Hi, I'm Brian Atkins, I'm an assistant professor down here at UT Southwestern in Dallas, Texas, and I'm medical director at Children's Medical Center in Dallas. Today we're going to be talking about transgender issues and blood banking and cellular therapy. So to start off, I have no relevant financial disclosures, but I will point out that this is a review presentation and none of this data is original or my own and is based on experiences that other individuals have had. So a little bit on my background, I am a male and I identify as a male. I come from West Virginia, that's my family. So I was born in Huntington, which is kind of a small college town, but it's actually where I first made friends who are transgender and that was in college. I worked at the tutor center and the physics tutors were both transgender and I got to know them and that was really formative for me in terms of understanding different people in different cultures, things like that, and has really made an impact on me to want to do research in regards to transgender medicine and transgender policy. So a little bit of an outline, first we'll go through some definitions and demographics, sort of get a starting point for our discussion, then we'll go into some donor considerations, some considerations for transfusion services, and then talk about cellular therapy. Our objectives are to review current terminology and demographics within this community, to discuss best practice, and to explore sort of future perspectives and where things may be going in the coming years. First, we'll take a look at some definitions. One important one to keep in mind is sex assigned at birth. So this is the sex label of the individual at birth. This is generally based on visual examination, but sometimes this is based on laboratory testing. We have our legal sex. So I will say that you can list your gender differently on driver's license and things like that now than you could a couple of years ago. So if someone identifies differently than their sex assigned at birth, that can be their legal sex as well. Cisgender is someone who identifies as their sex assigned at birth, and then transgender is someone who identifies as a different gender. I will say that both transgender and non-binary are often used as umbrella terms, either in surveys or in health texts, though that may not necessarily be appropriate in every situation, and I encourage you when speaking with individuals to allow them to share that information with you. Non-binary simply refers to individuals who do not identify with a specific gender or if they identify with both genders. So this includes agender, genderfluid, genderqueer, all of that, and can be used in that situation. So how do we figure out these demographics? As you might imagine, this is kind of a challenging thing to pin down, and a lot of what we rely on is survey data, which may or may not be representative of the population as a whole. The U.S. Census did take a look at trying to evaluate the transgender population within the United States and did some focus groups to try to assess the feasibility of assessing gender on U.S. Census materials and determined that they were not capable of doing so at this time, and there wasn't a really good proxy response by which they could determine gender. Moreover, it's not evaluated by the Public Health Agency of Canada. There is a lot of data from Canadian Blood Services. They've done some really great work up there, and I'll touch on some of that later, but at this time, it is not evaluated by their public health agencies. So like I said, we have to rely on survey data. The survey data, I think, is pretty good, but again, may not be representative of the population as a whole. Also, not every individual is at the same level of outness, and that may preclude some individuals from sharing this information with the surveyors. However, in most recent Gallup polling, as of 2021, 5.6% of Americans identify as LGBT. The estimated transgender population, 0.6% of U.S. adults, and with that, 0.2% of individuals are reporting as other, and then that leads to an estimation of about 2 million adults identifying as transgender. It's important to keep in mind that even as recently as 2018, that estimate was about 1 million. So if we're including non-binary individuals, that number could be as high as 2.6 million within the United States. So it's an emerging population that healthcare providers should be familiar with. And this goes into some more granular detail in terms of splits. So again, transgender individuals make up about 11.3% of the LGBT community, as assessed by Gallup, and then non-binary individuals and other make up 3.3%. And again, amongst all U.S. adults, that's about 0.8%. I think this is a really striking slide, though, because as you can see, the population is much larger in younger groups, such as millennials and Gen Z individuals. This is important to keep in mind, especially as blood donor medicine providers, especially because the donor age group is kind of aging out. A lot of our blood donors tend to be older, sort of in this baby boomer era, and as they age out, it's going to become more and more important to involve these younger individuals. I will say with HIV risk mitigation, in the 80s and 90s, the blood banking community sort of took a swing towards a more conservative stance, which I think was appropriate, maybe in older times, though I think we're swinging back the other way now to involve these individuals. And I think there are some hurt feelings on both sides. Moving forward, I think the blood banking community as a whole is trying to reach out to these groups. So again, often challenging to pick out good data on transgender populations. However, this was a survey put together by the National Center for Transgender Equality. These results are from 2015, published in 2016. It sounds like the updated survey has been delayed due to the pandemic. However, this did look at over 6,000 transgender individuals and gender non-conforming participants. Their sample size, a large proportion were male assigned at birth, but a large group was also female assigned at birth. So this has differing implications in terms of trolley risk as well as HIV risk. One more thing to keep in mind, amongst gender non-conforming individuals or non-binary individuals, a large proportion of these donors or patients were assigned female at birth. So again, keeping trolley risk in mind. And this survey is really cool. It allowed people to pick any title they wanted. And as you can see, all these percentages do add up to be greater than 100, because people could select more than one choice. There were a lot of different feelings and responses. 