Sickle Cell Trait, Inequity, and the Need for Change

HELEN: Welcome to Talking About Blood. I’m Helen Osborne, host of this podcast series and a member of the advisory board for The Blood Project. I also produce and host my own podcast series about health communication, and that’s called Health Literacy Out Loud. Today’s guest is Dr. Brian Carney, who is a hematologist and an apheresis physician at Beth Israel Deaconess Medical Center in Boston, Mass. He also is assistant professor of medicine at Harvard Medical School. Brian has a strong interest in issues affecting health care equity in hematology, particularly in regards to sickle cell trait. Brian and some colleagues authored the paper recently published in New England Journal of Medicine called Sickle Cell Trait, Inequity, and the Need for Change. Brian, welcome to Talking About Blood.

BRIAN: Thank you for inviting me.

HELEN: So let’s take it from the beginning here. What is sickle cell trait, and how is that different from sickle cell disease?

BRIAN: So I think that the first and most important thing is sickle cell trait is not a disease. So it’s a genetic carrier condition where people have one copy of the sickle hemoglobin. Everybody is born with two copies of the beta hemoglobin gene, and people with two sickle copies have sickle cell disease, which is very significant, and there are a lot of clinical implications. Sickle cell trait is a carrier state. You only have one of the copies, and the clinical implications are really limited.

HELEN: So why is this something that’s an issue of health equity? It sounds like to me like they’re two different states.

BRIAN: So they’re two different states, and what’s happened is people have, in many cases, inappropriately taken a lot of the complications and issues that can happen with sickle cell disease and applied that to individuals with trait. And some of the policies that have been developed, including practices in the medical field, are inequitable for people with sickle cell trait, kind of treating them as if they have a disease, when in actuality they don’t.

HELEN: That’s fascinating. Give us an example.

BRIAN: So one big example, one of the things that really got me into this field are inequities with regards to stem cell collection. And stem cell collection is not something that people hear a lot about, but it’s a really important procedure. Stem cells are used to treat a number of blood cancers, like leukemia, lymphoma, myeloma, and the collection of those cells, either from the patient who will be treated or a donor, is something that we need to do to provide those therapies. And a couple of years ago, I found out that even locally within Boston, stem cell collection practices varied widely in patients with known or suspected sickle cell trait. For example, patients who self-identify as African-American or Black may be asked about their sickle cell trait status. They may be made to undergo testing prior to stem cell collection. And if they answer in the affirmative or if the testing is positive, there will be a different approach to that collection.

HELEN: That raises some questions for me as I’m listening to this powerful story. You said people are asked about their sickle cell trait status. I want to know, is that something that everybody kind of knows about? Or is that like, where did that come from? And then I want to hear about how it affects care, treatment and care.

BRIAN: So patients sometimes do know about it. Females are more likely to know if they’ve ever been pregnant because sickle cell trait screening is part of the pre-pregnancy evaluation care. Males are less likely to know. But, you know, it could go either way. People could know or they could not know. They could find out as a result of the pre-stem cell collection screening if that’s something that’s mandated.

HELEN: All right.

BRIAN: In the implications for care, one of the things that we need to do when performing a stem cell collection is we need to mobilize the stem cells from the bone marrow and into the peripheral blood so that we can collect the cells through an IV. If we’re not able to use these mobilization therapies, then there’s a much higher likelihood that we’ll have to do multiple bone marrow biopsies to collect the cells, which is more risky, has more complications, and is a much larger procedure than just doing the collection with mobilization through an IV.

HELEN: So your interest, this is your world, is looking at these stem cell transplants. Was it one particular person? Was it kind of categorically you see whether, you know, whether sickle cell trait is an issue or was it one person that really got you going on this?

BRIAN: Yeah. It was a colleague of mine, Dr. Rich Haspel, who kind of brought this to my attention. And then really it was just kind of looking at the clinical practice, looking at how variable the practice was, even within my own city, Boston, that the five different major hospitals are doing five different things. So there’s incredible variability. And then looking at the data and the evidence that there is, there’s no evidence suggesting that mobilization and stem cell collection is associated with harm in people with sickle cell trait. So the clinical practice, and actually some of the guidelines as well, just are completely uninformed by the evidence.

HELEN: I’m just making a note of that. So this is a case where clinical practice and the guidelines are uninformed by the data? That sounds radical. No wonder you’ve gotten interested in this. Does this only show up for stem cell transplants or you talked about pregnant women may know about this? Like, is this just a broad-based factor in society?

