're always ABO, Rh, C, E, and K matched, to try and prevent allo-antibody formation. But unfortunately, there is no magic way to prevent it from happening overall. So yeah, one thing that we would love is if we had a stronger African American donor base to help out our sickle cell program, because that would provide blood less likely to incite allo-immunization in these patients, which makes them much, if you develop these antibodies, you're much more difficult to find compatible blood. So these patients, we have to plan days, if not weeks ahead of time, to make sure that we have blood that will match them.

Dr. David Oh (14:04):

I think the other challenges with this population is oftentimes when we give transfusions, we're giving a couple of units, right? One or two units, whenever a red cell exchange occurs, we're having to do based on, on volume, right. Or size of the patient. So very small kids would have a smaller blood volume, but for an adult, you know, we were exchanging what, between 10 and 15 units, I would say, or donated units per event.

Dr. Caroline Alquist (14:29):

Well, it depends on your, your body size. Your blood volume is very dependent on what your weight is. So we see some people that require five, and we see some people they require 15. Um, it's very dependent on what your stature is and, and how much blood we need to replace to get that fraction of hemoglobin S under 30%.

Dr. David Oh (14:45):

Yeah. And you talked a little bit about matching beyond ABO, and we'll have to have another episode to talk about minor red cell antigens as well. But it provides a lot of additional challenge for us to match this population.

Alecia Lipton (15:01):

Ideally the blood supply at the blood center should match the demographics of the city that you're serving. Right now, as you said, we do need more African-Americans and that, so that we can serve people here close to home, sickle cell patients right here, children and adults in the tri-state.

Dr. David Oh (15:18):

Yeah, it's, it's one of the really neat procedures. I think that we perform that really affects a lot of children in terms of, of needing these to prevent for stroke and other events. I'd like to talk a little bit about STEM cell collection as well, because that's a major activity for the therapeutic apheresis department, and people may not be aware of this activity. So we do collections not only for local patients, to find matches, but also for the NMDP or the National Marrow Donor Program. Can you talk a little bit about STEM cell collection performed?

Dr. Caroline Alquist (15:55):

Absolutely. So STEM cell collection is typically performed before a patient undergoes some kind of myeloablative or non-myeloablative chemotherapy regimen, which is essentially...

Dr. David Oh (16:06):

So, so what is myeloablative and non-myeloablative?

Dr. Caroline Alquist (16:10):

It means "how bad do we bomb your bone marrow?" Um, essentially....

Dr. David Oh (16:16):

It sounds like we're very violent here, right?

Dr. Caroline Alquist (16:19):

We are very violent! Bone marrow transplant, if you want to replace your bone marrow with someone else's, you've got to clear the field. So you just gotta decide what regimen you're going to use to clear the field. You can actually donate stem cells to yourself in certain diseases, for example, in multiple myeloma, you can donate your own stem cells, which has been shown to give you longer disease-free survival. Meaning we collect your stem cells, you receive your chemotherapy and then we give them back and you repopulate your marrow with your own cells. There's a number of diseases where we can approach it like that, where you donate your own stem cells, we bank them and give them back to you later. But more commonly, I think, um, with, as with NMDP, we use healthy donor bone marrow cells, which we collect in any location.

Dr. Caroline Alquist (17:04):

We can cryopreserve them or ship fresh to the patient in need. So for the National Marrow Donor Program, they help us select and find healthy donors that are perfect matches or good matches or haplo matches, whatever the program needs. We collect those cells from those healthy donors here at Hoxworth, keep everyone comfortable--we're so grateful for those donors when they come in--we take those cells and we will do whatever the clinical program needs so we can freeze them, we can keep them fresh, we can do whatever manipulations they need. And then we make sure that product gets to the patient in need wherever they're located, it could be here or it could be international.

Dr. David Oh (17:41):

Yeah, actually, I guess I just caught myself. We use such alphabet soup here and I thought it was being good defining what an NMDP means, but I think they actually changed their name to Be The Match. So that may be what more people are used to hearing, but we are a center of a collection, apheresis center pf collection, a center of excellence for NMDP or Be the Match, which I think is a great activity for us. How many nurses do we have in our department?

Dr. Caroline Alquist (18:06):

We currently have eight full-time RNs in our department, which are amazing. We are, they're able to be available seven days a week, 24 hours a day to patients in need for anything from planned stem cell collections to emergency TTP situations. This is a really dedicated, hardworking team that allows this program to exist. Without their commitment, we couldn't, we couldn't serve our population with the strength and ability that we do.