17% identified as other. And in that other, there was room for free text. And there were over 500 different responses. So I think a lot of policy and stuff tries to be one size fits all. Though I think this population is really telling us that maybe we shouldn't really be trying to think one size fits all and trying to just be more inclusive whenever we make our policy. Which sort of brings us to another point. This same group, the National Center for Transgender Equality, did a discrimination survey in 2011. And they showed that 63% of these participants experienced a serious act of discrimination. This involves either being denied a job, or losing a house, or even being assaulted because of bias. This is a population where we really need to be compassionate and sensitive to their backgrounds. And I think understanding that as they come in to donate blood or to receive care in a hospital, that is sort of the perspective that they're coming in from. And we may not see that, we meaning cisgender healthcare providers, every time. So I think trying to meet people where they're at, and being thoughtful of things like that is really important. And moreover, not everyone who is transgender has fully transitioned and is not completely out with all groups. So outness varies amongst situation and amongst individual. So people are more likely to be out with their immediate family or with their friends, but less likely to be out with current healthcare providers. So this is from that 2015 survey. As you can see, only 40% of individuals are out completely with all healthcare providers, and 31% are not out at all. So really coming to these situations with a certain level of understanding and openness is really important in terms of making people comfortable and making sure we get the best information possible. And then this is amongst non-binary individuals, trying to assess reasons for not telling people their non-binary gender identity. Again, this sort of goes back to the experience with discrimination, worry about violence, worry that people might reject them, things like that. And sometimes, 24% of the time, actually, they worry they might not receive appropriate medical care. So getting more information and sort of coming at this population, trying to be as understanding as possible, I think is the best thing that we as healthcare providers can do. So considerations for the blood center world. I will say that I do not work at a blood center. I am the director of a hospital blood bank. However, I have spoken to my friends who work in blood center world and tried to sort of pick their brains to get some ideas. Ultimately, a lot of this is very policy-driven, and there are certain things we need to work around to make things better for this population. So changes in recent years. This is a paper from 2017 sort of taking a look at the state of blood donation for transgender individuals. It says, I am Kate, and I am a transgender blood donor. That's, of course, a reference to Caitlyn Jenner. So at that time, there were only four entries for the word transgender in transfusion publications. Likewise, at that time, FDA had an option for sex assigned at birth or gender as self-reported. Karp and Hall sort of brought this issue to the fore, which I think is really important and the kind of stuff that I like to read in transfusion. So I'm glad that they did that. And with that, in the past couple of years, there has been a move towards more resources and increased awareness. So if you go on PubMed today and look for transgender blood donation, you can see there are now 10 results and, of course, a number of papers occurring in the past two years. And if you go to blood donation websites, either for Canadian Blood Services or Red Cross or Diversity, you can see that there's information for LGBTQ plus donors. So with that, there is a need for donor health questionnaire resources for these individuals. So the current DHQ that's put together by the AABB and FDA contains a lot of cis-normative verbiage, meaning that it's written from the perspective that everyone is sex assigned at birth. However, as we've sort of been discussing here, that's not necessarily the case with everyone. Maybe things need to be tailored a little bit differently. With that, there is still a need to assess for HIV risk as well as assess donors for pregnancy history to reduce the risk of trolley in our blood recipients. So it's sort of a back and forth between trying to offer compassionate care for our donors and safe blood products for our patients. And I don't think that those two things need to be mutually exclusive, but there are some steps that need to be taken in order to provide better DHQs. I will say that you can always contact your CSO or safety officer with the FDA if you want to make any modifications to your DHQ or to implement a universal DHQ. With that, different donor centers do different things. Some places already are using a universal DHQ where everybody answers all the same questions with regard to pregnancy history and MSM contact. Other places describe using sort of a tiered response where first gender is assessed and then if someone is sex assigned at birth male, gender male, they will answer the male DHQ versus female sex assigned at birth. Female identifying would answer the female questions and a universal DHQ would be reserved for transgender or non-binary individuals. With that, there's been a relaxation of risk reduction of HIV transmission deferral guidelines. This occurred last April sort of in conjunction with the pandemic as there were shortages in numerous blood products. And I think it was something that was about time that that happened, so I'm glad that they were able to make that happen in that moment. I will say that there are certain things within the DHQ that don't always make sense. For example, we're still screening