BRIAN: That’s one of the things that this led us to. So I was kind of beginning within my world, which is stem cell collection for patients. But the more we dug into it, the more it appeared that this is really a systemic issue throughout multiple organizations and society in general, where sickle cell trait is being used as a basis for inequitable treatment. And there’s a lot of either misunderstanding or misapplication of the evidence, as well as frankly, some pretty poor studies that are being used to inform both policy and decision-making.

HELEN: So, Brian, I’m fascinated this. You talked about this information that has a kind of a weak underpinning, it sounds like, in ways. It has implications both organizationally and for health care, but also in society. So you talked about some implications in health care when it comes to, you know, collection of stem cells. What about other implications in health care?

BRIAN: Well, one of the big ones that we’ve looked at is actually health care provided in the U.S. military. As part of the military, sickle cell trait screening is mandated. So soldiers who self-identify as African-American or Black are forced to undergo screening for sickle cell trait. And what do they do with that information? They identify these recruits during basic training with either red dog tags, which have been used in the Army, or for example, in the Navy, recruits are made to wear a white belt to identify them as either specifically having sickle cell trait in the case of the white belt, or the red dog tag is meant to signify a medical condition, which is, again, problematic because we’re talking about a carrier state and these recruits are being identified as if they’re ill.

HELEN: Because it’s not a disease.

BRIAN: It’s not a disease, no.

HELEN: How did this get started? I mean, there’s, you know, to make a decision for all of the military or all the patients in health care, you look carefully at the data and you said there’s some not good data out there. How did this get started? Do you know?

BRIAN: So a lot of this got started in the late 60s and early 70s, when there were a number of soldiers, three of them were Marine Corps, who died during basic training at high elevation. And that prompted the military, the Army in particular, to do a large retrospective study where they looked at millions of recruits, both Black and non-Black, and they found increased rates of sudden death in recruits who self-identified as African-American or Black. The problems with this study, it was not controlled. And actually in sickle cell trait negative Black recruits, there was a twofold increased risk of death.

HELEN: So in sickle cell trait negative?

BRIAN: In sickle cell trait negative recruits who self-identify as Black, there was a twofold increased risk of death, just Black versus non-Black, suggesting that there was some background issues with what was going on in basic training that are unrelated to sickle cell trait. This was a very poorly done study that was used as the basis for military practice for about the next 20 years.

HELEN: Now, did this research come from a good place? I mean, you’re dealing with a lot of people, whether it’s the military or pregnant women, you want the best outcomes possible. Did this come from a good place or was this, you keep mentioning about people who self-identify as Black or African-American. Is this a way to divide us or is this a way to bring us together as bringing the highest level of health care possible? And this is just your opinion, I know.

BRIAN: I think it was from a good place, kind of in the interest of keeping people well. I think that there were a number of problems with the methodology of the study. I think to some extent for a long period, it was kind of used as an end-all be-all when the data underpinning it was pretty shaky. I think there are also a lot of implications with this and kind of the military mandatory screening in terms of genetic self-determination. These people are being forced to screen for a genetic disorder, which to me just seems crazy.

HELEN: Okay. I’ve got notes as I’m talking to you, I want to keep asking, and you just use a term I want to follow up with about genetic self-determination. Tell us more about that because now you’re talking about mandated screenings, mandated tests, whether it’s in the clinic, for the stem cell, military, people who are pregnant, but genetic self-determination. Can they go into any of these situations and go, I don’t think I want that test? Or is it like, you’re here, this is what happens?

BRIAN: So in the military in particular, they do not have the option to say no, which there have been some federal laws passed on this issue about not being able to mandate genetic screening. Soldiers, military personnel are not falling under that legislation. So they don’t have an option to say no, which someone like me who’s never been involved in the military, it just seems crazy because someone’s genetics is about as personal as you can get. And prior to sending any genetic testing, I as a physician am required to get informed consent from the patient. They need to know what they’re getting into. Not at all what’s happening here.

HELEN: It’s interesting. I’m hearing more and more about this in more settings and more situations, whether it’s for this trait or other conditions. It’s about that genetic information is coming out there. I think we as more of a society are starting to really figure out what the roles of genes and our genetic histories are. Brian, you also talked about its impact on society. Tell us more about that, about this sickle cell trait issue versus sickle cell disease.

BRIAN: Yeah, I think in society in general, there’s a lot of conflation. And this is both in society and actually in the medical field as well. I think people hear sickle cell and they almost stop there. They think, okay, sickle cell, that’s a disease. But sickle cell disease is so much different from sickle cell trait. Not only does that happen in society, I have in my clinic gotten many referrals from doctors not specializing in hematology who get a new patient, here they have sickle cell trait and they think it’s some disease that requires treatment and follow-up, which is just not the case.