Alecia Lipton (18:35):

I think important to point out is this team is mobile. So they're not just staying at Hoxworth. You have them going out to hospitals.

Dr. Caroline Alquist (18:42):

That's right. When we get the call, we will be there for you. We have clients throughout the tri-state area, and if there's a patient in need, we get our machine bedside to you. We don't expect you to transfer your patients to us. We'll come to wherever you need us to be, which is really a pretty amazing service that we're able to provide here. Many programs do not have that capability. So that is certainly a unique strength to the Hoxworth system.

Dr. David Oh (19:08):

Yeah, that's a great point, Alecia, you know, we actually have devices that are stationed at one of the Mercy hospitals in town, at TriHealth, at Children's Hospital. And so, of course we're so close to UC as well. So yeah, so we often do procedures at the hospitals for those patients. And we actually, we'll go into a little bit more of the alphabet soup here. Can you talk a little bit about FACT and the fact that we are an accredited FACT collection center?

Dr. Caroline Alquist (19:38):

I think FACT just goes by FACT now, too, right? I don't think that they don't, they don't use a longer name anymore. Um, so FACT accreditation is essentially accreditation system for the collection and transfusion of stem cells. We are a FACT accredited location, meaning that we follow the highest standards for protocols, procedures, facility standards, to make sure that we serve our population in the most safe way for both our donors and recipients.

Dr. David Oh (20:08):

And we're also AABB accredited for this activity as well.

Dr. Caroline Alquist (20:11):

Absolutely.

Dr. David Oh (20:11):

Yes, definitely. So I don't want to leave them out. And AABB just stands for AABB right now.

Dr. Caroline Alquist (20:18):

Formerly known as an American Academy or Association of Blood Banks! AABB is a very important force in the blood banking world and they also do govern cellular therapy practices and do have a large say in making sure our cellular therapy practices are, are up to snuff.

Dr. David Oh (20:35):

Yeah. And so for some of our hospitals in the area, we prefer provide the apheresis collection services under FACT, so that they can be FACT accredited as a program overall, as well. And we're really an integral part of that whole process.

Dr. Caroline Alquist (20:49):

Absolutely.

New Speaker (20:50):

I know another activity that, that we have at Hoxworth is as part of our mission is research, and I believe therapeutic apheresis supports that mission in many different ways. Maybe you could mention, maybe you could discuss that a little bit.

Alecia Lipton (21:05):

Absolutely. Our apheresis team plays an integral role in the research happenings in the tri-state area. Most cellular therapy programs are doing work on mononuclear cells, known as MNCs. So this is going to be the same layer that stem cells hang out in, but we know we can collect them, right, cause it's just a layer of the centrifuge blood. So we collect that mononuclear cell layer, and we put it in a bag and we'll send it to whatever lab we need to for processing. Some of these technologies are going to be educating T cells, getting them to target certain tumors or target certain systems. There's also gene editing research going on. Basically, if you need that raw source material of mononuclear cells, our team can get them for you.

Dr. David Oh (21:51):

And I guess the last question I have for you is, from my experience, before joining Hoxworth, therapeutic apheresis was actually something that, that we did not do very much when I was in San Diego for about 10 years. And when I was at Stanford, that activity occurred, but it was not under the transfusion service. And so I think it's interesting at Hoxworth, that this really is run by, by us as transfusion medicine professionals. And I guess I would just like your thoughts on that.

Dr. Caroline Alquist (22:21):

No, absolutely. I mean, apheresis has been a technology around for quite some time. I mean, since the 1950s we've been developing these cool new instruments and they get new iterations regularly. What we know is that it's applicable to just about every facet of medicine there is. So it's really no surprise that certain areas have, have started operating apheresis services. I know that nephrology is a service that commonly also is involved in apheresis and dermatology for ECP reasons, that photophoresis, I had mentioned earlier. We know that the service can be run by a lot of different specialties, but given that it is really very transfusion medicine based, it does fit quite naturally into the purview of a transfusion medicine service under physicians that are boarded in transfusion medicine. This is, this is our bread and butter. So it feels like a comfortable service for us. And it's something I'm really proud that we include in the, in the Hoxworth portfolio.

Alecia Lipton (23:17):

Dr. Ahlquist, thank you so much for joining us today. I hope that you'll come back again and you've been listening to in the know with Dr. Oh presented by Hoxworth Blood Center. We'd like to hear from you. What do you want to hear about in future episodes? You can email us at hoxworthintheknow@uc.edu. You can also always give us a call at (513) 451-0910. Thank you. On behalf of Dr. Alquist and Dr. Oh, you've been listening to In the Know with Dr. Oh! 

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