for syphilis, even though we haven't had any syphilis transmission in the blood supply since 1966. So I think a lot of things in DHQ world move kind of slowly. And again, that's sort of that pendulum moving back and forth in terms of more conservative practice versus less conservative practice. And again, the ultimate goal is to offer compassionate care to our donors while offering safe blood to our recipients. So here we go. These are the FDA requirements. So it used to be 12 months for MSM individuals, a deferral. Now it's only three months. With that, they've also given some guidance relating to pre-exposure or post-exposure prophylaxis for HIV medications. Now it's only three months. They also changed a lot of other things such as needle stick, tattoo, exposure to blood. Now those are only three-month deferrals, which again, I think is appropriate as we do have increased sensitivity for screening in the window period. We've got that window period down to about a week or less with nucleic acid testing for HIV. I think we're doing a pretty good job with things like that, but it is a back and forth between testing and DHQ questions. I will say that taking a look at testing, there has also been a move towards pathogen reduction technology. And hopefully as pathogen reduction technology moves beyond just plasma and platelets, that it can also move into the realm of red cells. And maybe we can start to roll back some of these questions and get to involve more people in blood donation. HIV prevalence is higher in the trans population based on data that's available. Again, this is survey data. It may not necessarily be representative of the trans population as a whole. It's often challenging to assess because many of the individuals who are enrolled in some of these surveys have been selected because they're HIV positive or because of certain high risk behaviors that have put them into the healthcare realm. And that's why they're being evaluated by surveys like this. I will say that the USTS 2015 survey did find a 1.4% prevalence of HIV amongst their surveyed individuals. This is about five times higher than the general US population. And again, the question remains very cis-normative in its verbiage, which might require some modification moving forward. TROLLI risk mitigation strategies. So it was recognized in the early 2000s that TROLLI is of course related to HLA and HNA antibodies. It was the number one leading cause of transfusion related mortality, though in recent years that has decreased with now TACO or transfusion associated circulatory overload being the number one cause of transfusion related mortality. So the main concern is for females sex assigned at birth who have previously been pregnant to develop HLA antibodies. These HLA antibodies occur at a rate of about 10% with each pregnancy, meaning about 10% of females assigned at birth who have had pregnancies, 10% of them if they've had one baby would have HLA antibodies, whereas 30% of them would have HLA antibodies if they've had three pregnancies and so on and so forth. By excluding sex assigned at birth females from plasma donation and platelet donation, we have been able to reduce that number of trolley cases, which I think is really fantastic, and also by screening for HLA antibodies. In terms of trolley risk and determining how many trans or non-binary individuals have had pregnancies, that's once more very hard to pin down. Of the respondents in the 2015 survey, 18% were parents, though that does not speak to the number of individuals who were sexicide at birth female. Once more, the question wording is very normative, and it would be expensive to screen all blood donors for HLA sensitization, and we do not currently screen everyone for human neutrophil antibody levels currently in the blood supply. So it is kind of a challenge, and I think that determining how to implement a universal donor health questionnaire might be useful. And then I will say there have been a lot of positive changes as evidenced by both materials released from blood centers, as well as an increase in publications relating to trans people and blood donation. I think we're moving in the right direction, though there are some sort of practical considerations as well. We have hemoglobin requirements, and these are for sexicide at birth men and women in the United States. So it's 12.5 for sexicide at birth women, and 813 grams per deciliter for sexicide at birth men. Once more, you could just use the sexicide at birth male hemoglobin requirements be more conservative, and this would not likely exclude sexicide at birth women or sexicide at birth men from being able to donate, and would help in terms of iron deficiency, things like that. Apheresis machine settings vary from sexicide at birth men and sexicide at birth women. The blood volume is going to be lower in sexicide at birth female individuals, though it should be noted that use of androgen therapy for transitioning will change the hematocrit as well as blood volume. So it may not always be appropriate to use sexicide at birth female apheresis machine settings, though once more, that would be more conservative. In some places, they have gender-based deferral policies, specifically in Canada, where they have longer inter-donation intervals for sexicide at birth females. And then there's also working around your blood establishment computer software. So the BEX is sort of the laboratory information software of the blood center world. Most of these BEX are not going to have options for a third gender, and it may be challenging to change the gender or override the gender on someone's current entry. And finally, there's need for sensitivity training. With that involvement of the LGBTQ plus community, I think it's very important for blood centers. In the Canadian Blood Services experience, and this comes directly from their paper, they said that they ran into some issues because they were using screening in individuals who had had gender-confirming surgery. They would screen those individuals as their gender-confirmed surgical state. So that kind of got them into some hot water because it was argued that that put unnecessary weight on gender confirmation surgery in terms of identity. So with that, they've reached out to the LGBTQ plus