HELEN: It’s fascinating. And our worlds are overlapping because my world in health literacy that I deal with is all about communication and often about word choice. Here you have the first two words are the same, sickle cell trait, sickle cell disease. And you’re talking about very different entities. So it sounds like it’s an issue of practice, an issue of screening, and also an issue of understanding. How would this affect the public at large?

BRIAN: It can really significantly affect the public at large, just given how prevalent it is. In the United States, eight to nine percent of people who self-identify as African-American or Black are positive for sickle cell trait. And some of those people know, some of them don’t, but it can be significantly impactful on those people. Some of them have received bad information and they are walking around day-to-day feeling like they have a disease.

HELEN: Or perhaps they’re thinking that they’re on a continuum of perhaps getting the disease.

BRIAN: Yeah, perhaps.

HELEN: This is powerful information. So the listeners to this podcast, Brian, could the accomplished physicians like yourself, people who know a lot, have been in practice, listeners to this may be those newer in the health sciences or newer in their medical field or just thinking about going into science or medicine. And listeners may be people like me and the general public who just are curious about all things about blood. I’m eager to hear your recommendations and your thoughts about what can any of us do from any of our perspectives about this situation.

BRIAN: Yeah, well, I mean, I think starting with society in general, what I would advise is whenever you hear about something that is being attributed to sickle cell trait, take that with a grain of salt and really exercise caution. I think a great example of this is a lot of cases where people, for example, George Floyd has either died in police custody or been killed by police officers. Defense attorneys have tried to attribute that to sickle cell trait. And it’s happened on the other side, too, by prosecutors, police. There’s been kind of false attribution of deaths in police custody to sickle cell trait. There was a nice New York Times article from 2021 looking at 47 cases where this happened.

HELEN: False attribution of things that affect us in life and death issues of that one. Wow.

BRIAN: Yeah. So that’s a big issue. And that’s a major equity issue because, you know, as we’ve discussed, the vast majority of people with sickle cell trait will be those self-identifying as African-American and black. So it’s being used really to provide cover for police and official misconduct. And we hear about that in the media continuously. George Floyd, there was recently a case in New York as well. This was 2024 where the defense for a black man being killed on a subway was, oh, he had sickle cell trait, which is just it’s not based in reality.

HELEN: Oh, my goodness. I’m glad you are doing your part to help inform at least the professional community. And I hope that this podcast gets heard widely so we can all be learning more. Tell us more about recommendations you have for the seasoned professionals, for the hematologists and also for those newer in sciences and medicine.

BRIAN: Yeah. So I think people newer in science and medicine, what I would advise is to really study both sickle cell disease and trait and to really fight against the inclination to conflate the two. I’ve heard this among trainees, even some of my colleagues, just kind of referring to it as sickle cell. And that’s non-specific because it’s the same thing at that point.

HELEN: Right. Okay. So don’t conflate the two terms, but that’s easy to do. I’m putting on my health literacy hat. It would be nice if there was a distinct term for one versus the other, not wait to the third word to make that distinction. I don’t know if that’s moving along there.

BRIAN: Yeah, it’s a great idea.

HELEN: And then what about for the professional community, you and your colleagues?

BRIAN: Yeah, for the professional community, as Dr. Haspel and I really highlighted in our perspective piece, it’s really the importance of critically appraising the data. And, you know, looking at these studies, looking at the studies that have come out of the military, looking at some of the studies on exertion related death and people with sickle cell trait and, you know, not just accepting the conclusions, really dig in and determine if what the evidence is telling you, what the guidelines telling you, is that actually based on anything? And if our practice is being informed by bad evidence and inappropriate guidelines, it’s really kind of our responsibility as a medical community to work to develop better evidence, better guidelines.

HELEN: Brian, I’m so glad you’ve brought this to everyone’s attention. Thank you. I’m glad that that story and that clinical situation you described a while ago with the collection of stem cells has led to this. And you talk about much bigger, bigger issues. And I really like your recommendation. I hope people will pay heed to it. Wherever our walk in life, don’t always just accept somebody else’s conclusions. Look for the evidence. Put that all into context. Brian, thank you so much for being a guest and talking about blood and for leading the way and letting us know all about this important issue to pay attention to, to this. Thank you for all your good work.

BRIAN: Yeah, thank you.

HELEN: As we just heard from Dr. Brian Carney, it’s important to put information we get into context, look for the evidence, make your conclusions about what is strong and worthy. To learn more about The Blood Project and explore as many resources for professionals, trainees, and patients, go to thebloodproject.com. I invite you to also listen to my other podcast series, and that’s about health communication at healthliteracyoutloud.com. Please help spread the word about this podcast series and The Blood Project. Thank you for listening. Until next time, I’m Helen Osborne.