community in Canada to try and involve them to make more considerate decisions. And I think they're doing a really fantastic job saying we're not sure about all this stuff, but we're asking the experts, which is the LGBTQ plus community for help. So hopefully we can get to a spot that's a little better for both sides, which ultimately again, we're trying to involve the LGBTQ plus community as much as possible these days, which I think is fantastic. But they suggest these culturally competent discussions and sort of some different ways to ask questions. Blood centers should likely develop sort of more formalized training or hire individuals to come in and perform training modules or provide people with electronic modules. Often individuals who have less experience knowing people who are trans or non-binary will have some inherent bias and many healthcare providers lack experience caring for these diverse populations. So now after sort of blood center world, we'll move to the hospital. So these will be some considerations for transfusion services. So RH alloimmunization risk, I think is the biggest thing to keep in mind here. I will say that in terms of transfusion, there are fewer issues related to gender than on the donor side, but there's still a lot of important things to keep in mind. And I think the biggest thing is probably this, RH alloimmunization risk. So this is a case that was put together by Mays in 2018. This was a patient, they encountered a 40-year-old transgender man who blood typed as O-RH negative. There was severe bleeding after a biopsy of a cervical mass and with that, the MTP was initiated or massive transfusion protocol. The blood bank was preparing RH positive units. And then the text noted that it was, the MTP was destined for an OB floor. So they contacted the clinician and determined that the patient still was of childbearing age and had a retained and had not undergone gender confirming surgery. So with that, they did switch to RH negative units. So this sort of sets up the issue of RH alloimmunization in this population. So many institutions are gonna have a policy requiring RH negative trauma units for sex assigned to birth females, less than 50 years of age. This is important as in the United States, at least we've done a really fantastic job of RH immune globulin usage and prevention of D alloimmunization and hemolytic disease of the fetus and newborn. And on the right, this is a study put together by Schultz that also involved a number of different groups looking at this from eight different countries. And they were able to show that the age at which someone receives RH positive units in FCP, that's sex assigned to birth female of childbearing potential. So these individuals, it was shown that the rate of HDFN was higher if these people received RH positive blood at a younger age. I will say that in trauma, the rate of alloimmunization is a little bit lower, though another recent study by some of the same docs looking at RH alloimmunization in trauma patients, predominantly sex assigned at birth male put together by Mark Yaser, they were showing a 42.7% alloimmunization rates. That's actually really high and higher than was previously shown. So I think hospitals need to have some sort of policy in place and that's supported by standards. Similar policies will exist for platelet products and that should be greater than two mils of RH positive red cells. And weak D testing policies are often put in place for sex assigned at birth women of childbearing age. And this comes from standards. So RH type should be determined with an anti-D reagent and this should be in patients of all childbearing potential. So I think they're doing a good job writing that. And then the transfusion service should have a policy in place for RH immune globulin prophylaxis. Again, weak D testing is not required for all individuals of childbearing potential. However, many hospitals will perform weak D testing. So I think putting together policy for LGBTQ plus individuals is really just gonna be something that's necessary moving forward. Considerations here, I will say that there is a little bit less literature in terms of transfusion services as compared to donor medicine. And I think that may stem from fewer issues relating to gender when it comes to a hospital transfusion service. However, we are definitely lacking in this area in terms of a robust library of literature to use. We will need unique policies at each hospital. I will say I work predominantly at a children's hospital and we currently give RH negative units to anyone who's RH negative in a trauma. And we give RH positive units to anyone who's RH positive in a trauma. Our LIS does not currently support addition of gender as well as sex assigned at birth. And it does not currently have any options for identification as transgender or non-binary. Though I will say that our electronic health record does offer a module where you can input that. So that is good. But I think moving forward, at least for my blood bank, I think that we need to get policies put in place. So laboratory information systems, you may be able to work with your vendor to input different genders or histories. And then once more, apheresis machines still require sex or gender determination for the total blood volume. With that, I think it's always gonna be more conservative to use female sex assigned at birth for the apheresis machine settings. And obviously I'm sort of in a special situation where we're always giving RH negative and RH positive units based on RH status. I think obviously in an adult transfusion service, that would be kind of untenable, especially with recent supply shortages. So again, I think putting together specific policies for this population would be important in those situations. And finally, cellular therapy. Do transgender individuals represent an overlooked population amongst stem cell donors? So sort of in a similar way to the transgender donation paper in transfusion a couple of years ago, I wrote this paper with a couple of my attendings in residency looking at transgender individuals in terms of stem cell donation. So keeping in mind that the transgender population is significantly younger as time progresses, we're seeing more and more young people identifying as trans or non-binary, it's going to be really important to involve them in stem cell donation. So there has been shown increased GVHD in sex assigned at birth female donors to sex assigned at birth male recipients. Many studies have shown sort of equivocal results, but there have been studies that have shown that. However, the more important thing to keep in mind is that overall survival increases with the young stem cell donors. And this is based on CIBMTR data. They had a cohort of about 4,000 people and showed that only donor age was predictive of survival outside of HLA matching. And there was a decrease in two-year survival associated with increasing age. And that's what's being shown over here. So as you can see, the donor age goes up and survival goes down. So there's definitely an interest in involving younger donors and with that reaching out to the LGBTQ plus community. A lot of what I spoke about in my paper, which was an editorial, was what is currently required in standard accrediting body or regulatory information. So FACT-JC is responsible for accrediting stem cell donor centers and things like that. And in their standards, they do require a pregnancy test for all female donors with childbearing potential. This can be challenging to determine based on gender and may require asking sex assigned at birth in order to determine if an individual has childbearing potential. Again, the wording is kind of cis-normative. And finally, this could lead to delay in collection amongst donors. It has been shown that there's sort of equivocal impact of outcomes based on sex assigned at birth, but I think it's much more important for follow-up testing for engraftment. So it's important to establish a rapport with our stem cell donors in order to get accurate information. Recipients of stem cell transplants will undergo karyotyping as well as engraftment studies following their transplant. And though oftentimes the people who are performing the engraftment studies do not have information about the donor, it would be important if suddenly a Y chromosome were to show up on a karyotype, and that was not described in the donor information. So keeping that in mind, it is really important to sort of get to the bottom of this. And I think the best way to receive accurate information is just to go in with a sort of open and understanding tone, and really pointing out that the reason we're trying to get to the bottom of this information is not because of any kind of bias or anything like that, but it's specifically for the care of our patients on the other side. So again, trying to offer a compassionate care for our donors while offering optimal care for our patients and recipients. So as far as regulatory information goes, the Code of Federal Regulations, or CFR, Title 21, relates to hematopoietic stem cells coming from peripheral blood. And there's no update since 2005 and no specific guidance related to sex or gender. And then the Public Health Service Act, that relates to umbilical cord transplants as well as bone marrow transplants. There's no specific guidance relating to sex or gender, though underneath Section 379, which is the Bill Young Cell Transplantation Program, we do get into sort of looking at Be The Match, which is sort of the private public partnership with the Bill Young Cell Transplantation Program. Be The Match is a nonprofit responsible for a lot of the stem cell donor recruitment and collections or facilitating collections within the United States. And in 2018, they published this article in Biology of Blood Marrow Transplantation. They had identified that there was unique needs amongst the LGBTQ community and said that they wanted to reach out to that group. And I am happy to report that since I've written my paper and since they have said that, they stuck with it. And now whenever you get on their website, they have facts and myths about stem cell donation and they say, yes, you can join the registry and donate. And I was going through, if you wanna donate, as you can see, I have a million tabs because I was getting ready for my talk. You can select your gender identity and you can also select your sex identified at birth. And I think they do a good job communicating that the sex assigned at birth is important, not because they have some sort of aversion to trans donors or anything like that, but they're just trying to say that this is important for both the health of the donor and the patient. And that's really what we're getting at. And why talks about this and research about this are important is we're trying to get to the bottom of how do we best reach out to this community to ensure that we get accurate information for both the donor and the recipient. So sort of some final things to think about, the LGBTQ plus population is expanding and it's definitely got a large number of younger individuals. These younger individuals are gonna be our blood donors and our stem cell donors moving forward. There needs to be increased awareness by both accrediting bodies, as well as blood centers and donor networks. There is limited literature for guidance of best practice at this time. I will say that the AABB has put together a lot of fantastic literature, both through their journal, Transfusion, as well as AABB News had an article in 2018 that was really nice. There was an AABB platform and I think there's an e-cast as well. But anyways, if you are interested, I would encourage you to check out those resources because I think they're really fantastic. And the people who did that work were definitely at least influential on me as I put this presentation together. And finally, I think there's definitely a need for sensitivity training and involvement of the LGBTQ plus community when you're making these decisions and whenever you're trying to put together materials for donors, especially in order to use appropriate language and sort of meet people where they're at. And with that, I think it's about time for the end and some questions. These are my references. I know everybody's probably on their laptops. So I made this super small, but you can look in on there and pull out whatever you need. So thank you very much.

transgender issues

blood banking

cellular therapy

donor policies

HIV risk

sensitivity training

LGBTQ+ community